Biochemistry and Physiology

requires glucantransferase and amylo-alpha-1,6 glucosidase

Glycogen storage diseases:
Von Gierke disease (type I glycogenosis) autosomal recessive G6Pase deficiency that causes
hepatomegaly, renomegaly, platelet disfunction, stunted growth
Pompe disease (type II glycogenosis) autosomal recessive lysosomal glucosidase deficiency that
causes hepatomegaly, cardiomegaly, muscle hypotonia
McArdle syndrome (type V glycogenosis) autosomal recessive muscle glycogen phosphorylase
deficiency that causes muscle crapping and myoglobinuria
Inulin fructose polymer, highly water soluble, determines GFR

Glycosaminoglycans (GAGs) AKA mucopolysaccharides heteropolymer, unbranched chains of repeating

disaccharide units of an amino sugar (hexosamine) or an uronic acid; they are the major structural
polysaccharides of ECM, CT and outer cell membranes. They are highly negatively charged and easily attract
water. Accumulation of GAGs can cause disease.
Their high viscosity imparts low compressibility, making them ideal for lubricating joints. However,
their rigidity provides structural integrity to the cells and provides passageways between cells allowing
for cell migration. They act as a molecular sponge
The disaccharide units contain either of 2 modified sugars: GalNAc or GlcNAc an da uronic acid such
as glucoronate or iduronate
Chondroitin sulfate most abundant GAG; found in cartilage, bone, tendon and ligaments, heart
valves
o N-acetylgalactosamine + D-gluconuric acid
o Acts as a building block for proteoglycan molecules and has anti-inflammatory properties
Hyaluronic acid doesnt form proteoglycan and doesnt contain sulfur; found in ECM, synovial fluid,
vitreous humor
o N-acetylglucosamine + D-glucoronic acid
o Known as the cement substance of tissues; they are large, shock-absorbing polymers
o Hyaluronidase promotes depolymerization of the extracellular matrix GS. It slits hyaluronic
acid, lowering its viscosity and increasing the permeability of CT to absorption of fluids.
Heparan sulfate basement membranes; formed by N-acetylglucosamine + L-glucoronic acid (or Liduronic)
o Contains higher acetylated glucosamine than heparin
Heparin found in mast cell granules; made of same components as heparin sulfate but more sulfated
o Serves as an anticoagulant
Dermatan sulfate skin and vasculature; N-acetylgalactosamine + L-iduronic acid
Keratan sulfate cornea, cartilage, bone; contains N-acetylglucosamine + galactose (this is the most
heterogeneous GAG)
Mucopolysaccharide Disorders
Hurlers syndrome deficiency of -L-iduronidase accumulation of heparin sulfate and dermatan
sulfate
o Mental retardation, corneal clouding, gargoylism
o Autosomal recessive
Hunters syndrome deficiency of L-iduronate sulfatase accumulation of heparin sulfate and
dermatan sulfate
o Mental retardation, gargoylism (no corneal clouding)
o X-linked recessive
Proteoglycans linkage of GAGs to core protein involves a specific trisaccharide composed of 2 galactose and 1
xylose residue. The protein cores are rich in serine and threonine residues, allowing multiple GAG attachments.
Proteoglycans lubricate, form ECM, and act as a molecular sieve.

Cellulose homopolymer of -D-glucopyranose linked by -1,4 bonds

Chitin homopolymer of N-acetyl-D-glucosamine linked by -1,4 bonds
Bacterial Polysaccharides
Dextran homopolymer of glucose (1,6 with some 1,3 branches) formed by hydrolysis of sucrose;
made by Strep mutans
o Produced outside of the cell by dextran sucrase (glycosyl transferase), which splits sucrose
into glucose and fructose then links the glucose molecules into dextran, which is deposited
as a thick glycocalyx around the cell
o It is essential for cariogenicity of Strep mutans
Levan homopolymer of fructose formed by hydrolysis of sucrose by the enzyme levan sucrase
o Also increase the adhesion of bacteria to teeth, and promote formation of dental plaque
o They are considered to be reserve nutrients for bacteria
The bacterial cell wall contains heteropolysaccharide made up of alternating N-acetylglucosamine and Nacetylmuramic acid units.
Glycoproteins structural components, transport molecules, enzymes, receptors, hormones, cell-to-cell
interactions; they include collagens, proteoglycans, immunoglobulins, selectins, fibronectin, laminin, TSH,
alkaline phosphatase
The carbohydrate portion of glycoproteins differes from proteoglycans in that it is shorter and
branched.
Glycolipids sphingolipids with attached carbohydrates; found on outer cell membranes especially of the brain
and NS
Derived from the lipid ceramide
Gangliosides, galactosylceramide, glucosylceramide
**Sugars that contain aldehyde groups that are oxidized to carboxylic acids are called reducing sugars.
Examples include: lactose, maltose, glucose, galactose, and fructose. Reducing sugars have a free anomeric
carbon (the oxygen on C1 is available for redox) that can be oxidized. If the oxygen on the anomeric carbon (the
carbonyl group) isnt attached to any other structure, then the sugar is a reducing sugar. A reducing sugar can
reduce other substances as the anomeric carbon itself becomes oxidized.
This used to be the basis for reducing-sugar tests for things like diabetes, but now most blood glucose
tests use glucose oxidase reactions.
Sucrose is not a reducing sugar because both anomeric carbons are involved in the bond.
Common test reagents are: Benedicts reagent (CuSO4/citrate) and Fehlings reagent
(CuSO4/tartrate); they are reducing sugars because they reduce Cu2+ to Cu+ which forms a red
precipitatecopper (I) oxide.
SALIVA hypotonic fluid with pH ranging from 6-7 and containing mostly water, electrolytes, and organic
factors
Functions of saliva
Antimicrobial:
o Secretory IgA opsonization
o Lysozyme hydrolyzes bacterial cell walls
o Lactoperoxidase inhibits lysine/glutamic acid accumulation
Dental integrity calcium and phosphate for mineralization, glycoproteins for pellicle formation
Also cleansing, digesting (alpha-amylase), buffering (HCO3-) and lubricating
High K+ and HCO3- concentrations, low NaCl concentrations, production inhibited by vagotomy,
hypotonic solution.
Main organic components are lingual lipase, mucopolysaccharides, proline-rich glycoproteins; also IgA
(only Ig in saliva), lysozyme, lactoferrin, albumin, urea and glucose
Parasympathetics serous secretions
Sympathetics mucous secretions
PROTEINS

All amino acids in protein are L configuration; D-amino acids are found in some antibiotics and
bacterial cell walls
Polar, uncharged
Nonpolar, alipathic Acidic
Basic
Aromatic
Thiol
(hydrophilic)
(hydrophobic)
(negatively
(positively
charged)
charged)
Asparagine
Alanine
Aspartate
Arginine
Tyrosine*
Cysteine
Cysteine
Glycine
Glutamate
Histidine
Phenylalanine*
Methionine
Glutamine
Proline
Lysine*
Tryptophan*
Serine
Valine
Methionine
Leucine*
Threonine
Isoleucine*
Generally nonpolar
**The nine amino acids in bold are ESSENTIAL amino acids.
**Hydrophobic amino acids have side chains that contain alipathic groups (Val, Leu, Iso) or aromatic groups
(Phe, Tyr, Trp)
**Non-essential amino acids are synthesized from glucose, except for tyrosine.
Tyrosine is made from the essential amino acid phenylalanine
Important: nonessential amino acids can be made from corresponding alpha-keto acids, an alphaamino acid, a specific transaminase enzyme, and the coenzyme pyridoxal phosphate (Vitamin B6).
These amino acids include alanine, aspartate, and glutamate.
Dopamine, the thyroid hormones, melanin, NE and Epi are all made from tyrosine.
The other nonessential amino acids are synthesized by amidation (glutamine and asparagines).
Note: cysteine, although its carbon skeleton can be formed from carbohydrates, requires methionine
(essential amino acid) to supply the sulfhydryl group
Amino acids can be categorized by their metabolic end products, also. They are either
*Ketogenic (producing ketone bodies and acetyl-CoA)
Glucogenic (producing glucose, and thus pyruvate)
*Some amino acids produce both
Cysteine and methionine both have sulfur-containing side groups.
Peptide bonds short, polar, allow alpha-carbon to rotate freely, generally trans, proteolytic enzymes required
to break them
Has partial double-bond character due to the carbonyl group
Peptide bonds are NOT cleaved by denaturing agents, stable to heating in strong acids
The peptide bond does not accept or give off protons, so it is not ionized at physiologic pH
Uncharged, but polar bond
Proline restricts the rotation around the alpha-carbon in the peptide bond
Note: disulfide bonds are formed from sulfhydryl groups of 2 cysteine residues, forming a cystine
residue; these help protect proteins from denaturation in the extracellular environment (insulin and
Igs are examples)
Amino Acid derivatives:
Phosphoenol pyruvate tryptophan and
tyrosine
Erythrose-4-P phenylalanine
tyrosine Dopa, etc
Tryptophan serotonin, melatonin, niacin, NAD and NADP
o Serotonin, released from platelets upon vessel damage, is a potent vasoconstrictor and
increases vascular resistance; in gastric mucosa it is secreted by enteroendocrine cells to
cause smooth muscle contraction; in brain it is a NT
o Lysergic acid diethylamide interferes with the action of serotonin in the brain

Histidine Histamine
Histamine is released by basophils and mast cells, causing vasodilation and
bronchoconstriction
H1 receptors mediate Type I hypersensitivity, H2 receptors mediate gastric acid and
pepsin secretion
Arginine NO; nitric oxide is released largely by vascular endothelium, causing vasodilation
Glycine porphyrin heme

Synthesis of other amino acids:

Alpha-KG + ammonia Glutamate Glutamine, proline or arginine
3-phosphoglycerate serine glycine or cysteine
Oxaloacetate aspartate asparagines, methionine, threonine, or lysine
Pyruvate alanine, valine, leucine, isoleucine (Isoleucine can also be formed from
threonine)
Phosphoenolpyruvate + erythrose-4-P shikimate chorismate Tryptophan, tyrosine,
phenyalanine (in humans tyrosine is made from phenylalanine)
Ribose-5-P histidine
Transamination Reactions
Involve the transfer of an amino group from one amino acid to an alpha-keto acid (often glutamate
and alpha-KG)
Transaminases or aminotransferases catalyze the reactions
Pyridoxal phosphate, derived from vitamin B, serves as the cofactor for these reactions; it functions as
a carrier of amino groups because it undergoes reversible transformation between its aldehyde form
(PLP) and aminated form (PMP)
Lysine, serine and threonine are not transaminated
Oxidative Deamination Reactions - result in the liberation of the amino group as free ammonia (NH3); these
reactions occur in the liver and kidney to provide ketoacids and ammonia; enzymes involved in deamination
include:
o Glutamate DH an oxidoreductase that catalyzes the oxidative deamination of glutamate;
unusual enzyme because it can use either NAD or NADP as a coenzyme [only amino acid
undergoing rapid oxidative deamination]
o Histidase creates ammonia and urocanate from histidine
o Serine dehydratase -- converts serine pyruvate and also threonine alpha-ketobutyrate
o Asparaginase deaminates asparagines to aspartate
Defects of amino acid metabolism
Phenylketonuria deficiency of phenylalanine hydroxylases severe mental retardation, skin/hair
pigmentation
Albinism deficiency of tyrosinase lack of melanin pigmentation
o Albinos do not have deficiency of NE or Epi because a different enzyme is used in
melanocytes for DOPA synthesis
Alkaptonuria deficiency of homogentisic acid oxidase (helps degrade tyrosine) excessive excretion
of homogentisic acid, a tyrosine degradative byproduct, causing black urine
Cystinuria impaired renal reabsorption of cysteine excessive urinary excretion of cysteine
Collagen
3 polypeptide alpha-chains wound around one another to form a triple helix with high tensile strength
Collagen is produced by fibroblasts, epithelial cells, odontoblasts, osteoblasts, and chondrocytes
Collagen is 35% glycine, 21% proline and 11% alanine; hydroxyproline and hydroxylysine are also
present
Synthesis: three preprocollagen peptide chains (alpha chains) are made at the RER; their sequence is
Glycine-X-Y

o
o

Hydroxylation of proline and lysine (Vit C dependent) occurs in the RER lumen
Glycosylation of alpha chains occurs in the Golgi and the procollagen triple helix (with N- and
C-terminal propeptides) is formed
o Outside of the cell, endopeptidases cleave the N and C terminal propeptides from
procollagen (procollagen peptidase), forming tropocollagen; tropocollagen molecules
aggregate at specific intervals to form collagen fibrils
o Multiple fibrils form fibers and collagen is attached to cell membranes via fibronectin and
integrin.
Tropocollagen is the longest known protein; it is also present in reticulin, a component of reticular
fibers.
Mature collagen lacks aromatic and sulfur-containing amino acids
**Vitamin C deficiency stops collagen synthesis at hydroxylation stage Scurvy
**Osteogenesis imperfecta collagen synthesis halted at the glycosylation stage
**Ehlers-Danlos peptide cleavage does not occur that would allow collagen fibrils to closslink
Random: collagen and reticular fibers make up the stroma of all lymphoid tissues except the thymus.
Elastin
Elastin is rich in small, nonpolar aliphatic residues such as glycine, proline, alanine, leucine and
isoleucine. Contains small amounts of hydroxyproline but no hydroxylysine.
Synthesis similar to collagen; the amino acid sequence of proelastin is Glycine-X-Y, and other residues
include proline, lysine, alanine and hydroxyproline
Endopeptidases cleave in the same way as procollagen peptidase and form tropoelastin; tropoelastin
molecules cross-link via desmosine, forming elastin fibers
Cross-links involve lysine and oxidized lysine residues, which are covalently linked to produce a
desmosine cross-link.
The oxidation of lysine residues in both elastin and collagen is an extracellular process catalyzed by
lysyl oxidase.
Plasma Proteins
Plasma proteins act as buffers that help stabilize internal environment pH; intracellular proteins absorb H+
made by metabolism.
Albumin (60%) maintains plasma pressure, transports calcium, copper, free FAs, bilirubin, steroid
hormones, drugs
o Normal albumin level is 3.5-5g/100mL, but albumin is decreased in malnutrition, liver failure
and pregnancy
o Albumins also transport T4 and T3, bile acids, and inorganic ions (along with the things
mentioned above)
o Almost all plasma proteins except albumin are glycoproteins; albumin I not glycosylated
Fibrinogen (Factor I) hemostasis
Alpha globulins transport, substrates for formation of other substances
o Lipoproteins (HDL) transports cholesterol esters
o Prothrombin hemostasis
o Erythropoietin erythrocyte synthesis
o Angiotensinogen regulates blood pressure
o 2-macroglobulin protease inhibition
Beta globulins- transport, substrates for formation of other substances
o Lipoproteins (LDL) transport cholesterol
o Transferring transports iron and copper
Gamma globulins Igs (antibodies); these are the only plasma proteins not made in the liver
Complement proteins bacterial cell lysis, inflammation
Hemoglobin 1 globin containing two alpha and two beta chains, 4 hemes that reversibly bind a molecule of
O2 when the iron is in a reduced ferrous (Fe2+) state
Heme is a nitrogen-containing organic pigment molecule with a single reduced iron at th center
Heme binds CO (carbon monoxide) with a higher affinity than O2

Hb binds only 15% of CO2 carried in venous blood (most travels as HCO3-)
Mutations of the alpha or beta subunits results in numerous hemoglobin types:
o Hb A normal Hb
o Hb F fetal Hb
o Hb C chronic anemia; lysine replaces glutamic acid, causing reduced plasticity of RBCs!
o Hb H -thalassemia; defect of alpha chain genes, so Hb is composed of 4 beta chains
o Hb M methemoglobinemia; tyrosine replaces histidine (it cannot function as an oxygen
carrier)
Fe2+ is oxidized to Fe3+, which cant bind oxygen; methemoglobin is formed due to
decreased activity of methemoglobin reductase, which could be a drug side effect
or a hereditary phenotype of increased Hb M
A group of abnormal Hbs in which a single amino acid substitution favors
formation of methemoglobin
o Hb S sickle-cell anemia; valine replaces glutamic acid in the beta chain; causes the cells to
deform into a sickle shape when exposed to low oxygen (like during exercise or in peripheral
circulation); they block small vessels causing pain and impaired circulation, and the cells have
a short lifespan; the deoxyHb has decreased solubility; oxygen-carrying capacity is greatly
decreased
Heme is a cyclic structure composed of 4 pyrrole rings with a central iron atom.
Myoglobin has only 1 heme, is located in muscle exclusively, is used for O2 storage, and has a much higher
affinity for O2 than Hb.

LIPIDS
Fatty acids all are alipathic carboxylic acids; most are esters, but some exist as unesterified free fatty acids
The only essential fatty acids are: linoleic acid and linolenic acid because we lack enzymes to place
double bonds at certain positions (omega-3 and omega-6)
Basic structure is carboxylic acid end with a hydrocarbon chain (seen on right )
Classified as:
o Saturated arachidic, butyric, capric, caproic, caprylic, lauric, myristic, palmitic, stearic
o Monounsaturated erucic, oleic, palmitoleic (note: most monounsaturated fats are in cis
configuration)
o Polyunsaturated arachidonic, linoleic, linolenic
Cells derived energy from FAs through beta-oxidation
TAGs
3 fatty acids and glycerol; stored in adipose tissue as an energy source
Transported in the plasma by lipoproteins
Basic triglyceride structure seen on the right
Phospholipids
2FAs + phosphate + glycerol; derived from the substance phosphatate
Precursors for second messengers and metabolic intermediates
Lecithins (phosphatidylcholines) water soluble emulsifiers formed from choline
o Upon hydrolysis, lecithins yield 2 fatty acid molecules and 1 each of glycerol, phosphoric acid,
and choline
o Also found as membrane constituents
Cephalins (phosphatidylethanolamines) formed from ethanolamine or L-serine
o Have hemostatic properties and found especially in nervous tissue of the CNS
o Resemble lecithin except that they contain either 2-ethanolamine or L-serine in the place of
choline
Sphingomyelins plasma membrane components formed from ceramide; do not contain glycerol!!
o Most membrane phospholipids contain glycerol, but sphingomyelin is based on sphingosine
instead

o
o
o

Found especially in nervous tissue

Yield sphingosine, choline, a FA, and phosphoric acid upon hydrolysis
**Remember that Niemann-Pick disease is associated with accumulation of sphingomyelin in
the CNS

Steroids
Cholesterol is synthesized throughout the body for cell membranes, but is produced mainly in the liver
from acetyl-CoA
Conversion of HMG-CoA mevalonate via HMG-CoA reductase is the rate limiting step in cholesterol
synthesis
Other important intermediates are isopentenyl pyroP and squalene
Precursor for bile salts, sex hormones, adrenocortical hormones, vitamin D
Cholesterol is mostly esterified with FAs when circulating; circulating cholesterol is taken up into liver
cells where it inhibits synthesis of more cholesterol from acetyl-CoA via allosteric inhibition of HMGCoA reductase
Thiolase and HMG-CoA reductase catalyze reversible reactions in cholesterol synthesis
Eicosanoids
20-C long polyunsaturated FAs that are derivatives of arachidonic acid
Phospholipase A2 releases arachidonic acid from plasma membrane phospholipids upon
hormone/cytokine stimulation or cellular damage
o Corticosteroids inhibit PLA-2
Prostanoids prostaglandins, prostacyclines, thromboxanes (formed by COX)
Leukotrienes formed by lipoxygenase (LOX)
Lipoxins formed by LOX
**Eicosanoid formation pathway on back (from page 257)

Lipid Transport Lipoproteins

Composed of nonpolar lipid core (TAGs, cholesterol esters) surrounded by a single layer of
amphipathic phospholipids and free cholesterol
Characterized by the apoprotein embedded in their outer layer
Contain TAGs, phospholipids, cholesterol, cholesterol esters (in highest %), and free FAs
Choline is essential for the secretion of lipoproteins from hepatocytes, especially VLDL
Familial hypercholesteremia autosomal dominant defect of the LDL receptor, leading to increased
plasma LDL and atherosclerosis
Major lipoproteins
Chylomicron lowest density (1% protein), major lipid content is TG, carries lipid from the small
intestine to extrahepatic tissues
Chylomicron remnants very low density (7% protine), major lipid content is TG cholesterol, carries
lipid from the chylomicrons of extrahepatic tissues to the liver
VLDL 10% protein, major lipid content is TG cholesterol, carries lipid from the liver to extrahepatic
tissues
IDL (VLDL remnant) 11% protein, major lipid content is TG cholesterol, carries lipid from VLDL of
extrahepatic tissues to the liver
LDL 20% protein, major lipid content is cholesterol, carries lipid from VLDL of extrahepatic tissues to
the liver
HDL highest density (up to 55% protein), major lipid content is cholesterol esters, carries lipid from
extrahepatic tissues to the liver
Bile Salts the two main ones: glycocholic acid and taurocholic acid
Almost exclusively absorbed in the ileum and returned to the liver via the enterohepatic circulation
Bile acids are conjugated with either glycine or taurine to give the respective bile salts

Two important actions in the intestinal tract: help in the absorption of FAs, monoglycerides and
cholesterol from the intestine (by forming micelles) and have detergent action that decreases surface
tension of particles, allowing agitation from the walls to break fat globules into small sizes.
Lipid storage diseases inherited disorders of the reticuloendothelial system caused by incomplete lysosomal
breakdown of sphingolipids and mucopolysaccharides within phagocytes, leading to their accumulation (most
are common to Ashkenazi Jews)
Gauchers disease autosomal recessive -glucocerebrosidase deficiency accumulation of
glucocerebrosides
o Splenomegaly, hepatomegaly, anemia, skin pigmentation
o Most common disease
Niemann-Pick disease autosomal recessive sphingomyelinase deficiency sphingomyelin
accumulation
o Splenomegaly, hepatomegaly, anemia, CNS degeneration
o Rapidly fatal
Tay-Sachs disease autosomal recessive hexosaminidase A deficiency accumulation of gangliosides
o CNS degeneration, mental retardation, cherry red spots on retina
o Rapidly fatal
Fabrys disease X-linked recessive -galactosidase deficiency ceramide trihexoside accumulation
o Skin lesions (angiokeratomas), renal failure, cardiovascular issues, peripheral neuropathy
Glucagon and Epinephrine
Glucagon and epinephrine activate adenylate cyclase in adipocytes, increasing cAMP protein
kinases activates hormone-sensitive TAG lipase hydrolysis of TAGs forming free FA and glycerol.
The fatty acids that are released bind to albumin and travel to tissues where they dissociate and
diffuse into the cells
The glycerol released by lipase action is phosphorylated by glycerol kinase, and the resulting glycerol3-P is oxidized to dihydroxyacetone phosphate, which is then converted into glyceraldhyde-3-P (by
triose phosphate isomerase); glyceraldehydes-3-P is then oxidized via glycolysis.
Insulin causes activation of a phosphorylase that dephosphorylates the hormone-sensitive lipase and
diminishes lipolysis

ENZYMES
Isoenzymes enzymes with subtle molecular differences that catalyze the same reaction
Metals and B-complex vitamins serve as the majority of non-protein enzyme components (cofactors,
prosthetic groups)
Cofactors organic molecules (coenzymes) or ions (usually metal ions) that are required for an
enzymes activity; they may be attached either loosely or tightly (prosthetic group) to the enzyme.
o Apoenzyme (inactive) + cofactor Haloenzyme (active)
Enzymes requiring inorganic cofactors
Iron: cytochrome oxidase, catalase, peroxidase, ferredoxin
Cu2+: cytochrome oxidase, pyruvate phosphokinase
Zn2+: carbonic anhydrase, alcohol DH
Mg2+: glucose-6-Pase, hexokinase, pyruvate kinase
Mn2+: ribonucleotide reductase
K+: pyruvate
Nickel: urease
Se: glytathione peroxidase
Classifications (others were obvious by name):
Isomerases catalyze a change in molecular structure
Lyases catalyze bond cleavage by elimination (break CO, CC, or CN bonds)
Ligases catalyze the union of two molecules

Michaelis-Menten Equation
The Michaelis constant (Km) is the substrate concentration when the initial reaction velocity Vi is of
Vmax
Vi = [Vmax * [S]] / [Km + [S]]
Often incorrectly said to equal the dissociation constant of the enzyme-substrate complex; this is not
true but it does give a means of comparison of the affinity (reciprocal of dissociation) of an enzyme for
different substrates:
o Lower Km = higher relative affinity
Km values increase in the presence of a competitive inhibitor, but are not affected by a
noncompetitive inhibitor (but Vmax is reduced in noncompetitive inhibition)
Allosteric enzymes
Have both an active site for its substrate and an allosteric site for an effector
The hallmark of effectors is that when they bind enzymes, they alter the catalytic properties of the
active site
Allosteric modifiers may be either the substrate itself or some other metabolite; for example: ATP
inhibits phosphofructokinase even though ATP is also a substrate for the enzyme
Frequently catalyze a committed step early in a pathway
Often have 2 or more subunits, each with substrate binding sites that exhibit cooperativity
Allosteric activators cause the enzyme to bind substrate more readily; allosteric inhibitors cause it to
bind less readily
Do NOT follow michaelis-mentin kinetics
A non-competitive inhibitor is, by definition, an allosteric inhibitor
An uncompetitive inhibitor will bind away from the active site but ONLY to an enzyme with a
substrate already attached!
Covalent modification
Phosphorylation occurs on either Ser-OH, Thr-OH, or Tyr-OH groups
A modified enzyme means it is phosphorylated, unmodified means unphosphorylated
Gibbs Free Energy Change determines the direction of the reaction
G = GP - GS
If the reaction is negative (Gs > Gp) then the reaction will proceed forward toward equilibrium when
G = 0
Exergonic reactions have negative G, while endergonic reactions have positive G
G provides no information about the reaction rate and is independent of the path of the reaction
Equilibrium Constant: Keq = [C][D][enzyme] / [A][B][enzyme]
This shows that enzymes have no effect on reaction equilibrium
Reaction Rate - determined by the activation energy, attaining activation energy

Carbonic Anhydrase
Enables red blood cells to transport CO2 from tissues to lungs
Zinc is essential cofactor; the reaction can occur without the enzyme, but it speeds it up significantly in
both directions
One of the fastest known enzymes (1 molecule of enzyme can process one million CO2 per second)
H2CO3 is formed from waste CO2 in tissues and dissociates so HCO3- reenters plasma for transport to
the lungs; in the lungs HCO3- reenters the erythrocyte and makes carbonic acid again then CO2 and
H2O; the CO2 diffuses into the alveoli
Because HCO3- is more soluble in plasma than CO2, it allows the blood to carry more CO2 to the lungs
Carbonic anhydrase also functions in the kidney with the reabsorption of HCO3-

Thrombin converts fibrinogen found in plasma (essential for clotting) to fibrin; thrombin is produced from the
inactive precursor prothrombin formed in the liver. In the presence of thromboplastin and Ca2+, prothrombin
thrombin
Thrombin acts on arginyl-glycine linkages (specific peptide bonds) to produce fibrin
Plasmin (AKA fibrinolysin) dissolves fibrin; it is present in the blood as plasminogen until plasminogen
activators (like urokinase in the kidney) convert it to plasmin, which cleaves the peptide bond in fibrin
breakdown and dissolution of clots
Prothrombin --thromboplastin thrombin
Fibrinogen -----thrombin fibrin
Fibrin ---plasmin fibrin breakdown and dissolution
Zymogens are the inactive precursors of proteolytic enzymes. Pepsinogen is a zymogen produced by the
stomach. Those produced by the pancreas are: trypsinogen, chymotrypsinogen, procarboxypeptidase A/B, and
proelastase.
Presence of amino acids in the duodenum stimulates release of CCK, which causes the release of pancreatic
zymogens and contraction of the gallbladder to deliver bile salts. Trypsinogen trypsin by enteropeptidase.
Trypsin can then activate the zymogens of ALL the pancreatic proteases.
Trypsin cleaves peptide bonds with carboxyl groups from lysine or arginine (the basic amino acids)
Chymotrypsin cleaves aromatic amino acids or leucine
Elastase cleaves at the carboxyl end of amino acids with small, unchanged side chains like alanine,
glycine or serine
Carboxypeptidase B cleaves basic amino acids lysine and arginine
Pepsinogen is activated to pepsin by low pH in the stomach, or by other activated pepsin molecules.

NUCLEIC ACIDS
Nucleoside a nucleotide without esterified phosphate groups
CUT the Py
A=T/U (2 H-bonds), C=G (3 H-bonds)
Important point: the A=T pair promotes helix stabilization in DNA, but does not do so in RNA!
Two forces hold the double helix together: hydrogen bonds and base-stacking interactions
Transcription factors and other proteins bind in the major groove
A polynucleotide chain is formed by linking the 5-hydroxyl group of one nucleotide to the 3-hydroxyl
group of the next with a phosphate in a condensation reaction (phosphodiester bond), so you get
alternating phosphate and pentose residues
Backbone is made up of alternating phosphate and pentose units
The catabolism of a nucleotide results in no energy production as ATP (as opposed to catabolism of
protein, lipid or carbohydrate)
# purine residues = # pyrimidine residues
DNA backbone is: hydrophilic, constant throughout the molecule, highly polar
The ribose phosphate portion of purines and pyrimidines comes from PRPPsynthesized from ATP
and Ribose-5P from the PPP
Purines
Metabolic defects caused by antifolate drugs and anticancer drugs
Purines are catabolized uric acid (pure-ur)
Catabolic defects include: gout, hyperuricemia, G6P deficiency
Pyrimidines
Metabolic defects caused by methrotrexate and other anticancer drugs
Pyrimidines are catabolized to -alanine and -aminoisobutyrate
Catabolic defects are rare; pyrimidines are highly water soluble
Synthesis of Nucleotides

Catabolism of purines to Uric acid: Purines xanthine ------xanthine oxidase Uric acid
Nucleic acids, continued
Extremely polar and hydrophilic
Pentose sugar backbone linked by phosphodiester bonds at the 3rd and 5th carbons from 5 3 the
DNA chain goes:
P O CH2 (5) pentose sugar (deoxyribose) O P O CH2 etc (see page
280)
For RNA it is the exact same except for an extra OH instead of an H and the base T is changed to U
Hydrolysis of DNA yields: deoxyribose (ribose for RNA), phosphoric acid and nitrogenous base
3 types of RNA
rRNA synthesized in the nucleolus; most prevalent RNA
tRNA synthesized in the nucleus; carries amino acids from the cytosol to ribosomes; contains an
anticodon
mRNA synthesized in the nucleus; carries the genetic code from DNA to ribosome; least prevalent;
has codons to DNA template
DNA organization
Nucleosome = DNA wrapped around a histone octomer, held by ionic bonds
Histones are composed largely of arginine and lysine (basic, +-charged amino acids that bind the (-)
phosphate groups of DNA
Histones neutralize the large negative charge of DNA and stabilize DNA in a compact form
Core histones: H2A, H2B, H3 and H4
Linker histones: H1 and H5
Chromatin consists of nucleosomes, enzymes, gene regulatory proteins, and small amounts of RNA;
nucleosome beads-on-string
Each chromosome contains a single molecule of DNA complexed with an equal mass of basic histone
protein
Phosphorylation of serine and threonine residues in histones is part of replication, while acetylation of
lysine in histones is used for transcriptional activation
Naked DNA 10 nm beads-on-a-string chromatin fibril 30nm chromatin fibril non-condensed loops on
chromosome scaffold condensed loops on nuclear scaffold chromosome
DNA Synthesis
After helicase unwinds the DNA molecule, topoisomerase secures the replication fork into leading and
lagging strands
o Topoisomerases are responsible for unwinding supercoiled DNA to allow DNAP access to
replicate
o Topoisomerases catalyze and guide the unknotting of DNA by creating transient breaks in the
DNA then reform them
o The enzyme DNA gyrase reforms the supercoiled structure once the replication fork has
passed
Single-strand binding protein stabilizes the two separate strands
DNA polymerase adds 5 3 continuously on the leading strand and in Okazaki fragments on the
lagging strand
The RNA primer is provided by RNA polymerase, which itself doesnt require a primer

On the leading strand DNA polymerase III is able to synthesize DNA using the free 3' OH group
donated by a single RNA primer and continuous synthesis occurs in the direction in which the
replication fork is moving.
Along the lagging strand's template, primase builds RNA primers in short bursts. DNA
polymerases are then able to use the free 3' OH groups on the RNA primers to synthesize DNA in
the 5'3' direction. Exonuclease removes the nucleotide primers. DNA polymerase III adds new
deoxyribonucleotides to fill the gaps where the RNA was present. DNA ligase then joins the
deoxyribonucleotides together, completing the synthesis of the lagging strand.
RNA Synthesis (Transcription)
Occurs in the nucleus; DNA is unwound and replication fork is exposed
RNA polymerase binds to a promoter site on the DNA strand and synthesis occurs 5 3
Post-transcriptional modifications:
o Addition of a 5 cap and a 3 poly-A tail
o RNA splicing to remove non-coding introns and join the coding exons
WIKI
Only one of the two DNA strands is transcribed. This strand is called the template strand, because it
provides the template for ordering the sequence of nucleotides in an RNA transcript. The other strand is
called the coding strand, because its sequence is the same as the newly created RNA transcript (except for
uracil being substituted for thymine). The DNA template strand is read 3' 5' by RNA polymerase and the
new RNA strand is synthesized in the 5' 3' direction.
Unlike DNA replication, transcription does not require primers for initiation. However RNA polymerase does
require the presence of a core promoter sequence in the DNA, which it is able to bind to in the presence of
various specific transcription factors.
Promoters are regions of DNA which promote transcription and are found around -10 to -35 bp upstream
from the start site of transcription. Core promoters are sequences within the promoter which are essential
for transcription initiation. The most common type of core promoter in eukaryotes is a TATA box. The TATA
box, as a core promoter, is the binding site for a transcription factor known as TATA binding protein (TBP).
At the start of initiation in bacteria, the core enzyme (RNA polymerase) is associated with a sigma factor
(number 70) that aids in finding the appropriate -35 and -10 basepairs downstream of promoter sequences.
Transcription initiation is far more complex in eukaryotes, the main difference being that eukaryotic
polymerases do not directly recognize their core promoter sequences. In eukaryotes, a collection of
proteins called transcription factors mediate the binding of RNA polymerase and the initiation of
transcription. Only after certain transcription factors are attached to the promoter does the RNA
polymerase bind to it. The completed assembly of transcription factors and RNA polymerase bind to the
promoter, called transcription initiation complex.
After the first bond is synthesized the RNA polymerase must clear the promoter. During this time there is a
tendency to release the RNA transcript and produce truncated transcripts. This is called abortive initiation
[4]
[5]
and is common for both eukaryotes and prokaroytes . Once the transcript reaches approximately 23
nucleotides it no longer slips and elongation can occur.
Unlike DNA replication, mRNA transcription can involve multiple RNA polymerases on a single DNA template
and multiple rounds of transcription (amplification of particular mRNA), so many mRNA molecules can be
produced from a single copy of a gene. This step also involves a proofreading mechanism that can replace
incorrectly incorporated bases.
Prokaryotic elongation starts with the "abortive initiation cycle". During this cycle RNA Polymerase will
synthesize mRNA fragments 2-12 nucleotides long. This continues to occur until the factor rearranges,
which results in the transcription elongation complex (which gives a 35 bp moving footprint). The factor is
released before 80 nucleotides of mRNA are synthesized.
In Eukaryotic transcription the polymerase can experience pauses. These pauses may be intrinsic to the RNA
polymerase or due to chromatin structure. Often the polymerase pauses to allow appropriate RNA editing
factors to bind.
Bacteria use two different strategies for transcription termination: in Rho-independent transcription
termination, RNA transcription stops when the newly synthesized RNA molecule forms a G-C rich hairpin
loop, followed by a run of U's, which makes it detach from the DNA template. In the "Rho-dependent" type
of termination, a protein factor called "Rho" destabilizes the interaction between the template and the
mRNA, thus releasing the newly synthesized mRNA from the elongation complex. Transcription termination

in eukaryotes is less well understood. It involves cleavage of the new transcript, followed by templateindependent addition of As at its new 3' end, in a process called polyadenylation.

Translation
Occurs in the cytoplasm on ribosomes; a small ribosomal subunit binds to mRNA
Prokaryotes have 70S ribosomes, eukaryotes have 80S ribosomes
Aminoacyl-tRNA synthetase adds each amino acid to the tRNA (based on the anticodon the
tRNA is carrying); each enzyme molecule is highly specific for one amino acid!!! Not one
anticodon!!!
The complementary anticodon of tRNA binds to the mRNA start codon
A large ribosomal subunit attaches, forming a complete ribosome
Synthesis occurs in the 5 3 direction until a stop codon is reached
No error-checking occurs during translation
WIKI
In activation, the correct amino acid (AA) is joined to the correct transfer RNA (tRNA). The AA is joined by its
carboxyl group to the 3' OH of the tRNA by an ester bond. When the tRNA has an amino acid linked to it, it
is termed "charged". Initiation involves the small subunit of the ribosome binding to 5' end of mRNA with
the help of initiation factors (IF), other proteins that assist the process. Elongation occurs when the next
aminoacyl-tRNA (charged tRNA) in line binds to the ribosome along with GTP and an elongation factor.
Termination of the polypeptide happens when the A site of the ribosome faces a stop codon (UAA, UAG, or
UGA). When this happens, no tRNA can recognize it, but releasing factor can recognize nonsense codons
and causes the release of the polypeptide chain.
Many proteins undergo post-translational modification. This may include the formation of disulfide bridges
or attachment of any of a number of biochemical functional groups, such as acetate, phosphate, various
lipids and carbohydrates. Enzymes may also remove one or more amino acids from the leading (amino) end
of the polypeptide chain, leaving a protein consisting of two polypeptide chains connected by disulfide
bonds.

**If the anticodon on a tRNA is 5 ACG 3 then the corresponding mRNA codon would be 5 CGU 3
Point Mutations
Missense: codes for the wrong amino acid
Nonsense: results in stop codon
Transverse mutation a purine is replaced with pyrimidine, or vice versa
Transition mutation a purine is replaced with another purine, or pyrimidine replaced with another
pyrimidine
Frameshift mutation deletion or insertion of 1 or 2 base pairs, changing the reading frame
Repeat mutations amplification of the sequence of 3 nucleotides
Restriction endonucleases cleave DNA at various points to allow addition of various vectors, plasmids, or
bacteriophages
AZT a thymidine analog that is a competitive inhibitor of HIV reverse transcriptase
The use of THF acid (TFA) by several enzymes in purine and pyrimidine synthesis have made TFA metabolism a
prime target for many antimetabolites such as methrotrexate used in chemotherapy.
UV light produces pyrimidine dimmers in DNA which then interferes with replication and transcription. These
lesions are removed by exonuclease, which excises a 12bp fragment surrounding the dimer. DNAP-I then fills in
the gap and DNA ligase seals it.
Degenerate nature of the genetic code many amino acids are designated by more than one codon (same as
redundancy)
Only Tryptophan, Methionine and Selenocysteine are coded for by just one codon; the other have 2 or
more codons (synonyms)

AUG = initiation codoncodes for methionine, so all proteins begin with Met!!
UAA, UAG and UGA termination codons (AKA stop or nonsense codons)
Southern Blotting used to detect mutations in DNA and also identify DNA restriction fragments; it uses
restriction enzymes and DNA probes
Enzymes used in recombinant DNA technology are: restriction endonucleases, DNA ligases, DNAP-I, reverse
transcriptase, exonucleases
Products of current recombinant DNA technology include: human insulin, anticoagulants (tissue plasminogen
factor), erythropoietin, hGH
Bacterial cloning vectors include plasmids, bacteriophages, and cosmids.
MEMBRANES SECTION
Phospholipids (50%), steroids and glycolipids make up the bulk of the lipid membrane; examples of
phospholipids include sphingomyelin, phosphatidyl choline (lecithin) and phosphatidyl ethanolamine
(cephalin)
Small, nonpolar molecules easily pass through
o Only water and gases can easily pass through the bilayer, plus some small nonpolar
molecules (oxygen, CO2, alcohol); large or polar molecules (ions, glucose, urea) cannot cross
the bilayer without assistance from active transport systems
Integral proteins and lipids noncovalently linked to allow movement; theyre held by hydrophobic
interactions with the lipids
The fluid mosaic is lipid + protein
Attractive van der Waals forces between hydrocarbon chains and repulsive forces between polar head
groups form the bilayer
Membrane lipids:
o Phospholipids: phosphoglycerides and sphingomyelin
o Glycosphingolipids
o Cholesterol
Integral proteins: embedded in either 1 or both portions of the bilayer
Peripheral proteins: weakly bind to hydrophilic head groups on inner or outer membrane surfaces
Peripheral proteins are embedded at the periphery, integral proteins span from one side of the
membrane to the other side; integral proteins are associated with the hydrophobic phase of the
bilayer
Peripheral proteins seldom flip from one side of the membrane to the other, but they move laterally
often
The proteins of the cell membrane function as transporters, enzymes, receptors and mediators
Carbs attach to proteins and lipids only on the external surface

NEUROPHYSIOLOGY
Thalamus
Ovoid mass of gray matter; part of diencephalon
Ascending input of all sensory stimuli except olfactory is relayed through the thalamus to the cerebral
cortex
Descending output from the cortex can also pass through or synapse within the thalamus
Hypothalamus
Collection of nerve cells (nuclei) lying subcortical at the base of the cerebrum that controls
homeostatic processes
Often associated with the ANS, the hypothalamus regulates:
o Autonomic functions: GI and cardiac activity
o Body temperature - the posterior hypothalamus controls both heat generation and heat loss
o Appetite, water balance, sexual activity, sleep, emotions
o Pituitary secretions: releasing endocrine hormones to the pituitary
Stimulation of the posterior hypothalamus by a reduction in core temperature will produce shivering
Heat Transfer - emission of heat as infrared rays; the body is continuously exchanging heat by radiation with objects
in the environment
Conduction flow of heat energy through direct contact between two objects
Convection movement of heat by currents in the medium; air molecules exchange heat with body surface and
continue to breeze past
Evaporation includes insensible water loss via respiration and skin, sweating, and active fluid secretion by sweat
glands
More effective in low-humidity environments
Limbic System
Primitive brain area found deep in the temporal lobe; it communicates with the cerebral cortex to initiate
basic drives:
o Hunger, aggression, emotional feelings, sexual arousal
It also screens all sensory messages traveling to the cerebral cortex
Consists of the:
o Hippocampus functions in learning and memory
o Amygdala center of emotions, communicates with the ANS, oxytocin and ADH receptors (for
negative feedback)

Motor Control and Coordination

Basal Ganglia located deep to the cerebral cortex, they control complex patterns of voluntary motor behavior
Caudate nucleus
Putamen
Globus pallidus
Substantia nigra

Subthalamic nuclei
**Parkinsons, Huntington and Wilson disease are disorders of the basal ganglia; the person has unwanted
movements.
**The caudate nucleus and putamen are interposed with the anterior limb of the internal capsule; collectively they
are known as corpus striatum.
**The putamen and globus pallidus together resemble a lens and are called the lenticular nucleus
**The cerebral cortex sense info to both the basal ganglia and cerebellum, and both send info back to the cortex via
the thalamus. The output of
the cerebellum is excitatory, while the basal ganglia output is inhibitory.
**The basal ganglia (or subcortical nuclei) are the major constituents of the extrapyramidal system
Cerebellum divided into two lateral hemispheres with a middle portion called the vermis
Maintains muscle tone, coordinates muscle movement, controls balance
Basal ganglia and cerebellum modify movement on a minute-to-minute basis; output of the cerebellum is
excitatory whereas that of the basal ganglia is inhibitory!!! They work together to achieve smooth,
coordinated movements. Movement disorders result from aberration to either of the systems.
Motor Pathway:
Precentral gyrus (M1) upper motor neuron internal capsule corticospinal tract cerebral peduncles
pyramids of medulla (fibers cross) ventral horn of spinal cord lower motor neuron muscle
Brainstem
Midbrain (mesencephalon) connects dorsally with cerebellum; large voluntary motor nerve tracts pass
through the midbrain
o Location of CN III and IV nuclei plus substantia nigra
Pons between the midbrain and medulla; connects to cerebellum posteriorly
o Location of CN V and VI nuclei, motor nuclei of VII, exit points for CNs 5-7
Medulla Oblongata contains important regulatory centers for swallowing, cardiac function, vasomotor,
respiratory
o Location of nuclei for CNs 8-12
PNS
Somatic NS
o Cranial nerves + 21 pairs of spinal nerves
o Motor: innervates skeletal muscle with no synapse in peripheral ganglia; uses 1 efferent neuron
from CNS to end organ
o Sensory: synapse within the dorsal root ganglion prior to CNS entry

Touch, movement, temperature, pain

ANS no action on skeletal muscle; motor neurons synapse within autonomic ganglia; uses 2 efferent
neurons from CNS effector
Autonomic Nervous System
Pregangionic neuron in CNS ganglion (cell bodies of postganglionic) outside CNS postganglionic
neuron outside CNS effector
Autonomic ganglia collections of cell bodies of postganglionic neurons
o Sympathetic sympathetic chain ganglia near the spinal cord; short preganglionic, long
postganglionic
o Parasympathetic ganglia at or within the organ; long preganglionic, short postganglionic
Exception to rule: sympathetics to sweat glands and blood vessels within skeletal muscle are cholinergic @
muscarinic receptors
Parasympathetic
Composed of CN nuclei and S2-S4
Preganglionic neurons are cholinergic nicotinic receptors on postganglionic neurons (always excitatory)
Each preganglionic parasympathetic neuron synapses on only a few postganglionic parasympathetic
neurons
Postganglionic neuron is cholinergic muscarinic receptors in tissue (can be excitatory or inhibitory)
Postganglionic receptors:
NEED TO FIND OUT
THE TRUTH ABOUT THESE!!!!!!
o Muscarinic (M) found in effector organs; can be excitatory or inhibitory

Located on all effector organs innervated by parasympathetic division, and some

innervated by the sympathetic division

Nicotinic

Located at the ganglia in both divisions of the ANS

N1 found in autonomic ganglia; excitatory only, leading to nerve

transmission/postganglionic activation

N2 found in motor end plates (@ NMJ); excitatory muscle contraction ??

WIKI: ACh has two types of effects. The first type is termed muscarinic, which is the parasympathetic effect on the
secretory exocrine gland and smooth and cardiac muscles upon their corresponding receptors. The other type of ACh
effect is termed nicotinic, which is on the skeletal (voluntary) muscles and not considered to be part of the peripheral
autonomic nervous system.
All preganglionic autonomic neurons (both ANS branches) and all postganglionic parasympathetic neurons
are cholinergic
Cholinergic effects of preganglionic autonomic systems (at the ganglia) are always excitatory; effects of
postganglionic cholinergic fibers are either excitatory or inhibitory, depending on the end organ
**Atropine blocks the action of Ach!
Sympathetic
Composed of spinal segments T1L3
Exerts widespread effects due to high ratio of postganglionic:preganglionic fibers; each preganglionic
neuron branches extensively
Postganglionics bind adrenergic receptors in tissue, except sweat glands and skeletal muscle blood vessels
Three cervical sympathetic ganglia supply the head and neck
Adrenergic receptors
o Membrane-bound G-protein receptors on autonomic effector organs
o NE stimulates mainly alpha receptors
o Epinephrine stimulates both alpha and beta equally
Monoamine oxidase (MAO) an enzyme that catalyzes oxidative deamination of monoamines (including
NE, serotonin and Epi); the deamination process increases breakdown/metabolism of excess NTs that
accumulate at postsynaptic terminals
Alpha-1 excitatory; cause vasoconstriction or contraction in vascular smooth muscle of the skin, mucosa and GI
Alpha-2 found at presynaptic nerve terminals, platelets, fat cells, GI tract wall; inhibitory (relaxation or dilation)
Beta-1 found in the heart, exctitatoryincreases HR and contractility
Beta-2 inhibitory; found in skeletal muscle and smooth muscle; causes vasodilation/bronchodilation
**NE stimulates mainly alpha receptors, Epi stimulates both alpha and beta receptors!
**Beta-blockers are used to treat arrhythmias and other cardiac anomalies through reduction in rate/force of heart
contractions
Summary of Autonomic Effects
Pupils
Salivation
Bronchi
Adrenal Medulla

Sympathetic
Mydriasis (dilation)
Thick
Bronchodilation
Causes Epi and NE release

Parasympathetic
Miosis (contraction)
Watery (ready to eat)
Bronchoconstriction
No effect

SPINAL TRACTS
Axons of a tract have the same origin, termination and function; theyre often named for their origin and
termination (e.g. spinothalamic)
Sensory tracts (ascending)
o Spinothalamic pain and temperature
o Dorsal column, medial lemniscus touch, pressure, vibration, proprioception
Motor tracts (descending)
o Corticospinal (pyramidal)
o Extrapyramidal
Receptor peripheral nerve DRG spinal cord spinal tracts brainstem nuclei thalamus cortex
Receptors 2 broad types according to location of stimuli

Exteroreceptors receive external stimuli from the body surface: touch, pressure, pain, temperature, light,
sound
Interoreceptors (visceroreceptors) receive input from the internal environment of the body: pressure,
pain, chemical changes
o Proprioceptors type of interoceptor; separate from visual input (which is kinesthetic sense);
located in muscles, joints and tendons communicate with the vestibular apparatus
**Types of joint receptors
Nonencapsulated free nerve endings relaying pain
Encapsulated Pacinian (vibration, pressure) and Ruffini (stretch)
Neuromuscular spindles stretch
Neurotendons tension
Nonencapsulated
Free nerve endings pain primarily, but also touch, pressure, tickle, temperature; found in epithelial cells,
skin, cornea, GI tract, CT, haversian system of bone, dental pulp
Hair follicle receptors mechanoreception; bending hair stimulates touch; fiber winds around the hair
(transduce hearing and balance)
Merkels disc (considered nonencapsulated) tactile touch, pressure; in hairless skin like the fingertips it
senses pressure
Encapsulated
Meissners corpuscles mechanoreceptors allowing 2-point discrimination; in the dermal papilla of skin;
the capsule is an ovoid stack of Schwann cells
Pacinian corpuscles mechanoreceptors sensing vibration, pressure; in the dermis, subcutaneous tissue,
ligaments and joints; concentric lamellae of flattened cells
o Sense deep cutaneous pressure, vibration, proprioception
Ruffinis corpuscles stretch; in the dermis of hairy skin large unmyelinated fibers ending within bundles
of collagen fibers
o Sense continuous touch or pressure, and are found primarily in the dermis of the fingers

*Afferent nerve endings in joints and tendons are called proprioceptors.

*Exteroreceptors sensory nerve endings associated with the skin that provide info about the external environment
*Visceroreceptors provide info about the internal environment

Somatosensory Pathways
Sensory Tracts (ascending)

Figure on
page 302:
Spinothalamic Tract (anterolateral system)
o Lateral spinothalamic tract transmits pain, temperature and
crude touch from the opposite side; originates in posterior gray
column of opposite side and terminates in the thalamus
o Anterior spinothalamic tract transmits crude touch and
pressure; same origin and termination
Sensory nerve dorsal horn of spinal cord cross to opposite side of cord
ascend contralateral spinal cord (through anterior or lateral white matter tracts
thalamus somatosensory cortex
Dorsal Column, Medial Lemniscus System conveys touch, pressure and
vibration
Sensory nerve dorsal horn ascends ipsilateral spinal cord in posterior columns
(fasciculus gracilis for lower extremities and fasciculus cuneatis for upper extremities)
synapse in the medulla (nucleus gracilis or nucleus cuneatis) then decussage
and ascend the contralateral brainstem in the medial lemniscus thalamus
somatosensory cortex

**fasciculus gracilis and cuneatus are the largest ascending tracts of the spinal cord; they arise from either cells of the
spinal ganglia or from intrinsic neurons within grey matter that receive primary sensory input
Fasciculi gracilis and cuneatus discriminating touch and pressure, including vibration, stereognosis, and 2-point
discrimination; also conscious kinesthesia; originate in the spinal ganglia of the same side and terminate in the
medulla
Anterior and Posterior Spinocerebellar unconscious kinesthesia; go from anterior/posterior gray columns
to the cerebellum
Somatosensory cortex (postcentral gyrus) representation is the homunculus; huge representation of lips, fingertips
and hands
Looking at the lateral brain, the face and tongue are near the bottom of the postcentral gyrus (just above
the temporal lobe) and the trunk is near the top of the brain (face, tongue, hand, trunk as you move up)

Descending Motor Tracts (efferent pathways)

Motor area of the brain (precentral gyrus) upper motor neurons (= descending tracts) lower motor neurons
skeletal muscle
Upper motor neurons originate in the white matter of the brain and form 2 major systems: corticospinal
and extrapyramidal
The pyramidal motor system moves your muscles under the direction of your mind; extrapyramidal controls
muscle tone, posture and activity without conscious thought
Corticospinal Tract (pyramidal system) Seen on the right:
o Originates from pyramid-shaped cells in the premotor, primary motor
and primary sensory motor areas (80% of cell bodies are in precentral
gyrus, AKA the motor strip)
o Direct and monosynaptic tract; axons do not synapse until their final
destination in the brainstem or spinal cord
o Fibers of the pyramidal tract that synapse with CNs form the
corticobulbar tract
o 2 components: lateral (70-90%) and anterior/ventral (10-30%)
o Travel via M1 through the internal capsule to the medulla
o Decussate in the medulla and continue down opposite side of spinal cord
ventral horn lower motor neurons muscles
o Right brain controls left somatic muscles; controls fine, skilled
movements of skeletal muscle
o Called the pyramidal system because fibers of the corticospinal tract
form pyramids in the medulla
Lateral Corticospinal (crossed pyramidal 90%)

Voluntary movement, contraction of individual or small groups

of muscles, particularly those moving hands, fingers, feet and
toes of the opposite side

Originates in motor areas of cerebral cortex on opposite side

from tract location in cord; ends in lateral columns
Anterior Corticospinal (direct pyramidal 10%)

Same as lateral corticospinal but mainly muscles of the same side

Origin is motor cortex but on same side as the location of the cord
Extrapyramidal System collection of smaller tracts
o This motor system works with the ANS to help with posture and muscle tone, and has more
influence over midline structures than those in the periphery
o Involved in gross, rather than fine movement, including facial expression
o In contrast to pyramidal, it is an indirect, multisynaptic tract
o Relies on dopamine to maintain proper muscle tone and motor stability
o All of the nuclei are synaptically connected to one another, the brainstem, the cerebellum, and
the pyramidal system

Rubrospinal originates in the red nucleus; the cerebellum sends messages to the
spinal nerves along this tract. Information flows from the superior cerebellar peduncle
to the red nucleus and finally to the spinal nerves. This info is important for somatic
motor control and regulation of muscle tone for posture.

Coordination of body movement and posture

Reticulospinal originates in the reticular nuclei of the pons and medulla to the spinal
nerves; involved in somatic control like rubrospinal, but also plays a role in control of
autonomic functions

Lateral reticulospinal facilitatory influence on motor neurons to skeletal

muscle

Medial reticulospinal inhibitory influence on motor neurons to skeletal

muscle
Olivospinal

Vestibulospinal originates in vestibular nuclei of lower pons and medulla to the spinal
nerves; involved in balance

Mediates the influences of the vestibular organ and cerebellum upon extensor
muscle tone
th

Origin is the lateral vestibular nucleus (4 ventricle)

Tectospinal points of origin throughout the brainstem, but especially the midbrain,
and ends in spinal nerves; involved in control of the neck muscles (tec = neck)
Travel from the premotor area of the frontal lobe (and other areas) to the pons; decussate in the
pons and continue down the opposite side of the spinal cord ventral horn lower motor
neurons muscles
Again, right brain controls left lower motor neurons; this time it controls gross motor movement,
posture and balance.

Spinal Cord Lesions

Lesion on one side causes:
Same side motor loss (corticospinal tract)
Contralateral pain and temperature loss (spinothalamic tract)
If you hemitransect the right side of the spinal cord, you lose right-side motor control and left side pain and
temperature sense.
Neurophysiology
K+ leak out of the cell is the most important determinant of RMP!!!
Visceral smooth muscle and cardiac pacemaker cells lack a stable resting membrane potential
Na/K pump creates the gradient that allows K+ leak to occur; 2K+ in for every 3Na+ out = net loss of + from
the cell
Smooth muscle and cardiac pacemakers lack a stable RMP
AP threshold is about +20mV
K+ conductance (channels stay open and efflux is greater than at rest) is what causes hyperpolarization after
an AP
Hyperpolarization is responsible for the relative refractory period; an influx of Cl- will also hyperpolarize and
make AP less likely
Local Anesthetics
Block sodium channels, decreasing Na+ permeability
Bind to the inactivation gates of fast, voltage gated Na+ channels, keeping them closed and prolonging the
absolute refractory period
Decrease excitability so cant generate and AP and there is no nerve impulse conduction
K+, Cl- and Ca2+ conductances are unchanged
Affect small unmyelinated C fibers first, then small myelinated (pain, temp) then larger A-fibers (touch,
proprioception, Golgi)
Inhibitory NTs increase membrane permeability to Cl- or K+; examples are: glycine and GABA (both open Clchannels/increase Cl- permeability)

Spatial summation 2 inputs arrive at the same time from multiple presynaptic fibers
Temporal summation 2 inputs arrive at the postsynaptic neuron in rapid succession; frequency of impulses from
a single presynaptic fiber

Nerve Conduction
Saltatory conduction conserves energy because only Ranvier nodes depolarize, so less energy is
required for Na+/K+ ATPase to reestablish resting ion gradients; the pumps only have to work at
Ranvier nodes instead of everywhere
o It allows repolarization to occur with less transfer of ions
o Myelin decreases membrane capacitance and increases membrane resistance (goodfor
saltatory conduction)
Nodes of Ranvier are located every 0.2 2mm along the myelin sheath
Continuous conduction occurs in unmyelinated fibers and is slow (1m/sec vs. saltatory 100m/s)
Conduction velocity depends on the diameter of fiber; bigger diameter means more resistance to
flow and faster velocity
Problems with Nerve Conduction
Wallerian Degeneration the axon is cut, and the axon remnant distal to the cut degenerates;
regeneration of axons is possible if the endoneurial sheath is intact (when this sheath is intact and
regeneration is possible, it is called Axonotmesis).
o Regeneration occurs at a rate of 2-4mm/day
o If the cell body is irreversibly injured, the entire neuron degenerates
Neuropraxia transient block (bruise) that causes incomplete paralysis or loss of sensation with rapid
recovery
Neurotmesis complete transaction of nerve trunk results in:
o Motor: flaccid paralysis and atrophy of the organ
o Sensory: total loss of cutaneous sensation
Neurilemma sheath of Schwann; thin membrane spirally enwrapping the myelin layers of nerves or axons of
some unmyelinated nerves; all axons of the PNS have a sheath of Schwann cells (and thus a neurilemma made
up of the outer layer of Schwann cells) when a Schwann cell is wrapped successively around an axon, it
becomes a myelin sheath.
**If the nerve led to skeletal muscle, the muscle atrophies in the absence of innervation but regrows when the
connection is reestablished.
**The CNS has no neurilemma, so regeneration is more difficult.

Chemical synapses are more common than electrical synapses.

Chemical NTs can be:
Small molecule NTs contained in vesicles glutamate, GABA, glycine, Ach, NE, Epi
Neuropeptides (large dense vesicles) somatostatin, endorphins, enkephalins, opioids
Electrical synapse cytoplasm of adjacent cells is connected by gap junctions; rare in the CNS but common in
cardiac/smooth muscle; also important in embryonic development (morphogenic gradients)
Neuromuscular Junction
Ach nicotinic receptor Na+ opens on motor end plate depolarizes voltage-gated Na+
channel on sarcolemma open AP stimulated AP travels down transverse tubules Ca2+
released from SR contraction
Ach is synthesized in the presynaptic terminal of the motor neuron:
o Acetyl-CoA + choline -----choline acetyltransferase ----> Ach
Breakdown is by acetylcholinesterase located on the muscle end-plate:
o Ach ----AchE---> acetate + choline
o If AChEs are inhibited, you get prolongation of the end-plate potential whicn can lead to
tetany

Special Senses
Vision
-

Anterior segment of the eyeball is full of aqueous humor; it is divided into anterior and posterior
chambers by the iris
Posterior segment is filled with vitreous humor
Choroid very vascular lining of the inner eyeball beneath the retina
Miosis occurs in response to light, narcotics, parasympathetic stimulation, pathologic conditions
Mydriasis occurs in response to low light, sympathetic, drugs or disease
Ciliary body made up of 3 muscles and the iris; the muscles accommodate the lens (they contract,
ligaments loosen, lens fattens); the ciliary body also produce aqueous humor,and holds the lens in
place
Four photopigments: rhodopsin, red, green and blue; each photopigment contains:
o Opsin protein bound to retinal; the difference among opsin molecules allows a
photopigment to have specificity for a particular color of light
o Retinal a chromophore molecule; retinal is constant among all photopigments and is
produced from vitamin A

Light retina rods and cones bipolar neurons ganglion cells optic disc optic nerve optic chiasm
lateral geniculate body of the thalamus optic radiations visual cortex (area 17) and visual association
cortex (18, 19)
Good picture on page 316!!
Lesions along the visual pathway
Left anopsia
Bilateral hemianopsia
Right homonomous hemianopsia
Right hemianopsia with macular sparing
Myopia (nearsighted) the eyeball is too long or the cornea is too steep; the focal point of far objects is
focused in front of the retina; near objects are focused correctly ; treatment is concave lenses
Hyperopia (farsighted) eyeball is too short or the lens cannot become round enough; the focal point of near
objects is focused behind the retina; distant objects are focused correctly; corrected with convex lenses
Astigmatism curvature of the lens is not uniform; treatment is with cylindrical lenses
Presbyopia loss of lens elasticity with age; the eye cannot focus sharply on nearby objects b/c lens doesnt
fatten up; treated with bifocals

HEARING
External ear
o Auricle (pinna)
o External auditory canal/meatus contains hair and cerumen; serves as a resonator and
conduit
Middle ear
o Tympanic cavity surrounds the bones of the middle ear; it is an air filled cavity in temporal
bone
Auditory tube
Ossicles : eardrum malleus incus stapes oval window
Inner ear formed by a bony labyrinth (perilymph) and membranous labyrinth (endolymph)
**endolymph is what stim. Hair cells
o Vestibule (saccule and utricle) associated with sense of balance

o
o

Semicircular canals equilibrium

Cochlea 2 membranes: vestibular and basilar
Spiral organ (organ of Corti) has receptors for hearing (hair cells); they transform
fluid vibrations from sound waves into nerve impulses
Human hearing range = 20-20K Hz
Pitch = Frequency
Loudness = Amplitude = Intensity (measured in decibels)
Timbre = Quality; related to the presence of additional sound-wave frequencies superimposed on the
principle frequency

Sound vibration tympanic membrane ossicles oval window waves in perilymph bending of hairs
(stereocilia)
hair cell depolarization within the organ of corti short axons to the spiral ganglion (within the bony
modiolus)
long axons form the cochlear nerve synapse with the cochlear nuclei (dorsal and ventral) superior olivary
nucleus (goes to both sides)
lateral lemniscus inferior colliculus medial geniculate of the thalamus transverse temporal gyrus
(Heschls gyrus)
**Unlike other sensory systems, hearing has a bilateral central representation (sound from one ear reaches the
auditory cortex in both hemispheres.
**Superior olives are important in sound localization

WIKI: Just as the inner hair cells are arranged according to the best frequency (BF), so is the cochlear
nucleus. This so-called tonotopic organization is preserved because only a few inner hair cells synapse on
the dendrites of a nerve cell in the spiral ganglion, and the axon from that nerve cell synapes on only a very
few dendrites in the cochlear nucleus. The cochlear nucleus receives input from each spiral ganglion, but
also receives input from other parts of the brain, such as auditory cortex, pontine nuclei, trigeminal
ganglion and nucleus, dorsal column nuclei and the second dorsal root ganglion. The inputs from other
areas of the brain play a role in sound localization.
Presbycousis hearing loss that gradually occurs because of changes in the inner or middle ear in individuals as
they grow older

TASTE
-

Foods taste-producing molecules bind w/ protein from von Ebners glands; these bound molecules
stimulate taste bud receptors
Taste bud receptors
Made of gustatory receptor cells that synapse with sensory nerve fibers; they are located:
o Within fungiform and vallate papillae of the tongue
Fungiform papillae rounded, located mostly at the tip of the tongue, contain
about 5 taste buds each
Vallate papillae in V arrangement on the back of the tongue; contain ~100 taste
buds each
Filliform papillae on the dorsum of the tongue do not usually contain taste buds!
o On the mucosa of the epiglottis, palate and pharynx
Taste bud receptor cell CN VII, IX or X nucleus of solitary tract (medulla) ipsilateral VPM of
thalamus insular cortex to the facial area of the post-central gyrus
Ageusia complete loss of taste
Dysgeusia disturbed sense of taste

Pathway on page 320!!

Smell
Odorants dissolved in mucous from Bowmans glands bipolar olfactory cells olfactory nerve olfactory
bulb (synapses with mitral and tufted cells) olfactory tract primary olfactory cortex and amygdale
Anosmia absence of smell; disease of the olfactory mucous membranes (common cold, allergic rhinitis)
Hyposmia diminished smell
Dysosmia distorted smell

MUSCLE HISTOLOGY
Myofilaments located in the sarcoplasm; thin filaments are 6-8nm and thick are 15nm in diameter
Tropomyosin blocks actin binding sites during rest
Troponin attached to each tropomyosin molecule
Skeletal muscle
Cells are multinucleated with nuclei around the periphery; contraction is by action potential and there
is no synctium
The Ca2+ source is the sarcoplasmic reticulum, and skeletal muscle does have T-tubules
Regulation is via actin; skeletal muscle does have troponin
Myofibril = the major structural unit
o Thick filaments
o Thin filaments (containing actin, tropomyosin, and troponin)
Cross-striations apparent due to alternating light and dark banding of the
myofibrils
H and I bands are what shorten in contraction!
A band is dark, I band is light!
Connective Tissue
Epimysium surrounds the entire muscle
Perimysium surrounds muscle fascicles
Endomysium surrounds each muscle fiber
Sliding Filament model
1. AP travels through T-tubules to the SR of two adjacent sarcomeres
2. Ca2+ released from terminal cisternae of each SR binds to troponin C, which causes a conformational
change in tropomyosin, allowing the myosin head to bind actin sites
3. An ATP molecule already bound to myosin is hydrolyzed to ADP + Pi and released; the actin filament is
pulled closer toward the center of the sarcomere, shortening sarcomere length
4. ATP binds the myosin head to release it from the actin filament
During relaxation, Ca2+ is taken up by the SR, causing the release of actin from myosin cross-bridges;
tropomyosin returns to normal confiburation, blocking this interaction.
**ATP sources for contraction are glycolysis, TCA cycle (oxidative phosphorylation), creatine phosphate
ATP hydrolysis is the
immediate source of energy for contraction; 3 sources keep the ATP pool replenished:
o
Creatine phosphate
+ ADP creatine + ATP
o
Glycogen skeletal
muscle fibers contain 1% glycogen that they can degrade by glycogenolysis to G1P, which

enters glycolysis to yield 2 ATP; this source is limited and eventually the muscle must depend
on cellular respiration
o
Cellular respiration
required for musle activity and also afterward to allow the body to resynthesize glycogen
from the lactic acid produced earlier
**During exercise, creatine phosphate is the immediate source of phosphate groups to replenish ATP!
**Compounds with higher phosphate-group transfer potential than ATP include: PEP, creatine phosphate,
carbamoyl phosphate, acetyl
phosphate, 1,3-DPG acid
**Compounds with lower phosphate-group transfer potential than ATP are G1P, G6P, F1P, creatine
Fractionation it is not necessary to activate all motor units in a muscle
Myesthenia gravis autoimmune disease in which the Ach receptors on the sarcolemma are blocked,
diminishing the number of muscle fibers responsive to the AP
Twitch Speed
Slow (Type I) fibers red in color, function in postural endurance, slow contraction speed and low
ATPase activity, get their ATP from oxidative phosphorylation, fatigue-resistant, small fiber diameter
have tons of mitochondria and myoglobin, but low SR
o Lipid accumulation
o Oxidative capacity is related to the number of capillaries, myoglobin content, and the
number of mitochondria
Fast (Type II) fibers white, rapid/powerful movement, fast contraction with high myosin ATPase
activity; ATP source is anaerobic glycolysis of stored glycogen, fatigue quickly, 2x as large fiber
diameter. Low %mitochondria and myoglobin
o Low lipid accumulation
o Enzymes for anaerobic glycolysis are abundant; have tons of glycogen while slow-twitch has
little
o More extensive SR
Extrafusal fibers make up the majority of skeletal muscle; innervated by alpha-motor neurons
Intrafusal fibers located in the bulk of the muscle; innervated by gamma-motor neuronsthe 2 main types
of intrafusal fibers that form muscle spindles are nuclear bag fibers and nuclear chain fibers
Nuclear bag fibers transmit information about length and tension; innervated by fast Type Ia
afferent fibers
o

A nuclear bag fibre is a type of intrafusal muscle fiber that lies in the center of a muscle spindle.
Each has a large number of nuclei concentrated in bags and they cause excitation of both the
primary and secondary nerve fibres.

Detect fast, dynamic changes in muscle length and tension; innervated by Ia afferents
(fastest in the body)
Nuclear chain fibers transmit information about length; innervated by slow Type II afferent nerve
fibers
o

A Nuclear chain fiber is a specialized sensory organ contained within a muscle. Nuclear chain
fibers are intrafusal fibers which, along with nuclear bag fibers, make up the muscle spindle
responsible for the detection of changes in muscle length.
Also note that a similar structure attaching one end to muscle and the other end to a tendon is
known as a Golgi tendon. However, golgi tendons differ from nuclear chain and nuclear bag fibers
in that they are considered in series rather than in parallel to the muscle fibers.

Detect static changes in muscle length and tension; innervated by slower group II afferents

Muscle Spindles detect muscle fiber length and tension; they are innervated by Type Ia and Type II afferent
nerve fibers
Composed of intrafusal fibers; they run parallel to the main extrafusal fibers
Stretch reflex (myotatic reflex): muscle stretch activates muscle spindles and reflex causes muscles to
contract

MONOSYNAPTIC reflex; Ia afferents synapse directly with alpha motor neuronsthat makes
them monosynaptic (however, they also synapse with inhibitory interneurons); the sensory
receptors are classified as proprioceptors
Found within the belly of a muscle as small, encapsulated intrafusal fibers running in parallel with
extrafusal fibers; they detect both static and dynamic changes in length; the finer the movement
required, the greater # of muscle spindles in that muscle

Golgi Tendon Organs detect muscle fiber tension; innervated by Type Ib afferent fibers
Tendon (inverse myotactic) reflex: muscle tension activates Golgi spinal inhibitory interneuron
inhibits alpha-motor neuron muscle relaxes
Golgi organs also depolarize in response to stretch, but they inhibit the alpha-motor neuron causing
the muscle to relax; this receptor uses Ib afferents and is polysynaptic because Ib synapses on an
inhibitor interneuron
**Flexor-withdrawal reflex stimulus is pain and the afferent fibers are II, III or IV; results in ipsilateral flexion
and contralateral extension
**all reflex arcs have 6 elements (except probably monosynaptic ones?): receptor, sensory afferent neuron,
integration center (CNS), interneuron, motor efferent neuron, effector
CARDIAC MUSCLE
Single central nucleus, autonomic innervation, intrinsic contraction, functions as syncytium
Calcium source is mostly extracellular but also somewhat on its less extensive SR, does have T-tubules
Regulation is by actin, and it does have troponin
Cells have similar contractile structure to skeletal, but cardiac muscle fibers are linked by
desmosomes
Cells have many branches that communicate with each other via gap junctions
Intercalated discs coordinate the action of cardiac muscle cells
Cells do NOT undergo mitosis; injury results in fibrosis with loss of function
Increased demand of both skeletal and cardiac muscle results in hypertrophy (growth in size of fibers,
not # of fibers)
No motor units
Contraction
o Ca2+ enters the cells via specific calcium channels regulated by cAMP protein kinases
o Influx of Ca2+ release of more Ca2+ from the SR, initiating troponin-C binding and
eventual muscle contraction
o Relaxation occurs when Ca2_ exits the myocytes through a regulated Ca2+/Na+ exchange
system
o The plateau in the cardiac muscle AP is due to the influx of Ca2+
SMOOTH MUSCLE
Single central nucleus, autonomic innervation, contraction by AP/hormones, functions as synctium
Ca2+ source is mostly extracellular but some SR (poorly developed), no t-tubules
Regulation is by myosin, and there is no troponin
Small diameter but very long cells
Hormones like epinephrine and oxytocin can stimulate smooth muscle contraction
There is considerable synaptic distance between the nerve terminal and sarcolemma because ANS
axons terminate in the surrounding CT; not all smooth muscle cells are directly innervated, so they
rely on gap junctions to propagate the AP
Muscle Contraction
o Ca2+ enters the cell and binds calmodulin in the cytoplasm; calmodulin activates myosin
light-chain kinase, which transfers a Pi from an ATP molecule to the myosin light chain
o Phosphorylation of myosin enables it to interact with actin in the same manner as striated
muscle

o
o
o
o
o

Relaxation occurs when Ca2+ is taken up by the SR or plasma membrane and the myosin
light-chain kinase is inactivated
Each contraction cycle requires 1ATP
Thin filaments lack troponin so they are always ready to interact with myosin!
Myosin light-chain phosphatase removes the P from myosin and releases the cross-bridge
relaxation
Because the cross-bridges detach very slowly, it maintains contraction for a long time

CARDIAC PHYSIOLOGY
Flow = P/R (flow is proportional to the pressure difference at 2 ends of a vessel)
Flow is greatest in large straight vessels, areas of low turbulence and low resistance, low viscosity
Perfusion P = P at arterial end P at venous end
Resistance to flow = 8nL/r4 (from Pouiseuilles law of flow)
o n = viscosity; determined by:
Hematocrit effect of viscosity is greater in larger vessels than smaller, and overall
vascular resistance is not affected unless viscosity changes are severe (as in
polycythemia vera)
Decrease in deformation of cells
Plasma concentration (ex: increase in protein from multiple myeloma)
o L = length of tube
o r = radius; has by far the most effect, involves size of the vessel, regulation of tone, and
pathologic narrowing
Series resistance: Rtotal = R1 + R2.
Parallel resistance: 1/Rtotal = 1/R1 + 1/R2
Resistance and conductance are inversely related
Laminar flow straight vessels; layer closest to vessel surface doesnt move; layer in center moves at
Vmax up to a certain critical velocity at which point flow becomes turbulent
Turbulent flow Reynolds # represents the probability for turbulent flow; it is related to velocity,
vessel diameter, and viscosity
o Very turbulent vessels: ascending aorta, atherosclerotic constricted vessels, cases of anemia
Velocity of Flow: aorta > large arteries > vena cavae > large veins > small arteries > arterioles > capillaries
When the vena cava is somewhat collapsed (as it often is), it has a lower x-sectional area and higher
velocity of blood flow compared to the aorta
Another diagram on page 335 says that velocity is highest in the aorta/large arteries then drops
through arterioles and capillaries then rises a bit in the venules/veins/vena cava but only a slight
rise!!!
Pressure is 100mmHg in the aorta, 30 at the end of arterioles, and 4mmHg at the vena cava
**arterioles are any arteries <0.5mm in diameter; they have a small lumen, thick tunica media with almost all
muscle and little elastin; they have an internal elastic lamina
Systolic and diastolic pressure are both highest in the aorta and arteries, then drop as you go through
circulation to the vena cava (lowest).
LaPlaces Law
Wall stress = (P*r)/thickness
A thin-walled, distended vessel under a lot of pressure has tons of tension/stress and is at great risk
for rupture.
A dilated, thin walled myocardium under increasing P and volume has higher wall tension and
myocardial O2 demand is high
o Pressure in the ventricle depends on afterload

Afterload can also be described as the pressure that the chamber of the heart
has to generate in order to eject blood out of the chamber, and thus is a
consequence of the arterial pressure, since the pressure in the ventricle must

be greater than the systemic pressure in order to open the aortic valve.
Everything else held equal, as afterload increases, cardiac output decreases.
o Radius of the ventricle depends on preload (the amount of venous return)
o Thickness of the ventricle: increased thickness decreases wall stress to a point, then
oxygen demand increases because of the greater muscle mass but oxygen supply
decreases by narrowing coronary vesels.
Review the cardiac section with book because some stuff I just highlighted.
Blood volume:
60% in systemic veins, 10% in systemic arteries, less than 10% in arterioles and capillaries
9% in pulmonary vessels
7% in the heart
During hypovolemia, sympathetics signal veins to constrict and return more blood; there is no clinical
manifestation of hypovolemia until 15-20% blood loss because of this compensatory constriction. It helps
maintain mean systemic filling pressure in the face of blood loss (preload is maintained). Arterial constriction
system has much less effect on mean systemic filling pressure because they contain little blood. Arterial
constriction increases afterload. Capillaries do not constrict because they lack smooth muscle in their walls!!
Vascular compliance = increase in V/increase in P (high compliance means huge volume change causes little
pressure change)
Pulmonary circulation low BP, low resistance, high compliance (store blood without changing BP)
BP is much lower in pulmonary circuit because the arterioles are usually dilated w/ little resistance to
flow; they are highly compliant vessels that store blood volume without changing blood pressure
Systemic circulation high BP, high resistance, low compliance
**Volume of blood flow in both circuits is 5L/minute
TPR = (MAP CVP)/CO

CVP = central venous pressure

Because MAP = CO x TPR sympathetic increase MAP by both increasing CO and increasing TPR by
vasoconstriction (alpha-1 receptors)
Decrease in TPR occurs by vasodilation, especially via sympathetic stimulation of beta-2 receptors in skeletal
muscle, and by local metabolites like lactate, K+ and adenosine
**endothelins are hormonal vasoconstrictors, while NO and adenosine are vasodilators!
Blood Pressure
Pulse Pressure = SBP DBP (normal is 40); pulse pressure increases with age due to stiffened arteries
and atherosclerosis
Mean arterial pressure = DBP + PP/3
o MAP is the average pressure throughout the course of the cycle; MAP is slightly less than
halfway between SBP and DBP because diastole is longer than systole

Compliance of arteries = stroke volume/pulse pressure

Therefore, PP = SV/Arterial compliance. making PP directly related to SV and inversely related
to compliance
Increasing SV pushes tons of blood into the aorta, increasing SBP greatly, but not really changing
DBP so PP widens.
Low compliance results in higher pressure for a given SV; atherosclerosis reduces compliance
Calcification of the aorta is something that happens with aging and also reduces compliance.
Reduced compliance widens PP by greatly increasing systolic and not having much effect on
diastolic!!
Aortic stenosis reduces stroke volume, so less systolic pressure against the aorta, reduces PP
(PP narrows)

Narrow PP according to class notes:

- Heart failure
- Low SV (SV is the most important determinant of PP)
- Cardiac tamponade
- Aortic stenosis
Narrow PP according to NBDE book: decreased compliance, atherosclerosis, aortic stenosis, cardiac
tampoande, HF, decreased SV
Wide PP according to class notes:
- Reduced compliance
- Atherosclerosis
- Calcification of the aorta
- Exercise
- Increased stroke volume
- Aortic regurgitation
- Arteriovenous malvormations (extra path for blood to travel from high P artery to low P vein
without capillary gradient)
- Patent ductus arteriosus very wide PP because LV is filled more and stroke volume increases
Determinants of Cardiac Function
-

SV = EDV ESV (average is 70-80mL)

Bradycardia < 60 100 < Tachycardia
Average resting CO for men is 5.6L/min (15% less for women)
CO = O2consumption / ([O2]pulmonary vein [O2]pulmonary artery)
Ejection fraction = proportion of end diastolic blood pumped out with the beat
o EF = EDV ESV/EDV or EF = SV/EDV

Frank-Starling Mechanism
Starling mechanism sympathetics decrease venous compliance and increase venous return, which
then increases CO and more blood is pumped back into arterial circulation
Most important determinant of CO is VR; increase in venous return increases ventricular filling during
diastole and increases preload; this ultimately increases EDV increases myosin-actin crossbridges
increases contraction force increases CO
The fibrous pericardium prevents the heart from overdistending during diastole, keeping it working at
an effective point on Starlings curve (if it is too overdistended you dont generate nearly as much
tension/force). Howeve,r with compensatory cardiac enlargement occurring over time, the
pericardium becomes lax and also expands. In this case the ventricle can fall off Starlings curve and
overfill.
Conversely, a too-stiff pericardium (or a pericardial space filled with fluid) results in underfilling of the
ventricle, leading to diastolic dysfunction and reduced stroke volumes.
Cardiac function is based on myocardial oxygen supply vs. demand:
Myocardial oxygen demand is influenced by: HR, contractility, and wall stress (LaPlaces Law)
Myocardial oxygen supply: arterial O2 content, coronary blood flow, coronary perfusion pressure,
patency (openness)
Chronotrope a drug that increases HR by increasing the rate of SA node depolarization; the increased HR will
increase CO until the rate is so high that filling time is too decreased
Inotrope increases contractility; sympathetic or drug-mediated stimulation causes increased intracellular
Ca2+ which increases contraction force; increasing the force of contraction increases SV so inotropes also
increase CO

Preload filling of the ventricles (EDV); determined by VR and the radius of the ventricle (chamber size and
expansion)
Afterload force against which the heart contracts; determined by TPR (sympathetic activation,
atherosclerosis), BP, aortic outflow tract
Example: aortic stenosis causes a fixed increase in afterload because the heart has to pump very hard
to get blood out
Coarctation of the aorta increases afterload; there is also a difference when measuring BP between
arms and legs (or right arm vs. left arm), which may be present in patients with atherosclerosis or
dissection
**Frank-Starling says VR has a greater effect on CO than TPR (afterload), so the best way to increase CO is
increase VR (increase preload)
Compliance and Venous Return
Increased intrathoracic pressure increased venous compliance, decreased venous return
Decreased intrathoracic pressure decreased venous compliance, increased venous return
Sympathetic tone increase decreased venous compliance (+ some constriction), increased venous
return
Respiratory inspiration increases VR because of a decrease in right atrial pressure.
An increase in resistance of the vena cava, as occurs when it is compressed during a Valsalva
maneuver or pregnancy, decreases venous return.
Cardiac Cycle
Diastole (filling) phase AV valves are open, but pulmonic/aortic valves are closed; blood enters
ventricles through open AV valves; 75% is passive and 25% is due to atrial kick contraction this is
the longest phase of the cycle
Isovolumetric contraction all valves are closed; closing of the AV valves creates the S1 lub; this
sound begins systole
Systole AV valves closed, pulmonary/aortic are open; blood is ejected out the open valves
Isovolumetric relaxation all valves are closed, semilunar valves closing creates the S2 dub; this
sound begins diastole
**The coronary arteries are perfused during diastole
**Aortic valve closes before the pulmonic, causing a splitting of S2 that is accentuated on inspiration
**S1 is louder and longer than S2
See the pressure-volume loop and the cardiac cycle pictures on page 343 in NBDE.
Heart murmurs with valvular disease
Diastolic aortic insufficiency or mitral stenosis
Systolic aortic stenosis or mitral regurgitation
Electrophysiology
SA node atrial muscle AV node common bundle of His bundle branches Purkinje fibers
ventricular myocytes ventricular contraction
Cardiac muscles very long refractory period allows for diastolic filling and prevents reentry
arrhythmias
It takes 0.22 seconds for the AP to spread through the heart; ventricular muscles refractory period is
0.25-0.3 seconds
Atrial muscles refractory period is 0.15 seconds
Absolute refractory period is due to Na+ channel inactivation/gate closure
Relative refractory period continues until membrane potential returns to RMP
**it takes 0.04 seconds for the impulse to travel from bundle of His to ventricular muscle
**ventricular conducting system is capable of 30-40 impulses per minute
Cardiac conductive tissues (differences in AP between the nodes and the muscle fibers themselves)

Nodal/pacemaker tissue phases 0-4; phase 0 is dependent on Ca2+

Cardiac myocytes gap junctions relay electrical signals causing contraction; phases 0-4, phase 0 is
dependent on Na+
Pictures of APs on page 345 NBDE!!! LOOK AT DIFFERENCES!! Draw on back, noting important
comparisons.
**Ventricular muscle has a longer refractory period (0.3 seconds) than atrial muscle (0.15 seconds); this
prevents re-entry and prevents the cardiac muscle from ever going into tetany
SA node in the posterior wall of the RA near the opening of SVC; drives depolarization of the rest of the heart;
atria contract before ventricles preventing fast, arrythmogenic beats from reaching the ventricle
Internodal pathways transmit wave from SA node to the LA and the AV node
AV node lower right interatrial septum; impulse is delayed at the AV node for 0.13 seconds allowing atria to
contract before ventricles
His-Purkinje system arises in AV node, then Purkinje fibers originate from L and R bundle branches and
extend to papillary muscles and lateral walls of the ventricle; depolarization wave travels extremely fast
through bundle branches and Purkinjetotal time being 0.03 sec
EKG
Single lead corresponds to an anatomic territory; look at a single lead for arrhythmias
Look at multiple leads together for voltage abnormalities and axis deviations
Types of EKG leads are listed on page 346 (standard bipolar, standard unipolar, chest leads; study these and
work out what each means.
P wave atrial depolarization prior to atrial contraction
PR interval length between depolarization of atria and depolarization of ventricles (0.16 seconds); increased
HR = shorter PR interval
QRS wave ventricular depolarization; during phase 0, atrial repolarization occurs within QRS; this is the period
of highest Na+ influx and maximum ventricular Na+ channel conductance; the shape of QRS is dictated by the
spread of the AP throughout ventricular muscle prior to contraction
ST segment length corresponds to AP duration in ventricular muscle; the entire ventricle is depolarized;
during phase 2, prolonged Ca2+ conductance is slow through the channels; isoelectric
o Ventricles are completely depolarized during this isoelectric portion of the EKG (the only
time this happens)
o The EKG is also isoelectric between the T and P waves, where the ventricle is at RMP
(ventricular diastole); this TP segment is greatly diminished at high heart rates.
T wave ventricular repolarization
QT interval period between ventricular depolarization and repolarization (0.35 seconds)
**The isoelectric point between T and P waves (ventricle is at resting potential) occurs during ventricular
diastole and is shortened with high HR
**U wave is occasionally found in EKGs; caused by repolarization of papillary muscle, or it can be seen with
hypokalemia
**an EKG with extra P waves before each QRS complex indicates partial heart block (2nd degree block)
**an EKG with dissociated P and QRS waves shows complete heart block (that is, there is no correlation
between the two)
Isovolumetric contraction (systole) all valves closed; corresponds to QRS wave
Ejection phase (systole) rapid ejection is during ST segment and reduced ejection is during the T wave
Isovolumetric relaxation (diastole) all valves closed; T-P interval
Filling phase (diastole) rapid ventricular filling and decreased filling are during Q-T interval, supplementary
filling is during the P wave

Regulatory Mechanisms
Sympathetic

Control Center
Medulla

Nerve
T1-4

NT
NE

Effect on HR
Increase HR, increase SA node discharge

Increase rate of depolarization through the heart

Increase intracellular Ca2+, which then
Increase ventricular contraction force
Parasympathetic
Medulla
X
Ach
Decrease HR, decrease SA node discharge
Decrease rate of depolarization through the heart
**The right vagus nerve supplies the SA node, while the left vagus nerve innervates the AV node.
**Sympathetics are from T1-T4
Bainbridge reflex
Increased blood volume stretches stretch-receptors in the atria, increasing HR and therefore
increasing CO
Mediated by X afferents to the medulla, efferent loop is slowing of X output
Pumps more blood out of the pulmonary system to the systemic system, helping to prevent
pulmonary edema
Baroreceptors effect changes in HR and BP; they modulate intravascular pressure and HR over a short time
span (activated by increased BP) and act to decrease HR, vasodilate, and decrease BP.
Baroreceptor reflex increased BP increase parasympathetic afferent activity (IX, X) medulla
increased vagal efferent activity to decrease sympathetic tone decrease HR, decrease BP,
vasodilation decrease CO
Carotid sinus spindle-shaped dilation of receptors in the adventitia of vessels at the bifurcation
(superior border of thyroid cartilage); afferent is CN IX; they are extensively branched and coiled
intertwined ends of myelinated nerve fibers
o Carotid sinus syndrome excessive stimulation of both caroted sinuses (as in convulsive
seizures) can lead to momentary loss of consciousness
o Stretch receptors in the carotid sinus are the MOST important for short term regulation of
MAP
o Stretch receptors in the atria respond to expansion of BV; they do not directly respond to
changes in systemic arterial BP
Aortic arch baroreceptor receptors in adventitia of the aortic arch; afferent is CN X
Response to sudden standing:
BP in brain and upper body is sensed by baroreceptors decreased Para firing (IX, X) increased
sympathetic discharge:
Increases HR, conduction velocity, cardiac contractility, and peripheral resistance
(vasoconstriction)
Decreases renal blood flow by alpha-1 vasoconstriction of afferent artery
Beta-1 stimulation on JGA increases renin production angiotensin II aldosterone
Increased blood back to heart to increase preload (constriction of large veins), increased CO and
returned BP
Hemorrhage or hypovolemia:
Compensations:
Baroreceptor reflex (mentioned above)increase sympathetic, decrease parasympathetic, increase
Epi and decrease vagal
RAAS
ADH
Chemoreceptors have a major effect on respiration, and also an effect on vasomotor.
Detect changes in blood oxygen, CO2 and H+ concentrations
Modulate the respiratory center in the brain
Carotid body (afferent is IX) and the aortic body (afferent is X)
Increased CO2 or H+ (or decreased O2) stimulates chemoreceptors increased parasympathetic afferent
activity (IX, X) medulla (respiratory center) increase ventilation increase BP and HR secondary to
simultaneous secretion of catecholamines from adrenal medulla
Exercise

Beta-2 receptors in muscle vasodilate, increase blood flow to muscles

Beta-1 receptors in the heart increase HR, contraction force, and CO
Alpha-1 receptors in other parts of the body vasoconstriction and increase arterial pressure
Decreased venous compliance enhances venous return (vasoconstriction and skeletal muscle activity)
Local metabolites are released as O2 drops; adenosine, CO2 and lactic acid all signal vasodilation to
increase blood flow!
As blood flow increases to muscles during exercise, the adenosine is washed out; decreased
adenosine means the arterioles vasoconstrict, keeping blood flow at a normal rate in the face of high
arterial pressure.
During exercise, increase in CO is slightly greater than the drop in TPR so MAP increases!
Initially, we see an increase in SV then an increase in HR follows when greater than 50% of maximal
work capacity is reached.
Because systemic vascular resistance decreases during exercise (beta-2 vasodilation), blood flow to
skeletal muscle can x20
TPR decreases during exercise due to accumulation of vasodilator metabolites (lactate, K+ and
adenosine). Arterial vasodilation accounts for the overall decrease in TPR. 3 major effects must
happen for the circulatory system to deal with exercise:
1. Mass discharge of sympathetic
2. Increase in CO (the decrease in TPR doesnt match the increase in CO so in total, MAP
rises)
3. Increase in arterial pressure (but dilation of skeletal muscle arteries)
**An anxious patient may have a higher SBP than previously noted; this is probably due to decreased arterial
compliance.
Male Hct = 44-46
Female Hct = 40-42
because of the chloride shift.
Male Hb = 15-16g/dL
Female Hb = 13-14g/dL

Venous Hct is typically higher than arterial Hct

Severe anemia < 7.5 g/dL

Anemia
Decreased Hct, can be due to decreased RBC or decreased Hb concentration!
Decreased O2 transport in blood fatigue, respiratory compensation, cardiac compensation,
arterioles dilate to increase blood return/preload, hypoxia in pulmonary circulation results in
vasoconstriction of those vessels
Cardiac Compensation
o Increased CO because chemoreceptors sense low O2 and increase SV and HR to get more O2
to tissues
o Low Hct decreases viscosity so resistance to flow decreases, pulmonary vascular resistance
decreases, blood return to the heart/preload increases
Respiratory Compensation
o Bohr effect: O2-Hb curve shifts to the right to unload more O2 into the tissues
o Increase in 2,3-DPG, CO and RBC H+
Types of anemia
o Decreased production anemias: Fe deficiency, Folate deficiency, B12 deficiency
o Increased destruction anemias: blood loss, hemolysis, hemoglobinopathies
**Anemix px have normal oxygen tension, but reduced oxygen content in their arterial blood
**the amount of bile pigments excreted by the liver is a good indication of the amount of erythrocyte
destruction per day
Carbon monoxide poisoning CO has 240x the affinity for Hb than O2 does, so at a normal Hb level there is
decreased O2 content
Cyanosis deoxygenated Hb in tissues gives the skin/mucous membranes a blue tint; it does not occur in
severe anemia because you need over 5g deoxygenated Hb per 100mL to appreciate it

Erythropoeitin

Glycoprotein hormone produced in the kidneys that increases RBC production by bone marrow (acts
at the hemocytoblast)
Decreased erythropoiesis anemia, increased eryhtropoiesis polycythemia (sluggish blood flow
due to high viscosity)
Negative feedback: decreased oxygen tension (hypoxia) increased erythropoietin (and opposite:
ample O2 erythropoietin)

Coagulation and Hemostasis

Virchows Triad 3 broad factors that contribute to thrombosis:
o Endothelial injury
o Stasis
o Hypercoaguability
Hemostasis has 3 parts: vasoconstriction, platelet plug/aggregation, coagulation
Coagulation SEE THE FIGURE ON PAGE 353!! DRAW ON BACK!!!
When blood vessels are damaged, both intrinsic and extrinsic pathways are activated.
The common result of both pathways leads into prothrombin being cleaved into thrombin by
prothrombin activator (factor Va)
Thrombin then cleaves fibrinogen to fibrin, which forms the clot and cross-links with the platelets
Tissue factor (tissue thromboplastin) is part of the extrinsic pathway; it is not present in the blood.
*In cirrhosis, prothrombin and fibrinogen are deficient.
Three essential steps for blood clotting:
1.
Prothrombin activator is formed by extrinsic or intrinsic pathways; extrinsic pathway uses
tissue thromboplastin
2.
Prothrombin activator catalyzes prothrombin thrombin
3.
Thrombin acts as an enzyme to convert fibrinogen fibrin threads that enmesh RBCs and
platelets to form the clot

Respiratory Physiology

TLV = IRV + TV + ERV + RV

VC = TLV RV
TLC = 6L, RV = 1.5L, ERV = 1.5L, IRV = 2.5L
Inspiratory Capacity = TV + IRV
Functional Resicual Capacity = ERV + RV = 3L
o At FRC, collapsing forces = expanding forces and there is balance between
inspiratory/expiratory forces; muscle contraction is needed to either increase or decrease
lung volume from FRC
o

At FRC, alveolar P = 760mmHg (atmospheric) and intrapleural pressure = 756mmHg

(subatmospheric, or negative)
Inspiration decreases both intraalveolar pressure and intrapleural pressure!
During expiration, intrapleural pressure becomes less negative and intraalveolar pressure also rises
RV is increased in older people and in people with COPD or asthma because of air trapping

Expanding forces include elastic CT of the chest wall.

Collapsing forces include elastic CT of the lungs; surfactant decreases surface tension to help counteract
collapse.
Surfactant increases lung compliance and decreases surface tension (preventing atelectasis at the
end of expiration); prevents small alveoli from collapsing
Asthma chronic reactive airway disorder causing obstruction from bronchospasm, increased mucous
secretion, and mucosal edema. It is a type of COPD (which are characterized by increased airflow resistance);
immediate consequences of an asthma attack include:
Hypoxia, tachycardia, hypercapnia and acute respiratory acidosis
Bronchiolar constriction is the cause of obstruction. We give them beta-2 agonists to dilate the
bronchioles; short-acting beta-2 agonists include: salbutamol and terbutaline
Long-acting beta-2 agonists are for management; they cause dilation for 12 hours; they are only used
in conjunction with inhaled steroids; they include: salmeterol and formoterol
Minute ventilation = RR x TV
Alveolar ventilation the amount of gas that reaches the alveoli per minute; it is the amount of atmospheric
air that can undergo gas exchange; it is a good gauge for breathing effectiveness

VA = RR x (TV dead air space volume)

TV = 500mL, but only 350mL is used for alveolar ventilation because there is 150mL of dead
air space
VA = RR x (350mL)
**This dead space of nonventilated gas in the airways is called anatomic dead space; on the other hand,
physiologic dead space is due to alveoli that are ventilated, but not perfusedthis is only significant in disease.
Conducting zone airways have goblet and mucous cells; respiratory zone alveolar wall has:
Type I epithelial cells responsible for gas exchange; cover 95% of alveolar surface
Type II epithelial cells produce surfactant
Henrys Law - solubility of a gas increases as its partial pressure increases
Hb is normally:
98% saturated with O2 in the lungs (arterial)
75% saturated in tissues (venous)
300 million Hb per RBC; synthesis of Hb begins in the erythroblasts
PO2 determines the affinity of Hb for O2 binding because of a conformational change in Hb
Hemoglobin is saturated around PO2 of 100
***Remember that a single Hb can bind 4 O2s so it is actually carrying 8 atoms of oxygen

O2-Hb Dissociation Curve

Left shift favors O2 uptake (e.g. at the lungs); left shift is caused by:
o pH or CO2
o 2,3-DPG (a product of glycolysis)
o Low temperature
o When PO2 is high, Hb has a greater affinity for O2 binding at the lungs
Right shift favors O2 release to tissues
o pH or CO2
o 2,3-DPG (hypoxia stimulates DPG production, so again DPG shifts the curve right to deliver
more O2)
o High temperature
o When PO2 is low, Hb does not bind O2 as readily and O2 is released to the tissues
o In exercising muscle, temperature increases, 2,3-DPG increases and pH goes down due to
lactic acid
o Anemia shifts right to help unload O2 to the tissues (because there is high CO2, and low pH
in the RBCs in anemia)
Bohr Effect the curve shifts right in acidic environments to help unload O2 to the tissues (Hb has decreased
affinity for O2); H+ binds more readily to deoxygenated Hb than to oxyhemoglobin
Haldane Effect oxygen tension affects affinity of Hb for CO2; high oxygen tension in the lungs increase Hb-O2
binding and decreases Hbs affinity for CO2 low oxygen tension in the tissues decreases Hb-O2 binding and
increases Hbs affinity for CO2 (binds H+ and forms carbamino compounds) so CO2 is taken up in the tissues
and O2-Hb decreases
Total amount of oxygen carried in the blood = PO2 + Hb-O2, determined mostly by the amount of Hb and its
saturation.

Oxygen saturation = amount of Hb saturated with O2; it is determined by:

PO2
O2-Hb affinity is altered by changes in the Hb moleculeIntrinsic
(hemoglobinopathies) or extrinsic (changes in pH, PCO2,
temperature)and by competition for Hb binding
Blood Hb concentration does not affect O2 saturation of Hb or
PaO2
o Both SaO2 and ParterialO2 are independent of Hb
concentraiton
Oxygen content per 1g Hb = 1.34mL O2
Hemoglobin concentration = 15g/dL
Women = 12-16
Men = 14-18
Infants = 14-20
o Low Hb is found in anemia, hyperthyroidism and cirrhosis of the liver
o High Hb is found in polycythemia, COPD and CHF
Oxygen concentration in arterial blood is 20.1mL O2/100mL blood
Oxygen-carrying capacity of the blood depends on:
Oxygenation from the lungs:
o PaO2 gradient
o FiO2 (fraction of inspired oxygen)
o Effective gas exchange (no physiologic dead space or shunt)
Hb concentration

Hb affinity for O2 (presence of CO or left shift of curve)

Perfusion cardiac function, patency of vessels, adequacy of forward flow

CO2 carried in the blood mostly as serum HCO3-, but also as HCO3- in RBCs, as carbamino-Hb, or dissolved in
blood (PCO2)
Carbamino-Hb: CO2 binds the globin part of Hb (not Fe2+ like O2 or CO do); therefore it forms
CO2NH2 groups
Chloride Shift bicarbonate carried in serum is generated within the RBC; it is transported from RBC to serum
in exchange for ClCO2 in blood diffuses passively into the RBC
Carbonic anhydrase in the RBC combines CO2 + H2O H2CO3 H+ and HCO3Bicarbonate passes across the RBC membrane into serum in exchange for ClCarbonic anhydrase is not present in serum; bicarbonate can be produced in serum by non-enzymatic
means but its very slow.
Hypoxemia
Low oxygen levels in the blood (PO2 < 80); caused by:
o Low FiO2 high altitude or incorrect ventilator settings (usual FiO2 is about 21%)
o Hypoventilation low central respiratory drive, narcotics, medullary injury, decreased ability
for chest excursion, polio, rib fracture/chest trauma, diaphragm injury, phrenic nerve
paralysis
o V/Q mismatch unequal ventilation and perfusion (a segment of the lung is ventilated but
not perfused); caused by asthma, COPD, interstitial lung disease, alveolar disease, pulmonary
vascular disease
o Shunt segment of lung is perfused but not aerated; intra-alveolar filling affected by
atelectasis, pneumonia, pulmonary edema, intracardiac shunt, vascular shunt
o Diffusion limitation
Decreased surface area of the blood-gas barrier by pneumonectomy or emphysema
Thick blood-gas barrier due to diffuse interstitial fibrosis, sarcoidosis, asbestosis or
ARDS
Low Hb to carry O2 anemia or PE
Hypoxemia in COPD is secondary to both hypoventilation (increase in PCO2) and V/Q mismatch
***rate of gas diffusion across the respiratory membrane influenced by thickness, SA, solubility of gas (CO2 is
20x as soluble as O2), partial pressure difference of gas between 2 sides of the membrane
Hypoxic Vasoconstriction
Mechanism to minimize V/Q mismatch
Example: if air cant get into a particular alveolus, vasoconstriction sends blood away from that
alveolus and no/minimal gas exchange occurs vasoconstriction of pulmonary vasculature in that
region prevents blood from going to non-ventilated segments of the lung
If this vasoconstriction 2ndary to hypoxia exists for long enough, you can get permanent secondary
changes in the pulmonary vasculature and pulmonary hypertension
Hypercarbia
High CO2 in the blood; occurs because of either or both: CO2 production, low alveolar ventilation
(hypoventilation)
Respiratory compensation is by hypeventilation
Causes headache, confusion and even coma
Extreme hypercarbia depresses the CNS (including the respiratory center), so respiratory
compensation cant occur; the result is CO2 narcosis
Hyperventilation increase the rate and depth of breathing exceeding requirement for O2 delivery and CO2
removal; stimulated by:
Low PO2 usually (in non-COPD cases)

Chemoreceptor stimulation by high CO2, low pH or low PO2

Brain effects like anxiety, emotional situations, etc
Results in:
Decreased CO2 (hypocapnia/hypocarbia)
Respiratory alkalosis (pH increases)
Increased cerebrovascular resistance and decreased cerebral blood flow
o Decreased PCO2 vasoconstriction and low cerebral blood flow
o Increased PCO2 vasodilaiton and increased cerebral blood flow
Increased PO2 and arterial oxygen concentration
Symptoms are related to decreased cerebral blood flow (due to low CO2)
Faintness, dizziness, blurred vision, experience sensations of chest tightness and suffocation
To terminate an attack you must increase PCO2 by breathing in and out of a plastic bag, or inhale 5%
CO2 mixture
**In shock, hyperventilation is caused by chemoreceptor stimulation (due to low PO2 and low pH) because of
local stagnation of blood flow
Respiratory Regulation
H+ derived from PCO2 is what triggers central chemoreceptors in the medulla
As PCO2 increases, CO2 diffuses from cerebral blood vessels into the CSF and H2CO3 is formed then
dissociates into HCO3- and H+; these protons stimulate the central chemoreceptors to increase
ventilation to get rid of the excess CO2
o So central chemoreceptors respond to increased PCO2 as its byproduct H+
o They are the major regulators of ventilation, and do NOT respond to PO2 or arterial PCO2
o Central chemoreceptors affect CV function either directly (by interacting with medullary
vasomotor centers) or indirectly (via altered pulmonary stretch receptor activity)
Peripheral chemoreceptors are a different story; they are in the aortic or carotid bodies and sense
high H+ or low PO2 in blood
o Less important than central receptors, but they respond more quickly and regulate abrupt
changes in PCO2
o They sense PCO2, O2 and H+ changes
Decreased O2 has no effect on respiratory drive until O2 is <60mmHg; then it stimulates the
carotid/aortic chemoreceptors to increase respiration
Carotid Body afferent is IX and the efferents are phrenic and intercostal nerves; highest blood flow per tissue
weight in the entire body
Aortic Body afferent is X and the efferents are the same

Acid-Base balance and respiratory changes

Metabolic acidosis
Can be caused by diabetic ketoacidosis; these patients exhibit Kussmaul breathing (rapid, deep,
labored breathing)
High H+ stimulates central and peripheral chemoreceptors
Respiratory compensation: increase respiration (hyperventilate) to blow off CO2 (you go into
respiratory alkalosis)
Metabolic alkalosis
Can be caused by low HCl production, leads to vomiting; may need to use NG suctioning to drain the
stomachs contents
Low H+ means there is little/no stimulation of central and peripheral chemoreceptors
Respiratory compensation: decreased respiration (hypoventilation) to increase CO2 and increase H+
(respiratory acidosis)
Hering-Breur Reflex if you inflate your lungs a ton, pulmonary stretch receptors signal myelinated fibers of
the vagus to the medulla (to inhibit the inspiratory center) and expiration results

Pulmonary chemoreflex lung hyperinflation causes:

First, apnea
Then, rapid breathing (tachypnea), bradycardia, hypotension
Mediated by juxtacapillary receptors (J receptors)C fiber endings close to pulmonary vessels
The pulmonary chemoreflex is analogous to the Bezold-Jarisch reflex in the heart
Stretch receptors located in airway smooth muscle, stimulated by lung distension, cause expiration by the
Hering-Breuer reflex
J Receptors located in the alveolar walls, stimulated by engorgement of capillary or alveolar walls with fluid
(like in CHF), causes rapid, shallow breathing
-

J-receptors respond to events such as pulmonary edema, pulmonary emboli, pneumonia, and barotrauma,
which cause a decrease in oxygenation and thus lead to an increase in ventilation/respiration. They may be
also stimulated by hyperinflation of the lung

Irritant receptors located between airway epithelial cells; sitmulated by noxious substances and histamine,
causes coughing and bronchoconstriction
Joint and muscle receptors outside of the lungs are stimulated during exercise to stimulate breathing
Dyspnea difficulty breathing, unpleasant sensation
Apnea cessation of breathing, usually transient (central vs. peripheral)
Hyperapnea abnormally deep and rapid breathing
Hypercapnea increased CO2 in arterial blood, secondary to under-breathing
Hypocapnea low CO2 in arterial blood, secondary to overbreathing (increased ventilation)
Respiratory arrest permanent cessation of breathing unless corrected
Hyperventilation increased alveolar ventilation leads to low PCO2 (with decreased cerebral perfusion and
fainting/syncope)
Hypoventilation decreased alveolar ventilation leads to high PCO2 (and increased cerebral perfusion)
High altitude low FiO2 results in alveolar hypoxia and arterial hypoxemia secondary to decreased barometric
pressure
Compensation is by:
o Pulmonary vasoconstriction (because theres alveolar hypoxia; dont want to waste blood
where theres no ventilation)
o Increased erythropoietin to increase Hct and O2-carrying capacity
o Increased mitochondria
o Increased 2,3-DPG shifts Hb-O2 curve to the right to dump O2 into tissues
o Increased respiratory rate (because of arterial hypoxia sensed by peripheral
chemoreceptors)
o Respiratory alkalosis because of the increased respiratory rate
o Renal HCO3- excretion increases, H+ excretion decreases (to compensate for the respiratory
alkalosis)
High altitude increases the RR so we accidentally go into respiratory alkalosis. Our body makes changes to
compensate and lower the pH.

GI System
-

Extrinsic innervation is mostly X, enteric nervous system has Auerbachs myenteric plexus (between 2
muscle layers) and submucosal plexus (Meissners) between the middle circular layer and the mucosa
Gastrin released by G cells in the stomach (antrum) in response to peptides/amino acids in the
stomach or stomach distension; gastrin stimulates HCl secretion and gastric motility
Cholecystokinin released by duodenum mucosal epithelial cells in response to fats, FAs and amino
acids in the duodenum; increases pancreatic enzyme secretion and gallbladder contraction
o CCK is also produced by neurons in the enteric nervous system, as well as abundantly
distributed in the brain
Secretin released by duodenum mucosal epithelial cells in response to HCl (low pH) in the
duodenum; increases HCO3- from pancreas to neutralize H+ and inhibits gastric acid secretion and
motility until the duodenum can neutralize itself; also stimulates bile secretion
GIP released by duodenum mucosal epithelial cells in response to fats and glucose in the duodenum,
decreases gastric acid secretion and gastric motility; increases insulin release when there are high
blood glucose levels
Sometimes called glucose-dependent insulinotropic polypeptide because it
stimulates insulin release
Enterogastric reflex duodenum distends with chime pyloric pump is inhibited decreased gastric motility
and emptying

Enterogastrone -- any hormone secreted by the mucosa of the duodenum in the lower gastrointestinal
tract in response to dietary lipids that inhibit the forward motion of the contents of chyme.
Secretin, CCK, GIP; all of which are released in response to chyme entering the duodenum
The hormones enter the bloodstream and the target organ is the stomach
They are enterogastric inhibitory hormones liberated from duodenal mucosa by acid chyme and the
presence of amino acids and free FAs in the chyme. They are carried to the stomach where they
depress the pyloric pump, inhibiting gastric motility/emptying.
GASTRIC secretions
Gastric glands make 2-3L of secretions per day, the pH of which is 1-3.5; these secretions include:
o Mucous cells Alkaline mucous in response to Ach
o Parietal cells HCl (stimulated by Ach, gastrin and histamine)
o Parietal cells Intrinsic factor for absorption of vitamin B12
o Chief cells Pepsinogen (converted to the proteolytic enzyme pepsin by HCl); stimulated by
Ach
o Gastrin hormone that goes to the parietal cells in gastric glands to stimulate HCl secretion
(stim by X and protein)
Cardiac region cardiac glands secrete mucous
Fundus and body gastric or oxyntic glands contain neck cells, parietal cells, chief cells, and
enteroendocrine cells (gastrin)
Pylorus pyloric glands secrete mucous and also secrete gastrin into the blood (decks do not say
oxyntic glands secrete gastrin)
Stages of Gastric Secretion
o Cephalic phase smell, sight, taste or thought of food triggers reflexes to stimulate gastric
secretion (parasympathetic) and also gastrin release, which prolongs the effect
o Gastric phase food enters stomach, the stomach wall distends and high pH triggers gastrin
release (70% of secretions)
o Intestinal phase acidic food enters duodenum, gastric secretion is inhibited by
enterogastric reflex and hormones

Gastric emptying is increased by eating, gastric distension, gastrin and vagal input; it is decreased by CCK,
secretin, GIP and duodenal distension (enterogastric reflex).
GI Contractions (3 major types)
Peristalsis controlled by local reflexes stimulated by distension and the enteric NS
Segmentation most common in small intestine; also stimulated by distension, occurs at rate of 12
cycles/min in duodenum and the rate is progressively slower as you progress further down the gut to
6 cycles/min in the ileum
o Intensity of segmentation in the small intestine is affected by mechanical, neural and
hormonal stimuli
Tonic contractions long duration (minutes to hours); examples are the sphincters in the GI tract
**Myenteric and parasympathetic stimulation both increase contractile force.
Gastric Emptying - can be slowed by: GIP, secretin, CCK, sympathetic NS, and activation of the enteric NS
Digestion and Absorption
Carbs salivary and pancreatic amylase, disaccharidases (sucrose, lactase, maltase, -dextrinase) in
the duodenum brush border
o Absorption is by Na+ cotransport of glucose or galactose; facilitated diffusion of fructose
o Disaccharides and small glucose polymers must be hydrolyzed at the brush border to form
monosaccharides
Proteins pepsin in the stomach; trypsin, chymotrypsin, carboxypeptidase from the pancreas;
peptidases in the brush border of the small intestine
o Abospriton is by Na+ cotransport or facilitated diffusion
o Final protein breakdown by brush border peptidases gives rise to dipeptides and amino acid
that are absorbed by secondary active transporters utilizing Na+ or H+ gradients
Fats lingual lipase and pancreatic lipase; absorption is by diffusion into the enterocyte and
exocytosis into lymph
o Bile salts emulsify TGs pancreatic lipase breaks them into monoglyceride + free FAs
(these stay associated with bile salts as micelles contact brush border and absorbed into
enterocytes by simple diffusion reconstituted as TAGs in the endoplastmic reticulum and
packaged as chylomicrons chylomicrons go into lymphatics by exocytosis
o Free FAs are absorbed by simple diffusion across the small intestinal mucosa
o In order for TAG to be absorbed, 2 things must occur: it must be emulsified and then
enzymatically digested to yield monoglycerides and free FAs, both of which can diffuse
freely into enterocytes
Exocrine Pancreas
Pancreatic secretion stimulated by Ach, CCK, secretin (and according to the decksgastrin)
Trypsin, chymotrypsin, carboxypeptidase, amylase, lipase, cholesterol esterase, phospholipase
Pancreatic ductal cells secrete fluid high in bicarbonate; the pH of pancreatic secretions is 8-8.3
Bile pH is 7.8, emulsifies lipids, gallbladder contraction and bile release stimulated by CCK of duodenum
**Intestinal secretions have a pH of 7.5-8.0; they are mainly mucous secreted by goblet cells and enterocytes
**vasoactive intestinal peptide from the pancreas relaxes smooth muscles and stimulates HCO3- secretion by
the pancreas
LIVER
-

Stores minerals, vitamins and iron as ferritin

o 75% of iron is tied up in Hb, the other 25% is stored in the liver, spleen and bone marrow
complexed with the proteins ferritin and hemosiderin (complex of denatured ferritin and
other proteins)
o Iron is resorbed almost completely in the duodenum then in plasma combines with a betaglobulin apotransferrin to form transferring; it is bound loosely with transferring and can be
released to tissues at any time

o
o
o

60% of excess Fe is stored in the liver, where it is called storage iron

Iron can only be absorbed as Fe2+, so reducing agents like Vitamin C promote iron uptake
The dominant factor controlling absorption of iron from GI is the saturation of mucosal cells
with iron
o Hemochromatosis is an iron-storage disease resulting in deposition of iron pigments in
peripheral tissues, with bronzing of the skin, diabetes and weakness
Synthesizes cholesterol important for bile salts, steroid hormones, and vitamin D
o Acetyl-CoA HMG-CoA reductase Mevalonic acid cholesterol (negative feedback to
HMG-CoA reductase)
Conjugates steroids
Metabolizes carbohydrates; regulates blood glucose levels by glucose megabolism, GNG and glycogen
formation
Metabolizes lipids: synthesizes lipoproteins and regulates lipid metabolism
o The liver is extremely active in oxidizing TAGs to produce energy
o Bulk of lipoproteins are synthesized in the liver
o Major site for converting excess carbs and proteins into FAs and TAGs
o Synthesizes large quantities of cholesterol and phospholipids, some of which are packaged as
lipoproteins and made available to the rest of the body; the remainder is excreted in bile
Metabolizes protein: deaminates amino acids to urea (urea cycle), synthesizes amino acids,
synthesizes plasma proteins
Detoxifies toxic elements
Destroys damaged RBCs
Phagocytosis of foreign antigens
Serves as a bile reservoir and secretes bile

Urea Cycle ammonia is fatal if it accumulates, so the urea cycle converts NH3 into urea: 2NH3 + CO2 urea
Hydrolysis of arginine also gives rise to urea
Ornithine regulates the turning of the cycle
Urea then passes to the bloodstream and to the kidneys and is excreted in the urine
Non-protein nitrogen in the blood is made up primarily of urea
Glucose Metabolism
Glucose is required by all tissues, especially the brain and RBCs
Liver releases glucose during exercise and between meals; released glucose is from one of two
sources: glycogenolysis or GNG
The presence of glucose in the urine occurs only when a person has exceeded the renal threshold for
glucose (diabetes)
Skeletal muscle lacks glucose-6-phosphatase so it cant deliver glucose to the bloodstream
The brain has no significant stores of glycogen and is completely dependent on blood glucose; the
brain oxidizes nearly 140g/day of glucose to CO2 and H2O, making ATP
GNG synthesis of glucose from noncarbohydrate compounds; occurs mostly in the liver (10% in the kidneys)
during prolonged starvation, the kidneys become major glucose-producing organs
Glycogenesis glucose uptake to the liver via GLUT proteins glucokinase converts glucose to G6P using ATP
Glucokinase is present only in the liver, and is expressed significantly only after a meal
Other tissues use hexokinase to do the same thing as glucokinase in the liver
Protein metabolism: deamination of amino acids and convert them to carbs or fat for energy; conversely,
amino acid synthesis
Jaundice yellowish discoloration of the skin, sclera and tissues secondary to hyperbilirubinemia; jaundice is a
common manifestation of liver disease under the tongue is the first place to spot jaundice; causes of jaundice:
Prehepatic (hemolytic) hemolytic anemia or malaria
Hepatic (hepatocyte damage) hepatitis, alcoholic liver disease, primary biliary cirrhosis
Posthepatic (obstructive) choledocholithiasis, pancreatic head cancer

Bilirubin derived from broken down Hb; it is carried to the liver and conjugated (converted to a diglucuronide
derivative) and excreted into the intestine as a component of bile
Normal plasma bilirubin = 0.5mg/100mL
In jaundice, it can rise to 40mg/100mL

Renal, Fluid, and Acid-Base Physiology

Fluid movement = k[ (Pc + i) - (Pi + c) ]
Osmolarity: osmotic pressure expressed in osmols/kg of solution
Osmolality: osmotic pressure expressed in osmols/kg of water
Edema: causes
Pc CHF, cirrhosis
c nephrotic syndrome, protein-losing enteropathy, cirrhosis, malnutrition
i lymphatic blockage (elephantiasis, lymph node resection)
Other causes of edema: increased capillary permeability (burns, sepsis, anaphylaxis, ARDS) and inappropriate
renal sodium/H2O retention
ECF fluid expansion symptoms: rales, edema, hypertension, bulging fontanelle
ICF fluid expansion: gauged by serum Na+, low serum Na+ = intracellular expansion; if chronic, formation of
intracellular osmolytes prevents drastic influx of H2O and resulting cell burst
Hypotonic fluid expansion (H2O > Na+) one possible cause is SIADH
Increase in both ECF and ICF volume, with a decrease in ECF osmolarity
Hct and [albumin] decrease due to expanded blood volume
[Na+] decreases
Isosmotic fluid expansion isotonic saline administration (0.9% NaCl or 5% glucose solutions)
ECF volume increases, but ICF volume remains unchanged, ECF osmolarity also stays the same
Hct and [albumin] decreases
[Na+] stays the same
Hypertonic fluid expansion hypertonic saline solution
ECF volume increases, ICF volume decreases, ECF osmolarity increases
Hct and [albumin] decreases
[Na+] increases
Hypotonic fluid loss sweating, fever, DI
Decreases ECF and ICF volume, increases ECF osmolarity; Hct and [albumin] increases; [Na+] increases
Hypertonic fluid loss adrenal insufficiency
Decrease in ECF volume, increase in ICF volume, decreases ECF osmolarity; Hct and [albumin]
increase, [Na+] decreases

Acid-Base Physiology
Henderson-Hasselbach: pH = pKa + log[A-]/[HA]
pH = pKa when the acid is half neutralized
The dissociation constant of an acid (Ka) is: Ka = [H+][A-] / [HA]
The larger the Ka, the stronger the acid
The pH of a buffer system depends on the pKa of the weak acid and the ratio of molar concentrations of salt
and weak acid.

Isoelectric point the pH where the number of (+) charges = the number of (-) charges; solute has no charge at
this pH, and it does not move in an electric field (pI for that solute); allows separation of proteins or amino acids
based on charge
Glycine has a net negative charge at a pH above its pI, so it moves toward the positive anode
Below its pI, glycine exhibits a net positive charge and moves toward the negative cathode
Metabolic Acidosis
pH
Because
Hyperventilation
pH By decreasing

HCO3-
compensates to:
PCO2
Ketoacidosis
Lactic acidosis
Chronic renal failure
Salicylate toxicity
Diarrhea
Metabolic Alkalosis
pH
Because
Hypoventilation
pH By increasing

HCO3-
compensates to:
PCO2
Vomiting
Hyperaldosteronism
Loop or thiazide diuretics
Respiratory Acidosis
pH
Because
Conservation of HCO3pH By increasing

PCO2
acts to:
HCO3Opiates
Sedatives
Anesthetics
COPD
High Nitrous-O2 mixture
Respiratory Alkalosis
pH
Because
Excretion of HCO3- acts pH By decreasing

PCO2
to:
HCO3Pneumonia
Pulmonary embolus
High altitude
Psychogenic
Salicylate toxicity
Buffer = weak acid + conjugate base; releases H+ when pH rises and accepts H+ when pH drops
NaHCO3:carbonic acid buffer is the major buffer in ECF fluid and blood (breaks down to CO2 + H2O w/
respiratory elimination)
Blood pH is 7.35 7.45
6.1 is the pKa of the bicarb-CO2 buffer system
Control of Acid-Base Balance
Renal in the tubules, carbonic anhydrase makes H+ and HCO3o H+ is secreted and excreted [excess acid is excreted as H+, NH4+, or combined with
phosphate]
o HCO3- is reabsorbed
o NH4 phosphates are excreted to compensate for acidity
Buffers bicarbonate, Hb and albumin
o Hb is a major H+ buffer; deoxyHb is less acidic than oxygenated Hb and is more ideally suited
to buffer H+ ions
o A 20:1 ratio of HCO3-:carbonic acid will maintain acid-base balance and normal blood pH
o Proteins are good buffers because of all the different amino acid side chains with different
pKas; they can buffer over a broad pH spectrum
o An increase in pKa means a stronger ability to bind H+ ions
Respiratory blow off CO2
Blood pH = 6.1 + log[bicarbonate] / (0.03*PCO2)
URINARY SYSTEM
Kidney functions filtration functions (water/solute balance and excretion of wastes) plus hormonal functions
(erythropoietin and renin)

Urine - slightly acidic, contains Na+, Cl-, K+, Ca2+, Mg2+, sulfates, phosphates, HCO3-, uric acid, ammonia,
creatinine, urobilinogen
Kidneys produce 1-2L of urine/day even though 180L of glomerular filtrate are produced/day (99%
reabsorbed)
Ammonia waste produce made from amino acids in the liver and kidney, amines, purines and pyrimidines
Renal Blood Supply
Renal arteries branch directly from the aorta; the left renal artery is longer than the right then renal
arteries become:
o Interlobar arteries
o Arcuate arteries
o Interlobular arteries
o Afferent arteriole
o Glomerulus
o Efferent arteriole
The glomerulus is just a tuft of capillaries that interface with Bowmans capsule epithelial cells
The majority of glomerular filtrate occurs at the proximal convoluted tubule
Filtration filtrate goes through endothelial capillary cells then through epithelial cells of Bowmans capsule
into Bowmans space, the first part of the tubule
Reabsorption occurs by active transport, facilitated diffusion, and solvent drag; can be transcellular or
paracellular
H2O proximal tubule, descending loop of Henle, distal tuble, collecting duct (stimulated by ADH);
ascending loop is impermeable
Na+ - 70% in the PT (Cl and H2O follow passively); ascending loop of Henle (Na/K/2Cl cotransporter);
DT, collecting duct (aldosterone-stimuated Na+ channels)
o Reabsorption of NaCl combined with impermeability to water in the ascending loop is the
basis of the countercurrent multiplier system
Glucose proximal tubule; all filtered glucose is reabsorbed in the PT and excretion is zero until
glucose gets above 350mg/dL and is spilled into the urine (glucosuria)
Proximal Tubule
Reabsorbs: H2O, Na, K, Cl, HCO3, amino acids, glucose,
proteins
Secretes: H+, ammnonia
About 2/3 of filtrate is reabsorbed here, including almost 100%
of filtered glucose and amino acids
Descending Loop of Henle
Reabsorbs: H2O (impermeable to Na)
Ascending Loop of Henle
Reabsorbs: Na, K, Cl (impermeable to H2O)
Distal Tubule
Reabsorbs: Na, Cl, Ca2+ (regulated by PTH)
Secretes H+ and K+
Collecting Duct
Reabsorbs: H2O (regulated by ADH), Na+ (regulated by
aldosterone)
Secretes: K, H+, ammonia, drugs
Collecting ducts drain multiple nephrons
In the absence of ADH, water reabsorption is MUCH less and dilute urine is excreted.
Picture from page 378 NBDE!
Phosphate compounds and ammonia act as buffers to tie up H+ in the tubular fluid; phosphate compounds are
excreted with cations like sodium, while ammonium ions are excreted with anions like chloride. Ammonia is

formed in the tubular cells by deamination of amino acids, particularly glutamic acid. Phosphate and
ammonium excretion measurements provide good info on how much acid is being eliminated by the kidneys.
Countercurrent Mechanism
Creation of gradient that allows us to make concentrated urine. Occurs in the loop and collecting duct.
The ascending loop is impermeable to water but actively reabsorbs Na+; this creates dilute tubular
fluid and hyperosmotic interstitium. Urine is dilute at the CCD and concentrates as it descends into the
medullary collecting duct because the gradient pulls water from the duct in the presence of ADH.
Vasa recta are looped, not straight, because straight would dissipate the countercurrent gradient and
concentrating ability.
o The loop minimizes removal of excess medullary interstitial solute and maintains the
gradient
Effective Renal Plasma Flow (ERPF)
Volume of plasma flowing through peritubular capillaries; determined by calculation of PAH
(paraminohippuric acid), which is completely filtered and secreted into the proximal tubule and fully
excreted in urine in one pass
Therefore the volume of plasma cleared of PAH is = ERPF
ERPF = CPAH = UPAH * V/PPAH

Renal Blood Flow decrease in renal blood flow decreases glomerular hydrostatic pressure and GFR
initially
This decreases delivery of NaCl to the macula densa (specifically Cl is important) and causes the
JG cells to secrete renin
Angiotensin II is formed and constricts the efferent arteriole, increasing glomerular hydrostatic
pressure, bringing GFR back to normal
GFR is calclulared using inulin or Cr clearance because they are freely filtered and not reabsorbed or
secreted (Cr is secreted minimally)
- GFR = Cinulin = Uinulin * V/Pinulin
- The rate at which a substance is cleared from the plasma = plasma V cleared/unit time = [in
urine]*Vurine
- Assessment of blood urea nitrogen (BUN) and serum creatinine can also be used to estimate the
GFR.
GFR is increased by:
o Increased renal perfusion (could be due to dopamine or afferent arteriole vasodilation);
increases hydrostatic P
o Efferent arteriole constrictionincreases hydrostatic P, but excess constriction will
decrease RBF and thus GFR
o Decreased plasma oncotic pressure (e.g. decrease in albumin production)
GFR is decreased by:
o Decreased renal perfusion (renal artery stenosis, low BP)
o Afferent arteriole constriction
o Efferent arteriole vasodilation (ACE-I)
o Increased hydrostatic pressure in Bowmans space (due to a blocked ureter or outflow
obstruction)
Renal Clearance
The rate at which a substance is cleared from the plasma
Clearance = (urine concentration * urine flow rate)/plasma concentration
Use inulin or Cr to estimate GFR because they are freely filtered and not secreted or reabsorbed; filtration
rate = excretion rate
Hormones and the Kidney
ADH released from posterior pituitary in response to thirst, Na+, high osmolarity or low ECF

o Acts on the distal tubule and mainly the collecting duct

o Increases H2O reabsorption, decreases serum Na+ concentration
o Increases blood volume
Renin released from JGA in response to low renal BP, low renal PO2, decreased GFR, low Cl- delivery to
macula densa, sympathetic stimulation (of B1 receptors?)
o Cleaves angiotensinogen from the liver to angiotensin-I, which ACE converts to angiotensin-II
o Angiotensin II is a vasoconstrictor that causes efferent arteriole constriction, increases GFR, and
stimulates aldosterone release
Aldosterone released from zona glomerulosa of adrenal cortex in response to renin via antiotensin II or in
response to K+
o Acts on the collecting duct to increase NaCl, HCO3- and H2O reabsorption, increase K+ excretion

Hormonal responses to volume changes:

Volume expansion:
o in ADH, ANP/BNP (natriuretic peptides), renal Na+ excretion, baroreceptor response (to
decrease HR and BP)
o RAAS
Volume contraction = exact opposite response
**Draw picture from page 381 on back!
Random shit
Sources of ammonia: the main one is amino acids; the liver in particular forms ammonia from amino acids by
aminotransferase and glutamate DH reactions
From glutamine the kidneys (tubular cells) forma mmonia from glutamine by the action of renal
glutaminase; this is excreted into the urine as NH4+
From amines in the diet, and monoamines that serve as hormones or NTs; done by the action of amine
oxidase
From purines/pyrimidines
NUTRITION (vitamin and mineral facts on cards)
Synthesis of Vitamin D: sun, skin
liver
kidneys
(active form)
7-dehydrocholesterol ------------------> cholecalciferol (D3) ---------------> 25-hydroxycholecalciferol ---------------> 1, 25dihydroxycholecalciferol
**Cholecalciferol (D3) is not biologically active.
Major minerals are > 0.005% body weight; minor minerals are less than 0.005%.
Major minerals include: calcium, chloride, magnesium, phosphorous, potassium, sodium and sulfur
Transferrin transports copper and iron in blood plasma
Vitamin B12 deficiency may not manifest itself until 5 years after the poor diet
It is found in muscle and organ meats, eggs, dairy products, fish
It is the only vitamin that contains essential mineral elements, and is the only substance containing cobalt
that is vital to life
May be present in inadequate quantities in a strictly vegetarian diet
B6 has been linked to cancer immunity and fights the formation of the toxic chemical homocysteine, which is
detrimental to heart muscle
Found in meats (liver), vegetables, whole-grain cereals and egg yolks
Beriberi severe thiamine deficiency found in areas where polished rice is the major component of the diet; it is
characterized by dry skin, irritability, disorderly thinking and progressive paralysis

Endocrine Physiology
Hormone Types
Steroid hormones derived from cholesterol (except retinoic acid), with a
cyclopentanoperhydrophenanthrene core (except Vitamin Dwhich has a different numbering system
and lacks this component)

Not water soluble and bind to intracellular receptors to form hormone response elements (HREs)
activate/inactivate genes
o Sex hormones, adrenal hormones (cortisol and aldosterone)
Amine hormones derived from amino acids; bind membrane receptors
o Tyrosine thyroid hormones and catecholamines (epi/NE)
o Tryptophan melatonin
Peptide hormones made in pre-hormone form and transported unbound in the blood; secreted in
secretory vesicles and bind membrane receptors to generate second messenger cascades
o Anterior pituitary hormones (GH, TSH, FSH, LH, prolactin) and posterior pituitary hormones
(oxytocin, ADH)
o Pancreatic hormones: insulin and glucagon
o PTH
o Peptide hormones can be further classified into:
Small peptides: TRH, GnRH, somatostatin
Large peptides: insulin, GH, PTH, hCG
Glycoproteins: LH, FSH, TH, chorionic gonadotropin
Proteins GH, prolactin, PTH, calcitonin, ACTH, insulin, glucagon
**Insulin works by increasing tyrosine kinase activity of cytoplasmic portions of the transmembrane receptors
Hormone mechanisms
Second messenger classes:
o Cyclic nucleotides (cAMP, cGMP)
o IP3 and DAG
o Ca2+
Protein kinases are involved in cAMP, cGMP and IP3 pathways
Hormones using each 2nd messenger type:
cAMP epinephrine, glucagon, ACTH, PTH, TSH, FSH, LH, calcitonin, ADH
Protein kinase activity insulin, GH, prolactin, oxytocin, erythropoietin, growth factors
cGMP ANP, NO
IP3/DAG ADH, TSH, angiotensin
Ca2+ - epi/NE, angiotensin-II, ADH, GnRH, TRH
**When epinephrine, glucagon or PTH activate cAMP pathways, the increase glycolysis and increase GNG
cAMP mechanism
Hormone binds G-protein receptor, G-protein activated and activates adenylate cyclase, which
converts ATP cAMP
cAMP then:
o Aactivates PKA phosphoproteins effects
o Stimulates gene transcription via CREB (cAMP response element-binding protein)
cAMP is metabolized by phosphodiesterase, shutting off the 2 nd messenger responseby converting
cAMP AMP

Pituitary and Hypothalamus -- study the book for this; only a few notes below:
Hypothalamic inhibitory hormones: Dopamine inhibits prolactin, somatostatin inhibits GH
ADH release stimulated by: high plasma Na/osmolarity, low blood volume, low BP, nicotine, sweating, SIADH
ADH release inhibited by: ethanol, caffeine, drinking water, diabetes insipidus
Oxytocin release stimulated by: suckling, cervical dilation, estrogen increases uterine oxytocin receptors
Oxytocin release inhibited by: stress, catecholamines
Milk Letdown (ejection of milk; contraction of myoepithlial cells), uterine contractions with birthing,
maternal behavior

It is TRH that stimulates prolactin release from anterior pituitary; it is also stimulated by estrogen, breastfeeding, sleep, stress and dopamine antagonists. Factors that decrease prolactin secretion are dopamine,
bromocriptine (dopamine agonist), somatostatin and prolactin. Prolactin inhibits ovulation and inhibits
spernatogenesis by decreasing GnRH.
GH release is stimulated by GHRH, low plasma glucose, high plasma amino acid levels (especially arginine),
sleep, stress, starvation and exercise.
Its release is inhibited by somatostatin, somatomedins, obesity, hyperglycemia, and pregnancy.
GH increases the rate of amino acid uptake by cells, protein synthesis and glycogenolysis; exerts its
effect on all tissues
Produced in acidophils of pars distalis, it causes the liver to form somatomedins (insulin-like GFs)
that increase all aspects of bone growth
Increased rate of protein synthesis, decreased carb utilization, increased mobilization and use of
fats for energy
Antagonize the effects of insulin on carb/fat metabolism.
GH causes positive nitrogen balance!!
Cells switch from using carbs and protein to using fat in the presence of GH
Somatostatin is released by the median eminence of the hypothalamus AND the delta cells of the pancreatic
islets. It inhibits secretion of GH, TSH, insulin, glucagon, and gastrin.
Theca cells of the ovary secrete estrogen and androgens (which travel to granulosa cells).

The major functions of granulosa cells include the production of sex steroids, as well as a myriad of
growth factors thought to interact with the oocyte during its development. FSH stimulates granulosa cells
to convert androgens (coming from the thecal cells) to estradiol by aromatase.
Both granulosa cells of the ovary and sertoli cells of the testis secrete inhibin B that inhibits the anterior
pituitary.

Reproduction
-

Menstruation without estrogen/progesterone, the endometrial lining is shed and you lose 50mL of
blood
Menstrual phase: days 1-5
Follicular Phase: days 6-14
o FSH and LH stimulate the ovarian follicle, estrogen is secreted
o Estrogen promotes endometrium proliferation
o Late in this phase, estrogen peaks, FSH secretion decreases, and LH secretion increases
(estrogen-induced LH surge)
Ovulation: day 15
o Earlier LH surge triggers ovulation; ovulation always occurs 14 days before your next period,
regardless of cycle length
o The LH surge leads to final maturation of the follicle, rupture of the follicle, and ovulation; in
the absence of LH, even in the presence of huge amounts of FSH, the follicle will not progress
to ovulation
Luteal Phase 16-28
o Decline in FSH and LH levels
o Corpus luteum forms and secretes estrogen and progesterone
o If no fertilization, CL degenerates and estrogen/progesterone levels decline, telling
hypothalamus to make more GnRH
o If pregnancy occurs, hCG from the placenta stimulates CL to persist and keep secreting
estrogen/progesterone.
**Oral contraceptives have synthetic estrogen-like (ethynyl estradiol and mestranol) and progesterone-like
(norethindrone, norgestrel) substances that inhibit ovulation; they suppress GnRH by the hypothalamus to
prevent the LH surge and block ovulation.

**Draw all-encompassing graph from page 411 on the back!!

Oogonia source of oocytes
Primordial follicles are sitmluated by FSH to form primary oocytes in the first meiotic division; the
primary follicles containing primary oocytes then form the antrum (cavity) to become secondary
follicles.
Mature Graafian follicles contain secondary oocytes (in 2nd meiotic division); LH surge causes release
of the secondary oocyte (egg) during ovulation.
Corpus Luteum ruptured mature ovarian follicle forms a yellow mass of cells after ovulation
No fertilization: CL retrogresses into corpus albicans and becomes a mass of scar tissue that then
disappears
Fertilized and pregnancy: CL persists for several months and granulosa cells secrete progesterone >
estrogen
Estrogen
Causes development of 2ndar sex characteristics at puberty
Development of breasts
Maintains pregnancy
Effective at very low concentrations and generates a slowly-developing long-term response by binding
intracellular receptors
Progesterone promotes secretory changes in the uterine endometrium during the latter half of the monthly
sexual cycle, thus preparing the uterus for implantation of the fertilized ovum
During early childhood, a boy does not secrete gonadotropins, and thus has little circulating testosterone. At
puberty, an alteration in brain function leads to increased production of GnRH from the hypothalamus.
Secretion of gonadotropins from the pituitary gland occurs between 10 and 15, marking the onset of puberty.
These pituitary gonadotropins stimulate testes funcgioning as well as testosterone secretion. FSH promotes
maturation of Sertoli cells, involved in development of sperm. LH stimulates Leydig cells to produce
testosterone. During puberty, the penis and testes enlarge and the male reaches full adult sexual and
reproductive capability. Puberty also marks the development of 2ndary male sex characteristics.
FSH stimulates sperm maturation in males, while LH stimulates synthesis and secretion of testosterone.
Precocious puberty a condition in which the changes associated with puberty begin at an unexpectedly early
age due to an excess of androgenic (in boys) and estrogenic (in girls) substances produced by the adrenal
cortexthese substances resemble male and female sex hormones.
Endocrine Pancreas
Insulin secreted by beta cells of the islets of Langerhans
Release is stimulated by elevated blood glucose, elevated amino acids (especially arginine, lysine,
leucine), glucagon secretion; as well as cortisol, GH, and GIP and parasympathetic stimulation
Release is inhibited by low blood glucose and sympathetic stimulation, norepinephrine, or
epinephrine
Actions decreases blood glucose by:
o Increasing glucose uptake and utilization by cells (increasing expression of GLUT
transporters)
GLUT-1: mediates glucose transport into RBCs and through the blood-brain barrier;
ubiquitously expressed
GLUT-2: liver and pancreatic cells
GLUT-3: neurons
GLUT-4: muscle and adipose; regulated by insulin
GLUT-5: transports fructose in the intestines and testes
o Stimulating glycogenesis in the liver to store glucose as glycogen
o Increasing synthesis of TAGs and protein from glucose

Insulin conserves proteins, carbs and fat in the body by stimulating protein synthesis (and
inhibiting its breakdown), glycogenesis (and inhibiting breakdown), and triglyceride synthesis
(and inhibiting lipolysis)
o Promotes the synthesis of glycogen, TAGs and protein
Removal of the anterior pituitary results in increased sensitivity to insulin

Glucagon secreted by alpha cells in the islets of Langerhans

Release is stimulated by low blood glucose, elevated amino acids (especially arginine), CCK,
sympathetic stimulation, Epi/NE
Release is inhibited by high blood glucose, insulin, somatostatin, free FAs, ketoacids
Actions increases blood glucose by:
o Stimulating glycogenolysis in the liver
o Increasing free fatty acids and amino acids
o Increasing urea production
o It does not stimulate glycogen breakdown in the muscle
*Poluria in diabetes mellitus is a result of osmotic dieresis, secondary to sustained hyperglycemia (distinguish
from polyuria in DI).
*Normal blood glucose is 80-100 mg/dL
Hypoglycemia hunger, nervousness, shakiness, perspiration, dizziness, sleepiness, confusion, difficulty
speaking, weakness, seizures
Diabetes Insipidus a problem with ADH secretion or action (nothing to do with pancreas or insulin)

Adrenal Gland
Adrenal cortex
Glomerulosa (outermost layer) salt balance (aldosterone)
Fasciculata sugar balance (cortisol)
Reticularis (innermost layer) sex hormones
Hypothalamus CRH via portal system anterior pituitary (basophils of pars distalis) ACTH adrenal
cortex (zona fasciulata) cortisol to the blood stream
Cortisol feeds back and inhibits both the hypothalamus and the anterior pituitary
ACTH controls production and secretion of cortisol; it is secreted in bursts, causing cortisol levels to
rise and fall; bursts are most frequent in the early morning (75% of cortisol production occurs
between 4am and 10am)
o Called the stress hormone because in times of stress CRH stimulates ACTH release which
then stimulates adrenal cortex to secrete cortisol
o Analysis of ACTH is used as an indicator of pituitary function, and is useful in diagnosing
Addisons or Cushings
o ACTH deficiency is characterized by adrenal insufficiency symptoms, such as weight loss, lack
of appetite, weakness, nausea, vomiting and low BP
*Corticosteroids = aldosterone (mineralocorticoid) + cortisol (glucocorticoid)
*Cortisol and aldosterone are produced from progesterone.
Cortisol action is to help deal with stressors and provide the brain with adequate energy sources; secreted by
zona fasciulata
Secreted in response to stress, illness, trauma, surgery, temperature extremes, psychological stress,
Cushings syndrome/disease
Release is inhibited by pharmacological adrenal-axis suppression, Addisons disease, WaterhouseFrederickson
Actions:

o
o
o

Raises blood glucose levels

Increases glucagon and epinephrine action, decreases insulin action
Cortisol allows glucagon and Epi to work more effectively at their target tissues, but
antagonizes the actions of insulin.
o Maintenance of BP by sensitizint arterioles to the action of NE.
o Decreases glucose uptake by cells
o GNG by synthesis of PEP carboxykinase, increases glycogenolysis (both produce more
glucose)
o Increases lipolysis to FAs (inhibits fat deposition), increases proteolysis to amino acids
o Anti-inflammatory action
o Effects on immune system, bone, calcium absorption from GI, CNS
Cortisol is produced endogenously; hydrocortisone is a synthetic exogenous corticosteroid. Other
synthetic forms are decadron and methylprednisolone
Patients taking cortisol for a long time suppress the adrenal-ACTH (pituitary) axis; lack of stimulation
from ACTH causes atrophy of the adrenal cortex. Adrenal insufficiency occurs when exogenous
therapy is ceased.

Cushings Syndrome
Caused by cortisolexogenously administered glucocorticoids (cortisol-like medications),
endogenous increase in cortisol (from a cortisol-secreting adrenal cortical tumor), ectopic ACTH
production (like in oat-cell carcinoma)
Symptoms:
o Central obesity
Glucose intolerance
o Moon face
Increased sensitivity to catecholamines
o Buffalo hump
Increased angiotensinogen, increase in aldosterone receptors
o Exophthalmos
Thromboembolism
o Skin atrophy (thin skin)
Irritability, anxiety, panic attacks
o Striae
Depression, insomnia
o infections
Proximal muscle wasting/weakness
o Bone loss
**Hyperpigmentation only when the cause is ACTH
o Red cheeks
Pendulous abdomen
o Fat pads at neck
Bruisability with ecchymoses
o Poor wound healing
Cushings DISEASE increased cortisol is secondary to ACTH increase (ACTH-secreting pituitary tumor);
hyperpigmentation is the main symptom!
Addisons Diasese adrenocortical insufficiency; decrease in corticosteroids; can occur at any age in both sexes
equally
Primary Addisons
Reduced cortisol due to destruction of the adrenal cortex; 90% of the cortex must be destroyed
before symptoms show
70% of causes are unknown, likely autoimmune; some known causes are infection (e.g. TB), cancer,
amyloidosis, hemorrhage in the gland
Bronze skin pigmentation
Low BP and low blood glucose
Low Na, Cl and HCO3, but high levels of K
Malaise, weight loss, depression
Oral signs: diffuse intraoral pigmentation of the gingiva, tongue, hard palate, buccal mucosa
Treatment: cortisol exogenously as hydrocortisone or prednisone
Cutaneous pigmentation tends to disappear following therapy, but oral pigmentation persists
Secondary Addisons
Reduced cortisol due to reduced or lack of ACTH
Can occur when you abruptly stop taking chronic exogenous corticoids, usually temporary

Could be due to decreased pituitary function, surgical removal, apoplexy, tumor or infection
No skin pigmentation and no oral pigmentation

Adrenal Medulla specialized ganglia of the sympathetic NS; preganglionic sympathetic (but cholinergic) fibers
synapse directly on chromaffin cells of the adrenal medulla; chromaffin cells then secrete 80% epinephrine and
20% NE
NE can be released by adrenal medulla into the bloodstream, or it can be released directly within an
organ via sympathetic innervation; the effects are more widespread the first way
Release of CRH from the hypothalamus is affected by trauma via nociceptive pathways, afferents from
NTS, emotion via the limbic system, and drive for circadian rhythm
Epi/NE are released from the medulla from storage vesicles in response to:
o Sympathetic stimulation
o Exercise
o Cold
o Low blood glucose
o Hemorrhage
o Emotional distress
They are regulators of carbohydrate and lipid metabolism; also have CV effects
o Both: Increase FAs by stimulating lipolysis
o Epi: Increases blood glucose by stimulating glycogenolysis, activates glycogen phosphorylase
in muscle, and GNG
o Both: Increase CO (increase rate, force and amplitude of heart beat)
o Both: Increase BP via vasoconstriction in skin, mucous membranes and kidneys (increases
TPR)
o Epi: Bronchodilation
Tyrosine DOPA dopamine NE Epi

Thyroid Gland
TRH from hypothalamus travels via the portal system to the anterior pituitary (basophils of pars distalis)
secretes TSH TSH receptor on the thyroid gland secretes T3 and T4 into blood stream for systemic effects
Thyroid hormones feedback and inhibit both the hypothalamus and anterior pituitary
TSH also inhibits the hypothalamus
Stress can inhibit TSH secretions from the pituitary secondary to neural influences that inhibit
secretion of TRH
The thyroid gland has one of the highest rates of blood flow/gram of tissue of any organ; it is composed of
follicles filled with colloid that contains thyroglobulin, which contains the thyroid hormones within its molecule.
Follicular cells collect and transport iodine, synthesize and secrete (into colloid) thyroglobulin, remove thyroid
hormones from thyroglobulin to secrete them into the bloodstream
Thyroglobulin 10% carbohydrate glycoprotein containint many tyrosine residues; synthesized by follicular
cells
Thyroglobulin is iodinated within the colloid; iodine attaches to tyrosine molecules
T3/T4 remain part of the thyroglobulin molecules until secreted
Iodine deficiency will increase the secretion of thyroglobulin instead of T3, T4 or TSH
Colloid is taken up into the cytoplasm of the follicular cell peptide bonds between iodinated residues and
thyroglobulin are hydrolyzed thyroglobulin releases free T4 and T3 T4 (mostly) and T3 are discharged into
capillaries for systemic effects
Thyroid hormones
Lipophilic hormonesthey exert effects via gene transcription
Necessary for normal cellular metabolism, growth, differentiation of tissues (especially neural tissues)

Increase HR, increase cardiac contractility

Increase O2 consumption and heat production
Increase glycogenolysis, GNG, and GI carbohydrate absorption
Increase lipolysis and protein synthesis and degradation
T4 acts as a prohormone to T3; enzymatic removal of one iodine in peripheral tissues creates T3the
more potent hormone!!
Stimulates bone maturation as a result of ossification and fusion of the growth plates
T4:T3 = 20:1

Hypothyroidism Cretinism (children), Myxedema (adults), Hashimotos thyroiditis

Weight gain
- Constipation
Cold intolerance
- Dry skin
Low-pitched voice
- Coarse hair
Mental and physical slowness
- Puffiness of the face, eyelids and hands
Hyperthyroidism *Graves disease, Plummers disease, Solitary toxic adenoma, toxic goiter, TSH-secreting
pituitary tumor
Restlessness and irritability
- Diarrhea
Fatigue
- Tremor
Heat intolerance
- Increased BMR
High body temperature
- Weight loss
Tachycardia
- Generalized osteoporosis
Fine hari
- Oral manifestations (in childrenpremature eruption of teeth,
loss of primary teeth)
Graves Disease
Caused by binding of Ig Abs to TSH receptors in the thyroid, stimulating the production of thyroxin;
typical signs include an enlarged thyroid and exophthalmos (bulging eyes)
Plummers Disease toxic multinodular goiter, multiple secreting thyroid nodules (adenomas) within the gland;
uncommon in young people and increases with age; exophthalmos is rare

Calcium and Phosphorous Metabolism

Normal Ca2+ is 8.5 10.5 mg/dL
Normal phosphorous is 3-4.5 mg/dL
Hypocalcemia irritability/excitability of nerves and muscles tetany
Hypercalcemia cardiac and CNS depression
PTH increases blood Ca2+ by stimulating bone resorption and renal tubular reabsorption of calcium; it
decreases P by decreasing renal reabsorption and increasing renal P excretion
Increases GI absorption via Vitamin D
Increase phosphate excretion in urine, also via Vitamin D
PTH is the principal controller of Ca/P metabolism; plasma Ca2+ is the main controller of PTH
secretion
PTH stimulates 1-alpha hydroxylase in the kidneys
Calcitonin linear polypeptide released by parafollicular thyroid cells to lower plasma Ca2+
Increases Ca2+ deposition in bone, and decreases bone resorption
Decreases GI absorption of Ca2+
Increases renal excretion of calcium
Also decreases plasma phosphate by increases renal excretion of phosphate (same as PTH here)
Calcitonin has only a minor role, it isnt even required in adult humans; its more important during
bone development

Hypoparathyroidism DiGeorge syndrome (congenital), iatrogenic from surgery, sarcoidosis

(infiltration/destruction), idiopathic
Decreased bone resorption and decreased renal reabsorption of Ca2+
Increased renal phosphate reabsorption
Decreased vitamin D
Low plasma calcium, but tons of Ca2+ in bone
Increased plasma phosphate
Tetany, mental status changes, seizures, decreased cardiac contractility, vomiting
Decreased serum Ca2+, but increased serum phosphate!
Hyperparathyroidism parathyroid adenoma, parathyroid carcinoma (rare), multiple endocrine neoplasm, von
Recklinghausens disease
Increased bone resorption and renal Ca2+ reabsorption
Decreased renal P reabsorption
Increased plasma Ca2+ but low Ca2+ in bones
Low plasma P
Bone pain, pathologic fractures, osteitis fibrosa cystic, brown tumors of bone, nephrolithiasis, muscle
weakness

Hormones and the Kidney

Erythropoeitin secreted by peritubular capillary interstitial cells in the kidneys to stimulate RBC production
Release is stimulated by hypoxemia (low PO2), due to anemia, lung disease, cardiac disease, high
altitudes
Release is inhibited by normal PO2 or high RBC volume
Acts on EPO receptors on erythroid progenitors to increase replication and maturation of RBCs
Aldosterone released by adrenal cortex glomerulosa
Release stimulated by increased K+ and angiotensin-II (not stimulated by ACTH)
Release is inhibited by low K+ and low angiotensin-II
Acts on the distal nephronthe distal tubule and collecting ducts
o Increases Na+ reabsorption to raise plasma Na+
o Increases H2O reabsorption to increase plasma volume
o Inhibits K+ reabsorption, and stimulates K+ excretion to lower plasma K+
In total it decreases Na+/water excretion to raise ECF volume and increase renal MAP and decrease
discharge of renal nerves
**Remember: low Na+ (or decreased renal blood flow) signals JG cells to secrete renin, which in a cascade
activates AT-II and aldosterone
release to raise Na+
**In Addisons disease, there is hyposecretion of both cortisol and aldosterone

Summary:
Insulin promotes glucose uptake into cells, amino acid uptake into cells, glycogenesis, lipogenesis (inhibits
lipolysis), protein synthesis.
Glucagon/Epi promote glycogenolysis, GNG, protein synthesis, increases blood FAs
Thyroxine promotes glycogenolysis, GNG, lipolysis
GH promotes amino acid uptake into cells, protein synthesis, glycogenolysis, lipolysis

Cortisol promotes GNG, lipolysis, protein degradation

Testosterone promotes protein synthesis

Random Notes:
Histamine causes:
Vasodilation of arterioles
Secretion of HCl
Bronchoconstriction
Increased vascular permeability (especially capillaries and venules)
Decreased BP
Formed by decarboxylation of histidine; found in all tissues but especially mast cells and basophils
(highest concentration in lungs)
For an allergic response, a free-floating IgE specific to the antigen for the foreign substance must first
attach to mast cell surface receptors. This activates the mast cell and it is degranulated to release
histamine. Causes a wheal.
o H1 receptors mediate typical allergic and anaphylactic responses
o H2 receptors mediate other responses like secretion of gastric acid and pepsin
The actions of bradykinin resemble histamine!
Heparin actions:
Unlike other GAGs, heparin is an intracellular component of mast cells that line the arteries; especially
liver, lungs and skin
Serves as a powerful anticoagulant
Used in treatment of lung, blood vessel and heart disorders or after surgery
Small quantities are produced by basophils of the blood
Concentration in the blood is very small
Contained in secretory vesicles or granules in mast and basophils in the blood; administration of
heparin results in increased bleeding time due to activation of antithrombin, a protease inhibitor that
inhibits thrombin. It treats patients who have suffered coronary thrombosis.
Heparin prevents activation of factor IX (Christmas factor) and can enhance the removal of lipoproteins in the
blood by binding apoE on liposomes and activating lipoproyein lipase BIOCHEMISTRY:

of tissues
-heparan sulfate: basement membranes
GAGS: repeating disaccharides, highly negatively charged.
Glucose Proteins (GLUT):
GLUT1: red blood cells, Blood brain barrier
GLUT3: nuerons
GLUT4: skeletal muscle and adipose, regulated by INSULIN
GLUT2: Liver, low affinity, high Km, high Vmax - not saturated, GLUCOKINASE
S-GLUT: kidney/intestine Na/Glucose transport
GLUT5: transports fructose into the intestestine and testis.
Glycolysis:
Glucose PFK-Glucose 6P ISOMERASE - Fructose 6P Fructose 16P, -ALDOLASE(DHAP, G3P), DHAP becomes G3P by triose isomerase,13BPG, 23BPG ENOLASE
(inhibited by NaF) - PEP, 2 pyruvate.
PFK-1: rate limiting step of glycolysis, make f6p-f1,6p.

PFK-2: Makes f2,6P in liver, which activates glycolysis and inhibits

gluconeogenesis/bisphosphatase).
1,3BPG and PEP produce ATP.
G3P to 1,3BPG uses dehydrogenase to make NADH.
Pyruvate kinase deficiency: causes a decrease in ATP production in RBC causing lysis
because of Na/K ATP dependent transport.
Pyruvate can be converted to lactate and alanine in the cytosol by transaminase.
Pyruvate dehydrogenase is irreversible there is no enzyme in humans that will reverse
this reaction. Five coenzyme are involved, thiamine pyrophosphate (E1), lipoic acid,
coenzyme A (E2), FAD, NAD (E3),
-Thiamine defieciency causes lactic acidosis, because no dehydrogenase.
-INACTIVATED BY PHOSPHORYLASE, INSULIN ACTIVATES PHOSPHATASE.
Three rate limiting steps: hexokinase (glucokinase), PFK, pyruvate kinase.
Gluconeogenesis:
Occurs mainly in the liver and kidney, (NOT IN MUSCLE, because doesnt have
pyruvate carboxylase).
Comes from lactate (in RBC-does not have oxidative mitochondria, and anaerobic
muscle), glycerol (fat), and AA (skeletal muscle).
Pyruvae kinase reverse reaction: PEPCK(and GTP) and pyruvate carboxylase/biotin.
Other enzymes: FBPase-1 (inhibited by F26P), G6Pase (deficiency causes Von-Gierkes
disease).
Overall reaction requires 6 ATP (4 for pyruvate to PEP and 2 for 3PG to 23PG).
Cori Cycle: Pyruvate lactate in RBC and skeletal muscle, the the lens of the eye,
medulla of kidney, testes, and leukocytes.
Glucogenic amino acids: can be converted to intermediates of TCA or glycolysis
Includes all except Lysine and Luecine which are ketogenic.
Glycerol becomes Glycerol 3 Phosphate
Odd numbered fatty acids: produce propionly-CA which can be converted to succinyl
CoA and acetyl-CoA which IS NOT a precursor of glucose.
GLUCAGON cause increase of protein degradation because AA can be converted to
glucose, and increases lipolysis and oxidation which supplies energy for gluconeogenesis.
Skeletal muscle degrades glycogen rapidy. In white muscle/fast muscle fibers,
glycogen is broken down, whereas in red muscle, pyruvate is completely oxidized by
the TCA.
Glycogenolysis:
Glycogen Phosphorylase: cleaves a1,4 linkages, activated by glucagon or epinephrine.
-active form phosphorylase a is phosphorylated.
-cAMP phosphorylates many molecules of phosphorylase kinase which activates
glycogen phosphorylase. cAMP also phosphorylates glycogen synthase (makes a14
linkages) which inactivates it to the D form. (SO PHOSPHORYLATION INCREASES
GLUCONEOGENESIS, no phosphatases are involved).

Glycogen synthesis: creates glucose 6P which is converted to glucose 1P by

phosphoglucomutase and activated by UDP-glucose to add to glycogen primer.

Hexose Monophosphate Shunt: DOES NOT CONSUME OR PRODUCE ATP

Produces NADPH for:
synthesis of cholesterol
fatty acids
steroids
Needed for RBCs to maintain gluthathione to neutralize superoxide and h202.
Help neutrophils to make superoxide for killing bacteria (deficiency causes chronic
granulomatous disease)
Produces ribose-5-phosphate which release c02 and NADPH and can be reconverted to
fructose 6-p. For every six moles of glucose 6 p, 6 c02 are released and 5 fructose 6 p can
be produced.
The whole cycle is inhibited by NADPH and palmitoyl-CoA.
Fructose metabolism: Fructose is converted to f1p then uses aldolase B to convert it to
DAH and G3P.
Galactose metabolism: galactose is converted to galactose 1 P which is transferred to
glucose 1p by uridyl transferase.
LIPID METABOLISM:
Saturated: no double bonds
Unsaturated fatty acids: Contain double bonds in CIS configuration
Monosaturated fatty acids: oleic acid (18C), palmitoleic acid, erucic acid.
Polysaturated fatty acids: linoleic acid & linolenic acid (essential fatty acids), arachidonic
acid
-essential fatty acids cannot be made by humans because lack enzyme to place
double bonds at certain positions (omega 3 and omega 6)
Ketone bodies: acetone, aceoacetic acid and B-hydroxybutyric acid, produced from fatty
acids and AA during starvation and diabetic ketoacidosis. They are excreted from the
urine, produce a fruity breath odor (also in diabetics type I).
Phospholipids: Ethanolamine cephalin, choline lecithin.
Sphingolipids & glycolipids contain ceramide composed of sphingosine.
Lipoproteins: Contain hydrophilic shell (phospholipid) and hydrophobic core
Chylomicrons: least dense, TAG and cholesterol ester, in smooth ER of intestinal cells
-apo B48 is unique to chylomicrons, apo E faclilitates chylomicrons to liver
VLDLs: higher density than chylomicrons, can produce IDLs
LDLs: generated from VLDLs and IDLs, transports cholesterol to extrahepatic tissues by
endocytosis. Disease is called familial hypercholesterolemia, insuffiency of LDL
receptors.
HDL: synthesized by the liver, they are a circulating resoivior for apoproteins, remove

cholesterol from tissues back to the liver.

LCAT: esterifies HDL cholesterol, reverse cholesterol transport
Apo D: transfer esters to VLDL and chylomicrons.
Fatty Acid synthesis: acetyl-CoA, bicarbonate, and NADPH. (Citrate has + effect)
Occurs in the cytosol, oxidation occurs in the mitochondria
Citrate shuttle is used to carry acetyl-CoA from the mitochondria to cytosol.
-citrate can be broken down to acetyl coa and oxalaocetate, and can produce
NADPH.
Acetyl-CoA carboxylase: biotin and bicarbonate produces malonyl-CoA. Uses 1 ATP.
- rate limiting enzyme
Fatty acid synthase: adds 2 carbons to the carboxyl end with ACP protein. It is
repeated until pamitoyl-CoA (16 Carbon) is produced (palmitoyl-CoA inhibits the HMP
shunt). Uses 2 NADPH, total process uses 7 ATP and 14 NADPH.
Glucagon (remember phosphorylation) inactivates synthase by phosphorylating it.
Coenzyme A used in fatty acid synthesis and metabolism.
Malonyl CoA is in synthesis but not breakdown of fatty acids.
Fatty Acid Oxidation: occurs in peroxisomes and mitochondria
Fatty acyl-CoA synthase driven by pyrophosphate.
Carnitine shuttle includes CAT I and CAT II to transport fatty acyl CoA into
mitochondria. (CAT I is rate-limiting enzyme)
Inhibited by malonly-CoA
Produces 1 acetyl CoA, 1 FADH2 and 1 NADH = 5 ATP
So palmitic acid (C16) produces 8 acetyl CoA, 7 NADH, 7 FADH2
Odd carbon fatty acids are carboxylated to methylmalonyl-CoA which with vitamin B12
becomes succinly CoA into the TCA.
Ketone Body formation: Acetoacetatic and B-hydroxybutyric acids.
Produce ketones (from spontaneous decarboxylation) when inadequate carbohydrate is
avalialble to the extrahepatic tissues. Synthesis by HMG-CoA synthase, not reductase.
HMG-CoA reductase is key in producing cholesterol. (inhibited by levostatin).
Lipase: EPI, NORE, and glucagon increase cAMP which activates this enzyme, causing
TAG hydrolysis. Glycerol is sent to liver for gluconeogenesis and fatty acids released
bind to albumin.
Lipoprotein Lipase: found in endothelial cells of adipose and muscle tissue. Hydrolyzes
VLDL and chylomicrons into muscle and adipose tissue.
Cholesterol Synthesis: Occurs in liver and other tissues in the cytosol or ER
First step: three acetyl-CoA to produce HMG-CoA then it is reduced to mevalonic acid.
Uses 2 NADPH.
KEY ENZYME: HMG-CoA reductase in cytosol, the one in the mitochondria is used for
ketone synthesis!
-rate limiting enzyme, promoted by insulin and thyroxine, inhibited by glucagon.

Then isoprene units IPP and DPP form squalene (30 carbon)
Fatty acids incorporated into cholesterol: OLEIC ACID
Cholesterol esters: Use LCAT (leaving cholesterol via HDL) and ACAT (Accumulation
of cholesterol in cells).
Steroid Hormone production: Comes from cholesterol
Cleavage of cholesterol creates pregnenolone (C21) which is converted to progesterone,
which are the precursors to ALL steroid hormones. Desmolase is the rate limiting enzyme.
-desmolase is promoted by angiotensin/ACTH (mineralcorticoid), LH (androgen
and estrogen synthesis)
5-a-reductase: reduces double bond in testosterone to form DHT which is a major
androgen.
Aromatase: converts androgens to estrogens.
Estrogen: unlike other steroid hormones, has aromatic A-ring.
Sphingolipid/glycolipid synthesis: palmitoyl-CoA, serine, fatty-acyl CoA. Use UDPsugars and CDP-choline, PAPS, and CMP-NANA (very similar to phospholipid)
Sphingolipid: only one with PHOSPHATE
Cerebrosides/globosides: contain glucose of galactose
Gangliosides: contains nueramic acid/sialic acid
Diseases are all AUTOSOMAL RECESSIVE:
Gaucher: glucocerebrosides
Fabrys: a-galactosidease, increase ceramide trihexoside
Tay-Sachs: increase gangliosides, hexosaminidase A deficiency
Niemann-Pick: sphingomyelin, sphingomyelinase deficiency
Farber: increase ceramide
Hurler syndrome: increase heparin sulfate, dermatan sulfate, deficiency of iduronidase.
Luekotrienes > SRS-A (smooth muscle constrictor in inflammation and chemotaxis)
AMINO ACIDS:
Non-essential are made in the LIVER
Arginine and Histidine are essential only in children.
Essential In adults: PVT TIM HALL (a=arginine??, t- tryptophan, threonine)
Digestion: enteropeptidase activates trypsinogen which activates other proteases.
Diseases: hartnup disease (causes decrease in tryptophan/niacin/pellagra)
Cystinuria: causes kidney stones by excreting amino acids.
Catabolism: pyridoxal phosphate, transamination, oxidative deamination of glutamate.
Most use a-ketoglutarate as an acceptor creating glutamate which can become ammonia
or transferred to oxoloacetate.
Glutamate fate: is unique in that it is the only amino acid that undergoes rapid
oxidative deamination (release ammonia).
Convert to a-ketoglutarate and NADH by using dehydrogenase
transamination with oxoloacetate to make a-ketoglutarate and aspartate

Urea formation: Arginase directly catalyzes urea formation.

apartate and ammonia/bicarbonate become fumurate and urea.
first two enzymes in mitochondra, the last steps in cytosol
Steps: Nh4 + Hc03 + ATP = Carbomoyl phosphate, add ornithine to get citrulline (COC)
Now in cytosol: citrullin combine swith aspartate to make arginosuccinate which makes
fumarate and arginine, and arginine becomes urea and ornithine (which is recycled).
controlled by CPS-I and NAG (N-acetylglumate) activated by increase in proteins and
glutamate accumulation.
Alanine: converted to pyruvate and glutamate in the liver which becomes urea.
Glutamine: glutamine becomes glutamate when it loses ammonia, or the reverse can
occur.
Ketogenic amino acids: Luecine and Lysine can become acetyl-CoA or ketone bodies
Ketogenic and glucogenic: isoluecine, phenylalanine, tyrosine, tryptophan. Which can
also become acetoacyl-CoA which can become acetyl-CoA.
Asparagine and Aspartate can become oxaloacetate
Tyrosine and Phenylalanine and Arginosuccinate can become fumurate
Valine and propionly-CoA (odd chain FA and isoluecine and methionine and threonine)
can become succinly-CoA
Alanine, serine, cystiene, and glycine can become pyruvate.
Proline, Arginine, Histidine, Glutamine become glutamate which can become aketoglutamate.
Non-essential: Phenalalanine becomes tryptophan with hydroxylase
Cysteine is made from serine and methionine.
Glutamate GABA
Histamine Histidine
Serotonin tryptophan
Tyrosine: Catecholamines, melanin, thyroxine.
Arginine: becomes nitric oxide and ornithine
AST (aspartate transaminase), ALT (alanine transaminase): not involved in oxidative
deamination reactions which liberate ammonia.
Remember: Fat can never be converted to carbohydrate or protein
Kidney cortex only uses fatty acids for energy
Kidney medulla only uses glucose
RBCs can only use glucose for energy source
Growth Hormone (stomatotropin): Causes increase in gluconeogenesis and increase in
liver glycogen, CAUSES SHIFT from using carbohydrates to USING FAT FOR
ENERGY. It is increased by sleep, starvations, exercise, hypoglycemia, it is
decreased by obesity, somatomedins, somatostatin, and PREGNANCY.
Molecular Biology:
B-DNA: most common, right handed, antiparallel, helical, 10.5 bases per turn
Z-DNA: left handed, GC rich, rare

A DNA: bases are not perpendicular to axis, but 20 degree shifted

DNA polymerase III is the major replicated enzyme in E. coli.
-another enzyme unique to E. Coli is DNA Gyrase (topoisomerase)
-E. Coli contains a SINGLE ori start replication site.
-E. Coli also has 2 recognition sites for RNA Polymerase
Recombination occurs during metaphase, causes allelic changes not the gene sequence.
Negative supercoils: found in prokaryotes and linear eukaryotic DNA
Pyrimidines are synthesized while attached to ribose 5 phosphate
Defect in purine and pyramidine metabolism can lead to gout.
-Other diseases:
Lesch-Nyhan Syndrome gout and mentally retarded
SCID: deficiency of adenosine deaminase, results in defectinve T & B lymphocytes,
increase in dATP which inhibits DNA synthesis (ribonucleoside reductase)
Both prokaryotic and eukaryotic DNA synthesis is bidirectional, begins at ori sequence
Lagging strand is discontinous Okazaki fragments, while leading strand is continous
DNA Repair diseases:
Xeroderma pigmentosa: cant fix UV mutations, defect in excision repair
Ataxia telangiectasia: dilated blood vessels, lymphomas, defect in endonuclease base
excision repair
Transcription:
Pribnow box: AT RICH, -10, promoter, initial unwinding.
Hexamer at -35 site, bind to promoter of RNA polymerase
TATA box: initiation site in eukaryotes.
Termination: Rho-independent with a hairpin loop, or Rho factor that terminates
transcription of RNA Polymerase
RNA synthesis is NOT proofread, usually no primer is required.
In prokaryotes, translation and transcription are coupled, to translation begins before
transcription ends.
In eukaryotes, trxn and translation are not coupled to extensive modification occurs
before translation. (splicing, capping, polyadenylation)
Translation
Shine-Dalgarno sequence AUG
rRNA: most common RNA
prokaryotes: 23s, 16s, 5s rRNA (30S, 50S = 70S)
Eukaryotes: 28S, 18S, 5.8S, 5S (40S, 60S = 80S)
tRNA: Amino acid attachment site has CCA
E-P-A: the A site tRNA is bound to carboxyl group of amino acid bound to P site tRNA.
Translocation involved peptide formation and GTP hydrolysis.

Lac operon: activated by absent repressor (bound to inducer) and presence of activator
(low amount of glucose which increases cAMP production of promoter)

PHYSIOLOGY:
Gastrointestinal:
Feeding center is in the lateral hypothalamus, satiety center is in the ventromedial nucleus
of the hypothalamus (glucostats)
CCK receptors in brain to reduce apetite when stimulated. (calcitonin can also decrease
appetite)
Salivary composition (hypotonic): Na and Cl are reabsorbed, and K+ and HC03 are
secreted so saliva is alkaline. Resultant saliva is hypotonic because more ions are
reabsorbed, when high parasympathetic stimulation the osmolarity of saliva is equal to
plasma.
Enzymes: lingual lipase, ptyalin(amylase)
Beta-amylase: converts starch to maltose and dextrins
Alpha-Amylase: increase with sympathetic sys, hydrolyzes a14 glycosidic link
Other: lactoferrin, mucin, proline proteins for enamel protection, kallilkrein which
cleaves kinogens to form bradykinin. ->> increase blood flow to increase salivary flow.
Swallowing: Nucleus of solitary tract (CN9 & 10) mediated by nucleus ambiguous and
hypoglossal nucleus. OCCURS about 600x a day. (1/3 eating, mostly during rest)
Upper esophageal sphincter: relax when swallow, contract when preventing reflux.
Vomiting is stopped by contraction of the UES.
Lower esophageal sphincter: relax on swallow, phrenicoesaphogeal ligament, gastrin
increases tone, while secretin and CCK decrease tone.
Achalasia: inability for LES to relax
Esophageal reflux: occurs because of incompetent LES, allow gastric to go up esophagus.
Stomach: outer longitudinal layer and inner circular muscle and UNIQUE third inner
oblique layer.
-pylorus is continous with circular muscle layer, and contraction is modulated by opiods
like enkephalins.
-afferent and efferent impulse by vagus, relaxation by VIP and N20.
-contraction occurs from outer long. And inner circular muscle
-emptying is controlled by CCK, which inhibits gastric emptying
Duodenum: Brunners glands and goblet cells in the mucosa
-G cells produce Gastrin in the atrum(near pyloric sphincter) of stomach and duodenum
-causes stimulation of HCL secretion by parietal cells (also secrete intrinsic
factor)
-stimulate histamine release from enterchromaffrin cells (also release serotonin)
-stiumulate pepsinogen secretion from chief cells
-contraction of circular muscle of stomach.

Antrum: Mucous cells (secrete mucus and pepsinogen) & G cells (Gastrin)
Body: Chief Cells and Parietal Cells (body)
Fructose is by FACILITATED diffusion, GLUCOSE by active transport (Na)
CCK: I cells, gallbladder contraction, pancreatic enzyme secretion, inhibit gastric
emptying.
Secretin: S cells, in duodenum, stimulation of bile and inhibit H+ of parietal cells,
inhibits stomach motility, stimulates pancreas to release bicarbonate ions.
GIP: K cells, stimulate pancreatic insulin
VIP: stimulate water and salt secretion, relaxation of muscle and LES and relaxation of
stomach.
VIPoma: watery diarrhea
Somatostain: D cells, inhibits gastrin, CCK, and other hormones.
Substance P: pain impulses, myenteric plexus of vagus
Plasma cells: IgA
Vitamin B12 is absorbed in the ileum.
Oligosaccharides are hydrolyzed in the midjujenum and ileum by the brush border
-lactose intolerance: increase water secretion causing diarrhea
Water and electrolytes (Ca, iron and folate) are reabsorbed in the jujenum and duodenum
Cl- is exchange with HC03 in the ileum and colon
Large intestine: larger in diameter and shorter in length than the small intestine
-teniae coli: longitudinal bands of muscle, pouching causes HAUSTRA
-NO VILLI
-abundant lymph follicles in the cecum and appendix
-main function: reabsorption of fluid and electrolytes and temporary storage of feces.
-Na and water are reabsorbed, K+ and HC03 are secreted into colon.
-relaxation of internal anal sphincter (smooth muscle) produces urge to defecate, the
external anal sphincter is skeletal muscle innervated by pudental nerve.
-CCK, gastrin and stomach distension also cause defecation.
Phases of gastric secretion:
Cephalic: smell, sight, or thought
Gastric: vagus nerve stretch reflexes
Intestinal: protein degradation in duodenum
Pancreatic secretions: H20, HC03, digestive enzymes (acinar cells)
Hepatic secretions: bilirubin, cholesterol, drugs, lipid absorption, IgA delivery
-Secretin stimulates bile high in bicarbonate.
-bilirubin is conjugated with glucuronic acid prior to secretion in bile. In large
intestine, the bilirubin is deconjugated and metabolized by bacteria.
-bile acids are synthesized from cholesterol by hepatocytes. They are conjugated
with taurine or glycine before secreted into bile.
-bile is made up of water, bile acids, cholesterol, bilirubin, and phospholipids

-KEDA vitamins require bile acid micelle to be absorbed.

Vomiting center: reticular formation of the medulla, located in the area postrema in the
floor of the fourth ventricle, stimulated by dopamine
Nervous system of GI:
Enteric nervous system:
Myenteric (Auerbachs plexus) between circular and longitudinal muscle from esophagus
to the anus
Submucosal Meissners Plexus: lies in the submucosa
Disease in nueral innervation causes Hirshsprungs disease
Vagal Parasympathetic fibers: dorsal motor nucleus of vagus in the floor of fourth
ventricle
Innervates to ascending and right transverse colon
Sacral Parasympathetic fibers: flow from S2,3,4 and innervate anorectal area, descending
sigmoid and left colon.
LES is normally contracted, and PNS relaxes the muscle.
Remember: segmentation provides mixing of chime, while peristaltic movements propel
chime along the gut.
Cardiovascular Physiology:
SA NODE AND AV NODE ARE SLOW FIBERS: Phase 0
SA Node: located at junction of SVC and right atrium, below the epicardial surface,
innervated by right vagus
AV Node: just beneath the right atrial endocardium, anterior to coronary sinus,
innervated by left vagus.
-goes onto the His Bundle where conduction is rapid
-divides to right and left bundle branch (posterior and anterior division)
-become the Purkinje fibers which PENETRATE ventricular myocardium
(papillary muscles), purkinje fibers undergo RAPID CONDUCTION.
Effective refractory period: no AP can be elicited, whereas in relative refractory period
where propagated AP can be elicited but only with a strong depolarizing stimulus.
Myocardial contraction: L type Calcium channels, T-tubules from sarcolemma
invagination, entry causes release of stronger number of calcium ions (ca induced ca).
Calcium binds troponin, allowing binding to tropomyosin.
CARDIAC MUSCLE: CHANGES IN CONTRACTION DUE TO CHANGES IN
CONTRACTILITY OF FIBERS, NOT NUMBER OF FIBERS ACTIVATED LIKE IN
SKELETAL MUSCLE.
Left ventricular pressure at the end of systole represents: end-diastolic pressue
FOURTH heart sound: occurs during atrial systole, but audible only in pathological
conditions where there is forceful systole. (atrial gallop)
Ventricular systole: (QRS complex)
Left ventricular pressure increases with close the mitral valve and aortic valve is closed,
while the volume remains the same (isovolumetric contraction).

FIRST HEART SOUND: coincides with AV valve closure (mitral and tricuspid),
loudest and longest sound continuing into early ejection.
-can be loud in mitral stenosis, if it is absent it represents mitral calficication.
Ventricular ejection when left ventricular pressure rises above aortic pressue opening the
aortic valve.
AORTIC VALVE OPENS AFTER THE PULMONIC VALVE OPENS.
Ventricular diastole:
Isovolumetric relaxation: Both the mitral and aortic valves are closed and the ventricles
relax, aortic valve closure is the beginning of isovolumetric relaxation.
SECOND HEART SOUND: Coincides with semilunar valve closer of aortic
valve and the pulmonary valve closure.
-there is a splitting of the sound between aortic and pulmonary closure, due to the
aortic valve closing before the pulmonary valve.
Ventricular filling occurs when the ventricular pressure falls below the left atrial pressure
opening the mitral valve, which defines the beginning of ventricular filling.
THIRD HEART SOUND coincides with rapid ventricular filling/ventricular
gallop.
(heart sounds are best heard over the left ventricular apex with the patient in left lateral
decubitis position)
Murmurs: originating on the right side of the heart generally increase with inspiration and
those from the left side decrease with inspiration because inspiration increases venous
return.
-caused by stenosis or atrial septal defect. (systolic ejection murmer)
-usually occur between S1 and S2 sounds (pansystolic murmur)
-mitral, tricuspid, ventricular defect/regurgitation
-After S2: Diastolic murmur aortic, pulmonic, or mitral stenosis/regurgitation
Cardiac Output: SV (blood pumped by ventricle per beat) X HR
SV = EDV-ESV (end diastolic end systolic)
SV increases by increasing preload, and decreasing afterload
Preload: force of contraction during the initial muscle stretch, EDV (Starlings law)
Afterload: Aortic pressure, force of contraction, aterial resistance to the heart
Cardiac muscle: varying degrees in which ALL muscle fiber is activated.
Positive iontotropes: increase Ca influx, digitalis (ATPase blocker)
-decrease afterload, and increase heart rate
Negative ionotropes: verapamil (Ca blocker), acidosis, B antagonist
acetylcholine - ONLY EFFECTS ATRIA NOT VENTRICLES
-increases afterload
Blood flow:
Laminar: blood flow in concentric layers within the vessel
-Bernoullis principle: as diameter decreases, velocity flow increase.
Turbulent: blood flows chaotically, in proximal aorta and pulmonary artery

Mean arterial pressue: 1/3 systolic + 2/3 diastolic pressure

Venous compliance: under control of sympathetic nervous system (alpha receptors) and
greatly affected by gravity.
-abdominothoracic pump of inspiration: inspiration causes intrathoracic pressure
to decrease and abdominal pressure to increase causing blood flow to increase to thoracic
vena cava from abdominal vena cava.
-venoconstriction: cause by B1 receptors of sympathetics
Arterial blood flow: alpha causes constriction, b2 causes vasodilation
-arterioles can become metarterioles which are divided by the capillary sphincter.
Transcapillary exchange: (capillary hydrostatic pressure interstitial h.p) ( capillary
oncotic pressure interstial oncotic pressure)
During exercise: decrease in peripheral resistance (vasodilation) but increase in cardiac
output is greater, so pressure in arteries increases. Stress causes increase in peripheral
resistance (decrease in arterial compliance).
-largest drop in blood pressure occurs In transition from arteries to
arterioles.
Lymphatics: left side of head, arm, chest into thoracic duct which empties at junction
between internal jugular and subclavian vein.
-same on right side, but right lymph duct into right i.j. vein and subclavian
Coronary artery pressure: During systole, coronary artery pressure is less that aortic
pressure beause of rapid flow (bernoullis principle high compressive forces during
systole on artery), during diastole, aortic valve is competent and is transmitted to
coronary arteries. (diastole = coronary blood flow)
Coronary sinus pressure = right atrial pressure
Tachycardia causes decrease in duration of dystole more than systole effecting coronary
blood flow, compromising blood flow to the heart.
-during sympathetic stimulation, tachycardic, but release Adenosine to cause
coronary vasodilation to make up for increase in heart pressure.
Parasympathetic system: release Ach on ATRIAL muscle via M2 receptors.
Baroreceptors: carotid sinus (bifurcation) and aortic arch (arterial) and heart/lungs.
Function is to REDUCE acute symptoms, increasing during systole and decreasing
during diastyole. A decrease in arterial pressure causing a decreasing in firing which
causes vasoconstriction and increased heart rate.
-cartoid sinus: CN 9
-aortic arch: CN 10
Carotid receptors located between right atrium and the vena cava and of the left atrium
and pulmonary veins.
-activation during filling and contraction causes INCREASE in heart rate
(Bainbridge reflex), secreation of ANF (atrial natriuetic factor, which increase sodium
excretion), and decrease of ADH.
ECG:
p-wave: depolarization of atria

PR: depolarization of AV node and bundle of his/purkinje (time for SA node to reach AV
Node), ISOELECTRIC
QRS: depolarization of ventricles
ST: ISOELECTRIC, elevation of depression means pathology/MI
T: repolarization of ventricles, elevation or inversion shows pathology, hyperkalimia.
QT interval prolonged in CHF and hypocalcemia, shortened by digitalis and
hypercalcemia.
RR interval: HR = 60/RR
ARYTHMIAS:
First degree AV Block: prolonged PR interval
Second degree AV block: failure of conduction of impulse from atria to ventricles
Acquired third degree AV block: requires pacemaker
Bundle Branch Block: If unilaterial, cause splitting of the second heart sound
Escape beat: if SA Node fails to depolarize such pacemaker cells
Supraventricular arrhythmias: normal QRS complexes
-abnormal P wave, premature atrial contraction
-wandering atrial pacemaker
Paroxysmal supraventricular tachycardia: Re-entry mechanism originating from AV node
or atria.
Atrial flutter: flutter waves, SAWTOOH appearance, block is present
Atrial fibrillation: normal QRS complexes but an abnormal intervals.
MAT: slow atrial rate
Ventricular arrythmias: abnormal, wide, and bizarre QRS complexes.
-premature ventricular contraction: ectopic beat
-ventricular tachycardia: re-entry mechanism, decrease in CO, and decrease time
of ventricular filling.
-Ventricular fibrillation: multiple ectopic ventricular foci, need implanted
defribillator.
-Torsades de Pointes is a from of ventricular tachycardia in which QRS complex
change cyclically in patients with prolonged QT interval.
Congestive Heart Failure: inability of heart to deliver a sufficient cardiac output to meet
the metabolic demands of peripheral tissues, despiste elevated cardiac filling pressures.
-increased afterload, preload, valvular disease, tachy/brachycardiam, impaired
myocardial function
-constant sympathetic elevation, tachycardia, rennin levels are elevated, ADH is
elevated, development of peripheral and pulmonary edema.
Symptons: dyspnea on exertion, orthopnea, nocturnal dyspnea, S3 gallop because of
excess venous return to right atrium. Cardiac hypertrophy and cardiomegaly
-PULMONARY RALES/EDEMA, in portions of the lungs
-JUGULAR VENOUS DISTENSION 2cm above the sternal angle
-postive Kussmauls sign: jugular venous pressure increases with
inspiration
-Hepatojugular reflex, venous pressure increase while put pressure over abdomen,

HEPATOMEGALY and SPLENOMEGALY.

-EDEMA: pitting, (of the entire body is anasarca) & CYANOSIS.
-ASCITES: right-sided heart failure or biventricular failure
Cardiovascular response:
Isotonic: rhythmic contractions of flexor and extensor (running), increase 02
consumption, systolic increases BUT NOT DIASTOLIC.
Isometric or static exercise: weight lifting, fueled by lactate production, no movement,
blood pressure and o2 consumption minimally increased.
Exercise causes muscle blood flow to increase 15x, causing vasodilation, increase heart
rate, and stroke volume.
Veins have a greater compliance compared to arteries, therefore can accommodate larger
changes in volume.
ENDOCRINE PHYSIOLOGY:
Anterior pituitary: pars distalis, pars tuberalis, pars intermedia (come from stomatodeum
Rathkes pouch).
Post. Pituitary: pars nervosa, infundibulum (comes from diencephelon)
Steriods: cortisol, aldosterone, estrogen, progesterone, testosterone
Proteins: glucagons, GH, Prolactin, Calcitonin, ACTH, insulin
Glycoproteins: FSH, LH, TSH, hcG
Peptides: ADH, oxytocin, atrial natruinetic hormone, TRH, GnRH
Amino Acid derivative: thyroxine, tyrosine (NORE, EPI, melatonin)
Pituitary gland lies beneath the brain, connected to it by the infundibulum.
Anterior pituitary (adenohypophysis): derived from somatic/oral ectoderm (the roof of
stomodeum), devoid of innervation. Connected by the hypothalamic-hypophysial portal
blood system and it originates from the median eminence, filled with releasing factors
and hormones.
-TRH stimulates release of TSH and prolactin
-Somatostatin inhibits both TSH and GSH and prolactin, while dopamine inhibits
prolactin.
-hormones contain disulfide-bridges.
-Growth Hormone: increase protein synthesis (GH increases when excess AA)
decrease insulin sensitivity, increased lipolysis, secreted as pulses throughout the day.
Inhibited by somatostatins and stomatomedins, obesity, hyperglycemia, and pregnancy,
which cause negative feedback inhibition of GSH and positive feedback to somatostatins.
RELEASED IN PULSATILE FASHION.
-MSH is secreted from chromophobe cells of pars intermedia, while ACTH is
secreted from pars distalis, but ACTH has the ability to stimulate MSH,
Prolactin and Growth Hormone is produced by acidophils of pars distalis (anterior
pit.)
Posterior pituitary (nuerohypophysis): derived from nueral ectoderm, supplied by pars
nervosa. The hormones are made in the supraoptic nucleus and paraventricular nuclei.
-Osmoreceptors in hypothalamus sense changes to release ADH in post. Pit.
-ADH secretion dependent on osmoreceptors and baroreceptors (l. atrium, etc)

which inhibit ADH. Ethanol and caffeine decrease ADH release, while nicotine
increases its release.
Adrenal Gland: all peptides are derived from pro-opiomelanocortin. Cholesterol is the
precursor to the steroid hormones and converted to pregnenolone. Retinoic acid is the
only steroid hormone not derived from cholesterol. Vitamin D also has a different
structure but is derived from cholesterol.
-21 B-hydroxylase deficiency means cant create aldosterone or cortisol from
progesterone.
Zones of adrenal cortex:
Outer zona glomerulosa: aldosterone
Zona fasciculata: glucocorticouds/cortisol (main product of adrenal cortex)
Innder zona reticularis: androgens/DHEA
-cortisol has anti-inflammatory effects: block phospholipase A2 inhibiting luekotrienes,
inhibits histamine release, and production of il-2 needed for proliferation of tlymphocytes, allows glucagon and EPI to work more effectively.
-cortisol drug causes secondary addisons disease and adrenal insufficiency once taken
off medication for up to 6-9 months.
-aldosterone: promoted by rennin (JG cells), increase water absorption in COLON and
kidney, and increases K+ and H+ secretion in the kidney. (**increased K+ in plasma
causes aldosterone synthesis**), addisons disease causes hyposecretion of aldosterone.
Diseases: REMEMBER ACTH DOES NOT CONTROL ALDOSTERONE OR
ADRENAL MEDULLA.
Addisons disease/adrenal insufficiency: hypotension, hypoglycemia, hyperkalemia.
-primary: ACTH levels are elevated, severe pigmentation
-secondary: ACTH is inhibited, due to drug therapy of cortisol.
Cushings syndrome: Adrenocortical excess: obesity, facial plethora, hirsutism, menstral
disorders, hypertension, moonface, muscle wasting, purple abdominal straie, truncal
obesity.
-due to adenoma or carcinoma or chronic cortisol therapy
Hyperaldosterism: hypokalemia, metabolic alkalosis, hypertension, can be offset by ANP
production from atrial baroreceptor.
-primary: Conns syndrome, adrenal carcinomas
-secondary: increases rennin levels from kidney problem.
ADRENAL MEDULLA: NUERAL CREST DERIVATIVE
-epinephrine is derived from nore plus a methyl group.
-broken down by COMT and MAO
-main source of catecholamines isnt adrenal medulla, can live without it.
Pheochromocytoma, ganglionueroma, nueroblastoma: adrenal medulla tumors with
homovanillic and vannilylmandelic acid in urine, hypertension, hyperglycemia.
Epinephrine: glycogenolysis, gluconeogenesis. Which tend to raise blood glucose,
stimulates lipolysis in adipose tissue, increase HR, dilate briochioles in lungs, activates
muscle glycogen phosphorylase.
NORE: contrict blood vessels, lipolysis, increases heart rate.
THYROID GLAND: synthesizes T3 and T4

-thyroglobulin secreted from thyroid follicular cell and secreted into colloid space
-released via exocytosis and iodination occurs at the follicular cell surface.
-t4: thyroxine, t3:triiodothyronine
-goiter caused by low iodine uptake, pituitary enlargement can also occur, so t4 is
administered for negative feedback.
-formation of t4 includes coupling 2 DIT molecules, whereas t3 is couple of 1 MIT and
one DIT, these are catalyzed by thyroid peroxidase.
-reuptake of iodinated TG in follicular lumen by endocytosis
-both t3 and t4 are bound to plasma proteins (TBG), t4 (7 days) has a much longer half
life than t3 (one day)
-t3 and t4 enter cell nucleus and increase transcription for protein synthesis. T3 binds
with 10x higher efficiency, so it has stronger effect, but t4 (larger amount almost 20x) is
used for negative feedback and can be deiodinated to t3.
-thyroid hormone used for metabolic rate, appetite, maturation/puberty, skin, immune
system and healing.
-Goiter can occur with hyper or hypothyroidism, usually from iodine insufficiency.
-iodine insufficiency increases thyroglobulin, decreases thyroxine, TSH.
-Graves disease: autoimmune stimulate TSH receptors causing hypertrophy and
hyperthyroidism. EXOPHTHALMOS, weight loss, increased apetite, tremor, tachycardia.
-primary: high t3/t4, low tsh
-secondary: high t3/t4/tsh
Hypothyrodism: weight gain, lethargy, coarse skin and hair, cold sensitivity.
Autoimmune thyroiditis: destruction of thyroid gland.
Parathyroid Hormone:
PTH secreted by chief cells of parathyroid gland, caused by tumors.
-increase Ca, stimulate (1alpha hydroxylase) synthesis of 1,25D3 in the kidney from
25D3 of liver, OVERALL decrease plasma phosphate by increase excretion in kidney,
increase Ca and phosphate absorption of intestine, increase ca absorption in kidney.
-Vitamin D: made from UV actiation of 7-dehydrocholesterol, liver transports it
to 25D3, PTH makes it to active 125D3 which acts on the intestine.
-rickets/osteomalacia: vitamin D deficiency, decreased osteoclast count, needed
for new bone formation and remodeling.
CALCITONIN: plasma calcium AND phosphate decrease!!!
-calcium is usually excreted in the feces (think intestine). Not urine.
Pancreatic hormones:
Alpha: glucagon, beta- insulin, gamma somatostatin, pancreatic polypeptide
Insulin created from pro-insulin and cleavage at N-terminal, stimulated by amino acids,
GIP, GH, cortisol, acetylcholine (parasymp)
Inhibited by: epinephrine, somatostatin, NOT GLUCAGON.
Glut 2: liver, Glut 4: skeletal muscle and adipose tissue
Insulin inhibits lipase by activating phosphorylase, but not lipoprotein lipase which is
needed for fatty acid uptake into tissues.
-Stimulates amino acid/protein synthesis (so does GH), and inhibits protein
degradation

-also causes hypokalemia/increase uptake of K+ into cells. (insulin is good

treatment for hyperkalemia.)
Glucagon: stimulated by Ach, EPI, NORE, Amino Acids
-Inhibited by: insulin, fatty acids, ketones, somatostatin
-increases amino acids conversion to glucose leading to INCREASED
AMMONIA.

BOTH INSULIN AND GLUCAGON DECREASE AA and are activated by high AA,
insulin does it by protein production and glucagon by glucose production.
Diabetes main symptoms: polyphagia (increased food consumption but weight loss),
polyuria, polydypsia (thirst), glucose in urine (normal has 0mg/min excretion)
-over 126 or 140 glucose level.
-treatment: sulfonylurea which promotes insulin action for type II diabetes.
- ketoacidosis in type I diabetes. (acute)
-chronic: retinopathy, BLINDNESS, possible amputation, kidney failure,
neuropathy, thickening of basement membranes, artherosclerosis.
RESPIRATORY PHYSIOLOGY:
Conducting airways: trachea, bronchi, bronchioles, terminal bronchioles are all part of the
anatomic dead space. (150ml)
Respiration gas exchange occurs are the respiratory bronchioles, which divide into
alverolar ducts and terminate at alveolar sacs.
Residual volume: volume of air remaining in the lungs after maximal expiration
-cannot be measure through spirometry, must use gas dilution
Tidal volume: normal breath inspired and expired
TLC (total lung capacity & functional residual capacity): cannot be measured through
spirometry, it is the maximal volume to which lungs can be expanded in inspiration
Vital capacity: maximal expiration following maximal inspiration.
Inspiratory capacity: total amount of air that can be inhaled after a NORMAL expiration.
Flow rates: FEV1 is the forced expiratory volume in 1 second, in obstructive airway
diseases FEV1/VC ratio is reduced, in restrictive lung diseases all lung volumes are
reduced so the ratio stayed the same.
Physiologic dead space: anatomic dead space plus alveolar space that is not functional,
usually due to inadequate blood supply.
-lower regions of the lung ventilate better than upper regions because the lower
alveoli are better ventilated. In lower regions of the lung the hydrostatic pressure is
higher owing to gravitational effects so flow is the greatest. In the upper region aterial
pressure can sometimes fall below arteriole pressure so there is no flow adding to the
alveolar dead space.
Diffusion is based on surfactant lining, alveolar epithelial cell, basement membrane, and
capillary endothelial cell, surface area, and ability of 02 to bind to Hb.

-CO2 has a better diffusion constant thus it diffuses much faster in the lungs and
tissues.
-CO (carbon monoxide) is limited by diffusion NOT pulmonary blood flow.
Pulmonary veins terminate in a FOUR-vein hilum into the left atrium, and travel with
bronchi through the centers of the primary lobules of the lung until they reach the
terminal bronchioles.
Pulmonary circulation: low resistance, very low pressure gradient, pulmonary artery
pressure is much lower than mean arterial pressure (100), the flow rate is identical
because the two circulations are in series.
-when alveolar o2 decreases or c02 increases, pulmonary vessels constrict
because they divert blood away from poorly ventilated areas of the lung where low 02
concentrations are found and ensures better circulation of better ventilated areas.
-hypoxia causes vasoconstriction of pulmonary vessels, vasodilation of systemic vascular
tissue.
Obstruction of vessels which limit blood flow is the most frequent cause of low blood 02
because it mismatches ventilation with blood flow leading to respiratory acidosis. (high
co2). Normal V/Q (ventilation perfusion ration) is 1, if airway obstruction then V/Q is
zero and Pc02 and P02 is similar to venous blood, if there is blood flow obstruction, v/q
reaches infinity and no gas exchange occurs but p02 and pC02 approach value of inspired
air.
Hemoglobin (13-18g/100ml)binding decreases (moves curve to the right): with increase
2,3DPG, Pc02, temp or decrease in PH.
-fetal Hb, and CO move the curve to the left, fetus HbF has a higher affitinity for
O2 so can be extracted from mom.
Carbon dioxide transport: HC03 in plasma and Hb (carbaminohemoglobin), principle
way transported through the blood using carbonic andhydrase which combines C02 with
H20. It is transported in the opposite of Cl- influx.
-Haldane effect: for any pc02, Hb carries more c02 when 02 decreases.
-Hemoglobin H (four beta chains), alpha-thalassemia (4 alpha chains), Hemoglobin C
(reduced plasticity of Hb), Hemoglobin A (NORMAL), Hemoglobin S (Sickle Cell)
-Myoglobin: much greater affinity for oxygen compared to Hb, so can pick up 02 at
lower p02.
Blood serum: blood plasma (filled with proteins) minus fibrinogen or clotting factors.
-lacks fibrin, clear, thin, and sticky.
Respiratory control centers: reticular formation of medulla oblongata and the pons
-inspiratory neurons in upper medulla and send down alpha motor fibers to
muscles of inspiration, and inhibitory inspiratory neurons
-expiratory motor neurons in lower medulla only during FORCED expiration and
work via alpha motor fibers, can also inhibit.

CENTERS of PONS
-pnuemotaxic center is the inspiratory inhibitory center located in the upper pons
and is stimulated by the medullary inspiratory neurons during respiration to inhibit the
apnuestic center during inspiration until inspiration ends and expiration finally begins.
-apneustic center for inspiratory initiation in the LOWER PONS, activates medulla,
inhibited by lung inflation receptors\
Hering-Breuer reflex (stretch-inflation reflex): inspiration causes lung inflation which
activates stretch receptors with activates VAGAL FIBERS to the TRACTUS
SOLITARUS which causes apnuestic center inhibition and causes expiration.
Juxtacapillary receptors: (j receptors) cauased my pulmonary diease and causes rapid and
shallow breathing.
Propriocenter control: gamma efferent fibers
Peripheral chemoreceptors: carotid bodies located at birfurcation of common carotid
arteries which respond to low 02 and high c02, at the level of the thyroid cartilage.
(glossopharyngeal nerve like carotid sinus)
-remember: carotid sinus and aortic arch are for baroreception.
-peripheral receptors are not as important as central receptors in responding to
changes in arterial pC02.
-increase in acidity causing chemoreceptors to increase breathing rate independent
of Co2 level.
Central chemoreceptors: in ventral surface of MEDULLA exit of 9th and 10th cranial
nerves, activate apneustic center of brain.
-sensitive to CSF ph, increase in pC02, low 02 does not stimulate central
chemoreceptor AT ALL.
Chronic lung disease is due to hypoxemia, rather than C02 levels, high 02 is
contraindicated as treatment because it removes hypoxic drive leading to severe
hypoventilation.
Inspiratory muscles: diaphragm contracts, external intercostals pull ribs up and forward
-succinylcholine has inhibit muscles, so can myasthenia gravis.
ACTIVE expiration: rectus abdominas, internal and external oblique muscles, transversus
abdominus, and internal intercostals.
At FRC (fuctional reserve capacity) airway pressure equals atmospheric.
Inspiration: inspiratory muscles, chest expands pulling on parietal pleura, this lowers
intraplueral pressure making airway pressure subatmospheric.
-transmural pressure is negative
When transmural pressure is positive, there is a FORCED expiration, it is the difference
between the alveolar pressure and intraplueral pressure.
Lung Compliance; change per volume per unit change in pressure, at high volumes
compliance is low, and low volumes, compliance is high.
-compliance is reduced by stiffness and increased pulmonary venous pressure,
atelectasis (collapse of lung), of fibrotic dieases of lung. IT IS INCREASED BY

EMPHYSEMA!, and surfactant which decreases surface tension.

-with surfactant, alveoli remain patent at the lower pressures of inflation,
stabilizes alveolo, and keeps alveoli free of H20.
-surfactant is made by TYPE II pnuemocytes, made of CHOLINE.
-hysteresis: lung volume is greater at any pressure during deflaction versus
inflation.
Histotoxic hypoxia: Occurs when the tissue cannot utilize the delivered 02 because of a
toxic agent (cyanide), everything else is normal.
Respiratory response to exercise:
Phase 1: increase in ventilation due to cerebral input
Phase 2: peripheral chemoreceptors , ph continues to fall, increase in ventilation is
proportional to 2 consumption
Phase 3: steady-state, aterial c02 tension is regulated, after exercise there is an
abrupt decrease in ventilation, stimulus for ventilation remains because of acidity of
blood but pc02 is normal and 02 remains normal or high. ATP and phosphorlycreatine is
resynthesized and lactic acid is removed.
NERVOUS SYSTEM PHYSIOLOGY:
Resting membrane potential is formed largely because the neuron is permeable to K+ and
impermeable to intracellular anions. The positive K+ ions diffuse across the membrane
leaving a impermeant negative charge behind, they stop when the magnitude of the
electrostatic force is equal and opposite to that of the concentration gradient.
The absolute refractory period is that time during which Na channels cannot reopen, in
the relative period the Na channels can open but it is harder because of the K dependent
hyperpolarization.
-Anasthetic, binds to SODIUM channel put them in the closed position, they do
NOT effect potassium, chloride, or calcium conductances. Only sodium.
Ia: muscle spindle afferents, motor nerves
Ib: Golgi Tendon organs
II: muscle spindle/nuclear chain, touch pressure hairs and vibration
IIIA-gamma: muscle spindle efferents (intrafusal)
C fibers: pain, temperature, sympathetic, postganglionic (ONLY FIBER WITH NO
MYELIN)
Spatial summation: simultaneous inputs from different presynaptics neurons
Temporal summation: additive effect on the postsynaptic neuronal memberane is caused
by repeated rapid firing of a presynaptic neuron.
Long-term potentiation: basis for learning and memory
Serotonin is released from raphe nuclei of the brainstem and from the hypothalamus.
Glutamate: excitatory
Glycine: inhibitor of spinal cord, open chloride channels
GABA: inhibitor of basal ganglia, purkinje, spinal cord, and cortical relays.

Eaton-Lambert syndrome: similar to myasthenia gravis, but patients GET STRONGER

rather than weaker, so muscles improve with use.
Clostridium Botulism toxin: causes blockage in the release of the neurotransmitter
resulting in quick paralysis of skeletal muscle and death by respiratory failure.
Black spider venom: causes complete release and depletion of AcH, muscle spasms.
Smooth muscle: synaptic cleft is much smaller, terminal are dark for norepinephrine, and
there are NO transverse tubules in smooth muscle.
AUTONOMIC NERVOUS SYSTEM:
Coordinates and modulated the viscera.
Preganglionic is myelinated, the postganglionic is not myelinated, it is 100x slower than
skeletal motor conduction.
Sympathetic nervous system: originates in the intermediolateral cell column in spinal
segments t1 to l2. activates body in synchronous coordinated fashion
-Alpha and Beta receptors: (a1,b1 = excitiation, a2,b2=relaxation)
-preganglionics leave in WHITE RAMUS (myelinated) to join sympathetic chain.
-post-ganglionic neurons: PARAVERTEBRAL GANGLIA.
-splanchinc nerves pass through the chain without synapsing ending in a
neuron plexus such as a celiac ganglia.
-SIF (small dopaminergic/fluorescent cells) regulate sympathetic ganglia, they are
innervated by preganglionic cholinergic fibers.
-postganglionic acetylcholine is used for sweat glands and BLOOD vessels of
skeletal muscle dilation, arrector pilli muscles
G-protein: GTP replace GDP on the alpha subunit, as a result, the subunit
disassociates from the other two (beta and gamma), alpha activates adenylate
cyclase, the gamma and beta open potassium channels.
Superior cervical ganglion: lower four cranial nerves, pharynx, carotid, and superior
cervical cardiac nerve. (lesion causes Horners syndrome)
Middle and inferior cervical: known at stellate ganglion,
Thoracic chain ganglia and celiac ganglia: send fibers until the left colic flexure (left
colon)
Lumbar and sacral chain ganglia: mesenteric plexus, receive preganglionic from
splanchic nerve, send fibers to below the left colic flexure to the external genetalia.

Parasympathetic nervous system: CN 3,7,9,10 and sacral S2,3,4

Each preganglion synapses with a FEW postganglionic, (symp does many).
Preganglionics Terminate CLOSE to innervated structure (long fibers), whereas in
sympathetic terminate far from structure. (short fibers, send out to many postganglionics)
Post-ganglionics can inhibit transmission or excite the structure. (very short in distance)
CN 7 and 9 come from superior and inferior salivary nuclei of medulla oblongata

Nicotinic AChr: in skeletal muscle, autonomic ganglion, always excitatory.

-Ach binds to nicotinic cholinergic receptors of postganglionic RECEPTORS

-Ach release by postganglionic neurons bind to MUSCARINIC RECPTORS OF
TISSUE.
Somatic sensory system:
Exteroceptive: external senses like vision, hearing, skin and chemical senses
Proprioceptive: provide information about relative position of body
Interoceptive: blood pressure, internal
Nociceptive: pain
Mechanoreceptors: touch and pressure
-Rapidly adapting (aB and A-gamma fibers)
-Meissner corpuscle: hairless skin of palms, two-point discrimination
-Pacinian corpuscle: subcutaneous tissue, vibration, high frequency stimulation
-slowly adapting: mediated by aB fibers
-type 1: fire irregularly
-type 2: regular discharge in response to maintained pressure (Ruffinins end
orgain in hairy skin)
Afferent fibers and joint afferents mediate position sense and kinesthesia.
Spinal cord pathways:
Spinal gray matter:
Posterior marginal nucleus: afferent information
Substantia gelatinosa: relay for pain and temperature
Nucleus proprius: integrates sensory information in conjuction with descending control
Clarkes nucleus: relays limb position to the cerebellum.
Spinal white matter: (myelinated, ascending sensory systems)
Doral columns: discriminative touch go to nucleus gracilis and cuneate nucleus in the
lower medulla, these fibers cross and then ascend in the contralateral medial
lemniscus to terminate in the thalamus.
Anterolateral pathway: pain, temperature, crude touch sense, dorsal horn cross spinal
cord, terminates in thalamus via the spinothalamic tract then to the cerebral cortex.
BOTH terminates the ventral posterior lateral nucleus of the thalamus.
Sensory felt on body is found on the opposite side of the cortex.
A-gamma and C-fibers synapse in the dorsal horn.
Substance P: C-fiber afferents in central synapses
-spinal pain projections: spinothalmic tract, include reticular formation, superior
and inferior colliculi, and periaqueductal grey matter (opiate release e.g. serotonin)
-VPL of thalamus
-endorphins act in peripheral analgesia in part by preventing the release of
substance P from C-fiber afferent terminals.
Pupil:
Light entering one eye causes constriction of the contralateral pupil (consensual light
reflex), it is mediated by the Edinger-Westphal nuclei.

Pupillary constriction occurs when focusing for near vision (accommodation). It is

mediated via a different pathway from the light reflex.
-tertiary syphilis: Argyll-Robertston pupil, reflex constriction is lost but
accommodation constriction is preserved.
Focusing of eye triad: accommodation, papillary constriction, eye convergence.
Receptors: rods and cones are exited and that inhibit bipolar cell in the dark
(hyperpolarization)
Rhods: contain rhodopsin, which contiains sctotopsin, and vit A. (11-cis-retinal) for light
trapping.
Cones: visual acuity and color vision, central location.
Horizontal and amacrine (local-circuit neurons of the retina) bipolar(inhibited in the dark)
and ganglion cells (transmit to brain, synapses with bipolar cell)
Visual cortex: lateral geniculate which received input from contralateral field.
-pyramidal cells: project to other areas of the brain
-stellate cells: local integration
Ear:
Sound waves in the ear enter the eardrum (tympanic membrane) to vibrate and cause the
ossicles to produces pressure changes in the inner ear.
-tympanic reflex: tensor tympani and stapedius lock ossicles into place to
prevent damage to the inner ear to loud sounds.
-Organ of corti rests on basilar membrane, innervated by CN 8, the hairs of the
hair cells are embedded in the tectorial membrane, doformation of the hair cells occurs
when the basilar membrane generates action potentials.
-Basilar membrane: movement of stapes produces pressure waves in the
perilymph of the scala vestibuli to trigger hair cells in the organ of corti.
-Frequency of sound is dependent on the part of the basilar membrane that is
displaced. Higher pitched sounds produce maximum displacement closer to the
BASE, whereas lower pitched sounds maximally displace the APEX.
-increase in intensity of sounds causes an increase in the displacement of the
basilar membrane and increase of firing of CN 8 fibers.
CN 8 fibers terminate in cochlear nucleus of medulla, and go to superior temperal gyrus,
sound representation is bilateral but each hemisphere localizes sound from the
contralateral auditory hemisphere.
Vestibular system:
Each semicircular canal contains an enlarged ampulla (crista ampullaris) which detects
angular acceleration, caused my hyper or depolarization of hair cells dependent of
movement.
-heat: rotation towards a crista
-cold: away from the crista
The utricle and saccule contain maculae, which sense gravitational pull and linear
acceleration.
Olfaction: hair cells send unmyelinated axos to the cribiform plate and then form the
olfactory never, bipolar cells are the primary neurons of the olfactory system.

-SITE OF TERMINATION is on the ipsilateral olfactory nerve, DOES not

relay in the thalamus.
-projects to the amygdale, olfactory cortex, paraterminal gyrus.
Taste: tractus solitarius, fasciculus solitarius, to the VPM thalamus.
Anterior 2/3: CN 7
Poster 2/3: CN 8
Pharynx/epiglottis: may be carried to the vagus nerve.
MOTOR SYSTEM:
Large pyramidal tract: responsible for voluntary movement on the contralateral side of
the body, while small tract maintains muscle tone.
Upper motor neuron `:
-spasticity or hypertonus: leads to gamma neuron excitation
-patterned paralysis, hyperreflexia (hyperactive reflexes)
-positive Babinksis sign: exaggerated dorsiflexor withdrawal of foot in
response to stiumalation of the outer edge of the plantar surface.
Lower motorn neuron lesions:
-ventral horn and peripheral fibers
-flaccidity since alpha motor neurons are abolished
-hypotonicity, hyporeflexia but nociceptive and sensory may be intact
-muscle wasting, fibrillations (spontaneous contractions)., fasciculations
(repetitive firing of dying motor neurons)
Lesions of the CNS: cause loss of motor activity on the same side, and loss of pain
and temperature sensations of the opposite side.
Basal ganglia: movement, pars compacta of substantia nigra, dopamine, its function
is INHIBITORY, so if damaged causes tremor/tonic action. The CEREBELLUM IS
EXCITATORY.
Parkinsons: tremor at rest, cogwheel joints, tonic action of alpha motor neurons,
difficulty of initiating skilled movements (akinesia)
Huntingtons chorea: decreased levels of GABA, opposite of parkinsonism,
hyperkinesias, involuntary movements, spasmodic
Lesions of subthalmic nucleus: violent flinging of contralateral arm
Basal ganglia has initiating and directing complex movements.
Cerebellum: receives fast inputs of motor activity, thus it can make quick constant
corrections to motor activities while they are in progress.
Rubrospinal: coordination of body movement
Lateral reticulospinal: facilitary influence on skeletal muscles/motor neurons.
Medial reticulospinal: inhibitory effect on motor nuerons
Lateral & Anterior corticospinal: voluntary movement, muscles, movement on opposite
side.
Speech disturbances:
Dysarthria: motor output disturbance

Brocas aphasia: lesion to inferior frontal gyrus, no comprehension deficit, speech is

nonfluent
Wernickes aphasia: lesions of posterior portion of the superior temporal gyrus, no motor
problem just cannot understand
Conduction aphasia: lesion in fibers between Wernicke and Broca, cannot convert
auditory input to verbal output.
Sleep:
During REM, EEG resembles waking state, autonomic tone increases (increased HR and
blood pressure), and skeletal muscles are paralyzed. (after 90 minutes from onset of
sleep)
-drives by pons, lateral geniculate, and visual/occolumotor cortices
Wakefulness: B-waves
Non-rapid REM: slower frequency and high-voltage activity, stage 1-4, where stage 4 HR
and blood pressure and respiration declines, BUT GI motility increases and muscle tone
is maintained.

REPRODUCTIVE PHYSIOLOGY:
The major progestin, progesterone is made in the greatest quantities in the ovary, or can
be made in adrenal cortex.
Androgens and estrogens can be made in the ovaries, testes or adrenal cortex and have
activity in both males and females.
Androgen secretion: testosterone is created via pregnelenone, (17 a hydroxylase
enzyme) 17-hydroxy pregnelenone, DHEA (zona reticularis) then gets transformed to
Androstenedione and testosterone in the tests and ovaries, and is created in the Leydig
cells of the testis and the adrenal gland.
-transport to the blood is by sex hormone binding globulin.
-activates mRNA transcription in prostate, hair follicles, and external genitalia.
Spermatogenesis: initiation by Sertoli cells, under FSH and testosterone of Leydig cells.
(paracrine effect)
Internal ducts and organs:
-Epididymis: high levels of testosterone
-vas deferens: testosterone helps muscular components and epithelial lining
-seminal vesicles: production of seminal fluid
-prostate: convert testosterone to DHT, which causes growth and secretion in
the prostate gland, can cause benign prostatic hypertrophy.
-scrotum: DHT is responsible for thinning and development of fold of the scrotum,
increase surface are to keep testes cool
-penis: enlargement of penis at puberty controlled by DHT.
DHT: development of public and axillary hair in BOTH males and FEMALES. Increases
sebaceous gland activity causing acne, deepening of voice.
Testosterone: anabolic steroid to build mucles, increase protein synthesis in muscles and
overall muscle mass, increase growth at end plates of long bones and stimulate the
closing of the epiphyseal plates, so androgens also limit growth.

LH: stimulate leydig cell to synthesize and secrete testosterone

FSH: stimulate sertoli cells to synthesize and release ABP and inhibin.
-inhibin feeds back to the pituitary gland to block synthesis and secretion of
FSH. (in both females and males)
-testosterone synergizes with FSH to initiate and maintain spermatogenesis.
Sperm transport: testis to epididymis (not motile), stored in epididymis where they
become motile by forward motility factor in the tail, but they ARE NOT FERTILE.
Vas deferens push the sperm to the urethra, fluid from prostate and seminal vesicles is
secreted (which contains fructose and prostaglandins).
Female reproduction:
Cells in theca interna have receptors for LH, stimulates conversion of cholesterol to
pregnelenone, transported to androgens from the thecal cells to the granulosa cells where
they become estrogen, and are promoted by the FSH binding to the granulosa cells,
which also creates more LH receptors on the granulosa cells.
Corpus luteum: derived from both theca interna cells and granulosa cells. Theca
interna cells create more aromatase.
Progesterone binds to corticosteroid-binding globulin, wherease estradiol and DHT and
androgens binds SHBG.
-prepares uterus for preganacy, further proliferation of the endometrium
Estrogen acts by increasing oxytocin receptors in the fallopian tubes, and stimulate
contraction of the fallopian tubes. Estrogen promote endometrial growth and increase
both the length and number of the endometrial glands.
-estrogens promote protein synthesis, increase HDL and decrease LDL,
responsible for fat deposition, and inhibiting bone resorption.
Androgens are responsible for basal levels of libido and inhibit bone resorption
Menstrutation: estrogen has positive feedback on hypothalamus increasing GnRH, the
surge in LH in combination with high estrogen induces ovulation. (FSH decreases)
Luteal phase: progesterone is secreted, slows down the cyclicity of GnRH, LH and FSH
are constant. The corpus luteum undergoes luetolysis and progesterone and estrogen
levels decrease and the lining of the uterus sheds and the menstrual period begins.
Follicular phase: the estrogen/progesterone ratio is increased and remains high until the
luteal phase where the progesterone is higher. Ovary continues along the fimbrae of the
oviduct and fallopian tube.
Sperm undergoes capacitation once deposited in the vagina, seminal fluid contains
decapicitation factors. Prostatic and seminal vesicular secretions are alkaline and help
neutralize the acid media in the vagina.
HcG is synthesized in the synctiotrophoblast, it is found in high amount of urine in
women who are pregnant. HcG is used in the first trimester for the stimulating the
corpus luteum, not theca granulosa and interna, to produce the estrogen and
progesterone. 10-12 weeks of gestation the placenta takes over the production of

progesterone. (Estrogen DOES Not prepare endometrium, only PROGESTERONE

DOES)
Progesterone during pregnancy CALMS the uterus, by blocking oxytocin receptors, but
activates it during labor.
Estrogen during pregnancy keeps the endometrium functional, stimulates breast tissue,
and increase BLOOD flow to the uterus, and increases the number of progesterone
receptors in the breast.
Placenta does not have 17-a-hydroxylase but can still create DHEA.
Colustrum a thin water fluid that is rich in antibodies from the breast right after
pregnancy.
Oxytocin: uterine contractions and contraction of myoeptithelium due to baby suckling.
Oxytocin causes contractions of the myoepithelium resulting in milk let down, it
does NOT stimulate the milk production, PROLACTIN CAUSES MILK
PRODUCTION.
High levels of prolactin surpress LH and FSH after pregnancy, so as nursing continues
there is a longer surpression of FSH and LH.

RENAL AND URINARY PHYSIOLOGY:

Total body water is 60 percent of body weight, 2/3 of that is INTRAcellular fluid, and
1/3 is extracellular fluid which 75 percent is interstitial and 25 percent is plasma. The
more the adipose tissue the less the body weight is water, because fat has a low
water content.
NaCl is largely in the extracellular compartment.
Mannitol acts like NaCL in the blood for patients with cerebral edema so it drives water
from the brain to the blood vessels.
Capillary blood pressure/hydrostatic pressure (Pc) is more effected by increases in
venous pressure than arterial pressure, because arteries can regulate themselves. Thats
why, hypertension but without heart failure do not commonly exhibit edema.
Glomerulonephritis: causes primary salt and water retention as a result of damage to the
kidney, which causes a higher EDV, which causes increase in cardiac ouput.
-CHF and Glomerulonephritis increase hydrostatic pressure.(Pc)
-atrial natriuretic factor can be used to treat problem to decrease reabsorption and
promote diueresis. USES cyclic GMP as a second messenger.
Liver disease causes a reduction in plasma volume causing accumulation of fluid in the
perotineal cavity (ascities) or edema, causing the kidney to increase reabsorption
furthering the edema.
-hypoalbuminemia also causes generalized edema (occurs from low plasma
oncotic pressure, whereas low interstial oncotic pressure causes localized edema).
-albumin: decreased in malnutrition, liver failure, and PREGNANCY. Transports
thyroxin, fatty acids, bilirubin, bile acids, steroid hormones, ions. IT IS NOT
GLYCOSYLATED.

Nephrotic syndrome: Plasma protein falls from mass excretion of protein, lowering
plasma oncotic pressure causing GENERALIZED edema. The reduced oncotic pressure
causes fluid to leak into the interstitium, lowering plasma volume, resulting in secondary
salt and water reabsorption by the kidney. hypoalbunimia and secondary hypovolemia.
Nephritic syndrome: aka glomerulonephritis. Associated with high plasma volume,
whereas nephrotic syndrome is associated with hypoalbunimia and secondary
hypovolemia.
Burns increase capillary permeability which increase leakage of plasma protein into
interstitium cuasing increase in interstitial oncontic pressure, causing edema. Also
Histamine release causes vasodilation with increases capillary hydrostatic pressure.
Wuchereria bancrofti is a worm that causes a block in lymph channels causing local
edema. Malignancies also cause local edema of the lymph nodes because of blockage of
lymph flow.
Nephron: glomerulus, bowmans capsule (single layer of specialized epithelial cells),
proximal tubule, loop of henle, distal tubule, collecting duct.
Cortical nephrons: outer cortex, have short loops of Henle, hairpin turn in distal area
Juxtamedullary nephrons: deep into cortex, smaller percentage, have long loops of Henle
deep in medullary zone and papillary portions of the kidney.
Podocytes: specialized epithelial cells that lay down and maintain basement membrane
and scavenge proteins that slip through the filtration barrier, they contact glomerular
capillaries via pedicle, which are interdigitating foot processes that rest on the outer layer
of the basement membrane. Spaces between pedicle alow filtration of protein allowing
water and solutes to pass.
Countercurrent multiplier: in loops of Henle, resorption of sodium in thick ascending
limb to the vasa recta of medulla.
Urea: freely filtered at glomerulus, approximately half is passively reabsorbed in the
proximal tubule, and can be reabsorbed with ADH in the collecting duct.
Creatinine: not reabsorbed
Glucose: glucose only appears in urine in diabetes and renal glycosuria which there is a
defect in glucose reabsorbtive pump. (similar to amino acids)
Calcium and Phosphate will have opposing effects, if one increases the other decreases in
blood plasma due to reabsorption mechanism.
Sodium reabsorption: majority at proximal tubule and some at ascending loop, very
little at collecting duct and distal tubule.
-ascending limb is impermeable to water
-distal tubule is relatively impermeable to water
-collecting duct and promixal tubule are permeable to water (majority at proximal
tubule). ADH will increase permeability.
ADH effected by: increase osmolality detected by hypothalamus, baroreceptors in
carotid sinus (ninus), aortic arch, atria.
Potassium excretion: caused by acidosis or by aldosterone which reabsorbs sodium and
EXCRETES potassium, diuretics and decrease K+ excretions.

HyPOaldosteronsim: increase sodium loss, decrease cardiac output, decrease renal

flow. Increase potassium retention, cardiac arrythmias due to high K+, increase H+
retention because of coupled mechanism causing acidosis.
H+ ion: actively secreted in proximal tubule, most react wth HC03 the other react with
ammonia and phosphate buffers.
-For every H+ ion secreted, one HC03 is reabsorbed into the blood, so that a large
increase in H+ in blood increases HC03 in the blood
-affected by respiratory acidosis, which increases renal reabsorption of HC03
-aldosterone which causes H+ secretion
-SO KIDNEY HANDLES ACIDOSIS WITH HC03 WHILE LUNG controls C02
If H+, HC03, and Co2 all fall it is respiratory controlled, if H+ and Hc03 go in
different directions, then it is RENAL/METABOLIC controlled.
-alkalosis causes a decrease in H+ secretion by kidneys and decrease reabsorption
of HC03.
Renal circulation: efferent arterioles branch into peritubular capillaries and vasa recta
in the medulla. By increasing or decreasing renal vascular resistance, the kidney assures
itself constant blood flow over a wide range of blood pressures. The regulation occurs by
progressive constriction of afferent arterioles as blood pressure increases, which effects
GFR which increases amount of Na secreted.
-alpha receptors (sympathetic) cause constriction of afferent arteriole.
-Beta receptors of afferent arterioles release rennin when stimulated. Which
causes constriction of efferent arteriole, so pressure is increase even though blood flow is
reduced. Increase in GFR is due to increase in hydrostatic pressure (constriction of
efferent arteriole or vasodilation of afferent arteriole)
-angiotensin II also cause greater constriction of the efferent arteriole than of the
afferent arteriole. Can be released by B receptors, reduction of perfusion pressure in
kidney, or reduction of Na delivery to the macula densa.
-Para-aminohippuric (PAH) acid is a substance used to measure renal
plasma flow.
-decrease in plasma colloid osmotic pressure (decrease in plasma proteins),
causes an INCREASE in GFR.
Hematologic/Lymphoreticular Physiology
Platelets derived from megakaryocytes in the bone marrow.
Adhesion: lysine and hydroxylysine attract platelets, adhesion requires von Willebrand
factor, which binds platelet factor 8 and binds to platelet membrane glycoprotein GpIb.
F is released from platelets and promotes aggregation., TxA2 promotes platelet
aggregation, PGI2 made by endothelial cells inhibits aggregation.
Thromboplastin results in the formation of a clot
PF3 is involved in plasma coagulation.
Prostacyclin: vasodilator, inhibits platelet agregration (TxA2 is opposite)
Intrinsic pathway in which coagulation begins in the blood, whereas the extrinsic
pathwhay begins with trauma to tissues outside the blood vessels.

Extrinsic Pathway: initiated with tissue thromboplastin (tissue factor III) and tissue
phospholipids. Tissue thromboplastin along with calcium and forms a complex with a
factor VIIa which acts on factor X with factor 5 form complex prothrombin activator.
-assesed by measuring prothombin time (PT)
-3,7,10
Instrinsic Pathway: PF3 and calcium activate factor XII acts on factor XI which acts on
factor IX with factor VIII with phospholipids activate factor X which activates factor
V and platelet phospholipids active prothombin activator. (same as extrinsic)
-assessed by measuring PTT partial thromboplastin time
-12,11,9,8,10
Prothrombin made by extrinsic or instrinsic pathway needs vitamin K, creates thrombin
by breaking glycine and arginine bonds. (Warfarin is a analog of vit. K)
Factors 2,7,9,10, protein C, and protein S are all Vitamin K dependent.
Factor 13 (fibrin stabilizing factor) which is activated by thrombin creates fibrin
network, forms permanent clot at the injury site.
Fibrinolysis is activated by plasma protein plasminogen, the clot itself releases the
plasminogen activator.
ANTICOAGULANTS: Fibrin (keeps thrombin from spreading), antithrombin III,
heparin (prevents activation of factor 9), protein C and protein S which are vitamin
K dependent. (Protein C and S are endogenous).
Musculoskeletal Physiology
Skeletal Muscle: many parallel myofibers, each with a multinucleated structure
surrounded by the sarcolemma.
-shortening of muscle occurs from extent of thin-thick filament overlap. (sliding
filament mechanism) Sarcolemma shortens, but fibers remain the same size.
Contraction:
ATP in the cytoplasm replaces the previously bound ADP, resulting in the dissociation of
the myosin head, after hydrolysis of ATP, the potential of energy remains in the myosin
head.
-If ATP runs out, then remain in a rigor state, leads to inability of myosin head to
be released.
Action potential from depolarization caused by Ach binding, is transmitted down a Ttubule to the sarcoplasm reticulum, releasing Ca2+ into the cytoplasm into the myofibrils
and binds to the TnC subunit of Troponin and causes a conformational change and
moving TROPOMYOSIN with respect to actin.
-once the tropomysin goes out of the way, myosin ATPase can be activated, and
thick and thin filaments past each other.
-succinylcholine can inhibit Calcium re-uptake by the ryan-odine receptor causing
muscles to overcontract.
Isometric contraction: occurs when both ends of a muscle are fixed and no change in
length occurs, but TENSION increases.

Isotonic contraction: occurs when a muscle shortens during contraction while tension
remainds constant.
Most physical activity includes borth isometric and isotonic contractions. (dynamic)
Sarcomeres of the same myofibril do not generate additive force, to generate more
force more muscle fibers must be recruited.
Fast-twitch fibers are white, large in diameter, with few muscle fibers per unit, it has a
absence of red myoglobin (appears white), it has many sarcoplasm reticulum, myosin
ATPase but FEW mitochondria because use anaerobic glycolysis. FINE MOVEMENTS
Slow-twitch fibers are red because of presence of myoglobin. Smaller in diameter, less
sarcoplasm reticulum and fewer T-tubules than white muscle, used for sustained
contractions, oxidative metabolism is used for energy, so need many mitochondria.
Motor units are all muscle fibers that are inntervated by a single nerve axon (alpha motor)
-must be same muscle type, if neuron is dystroyed, associated muscles atrophy.
Tetanus is the summation of contractions when the fibers are stimulated repetitively
with a short time, resulting in greater contractions than from a single twitch.
Graded forces increase the number of motor units and increase the firing rate to increase
muscle tension (force).
Muscle receptors: Two types, muscle spindles and Golgi Tendon Organs
Muscle spindles: intrafusal fibers that are innervated by small neurons called gamma
motor neurons which terminate at the nuclear bag fibers
-Ia fibers innervate the nuclear bag and nuclear chains (intrafusal muscle fibers)
-secondary slower conducting type II fibers innervates only the nuclear chain
fibers
Muscle stretch of the muscle spindle afferents activates alpha motor neurons to activate
extrafusal fibers of the muscle spindle to cause muscle contraction.
Golgi Tendon organs afferent fibers fire in response to stretch and lengthening and are
in series with extrafusal muscle fibers and are supplied by Ib afferent fibers. Excessive
stretch of muscle causes inhibitory internuerons to synapse on alpha motor neurons
-tendon organs sense muscle TENSION, while muscle spindles sense
MUSCLE LENGTH!
Smooth muscle: is generally smaller and usually uninucleated.
-fewer myofibrils, less organized
-DENSE bodies: on the cell bodies similar to Z lines
-less myosin/thick filaments
-no T-tubules, sparse sarcoplasm reticulum. DOES NOT HAVE TROPONIN,
instead calcium binds to myosin kinase to mediate excitation of muscle.
Contraction occurs when thin filaments inserted into the dense bodies are pulled
close together by bridging myosin units.
Stretch reflex: MYOTATIC REFLEX, responds to passive stretch of muscle (1a
afferent)

Mitosis:
G1: growth and preparation of the chromosomes for replication
S: synthesis
G2: preparation for mitosis
M: mitosis (no synthesis, only division)
IgG: most common antibody, passes placenta and enters fecal circulation
IgA: second most abundant
IgD: receptor site for B-lymphocytes
IgM: does not past placenta, first antibody into circulation
IgE: basophils, mast cells, allergic and anaphylactic type I reacition hypersensitivity.
Hypertonic: higher salt concentration, water goes in
Hypotonic: lower salt concentration, water leaves.

Urea cycle
From Wikipedia, the free encyclopedia

Jump to: navigation, search

The reactions of the urea cycle.

The color scheme is as follows: enzymes, coenzymes, substrate names, inorganic molecules, Asp and
urea's nitrogen that comes from it, NH4+ and urea's nitrogen that comes from it, HCO3- and urea's
carbon that comes from it
The urea cycle, also known as the ornithine cycle, is a cycle of biochemical reactions occurring in many
animal organisms that produces urea from ammonia (NH4+). This cycle was the first metabolic cycle
discovered (Krebs and Hensenleit, 1932).
Contents
[hide]

1 Function
2 Reactions
3 Regulation
o 3.1 NAcGlu
o 3.2 Substrate concentrations

4 See also
5 External links

[edit]
Function
Organisms that cannot easily and quickly remove ammonia usually have to convert it to some other
substance, like urea or uric acid, which are much less toxic. Insufficiency of the urea cycle occurs in some
genetic disorders (inborn errors of metabolism), and in liver failure. The result of liver failure is
accumulation of nitrogenous waste, mainly ammonia, which leads to hepatic encephalopathy.
[edit]
Reactions
The urea cycle consists of five reactions - two mitochondrial and three cytosolic. The cycle converts two
amino groups, one from NH4+ and one from Asp, and a carbon atom from HCO3-, to relatively nontoxic
excretion product, urea, at the cost of four "high-energy" phosphate bonds (3 ATP hydrolyzed to 2 ADP
and one AMP). Orn is the carier of these carbon and nitrogen atoms.
Reactions of cycle:

Step Reactant

Product

Catalyzed by Location

2ATP + HCO3- + NH4+

carbamoyl phosphate + ornithine citrulline + Pi

OTC

mitochondrial

citrulline + aspartate + ATP

argininosuccinate + AMP + PPi

ASS

cytosolic

argininosuccinate

Arg + fumarate

ASL

cytosolic

Arg + H2O

ornithine + urea

ARG1

cytosolic

carbamoyl phosphate + 2ADP + Pi CPS1

Summary reaction:

2 NH3 + CO2 + 4 ATP + aspartate urea + fumarate + 4 ADP + 4 Pi

[edit]
Regulation

mitochondrial

Alternate representation of urea cycle. Numbering is different from that presented above. Aqua oval is
mitochondrion. CPS1 not displayed.
[edit]
NAcGlu
The synthesis of carbamoyl phosphate and the urea cycle are dependent on the presence of NAcGlu, which
allosterically activates CPS1. Synthesis of NAcGlu by NAGS, is stimulated by Arg - allosteric stimulator
of NAGS, and Glu - a product in the transamination reactions and one of NAGS's substrates, both of which
are elevated when free amino acids are elevated. So, Arg is not only a substrate for the urea cycle reactions
but also serves as an activator for the urea cycle.
[edit]
Substrate concentrations
The remaining enzymes of the cycle are controlled by the concentrations of their substrates. Thus, inherited
deficiencies in the cycle enzymes other than ARG1 do not result in significant decrease in urea production
(the total lack of any cycle enzyme results in death shortly after birth). Rather, the deficient enzyme's
substrate builds up, increasing the rate of the deficient reaction to normal.
The anomalous substrate buildup is not without cost, however. The substrate concentrations become
elevated all the way back up the cycle to NH4+, resulting in hyperammonemia (elevated [NH4+]P).
Although the root cause of NH4+ toxicity is not completely understood, a high [NH4+] puts an enormous
strain on the NH4+-clearing system, especially in the brain (symptoms of urea cycle enzyme deficiencies
include mental retardation and lethargy). This clearing system involves GLUD1 and GLUL, which
decrease the 2OG and Glu pools. The brain is most sensitive to the depletion of these pools. Depletion of
2OG decreses the rate of TCAC, whereas Glu is both a neurotransmitter and a precursor to GABA, another
neurotransmitter. [1](p.734)

PKU: phenylalanine hydroxylase

-deficiency in phenyalanine hydroxylase causes buildup of phenylalanine in the

bloodcauses mental retardation
Cystic fibrosis, sickle cell anemia, down syndrome know main things happening
-cystic fibrosis: diagnosis involves finding increased amounts of sodium chloride in
sweat; mechanism involves blockage of Cl- ion transporter in epithelial cell
membranesviscous secretions
-sickle cell anemia: single amino acid replacement in beta-chain (substitution of
glutamate in position 6 with valine)causes crescent shaped RBCs. Low oxygen or
dehydration precipitates sickling. An advantage is that heterozygotes are relatively
malaria resistant. Homozygotes may be subjected to complications such as aplastic crisis
(from B19 parvovirus infection), autosplenectomy, increased risk of encapsulated
organism infection, Salmonella osteomyelitis, painful crisis (vaso-occlusive), and splenic
sequestration crisis.
-down syndrome: trisomy 21lower than average cognitive function, simian crease,
heart/gastroesophageal defects
Protein hormones and lipid hormones difference and how they bind: vitamin D is both a
steroid and it does regulation of calcium, it binds to intracellular receptor bc its a steroid
hormone
-Lipid/steroid hormones cross the cell membrane and bind to specific cytosolic or
nuclear receptors. These receptor-hormone complexes accumulate in the nucleus and
bind to regulatory DNA sequences causing stimulation of inhibition of gene transcription.
The precursor for steroid hormones is cholesterol. They are primary produced by the
adrenal cortex and the gonads as well as the placenta during pregnancy.
*note: D Vitamins are a group of sterols with hormone-like functions
-Protein/peptide hormones are produced like regular proteins in an inactive form known
as a preprohormone which is cleaved to form prohormones by enzymes in the RER. This
prohormone is then packaged in the golgi for transport outside of thecell via exocytosis.
Most peptide hormones serve as neurotransmitters and therefore bind to catalytic or Gprotein coupled receptors on target cells (they are too hydrophilic and large to just diffuse
through the plasma membrane).
Ehlers donlons disease:
Ehlers Danlos syndrome (EDS) is the name given to a group of inherited disorders that
involve a genetic defect in collagen and connective tissue synthesis and structure. This
results in fragile and hyperelastic skin, unstable and hyperextensible (hypermobile)
joints, and fragile tissue and blood vessels. A genetic defect causes reduced amounts of
collagen, disorganization of collagen that is usually organized into bundles, and
alterations in the size and shape of collagen. There are six subtypes of EDS classified
according to clinical features.
Staph and strept for micro: anaerobes, read micro made for staph and strept
Staph aureus:

-Protein A (virulence factor)

-causes: inflammatory disease (skin infxn, organ abscesses, pneumonia) and toxinmediated disease
-gram positive (food poisoning, toxic shock syndrome, scaled skin syndrome)
-coagulase positivecauses clumping for abscess formation
Strep pyogenes (Group A):
-beta-hemolytic
-causes: pyogenic (pharyngitis, cellulites, impetigo), toxigenic (scarlet fever, TSS),
immunologic (rheumatic fever, acute glomerulonephritis) diseases
-bacitracin sensitivity
-antibody to M protein enhances host defense
-spread by respiratory route/close contact
Lateral ling swelling ant 2/3 of tongue bifid tongue
-also known as cleft tonguedivided in its anterior part by a longitudinal fissure
Facial expression is branchial arch 2
-involves these muscles: muscles of facial expression, posterior belly of the digastric,
stapedius, and the stylohyoid
-Bones, ligaments, cartilages: Reicherts Cartilage, stapes, styloid process, stylohyoid
ligament, upper part and lesser horn of the hyoid.
Arm innervation for arms, thumb, lymph nodes
ARM
Flexors:
Coracobrachialis- musculocutaneous nerve (C5, C6, C7)
Biceps brachii- musculocutaneous nerve (C5, C6)
Branchialis- musculocutaneous nerve (C5, C6) and small contribution by radial nerve to
lateral part of muscle
*note: musculocutaneous nerve provides motor innervation to all muscles in the anterior
compartment of the arm and sensory innervation to the skin on the lateral surface of the
forearm.
Extensor:
Triceps brachii- radial nerve (C6, C7, C8)
Thumbthenar muscles are innervated by the recurrent branch of the median nerve
Five lymph groups that drain the upper limb:
Humeral (lateral) nodes
Pectoral (anterior) nodes
Subscapular (posterior) nodes
Central nodes (embedded in axillary fat)
Apical nodes (most superior group)

Vitamin k is gamma carboxylation

-contained in cabbage, cauliflower, spinach, egg yolk, and liver
-also synthesized by gut bacteria
-required for hepatic synthesis of prothrombin, factor II, VII, IX, X
-formation of clotting factors requires vitamin K-dependent carboxylation of glutamic
acid residuesform a mature clotting factor that contains gamma-carboxyglutamate
(Gla)
Insulin is gonna cause storage
-insulin favors uptake of glucose and other biosynthetic reactions
Kaposki:H 8
Kaposis sarcoma caused by HHV-8 (human herpes virus) via sexual contact
Oral hairy leukoplakia is Epstein barr
OHL is caused by the Epstein-Barr virus (EBV). Oral hairy leukoplakia (OHL) refers to a
white patch or white patches that can develop in the mouth. These patches usually
occur along the sides of the tongue, although they can sometimes develop on the top and
underside of the tongue or along the inside of the cheek. Looking carefully at these
patches, they may appear shaggy or may contain a number of tiny folds or ridges. OHL is
often one of the first opportunistic infections to occur in HIV-positive people.
H. Pylori causes gastritis
Interstitial pneumonia is viral
Deep lingual: tip of tongue
I think we agreed on this:
-the deep lingual artery supplies the tip of the tongue
-the lingual nerve (branch of V3) provides general sensory innervation to tip
-chorda tympani provides taste fibers to the tip
Brachial plexus question
Brachial Plexus (from medial to distal):
Roots (anterior rami of spinal nerves C5, 6, 7, 8, and T1)
Trunks (superior, middle, inferior)
Divisions (anterior and posterior of each trunk)
Cords (lateral, posterior, and medial)
Branches
Nucleus solitarius: taste
Chemoreceptors and baroreceptors inputs reach the nucleus solitarius bringing and
processing sensory visceral inputs to cranial nerve nuclei of X and IX (eg. from the
carotid body and sinus) via the solitary tract.

The nucleus solitarius also processes taste afferents. These visceral sensory inputs
enter at the medullary level to reach the solitary tract nucleus from VII (ant 2/3 portion
of tongue), IX (posterior 1/3 of tongue), and X (back of throat, including the
epiglottis). Some somatic input (eg. touch) also travels in through these nerves to
terminate in the spinal trigeminal nucleus. It is also interesting to note that the nucleus
solitarius collaborates with the reticular formation and is the major sensory component
of the medullary respiratory center and of the ill-defined cardiovascular center.

Tumor of infancy: hemangioma

-an extremely common benign tumor, occurring most commonly in infancy and
childhood, made up of newly formed blood vessels, and resulting from malformation of
angioblastic tissue of fetal life. There are two main types: capillary and cavernous. 2. a
general term denoting a benign or malignant vascular tumor that resembles the classic
type of hemangioma but occurs at any age.
Hodgkins and non-hodgkins
Hodgkin's lymphoma is a malignancy (cancer) of lymph tissue found in the lymph
nodes, spleen, liver, and bone marrow. The first sign of this cancer is often an enlarged
lymph node which appears without a known cause-extranodal is rare. The disease can
spread to adjacent lymph nodes and later may spread outside the lymph nodes to the
lungs, liver, or bone marrow.
*Presence of Reed-Sternberg (RS) cells: giant histiocytic cells, typically multinucleate,
most often binucleate with the two halves of the cell appearing as mirror-images of each
other; the nuclei are enclosed in abundant amphophilic cytoplasm and contain prominent
nucleoli. The presence of the cells is the common histiologic characteristic of Hodgkin's
disease.
The cause is not known. The incidence is 2 in 10,000 people. Hodgkin's lymphoma is
most common among people 15 to 35 and 50 to 70 years old. Symptoms:

Painless swelling of the lymph nodes in the neck, armpits, or groin (swollen
glands)
Fatigue
Fever and chills
Night sweats
Weight loss
Loss of appetite
Generalized itching

50% cases associated with EBV

Non-Hodgkin's lymphomas are cancers of lymphoid tissue (lymph nodes, spleen, and
other organs of the immune system). Non-Hodgkin's lymphomas can be slow-growing
(low-grade) or rapidly growing (high-grade) cancer. For most patients, the cause is
unknown, but lymphomas may develop in people with suppressed immune systems as a
result of organ transplantation or HIV, for instance.
It is characterized by multiple peripheral nodes with common extra-nodal involvement
without spreading. Usually involves Bcells and occurs in persons age 20-40 yrs.

Five Types:
Small lymphocytic lymphoma (occurs mainly in adults and affects B cells)
Follicular lymphoma (occurs mainly in adults and affects B cells; genetic mutation bcl2)
Diffuse large cell (usually occurs in older adults with 20% in children80% B cells and
20% T cells)
Lymphoblastic lymphoma (occurs most often in children and affects immature T cells)
Burkitts lymphoma (occurs most often in children and affects B cells; genetic mutation
c-myc)
Symptoms:

Enlarged lymph nodes (such as an armpit lump), isolated or widespread

Fever
Excessive sweating, with night sweats
Unintentional weight loss

What is this cross section of brain: saw ventricles and pons and midbrain saggital?
Tunica intima, media and adventitia, whats in each and the composition;
-Tunica intima is composed of a lining layer endothelium that sits on the basal lamina.
-Tunica media is the middle layer and is composed predominantly of smooth muscle
reinforced by organized layers of elastic tissueelastic laminae; very prominent in
arteries.
-Tunica adventitia is collagen and loose CT but smooth muscle cells may be present;
most prominent in veins.
Tympanic membrane is lateral wall of ear
Boundaries of the middle ear cavity include:
-Roof (tegmental wall) -petrous part of temporal bone
-Floor (jugular wall)-separates space from internal jugular gein
-Lateral (membranous wall)- tympanic membrane (mostly)
-Posterior (mastoid wall)-lower part consists of bony partition between tympanic cavity
and mastoid air cells; upper portion is continuous with aditus to the mastoid antrum
-Anterior wall-lower part is thin later of bone separating tympanic cavity from internal
carotid artery; superior wall containing opening for entrance of pharngotympanic tube
and opening for tensor tympani muscle; this is also where chorda tympani exits.
Middle ear is what part of temporal bone? Petrous is inner and tympanic is middle
-Arcuate eminence (rounded protrusion near superior ridge of the petrous part of the
temporal bone) lies right over the anterior semicircular canal of the inner ear.

-Tegman tympani (depression that is anterior and lateral to arcuate eminence) is thin
bony roof above middle ear cavity.
Alpha fetoprotein- tumor marker for hepatocellular tumor?
AFP normally made by fetus detected in amniotic fluid. Increased amounts is tumor
marker for hepatocellular carcinomas and neural tube defects as well as Edwards
syndrome (trisomy 18).
What is found in striated ducts?
cytoplasm with basophils
lots of granules in the apical portion
Know boundaries of temperatures
Autoclaving 250 F (121 C) for 15-20 minutes
Dry heat 320 F (160 C) for 2 hours or 340 F (170 C) for 1 hour

0.3% glutaraldehyde is best used as a?

a. Immersing agent (usually 2% is used for 10 hours)
b. disinfectant for inanimate surfaces because 0.3% is too dilute?
Which cleaning agent has the broadest spectrum of cleaning?
ethanol
isopropyl alcohol
others (iodine?)
What is best for lipophilic and lipophobic substances?
Lipophilicuse cationic detergents
Lipophobicuse anionic detergents

In wound healing, myoepithelial cells come from or do what?

from stiated muscles
smooth muscles
help to bring wound together
Bone metastasizes to liver?
Things that metastasize to the liver: Colon>Stomach>Pancreas>Breast>Lung
(Cancer Sometimes Penetrates Benign Liver)
Things that metastasize to bone: Breast, Lung, Thyroid, Testes, Kidney, Prostate
(BLT with a Kosher Pickle)
-metastases from breast and prostate are most common
What is found in the deep dermis?
Deep dermismaybe she means hypodermis since thats the layer below the dermis.

The hypodermis contains:

loosely arranged elastic fibres

fibrous bands anchoring skin to deep fascia
fat:
o absent in eyelid, scrotum, penis, nipple and areola
o distribution is a secondary sexual characteristic: it forms the breasts of
females and accentuates the contour of female hips
blood vessels on route to dermis
lymphatic vessels on route from dermis
hair follicle roots
the glandular part of some sudiferous glands
nerves:
o free endings
o Panicinian corpuscles
bursae: only in the space overlying joints in order to facilitate smooth passage of
overlying skin
sheets of muscle: panniculus carnosus

What is not found in the pulp?

Lipocytes (these are fat-storing stellate cells of the liver)
lymphocytes
undifferentiated mesenchymal tissue
collagen
Lots on what drains into which lymph node (submandibular, submental, deep cerivical)
-lymphatics from the submandibular and sublingual glands drain mainly into the
submandibular nodes and then into deep cervical nodes
-submental nodes inferior and posterior to chindrain lymphatics from the medial part
of the lower lip and chin bilaterally; anterior teeth
-submandibular nodes superficial to the submandibular gland and inferior to the body of
the mandibledrain from the medial corner of the orbit, most of the external nose,
medial part of the cheek, upper lip and lateral part of lower lip that follow the course of
the facial artery; posterior teeth
-deep cervical nodesdrains lymph from the nasal cavity and the paranasal sinuses as
well as receiving lymph from the submental and submandibular nodes (which receives
lymphatics from the tongue and dentition)
The 2nd, 3rd, 4th right intercostals veins drain into?
azygous vein
hemi azygous vein (this would drain the left)
superior vena cava
inferior vena cava

Which artery has the same distribution as the pterygoid venous plexus?
maxillary artery
All are nerves of V2 except?
greater palatine
intraorbital
auriculotemporal V3
PSA
Main difference b/w coronal dentin and radicular dentin is?
a.. granular layer of Tomes (hypomineralized area of radicular dentin)
If a person has a fever, what enamal defect can be seen?
enamel tuft
enamel lamellae
enamel spindle
striae of Retzius
Enamel tuft: Areas of increased organic content that do not reach the free surface are
known as "enamel tufts." These arise from the DEJ (dentinoenamel junction) and
extend a short way into enamel. It is likely that enamel tufts are caused by abrupt
changes in rod direction on the corrugated dentinal surface (remember that dentin is
laid down before enamel).
Enamel lamellae: In many teeth there are areas (clefts) of increased organic content that
extend through the thickness of enamel. These imperfections are known as "enamel
lamellae." Some believe these are caused by clefting of enamel blocks to relieve
stress (organic matter not removed). There is a potential for microorganisms to gain
access to these lamellae causing dental caries.
Enamel Spindle: Since dentin is laid down before enamel, it is possible for odontoblastic
processes to be trapped in newly formed enamel matrix. The resulting appearance is
characteristic of "enamel spindles."

Repiratory quotient of 0.7 what does this show?

protein
nucleic acid
fat (see explanation below)
glucose

Example: In humans, the use of fats as a fuel source is quantitatively more important than
glucose. The general formula for a saturated fat is (CH2O)3(CH2)3n(CO2H)3 . For
example, if we take n = 17 we have the formula for the fat glycerol tristearate. We can
simplify the formula for a fat to write the following respiration equation:
C3n+6H6n+9O9 + (4.5n + 3.75)O2 --> (3n + 6)CO2 + (3n + 4.5)H2O
We can now calculate the respiratory quotient for a saturated fat. Since n is generally
quite large, we will approximate the respiratory quotient as

RQ = (3n + 6) / (4.5n + 3.75) -> 3n / 4.5n = .667

What is Von Ebners gland associated with?

circumvallate papillae
What is most commonly seen on the dorsum of the tongue in a seven year old?
fungiform papillae
filliform papillae
All are muscles of the rotator cuff except
teres major
teres minor
supraspinatus
intfrasinatus
subscapularis
All can be found in the posterior mediastinum except?
thoracic duct
esophagus
anterior interventicular artery (of the heart) which is located in the middle
mediastinum
If looking the mesial proximal view of a canine and it is bisected longitudinally at the
apex the line will be
lingual to the cusp (if its a maxillary canine, because the cusp tip is buccal to the
root axis)
mesial to the cusp
bisect at the tip of the cusp
*the cusp tip of a mandibular canine is lingual to the root axis
What part of the brain is the midbrain?
prosencephalon
mesencephalon
myelencephalon (medulla oblongata)
telonecephalon (cerebrum)
What becomes the copula? (brachial arch?)
copula linguae, a median ventral elevation on the embryonic tongue formed by union
of the second pharyngeal arches; it represents the future root of the tongue.
The ectomderm of the stomadeum and endoderm of the pharynx form what?
buccopharyngeal membrane

Where does the left coronary artery come from?

superior to the left aortic cusp on the ascending aorta
or inferior
What sinus is below the crista galli?
ethomidal sinus
sphenoid sinus
Which has an artery surrounded by lymphoid tissue?
spleen
lymph node
renal something
What is not part of the portal system in the liver?
portal vein
hepatic artery
central vein
bile canaliculi
What is cancerous?
divericulum
peutz-jeghers syndrome
villi adenoma (adenomas are benign)
tubular adenoma
Peutz-Jeghers syndrome is an autosomal dominant inherited disorder characterized by
intestinal hamartomatous polyps in association with mucocutaneous melanocytic macules.
The characteristic pathology of Peutz-Jeghers polyps includes extensive smooth muscle
arborization throughout the polyp with the appearance of pseudoinvasion because some
of the epithelial cells, usually from benign glands, are surrounded by the smooth muscle.
A 15-fold elevated relative risk of developing cancer exists in this syndrome over
that of the general population; cancer primarily is of the GI tract, including the
pancreas and luminal organs, and of the female and male reproductive tracts and
the lung.
What is collagen hydroxylated? Non-hydroxylated collagen is called procollagen.
What is in the anterior mediastinum?
-area anterior (part of the inferior mediastinum partitioned by the pericardial sac) to the
pericardial sac and posterior to the body of the sternum. The anterior mediastinal
compartment is bordered by the sternum anteriorly, and the ventral cardiac surface
posteriorly. This compartment contains fat, ascending aorta, lymph nodes, internal
mammary artery and vein, adjacent osseous structures (ribs and sternum), thymus.
Chorda tympani ganglion? geniculate

Preganglionic cell bodies of the head?

Sympathetics: sympathetic chain T1-L2
Parasympathetics: in brain stem nuclei
III-Edinger-Westphal Nucleus
VII- Superior Salvatory nucleus
IX- Inferior Salvatory Nucleus
X- dorsal nucleus of the vagus (the secretomotor parasympathetic nucleus)
Tertiary sensory neurons are located where?
Tertiary sensory neurons have cell bodies in a specific sensory nucleus of the thalamus
and send axons to the primary somatosensory cortex.
Where does aldosterone act on?
It diminishes the secretion of Na+ ions and therefore, water and stimulates the secretion
of K+ ions through the kidneys by working on the Na+/K+ pump located on the kidney
collecting ducts.
Most concentrated part of the kidney?
Base of the loop of henle
PTH leads to?
PTH acts to increase the concentration of calcium in the blood in three ways. It enhances
the release of calcium from the large reservoir contained in the bones; it enhances
reabsorption of calcium from renal tubules; and it enhances the absorption of calcium in
the intestine by increasing the production of 1,25-DiHydroxy vitamin D3.
If no bile then no ADEK?
Obstruction of bile flow in the duodenum interferes with digestion of fat, causes pale
stools and failure in the absorption of fat soluble vitamins (ADEK).
What hormone has intracellular long term effects?
estrogen
What genera of fungi effects skin, nail hair (tinea no an answer choice)?
Tinea is not an answer choice so maybe the following might have been on there:
Trichophyton species (19 species) Figure 9.
These infect skin, hair and nails. Rarely can cause subcutaneous infections, in
immunocompromised individuals. Take 2-3 weeks to grow in culture. The conidia are large
(macroconidia), smooth, thin-wall, septate (0-10 septa), and pencil-shaped; colonies a re a loose
aerial mycelium which grow in a variety of colors. Identification requires special biochemical and
morphological techniques (figure 10). Trichophyton rubrum is presently the most common cause of
tinea in South Carolina.

Microsporum species (13 species). These may infect skin and hair, rarely nails. Its prevalence has
decreased significantly. When prevalent (15-20 years ago), this organism could be easily identified
on the scalp because infected hairs fluoresce a bright green color when illuminated with a UVemitting Wood's light. The loose, cottony mycelia produce macroconidia (figure 11) which are thickwalled, spindle-shaped, multicellular, and echinulate (spiny). Microsporum canis is one of the most
common dermatophyte species infecting humans.
Epidermophyton floccosum. These infect skin and nails and rarely hair. They form yellow-colored,
cottony cultures and are usually readily identified by the thick, bifurcated hyphae with multiple
smooth, club-shaped macroconidia.
Where does glycolysis take place?
cytoplasm
Chicken Pox is latent where?

VZV is latent in sensory nerve ganglia including the dorsal root spinal ganglia
and the geniculate ganglion of each VII cranial nerve.
During this time the host defences are unable to detect and eliminate HSV from
the body.
o Accordingly, VZV infections are lifelong.
o Latent VZV is in an inactive state that is not directly toxic to the cell.
In contrast to primary infection, there is no cell lysis or indirect
cell damage due to inflammation.
In some individuals, HSV can be reactivated from a latent state and become
manifested as singles.

ANUG
Acute necrotizing ulcerative gingivitis: This is trench mouth (due to being common
among soldiers during WWI), a progressive painful infection with ulceration, swelling
and sloughing off of dead tissue from the mouth and throat due to the spread of infection
from the gums.
-Often associated with stress and/or smoking
-It may involve certain bacteria such as fusiform bacteria and spirochetes.
-It is a rare condition that affects people between the ages of 15-35.
-It is also known as acute membranous gingitivitis, fusospirillary gingivitis,
fusospirillosis, fusospirochetal gingivitis, Vincents gingivitis, etc.
Hand, foot, mouth disease cause by what? Coxsackie A
Clench down tight, what muscle protects the TMJ?
lateral pterygoid
Collagen Type 1 is located in the pulp

What would cause the heart to beat faster? Sympathetic innervation

How to distinguish between #30 and #31 teeth? Distal cusp on number 30
Know the ganglions of the head really well.
Parasympathetic Ganglia
-Ciliary Ganglion
Preganglionic fibers from oculomotor nerve (CN III)
Innervates sphincter pupillae (constriction) and ciliary muscles
(accommodation)
-Pterygopalatine Ganglion
Preganglionic fibers from facial nerve (CN VII) via the greater petrosal nerve
Innervates the lacrimal gland (pterygopalatine ganglionmaxillary
nervezygomaticotemporal nervelacrimal branch of ophthalmic nerve)
Innervates the mucous glands of the nasal cavity (pterygopalatine
ganglionpharyngeal/nasopharngeal branch)
Innervates the maxillary sinus (pterygopalatine ganglionnasal branch)
Innervates the palate (pterygopalatine ganglionlesser and greater palatine
nerves)
-Otic Ganglion
Preganglionic fibers from glossopharyngeal nerve (CN IX)
Innervates parotid gland (lesser petrosal V3 otic ganglion
auriculotemporal nerve)
-Submandibular Ganglion
Preganglionic fibers from facial nerve (CN VII) via chorda tympani
Innervates submandibular and sublingual glands (chorda tympanilingual
nerve submandibular ganglion)

Know the boarders of the intratemporal and pterygoid fossa

What makes up the posterior portion of the Circle of Willis?
Vertebral artery
The urine is more acidic, what hormone is being produced more?
Metabolic acidosisincreased insulin production and PTH production (which
upregulates bicarbonate excretion)
Cross section of the brain (coronal) midbrain, pons
Tympanic membrane-lateral wall of the middle ear
Middle ear- tympanic part of temporal bone
Inner ear- petrous part of temporal bone

Left condyle broken and deviates to the left why?

muscle collateral ligament
C3b opsonizes
Phrenic nerve runs on top of anterior scalene. Brachial plexus runs in between anterior
and middle scalene muscles.
Most common cause of death in peptic ulcer?
perforation
Unpaired branches of the abdominal artery are?
The N-terminal of protein is for what functional use?
attach to RER
What is secreted in saliva that is antibactericidal? Lysozyme, also present in tears and
sweat
All symptoms of Chlamydia except?
pruritis?
Intrafusal fibers maintain the posture of the jaw
Sigmoid sinus drains into internal jugular vein
Radial nerve originates from the posterior cord of the brachial plexus.
All of the following are located in the midcranial fossa except?
jugular foramen
How does acyclovir work?
-marketed as Zovirax
-Mechanism: Preferentially inhibits viral DNA polymerase when phosphorylated by viral
thymidine kinase (which is far more effective in phosphorylation than cellular thymidine
kinase).
-Clinical use: HSV, VZV, EBV, Mucocutaneous and genital herpes lesions. Prophylaxis
in immunocompromised patients.
-Toxicity: Delirum, tremor, nephrotoxicity.

How does antihistamine work?

An antihistamine is a drug which serves to reduce or eliminate effects mediated by
histamine, an endogenous chemical mediator released during allergic reactions, through
action at the histamine receptor. Only agents where the main therapeutic effect is

mediated by negative modulation of histamine receptors are termed antihistamines - other

agents may have antihistaminergic action but are not true antihistamines.
In common use, the term antihistamine refers only to H1-receptor antagonists, also
known as H1-antihistamines. It has been discovered that these H1-antihistamines are
actually inverse agonists at the histamine H1-receptor, rather than antagonists per se
The base of DNA is bond to the sugar by what type of bonds?
ester
covalent
hydrogen
phospodister
How do you over come inhibiton?
increase substrate
Vitamin B1- heat contracting?
thiamine
Vitamin K deficiency cannot produce active forms of clotting factor in liver
How is prothrombin activated?
gamma carboxylation
How do you make NADPH? HMP Shunt
If bacteria does not have catalase then in cannot tolerate H2O2 true
Pilus is used for attachment during conjugation
Know the direction of enamel rod oriented perpendicular to tooth surface
Where does beta oxidation occur?
mitochondria
Most common bacterial meningitis? Streptococcus pneumoniae (pneumococcus). This
bacterium is the most common cause of meningitis in infants and young children in the
United States. It most often occurs when the bacterium enters your bloodstream and
migrates to your brain and spinal cord. You may also have this type of bacteria in your
lungs, where it causes pneumonia. Pneumococcal meningitis may also be associated with
an ear infection. In these cases, it's not clear which came first the meningitis or the ear
infection since they usually occur together.
Other bacteria that cause meningitis are: Neisseria meningitides, Haemophilus influenzae,
and Listeria monocytogenes.
All of the following has endo or exotoxin except?
tuberculosis

Coccidioides immitans infects the lungs

Rubella virus causes congenital defects
HbE-Ag indicates infectivity a second, different antigen in the HBV core. It is an
important indicator of transmissibility.
A disadvantage of autoclave is that it dulls instruments
Deep caries is lactobacillus
Sabarouds agar is for fungi
HLA-B27 is a defect in what disease? Whipples disease/Whipples arthritis
HLA-DR3 is a defect in what disease? Diabetes mellitus Type I
Calculate MAP, osmolarity, filtration/absorption
Mean Arterial Pressure MAP=DBP + PP/3
Osmolarity: moles/Liter
Glomerular Filtration Rate (GFR)= Kf (forces inducing filtration-forces opposing
filtration)
Forces inducing filtration: hydraulic pressure in capillaries - oncotic pressure in
bowmans capsule
Forces opposing filtration: hydraulic pressure in bowmans capsule - oncotic pressure in
capillaries
Know why SLE happens
Systemic Lupus Erythematosis
Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by
immune dysregulation resulting in the production of antinuclear antibodies (ANA),
generation of circulating immune complexes, and activation of the complement system.
SLE is notable for unpredictable exacerbations and remissions and a predilection for
clinical involvement of the joints, skin, kidney, brain, serosa, lung, heart, and
gastrointestinal tract. The pathologic hallmark of the disease is recurrent, widespread, and
diverse vascular lesions.
Basicallyproduction of antibodies against nucleus of own cells
Innervation of TMJ
masseteric nerve
-The TMJ receives its nervous innervation via the auriculotemporal branch of V3 as
well as masseteric branches. The arterial supply is from the superficial temporal artery
and the maxillary artery.

Know all three branches of the maxillary artery.

Internal maxillary artery is divided into mandibular, pterygoid, and pterygopalatine
portions.
Addisons disease
-Primary deficiency of aldosterone and cortisol due to adrenal atrophy, causing
hypotension and skin hyperpigmentation
-Characterized by Adrenal Atrophy and Absence of hormone production; involve All 3
cortical divisions
-Secondary deficiency has no skin pigmentation
Cushings disease
-Increased cortisol due to a variety of causes
-Characterized by hypertension, weight gain, moon facies, truncal obesity, buffalo hump,
hyperglycemia, skin changes, osteoporosis, and immune suppression
Myxedema-hypothyroidism marked by dry skin and swellings around lips and nose as
well as mental deterioration
24 hours after myocardioinfarction
a. PMN and necrosis
Most common symptoms of esophageal varices?
Hemoptypsis-coughing up blood
Most common leukemia in kids?
ALL (acute lymphoblastic leukemia)
Horner Syndrome Triad is? Ptosis (slight drooping of eyelid), Anhidrosis (absence of
sweating and therefore flushing of affected side of face), Miosis (pupil constriction)
What most likely metasizes to the jaw? Breast cancer
The jaw metasizes to where? Not sure about this one but heres something about jaw
neoplasms:
If not initially detected on x-ray, jaw tumors are diagnosed clinically because their
growth causes swelling of the face, palate, or alveolar process (the area of the jaw around
the teeth). They cause bone tenderness and severe pain originating in the affected bone.
-Ameloblastoma, the most common epithelial odontogenic neoplasm, usually arises in
the posterior mandible; it is slowly invasive but rarely metastatic. On x-ray, it typically
appears as a multiloculated or soap-bubble radiolucency. Treatment is aggressive surgical
excision.
-Odontoma, the most common odontogenic neoplasm, is a tumor of the dental follicle or
the dental tissues that usually appears in the mandibles of young persons. Odontomas

include fibrous odontomas and cementomas. An absent molar tooth suggests a composite
odontoma. No treatment is usually needed for odontoma, although they are excised when
the diagnosis is in doubt. Osteosarcoma, giant cell tumor, Ewing's tumor, multiple
myeloma, and metastatic tumors may affect the jaw. Treatment is the same as that for
tumors in other bony sites.
Heres a weblink about malignant jaw tumors:
http://www.usc.edu/hsc/dental/opfs/SA/indexSA.html
Which layer is keratohyaline granules found?
Stratum lucidum
PKU enzyme is? Phenylalanine hydroxylase
Cystic Fibrosis is? Defective chloride ion transmembrane channel of exocrine
glandsviscous secretions; diagnosis by increased sodium chloride in sweat
-an autosomal recessive defect in the CFTR gene on chromosome 7.

Down Syndrome
-trisomy 21
-cause of congenital mental retardation
-decreased levels of AFP (alpha-fetoprotein tumor marker)
-characteristics: mental retardation, flat facial profile, prominent epicanthal folds, simian
crease, duodenal atresia, congenital heart disease, and Alzheimers in individuals greater
than 35 years old.

Tumor of infancy
Neuroectodermal Tumor of Infancy- benign, usually pigmented neoplasm commonly of
the anterior maxilla and composed of two cell types arranged in alveolar patterns and
derived from embryonic neural crest tissue. There is a genetic etiology to this and
treatment involves surgical excision.
Hemangioma- benign angioma consisting of a mass of blood vessels; some appear as
birthmarks; occurs most commonly in infancy and childhood resulting from
malformation of angioblastic tissue of fetal life; two main types: capillary and cavernous
Bifid tongue is due to? Cleft tongue common in tongue piercings
Know the different types of pneumonia
Lobar Pneumonia- most frequently caused by Pneumococcus; intra-alveolar exudates
leads to consolidation; may involve the entire lung
Bronchopneumonia- caused by Staph aureus, H. flu, Klebsiella, S, pyogenes; acute
inflammatory infiltrates from bronchioles into adjacent alveoli; patchy distribution
involving more than one lobe

Interstitial (atypical) pneuomonia- mainly caused by viruses; diffuse patchy

inflammation localized to interstitial areas at alveolar walls with distribution to more than
one lobe
In SCID, what is defective? bubble boy diseaseX-linkedlack of lymphocytes
(cellular component)
Wilms Tumor most common kidney tumor in kids
Wilms tumor is a cancerous tumor on the kidney. Also called nephroblastoma, it is the
most common form of kidney cancer in children, although it is totally unrelated to adult
kidney cancer. The kidneys are located at the back of the abdominal cavity, to the left and
to the right of the backbone. They serve to filter the blood and rid the body of excess
water, salt, and waste products.
Retinoblastoma- loss of Rb gene tumor suppressor activityrecessive
What is the most likely symptom of renal carcinoma?
a. hemauria
A patient doesnt have liver disease but has jaundice, what kind of bilirubin? What kind
of jaundice?
a. biliary duct obstruction
Legionella
-Legionaires disease
-Caused by Legionella pneumophila, a gram negative rod
-Gram stains poorly therefore use silver stain
-Grow on charcoal yeast extract culture with iron and cysteine
-Aerosol transmission from environmental water source habitat
-No person to person transmittion
-Treat with erythromycin
Hemophilia
A- deficiency in factor VIII production (increased partial thromboplastin time)
B- deficiency in factor IX (increased PTT)
What bacteria cause lung abcess?
Staph
Enamel tuft
fan shaped hypocalcification from the DEJ
Which can you not see from the surface of enamel?
enamel tuft

What hypersensitivity is Goodpastures disease Type II hypersensitivity

Know hypersensitivity of Type 1, 2, 3
Type 1
Antigen: extrinsic (non-self), non-cellular
Ab: IgE
Cell: basophil and mast cells
Chemical: histamine
i.e. anaphylactic shock from rxn to penicillin
Type 2
Antigen: intrinsic or extrinsic, tissue-associated
Ab: IgG or IgM (target tissue)
Cell: Neutrophils
Chemical: Complement
Site of damage: target tissue of antibody
i.e. blood transfusion reactions, Goodpastures disease
Type 3 a.k.a. serum sickness
Antigen: intrinsic of extrinsic, soluble
Ab: IgG
Cell: Neutrophils
Chemical: Complement
Site: Concentration tissues
i.e. post-streptococcal glomerulonephritis-antigen against strep deposit in kidneys
Type 4 a.k.a. autoimmune disease
Antigen: extrinsic, non-cellular
Ab: none
Cell: Lymphocytes
Chemical: cytokines
i.e. myasthenia gravis- antibody against Ach receptor
Pagets Disease (osteitis deformans)
-increased hydroxyproline in urine due to osteoclast activity
-increased alkaline phosphatase markers
-enlarged deformed bones
-usually occurs with persons greater than age 40
-bone pain is adjacent to joints
-treatment with bisphosphonates (to inhibit resorption of bone)
ADH secreted from pars nervosa but made in the hypothalamus
Hyperparathyroidism and hypoparathyroidism and what they do to the kidneys

Hyperparathyroidismkidney stones due to increased calcium excretion

Hypoparathyroidismno critical damaging effects to kidneys; risk would be due to
overtreatment; increased phosphate excretion can have effect on blood pH
Ulnar nerve is what root of the brachial plexus?
C8-T1
Know which organs are Retroperitonial
Kidneys
Adrenal glands
Pancreas
Abdominal aorta
Testes
Ascending colon
Descending colon
ureters
Where does the chorda tympani exit?
pterygotympanic fissure (temporal bone)
Middle meingeal artery exits which foramen?
foramen spinosum
Pterygomaxillary fissure
-in medial wall of infratemporal fossa (lateral plate of pterygoid, pharynx, and two
muscles of soft palate)
-allows structures to pass between the infratemporal and pterygopalatine fossa
-maxillary artery passes through this to enter pterygopalatine fossa from the
infratemporal fossa
Pterygopalatine ganglion
-Receives preganglionic sympathetics from Deep Petrosal Nerve
-Receives preganglionic parasympathetics from Greater Petrosal Nerve (CN VII)
-Sends postganglionic parasympathetics nasopalatine nerve, lesser palatine nerve,
greater palatine nerve, lacrimal nerve
-Relays general sensory from V2 through greater palatine nerve to innervate hard palate
The artery (sphenopalatine artery) that supplies the nose enters the nasal cavity
through?
sphenopalatine foramen
What does Meckels cartilage become?
1st branchial arch-->sphenomandibular ligament, anterior malleolar ligament, malleus,
incus
Hyaline cartilage in trachea and all synovial joints

Fibrocartilage in TMJ and vertebral discs

The buccal nerve of facial nerve innervates what?
buccinator
Long buccal nerve is a branch of V3 and it innvervates the buccal mucosa
Which does not have a latent period?
Herpes
HIV
Polio (answer)
Patient gets vaccine of live tetanus virus
active artificial immunization
Most characteristic of Actinomycetes
abscess
The characteristic muscles of a marathon runner slow-oxidative fibers
myosin ATPase activity low
with High oxidative capacity
mitochondria
Last enzyme in glycogenolysis phosphoglucomutase which converts G1P to G6P
Not directly synthesized from pyruvate?
PEP
If the mandibular and maxillary canine contact each other, where is the position of the
right condyle?
away from medial surface of the temporal bone
against the articular eminence
From ICP to right laterotrusion #6 could potentially contact? #26
What happens when there is no oxaloactetate? Decrease TCA flux
Bacteria that can use glycoxylate (?) pathway unique because can use what as sole carbon
source?
pyruvate succinate
someone looked up E coli can grow on acetate
Glyoxylate pathway
-Plants (process located in specialized peroxisomesglyoxysomes) and bacteria use this
pathway to grow solely on acetate

-Conversion of acetyl CoA to result in net increase in malate or oxaloacetate, which is

not possible with the TCA cycle alone. Two acetyl CoA are input per cycle with no loss
of CO2, making possible net synthesis of a 4-carbon product.
-The two additional enzymes of the glyoxylate cycle are isocitrate lyase and malate
synthase.

The physiologic dead space volume is equal to what?

a. tidal volume
b. residual volume
c. unperfused alveoli
d. trachea and bronchi
What best characterized Rubella?
Koplicks Spots
Not happening in developed nations
Teratogenic if acquired in first trimester of pregnancy
Pterygopalatine fossa opens into the nasal cavity via?
spheonopalatine foramen

The parathryroids are mostly supplied by what artery?

Inferior thryroid artery
What is the main function of the tunica adventitia of medium arteries?
Controls blood flow to capillary networks

Know how to calculate pH (no calculator allowed)

What does Type 1 and Type 4 hypersensitivity reactions have in common?
Antigen is non-cellular and extrinsic
What represents conduction from SA to AV node?
PR interval
A man has loss of control of facial musculature below the zygomatic arch on one side of
his face, where is the lesion?
a. know its CN 7
Know enterogastric reflex
- distention and irritation of the small intestine results in suppression of secretion and
motor activity in the stomach
-presence of fatty acids and amino acids causes small intestine secretes cholecystokinin
(CCK)
Where does the anterior jugular vein originate? In what triangle?
-may open into external jugular vein or subclavian vein
-receives tributaries from laryngeal veins and occasionally small thyroid vein
-located in anterior triangle of neck: bounded, in front, by the middle line of the neck;
behind, by the anterior margin of the Sternocleidomastoideus; its base, directed upward,
is formed by the lower border of the body of the mandible, and a line extending from the
angle of the mandible to the mastoid process; its apex is below, at the sternum.
DNA ligase is involved in all of the following except?
a. transcription
b. replication
c. repair
d. recombination
Nerve of the pterygoid canal is the greater petrosal and deep petrosal nerve and
components a.k.a. Vidians nerve

Sympathetic stimulation what would NOT happen?

a. papillary constriction (answer)
b. increase HR
c. increase respiration
d. skin would feel warm to touch
Sudden complete occlusion of artery is what type of necrosis?
Fibrinoid (some looked up and says this)
Coagulativedue to sudden ischemia

Is the buccinator only muscle pierces in an IA?

yes
It is also innervated NOT by the long buccal nerve, but by the deep buccal branches of
CN 7.
What stage in embryogenesis is the inner mass cells found?
Inner cell mass a.k.a. Embryoblast
-present in blastocyst formation
Person has lower face paralysis what is the cause?
a. LMN disorder
Cross section of the brain
a. pons, midbrain, medulla?
What will form NADPH?
pentose phosphate cycle
What produces IL-1
a. macrophages
b. neutrophils
AIDS or HIV affect what type of cells?
CD4
Calcium what are its function? Binds troponin C, blood clotting, functions in cardiac
muscle contractility, maintains bone density
Calcium hormone regulation
Thyroid gland C cellsCalcitonin reduces blood calcium levels in three ways:

decreasing calcium absorption by the intestines

decreasing osteoclast activity in bones
decreasing calcium reabsorption by the kidney tubules

Parathyroid hormone acts to increase the concentration of calcium in the blood in three
ways. It enhances the release of calcium from the large reservoir contained in the bones;
it enhances reabsorption of calcium from renal tubules; and it enhances the absorption of
calcium in the intestine by increasing the production of 1,25-DiHydroxy vitamin D3.

Cancer stages, oncogenes, know everything

Stage O: The cancer is located only in a precise tumor and is not invading
the organ.
Stage I: The cancer is limited to the tissue or organ of origin.

Stage II: There is a limited, local spread of cancer.

Stage III: There is an extensive local and regional spread of cancer.
Stage IV: The cancer has spread (metastasized) to a distant part of the
body.

-Initially start with hyperplasiasquamous metaplasiaintraepithelial neoplasia

(progressive dysplasia of cells and carcinoma categorized by three Grades)
-Grade 1: Very MildMild
-Grade 2: Moderate
-Grade 3: SevereIn situ

Benign smooth muscle cancer is leiomyoma

Choose a benign cancer out of 5
What type of epithelium is found in the ureters and renal pelvis?
transitional epithelium
The glands that are purely serous are parotid and Von ebners gland
6 year old with standing hair on end with radiograph and enlarged spleen has what type
of disease?
a. sickle cell anemia (I highly doubt this is the answer should cause atropic spleen.
Its some type of blood cancer)
-the answer should be thalassemia
Height of contours of multiple teeths
-Anterior teethfacial and lingual heights of contour in cervical third
-Premolarsbuccal height of contour is cervical third; lingual height of contour in
middle third
-Maxillary Molarsbuccal height of contour is cervical third; lingual height of contour is
middle third
-Mandibular Molarsbuccal height of contour is cervical third; lingual height of contour
is middle
Mandibular canine versus maxillary canine
Maxillary canine
-longest root
-bulky crown with prominent ridges
-well-developed lingual anatomy
-assymetry: mesial aspect like anterior tooh; distal is more like a posterior tooth
-distal cusp slope is longer and more rounded
Mandibular canine
-long, narrow crown with smooth lingual surface

-mesial cusp ridge much shorter than distal cusp ridge

-incisocervical crown length longer than for maxillary canine
-cusp tip is a bit more rounded and subject to attrition
-narrower
Know the primary mandibular first molar roots, canals and cusps. Comparison with
primary mandibular second molar.
Primary mandibular 1st molar
-mesial and distal roots
-mesial root is longer and wider
-apex of mesial root is flattened and squared off
-resembles no other permanent deciduous tooth
-four cusps MB>ML>DB>DL
-MB is acute and prominent because has cervical ridge
Primary mandibular 2nd molar
-closely resembles permanent mandibular 1st but smaller in all dimensions
-MB and DB cusps are nearly equal in size
-distal root is smaller
-mesial root is longer and wider

Multiple questions about excursive movements (no drawings)

When looking from a horizontal plane, what movement does the midline make when jaw
goes through laterotrusive movement?
2 pictures with Dr. Pullingers jaw opening/retursion. Can you see lateral movement on
the drawing?
Know contact points when patient is in Class 2 and Class 3
Class II-MB cusp of maxillary 1st molar aligns mesial to the MB groove of the
mandibular 1st molar (distoclusion)
Class III-MB cusp of maxillary 1st molar aligns distal to MB groove of mandibular 1st
molar (mesioclusion)
What will happen when a patients Class 2 becomes more overjet? Risk injury to
anterior teeth?
3 pictures of occlusal arch. Tell what tooth and cusps are contacting
Know what excursive contacts and interferences you will have. Know what would break
a cusp.
Picture of a right 1st premolar viewed from the facial. The movement shown is an arrow
moving up the mesial cusp ridge. What type of movement produced this result?

Protrusion?
What is considered is NOT a muscle of mastication but has a function in mastication?
a. Digastic
b. thyrohyoid
c. mylohyoid
Sublingual artery goes to the tip of the tongue
-Should be DEEP LINGUAL ARTERY
-the sublingual artery arises at the anterior margin of the hyoglossus and runs forward
between the genioglossus and the mylohyoid to supply the sublingual gland as well as
mucous membrane of mouth and gums
Which one isnt in the infratemporal fossa?

What separates the infratemporal fossa from the pterygopalatine fossa?

pterygomaxillary fissure
What innervates the circumvallate papilla?
CN 9
Which of the following is true?
the parotid is completely serous
the parotid is a mixed gland
the sublingual gland is completely serous
the submandibular gland is chiefly serous
the submandibular glandis chiefly mucous
Insertion and origin of the pterygomandibular raphe
the pterygoid hamulus and the mandible
The crista terminalis represents the primitive sinus venosus
Which artery supplies the SA node?
right coronary artery

What causes alveolar bone development?

the development of teeth
If you break the condyle the head of the condyle will still receive blood from?
a. the looked up answers say superficial temporal artery and maxillary artery
What produces synovial fluid? Synovial membrane

Synovial fluid is formed through an ultrafiltration process of serum by cells termed

synoviocytes, which form the synovial membrane. Synovial cells also manufacture the
major protein component of synovial fluid, hyaluronic acid, also termed hyaluronate.
Synovial fluid acts to provide nutrients to the avascular articular cartilage and to provide
viscosity for shock absorption with slow movements and elasticity for shock absorption
with rapid movements. The osteoarthritic joint is characterized by decreased
concentration of hyaluronic acid because of reduced production by synoviocytes and
increased water content as a result of inflammation, particularly during later stages of the
disease.
How does the non-vascular part of the TMJ obtain its nutrition?
a. direct from inferior alveolar artery
b. direct from superficial temporal artery
c. diffusion from a certain artery
d. osmosis via synovial fluid?
What causes the power stroke in the myosin head
a. the release of ATP
2 questions on the ansa cervicalis. It innervates the infrahyoid muscles except for
thyrohyoid. It consists of C2-4.
What will you hit if you go too posterior in an IA block?
a. parotid gland
Where is the trigeminal ganglion located?
a. sphenoid bone
b. petrous part of temporal bone
Where is the nucleus of the trigeminal ganglion located?
Pons
The ophthalmic artery is a branch of the internal carotid arterybecomes anterior
cerebral, middle cerebral in the circle of willis
What runs with the external jugular vein?
a. phrenic nerve
b. ansa cervicalis
c. vagus nerve
What empties into the left atrium?
pulmonary veins
What nerves exit the jugular foramen?
CN 9, 10, 11

The sphenoid bone is associated with all of the following except?

a. the middle earthe temporal bone
b. the orbit of the eye
c. infratemporal fossa
d. pterygopalatine fossa
e. cranium
What does the aorta have that is different from the inferior vena cava?
more elastic in the tunica media
Corticobulbar question
Upper motor neurons which innervate the muscles of the face and head are located near
the lateral fissure of the brain. Their axons coalesce to form the corticobulbar tract. These
axons then descend within the Genu of the internal capsule to the medial part of the
cerebral peduncle. The upper motor neuron axons then synapse on Lower motor neurons
of the cranial nerve nuclei which are located in midbrain, pons and medulla. This is a
pyramidal system.
Heres something about extra-pyramidal stuff we were wondering about:
The major parts of the extrapyramidal system are the "subcortical nuclei". This includes
the caudate, putamen, and globus pallidus which are also known as the Basal ganglia.
The caudate nucleus is especially affected in Huntington's chorea.
What artery supplies the medial pterygoid muscle?
a. pterygoid form maxillary artery
Innervation to the extensors and flexors of the forearm
Extensors: radial nerve
Flexors: Median and ulnar
Where does pain travel in the spinal cord?
a. lateral spinothalamic tract
The falx cerebri separates the hemispheres
The tentorium cerebelli sperates occipital lobe of the cerebrum from the cerebellum
An anxious patient sits in your dental chair, what is happening?
a. decreased chronotropy
b. decreased heart rate
c. increased inotrophy-myocardial contractility
Mesencephalic nucleus does proprioceptionunconscious proprioception to the jaw
Conscious proprioception to the chief sensory nucleus (from face to VPM of thalamus)
What type of collage in dentin?
a. Type 1

Brunners gland is located in the duodenumupper duodenumhistologically

distinguishes duodenum from stomach
What is NOT lined by stratified squamous?
a. maxillary sinusrespiratory epithelium (ciliated pseudostratified columnar)
b. epiglottis
c. buccal mucosa
Salivary ducts have what type of epithelium?
a. simple cubiodal
What is the anterior portion of the submandibular triangle?
anterior diagastric muscle
Innnervation for the TMJ is the auriculotemporal nerve and masseteric branches of V3
Blood supply is the superficial temporal artery and maxillary artery
What type of cartilage is the epiglottis?
elastic cartilage
What does the nasal bones develop from?
maxillary process?
The developmental precursors of the nose are the neural crest cells, which commence
their caudad migration toward the midface around the fourth week of gestation. Two
nasal placodes develop inferiorly in a symmetrical fashion. Nasal pits divide the placodes
into medial and lateral nasal processes. The medial processes become the septum,
philtrum, and premaxilla of the nose; whereas the lateral processes form the sides of the
nose. Inferior to the nasal complex, the stomodeum, or future mouth, forms.
What does the ala of the nose develop from?
From the lateral margins of the trabeculae carnii (a pair of prechordal cartilages in front
of the notochord), three processes grow out on either sideThe anterior part forms the
ethmoidal labyrinth and the lateral and alar cartilages of the nose.

A cut below C2 will impair breathingimpairs phrenic nerve innervation of the

diaphragm (C3-5)
Where does dopamine (also T3, T4, NE, E, melanin) from?
Tyrosine
Membrane potential is maintained through permeability of which ion?
K+
Why does glucose in the blood increase when alanine is released from muscle?

Alanine release from muscle cells indicates brief starvation and a need for production of
glucose via gluconeogenesis mainly by the liver (note that muscles are nongluconeogenic). L-alanine is synthesized in muscle cells from pyruvate by transamination.
Meanwhile, alanine is transformed into pyrvuate in the liver. This pyruvate is then
available for the synthesis of glucose via gluconeogenesis.

The glucose-alanine cycle is used primarily as a mechanism for skeletal muscle to

eliminate nitrogen while replenishing its energy supply. Glucose oxidation produces
pyruvate which can undergo transamination to alanine. This reaction is catalyzed by
alanine transaminase, ALT. Additionally, during periods of fasting, skeletal muscle
protein is degraded for the energy value of the amino acid carbons and alanine is a
major amino acid in protein. The alanine then enters the blood stream and is
transported to the liver. Within the liver alanine is converted back to pyruvate which is
then a source of carbon atoms for gluconeogenesis. The newly formed glucose can then
enter the blood for delivery back to the muscle. The amino group transported from the
muscle to the liver in the form of alanine is converted to urea in the urea cycle and
excreted.

What reflex occurs when you tap on the masseter?

stretch reflex
Which amino acid has a OH group?
serine
What amino acid can be produced from a hydroxylation of phenylalanine?

Tyrosine- a deficiency in this pathway causes phenylketonuriamental

retardation
Know the urea cycle
Synthesis of urea occurs in the liver and is the bodys way of getting rid of ammonia
(nitrogen buildup due to protein catabolism). Hepatocytes are able to perform this due to
the presence of arginosuccinase enzyme exclusively in the liver that cleaves arginine into
urea.
What molecule transfers fatty acid into the mitochondria for beta-oxidation?
a. Carnitine (CPS system)
Know the structure of antibody (Fc, Fab etc.)
Fc- heavy chain only; crystallizable
Fab- consists of both heavy chain and light chain; contains variable regions; can bind
antigen
What can cause cancer?
a. asbestos

Ethylene oxide is used for heat sensitive items

Males difficult urination- benign prostate hyperplasia
Rickettsia invades the endothelium
-Rickettsiae rickettsii (Rocky mountain spotted fever)vector: tick
-R. typhi (Endemic typhus)vector: fleas
-R. Prowazekii (Epidemic typhus)human body louse
-Coxiella burnetti (Q fever)aerosol transmission
-Obligated intracellular parasites that invade endothelial cells causing rash, fever,
headache
-Tx with tetracycline
What is NOMA?
Noma is a disorder that destroys mucous membranes of the mouth (and later, other
tissues) that occurs in malnourished children in areas of poor cleanliness. Risk factors
include Kwashiorkor and other forms of severe protein malnutrition, poor sanitation and
poor cleanliness, disorders such as measles or leukemia, and living in an underdeveloped
country.
What causes vasculitis in children?
a. Kawasakis disease
b. Bergers disease
c. Temporal arteritis
d. Giant cell arteridides

e. Polyateritis Nodosa
What causes most meningitis?
a. virus
b. bacteria
c. fungi
What never bind to enamel?
a. PDL
Review
Microsporum: capitis, corporis
Trichophyton: capitis, corporis, pedis, unguium, cruris
Epidermophyton: corporis, pedis, cruris

-what is the most renal malignancy of childhood?

-Wilms tumor (also called nephroblastoma)
-tumor suppressor gene WT1

Anatomy
The inferior buccal mucosa of the floor of the mouth is innervated by the trigeminal
nerve
The splenic artery branches from the celiac artery
The biceps brachii flexes the gleno-humeral and humero-ulnar joint
Lymphatics in the upper limbs follow the veins
The facial nerve innervates the 2nd pharyngeal arch (muscles of facial expression)
o V does the 1st arch, IX does the 3rd arch, and X does the 4th and 6th arch)
The facial nerve does not go through the cavernous sinus
o III, IV, V, and VI do
In the CNS, the phagocytic cells are the microglial cells
o Astrocytes are the repair cells
o Oligodendrocytes are the myelinating cells
In the TMJ, elastic fibers are found in the posterior-superior lamina of the
bilaminar zone
o The posterior-inferior lamina of the bilaminar zone is collagenous
The nerves of the internal thoracic wall are deep to the internal intercostal muscles
o The VAN runs in the groove in the ribs between the internal and innermost
intercostal muscles
Depression of the mandible is accomplished through the geniohyoid
o Also done by the lateral pterygoid
The pterygoid venous plexus is not connected to the vertebral vein (may not even
exist)

o It is connected to the maxillary, deep facial, infraorbital, and posterior

superior alveolar
Preameloblastsameloblasts require odontoblastic processes to touch them
o Preameloblasts differentiate from IEE in the presence of the SI
Vertebrae originate from two pairs of somites
During eruption of the tooth throughout life, the apex constantly has cellular
cementum deposited on it
o Acellular cementum makes up the coronal 2/3 of the root surface
Fibrocartilage is found in the IV discs
From the esophagusstomach there is a distinct change in epithelium along the GI
tract
Fenestrated capillary plexi are found in the dental pulp
Submucosal glands are found along the GI tract in the duodenum
o Also found in the esophagus
Sharpeys fibers insert into bundle bone and cementum
In hydrocephalus, CSF fills the ventricles due to a shunt in the neural tube that does
not reopen during development
Alveolar bone in the periodontium is primarily composed of hydroxyapatite
Cementum primarily functions to attach Sharpeys fibers
The junction between the tooth and crevicular epithelium is made of a basal laminalike structure
The mucosa of the anterior 2/3 of the tongue develops from the 2 lateral lingual
swellings
o The anterior 2/3 of the tongue as a whole develops from the tuberculum impar
and lateral lingual swellings (1st pharyngeal arch)
o The posterior 1/3 develops from the copula and epiglottal swelling
(collectively known as the hypobranchial eminence)
From the 2nd, 3rd, and 4th arches
Innervated by the facial, glossopharyngeal, and vagus nerves
o Musculature will migrate from the preoccipital somites into the tongue
Innervated by the hypoglossal nerve
The cephalic vein drains into the axillary vein

Biochemistry/Physiology
Iron is stored mainly as ferritin
o Is transported in the blood mainly as transferrin
Heparin combines with anti-thrombin III to prevent blood clotting
The aorta maintains diastolic blood pressure due to its elastic distensibility
Hyaluronidases are most likely to depolymerize the ECM
A rise in systolic blood pressure due to anxiety is a result of decreased arterial
compliance
Drugs that inhibit renal carbonic annhydrase act by decreasing the sodium
reabsorption in the PCT
Clearance > GFR for PAH (this means the substance is actively secreted by the
nephron)

Southern blots are used to identify DNA fragments

o Western = protein, Northern = RNA
Platelets release thromboxane A2 to become sticky
o Prostacyclin inhibits the aggregation of platelets
Peptide hormones cause their effects by binding cell membrane receptors and
alters specific enzyme activity in the cells
o Steroid hormones bind intracellular receptors to stimulate transcription of
DNA
Norepinephrine is released by the SNS and among other things, causes cardiac
acceleration
Cyanide poisoning prevents the extraction of oxygen by peripheral tissue
Increased carbon dioxide levels have the greatest effect on stimulating respiration
o Decreased oxygen levels have the greatest effect on stimulating
chemoreceptors
Catecholamines (norepinephrine/epinephrine) are inactivated by monoamine oxidase
Fatty acid biosynthesis does not require beta-oxidation to be occurring
o The process does require the activity of the TCA cycle, pyruvate
dehydrogenase, amino acid catabolism, and glycolysis

Dental Anatomy
Concavity = depression
o Convexity = elevation
Maxillary molars have a palatal root that has a concave facial surface
The lingual HOC of the mandibular 2nd premolar is in the occlusal 1/3
Two pulp canals are found in the mesial root of the mandibular 1st molar
o Also common in the maxillary 1st molar (MB root)
The buccal vestibule is where the parotid papillae is located (opposite the maxillary
2nd molar)
A tooth is mainly dentin
Germination = one root/pulp chamber but appears as 2 teeth
o Fusion = separate teeth (two roots/chambers) appearing as 1 tooth
o Concrescence = fusion of teeth at cementum (common in the mandibular 1st
premolar)
o Dens in dente = invagination of enamel in the crown (appears as an abscess on
the tooth)
Bifurcated roots can occur commonly on the mandibular canine
o Maxillary canine is the least likely anterior tooth to be bifurcated
Between the maxillary central and lateral incisors, the lingual embrasure > facial
embrasure
o This is also true for all posterior teeth, except the embrasures between the
mandibular premolars (facial > lingual)
Cementoblasts are not found in the pulp
o Arteries, veins, nerves, and lymph vessels are
The mesial root of the mandibular 1st molar is wide in the FL direction and has
concavities on the M and D surface of the root

A distinct cervical ridge is found on the MF surface of the primary 1st molar
Of the premolars, the mandibular 1st premolar has one pulp horn
o Also has a large transverse ridge and a ML groove
The cervical margin of the facial surface of the maxillary 1st molar is irregularly
convex towards the apex
Of the anterior teethpremolars from both arches, the maxillary 1st premolar is
most likely to have 3 roots
Antrum = sinus
The maxillary 1st premolar articulates with the mandibular 1st premolar
The stability of the dental arch is not affected by the plane of occlusion
o However, it is effected by the periodontal health, occlusal contacts forces,
interproximal contacts, and forces of the tongue/lips

Microbiology/Pathology
Atherosclerotic induced aneurysms are most commonly found in the abdominal
aorta
The poliovirus is spread mainly through fecal oral routes
o Attacks neurons, but they can be repaired, restoring lost function
HIV starts out as mononucleosis-like syndromes
Diphtheria toxin acts by inhibiting translation
Porphyromonas gingivalis forms black colonies when cultured and is anaerobic
Acquisition of plasmids with antibiotic resistance is the most likely cause of
developing resistance in bacteria (especially multiple drug resistance)
o This has not been demonstrated in streptococcus pyogenes
Eye infections are commonly associated with herpes simplex and adenoviruses
o Chlamydia is common for eye infections (prenataly) also
Mumps ( paramyoxviridae) is transferred via saliva
o Results in swelling of the parotid gland
A fungal disease resulting in hard and soft tissue necrosis is mucormycosis
Chlamydia often causes nongonococcal urethritis
Carcinoma of the tail of the pancreas is least likely to cause acute abdominal
symptoms
o Cholelithiasis, acute pancreatitis, and ampulla of Vater cancer do cause it
Osteogenesis imperfecta does not cause multiple, lytic lesions of the bone
o Multiple myelomas, metastatic carcinomas, hyperparathyroidism, and
eosinophilic granuulomatosis do
The coxsackievirus is spread through fecal means
o Other viruses spread fecally include: hepatitis A, and poliovirus
Herpangia (coxsackievirus) will show signs of vesicular lesions on the palate and
posterior oropharyngeal mucosa with an increased oral temperature
Lymphocytes are the most radiosensitive cells
Striated muscle has a low ability to regenerate (smooth muscle, bone, liver, and
collagen can)
Anthracosis does not predispose someone to cancer
o Asbestosis, hepatitis C, Gardners syndrome, and ulcerative colitis do

Metastatic calcifications are commonly a result of hyperparathyroidism

Picornaviruses (hepatitis A, polio, coxsackievirus) are least likely to cause cellular
transformation
o These are capsid, positive ssRNA viruses
Melena means there is digested blood in the stool
Chlamydia trachomatis does not cause primary atypical pneumonia
o It can cause trachoma, lymphogranuloma venereum, inclusion conjunctivits,
and nongonococcal urethritis
Hepatic failure does not cause Mallory bodies
o It does cause tremor, gynecomastia, hypoalbuminemia, and spider
telangectasia
Red hepatization is a stage of lobar pneumonia

Anatomy
The cephalic vein drains into the axillary vein
The parietal pericardium receives its sensory innervation from the phrenic nerve
Food is masticated primarily in lateral contacting movements
The buccal mucosa has a non-keratinized, stratified squamous epithelium
The palatine tonsils can be distinguished from the pharyngeal tonsils by their
difference in epithelium, although they perform similar functions
The upper compartment of the TMJ is translation
o The lower compartment of the TMJ is rotation
In steroid producing cells, smooth endoplasmic reticulums dominate
o Rough ERs, and Golgi apparatuses dominate in protein producing cells
The lingual artery is found between the hyoglossus and genioglossus within the oral
cavity
The majority of the lining of the tubular GI tract is made of simple columnar
epithelium
Inferior alveolar nerve blocks have a potential to damage the sphenomandibular
ligament
The thyrohyoid membrane is pierced by the internal branch of the superior
laryngeal nerve
Plasma cells are found within the medullary cords of lymph nodes
In the lateral neck, lymph nodes during a TB infections with show granulomas with
multinucleate giant cells and cessation necrosis
Exudate from the mylohyoid muscle most likely causes swelling at the
mandible/lateral neck
The buccal nerve transmits sensation from the buccal gingiva
An infection of the mandibular 3rd molars will not spread to the temporal fascial
space
o It can spread to the parotid, massteric, and buccopharyngeal spaces
o Fluid will drain from these teeth to the deep cervical nodes
Pain from the central incisors terminates in the spinal subnucleus caudalis of V
Pain from the mandible is carried via the auriculotemporal nerve

The monosynaptic jaw closing reflexes will not function properly if damage is done
in the motor nucleus of V
The chroda tympani runs through the petrotympanic fissure
The parotid duct crosses the masseter muscle
The thyrocervical trunk has the inferior thyroid, transverse cervical, and
surpascapular arteries branching from it
The anterior temporalis acts to elevate the mandible
The hypoglossal nerve travels from the carotidsubmandibular triangles of the neck
The phrenic nerve is not found in the posterior mediastinum
o The vagus/greater splanchnic nerves, sympathetic chain ganglia, and thoracic
duct are
The right vagus nerve travels posterior to the arch of the azygous vein
Infections from the vermiform appendix enter the blood stream via the thoracic duct
to the brachiocephalic vein
Tonofibrils and desmosomes are well developed in the keratinocytes
The articular disc is dense fibrous CT
Decreased parotid salivations will result form damage to the lesser petrosal nerve
since it carries the parasympathetic innervation
The middle ear receives its sensory innervation from the glossopharyngeal nerve
Pressure on the alveolar mucosa will cause it to transform into an orthokeratinized
epithelium
The mylohyoid muscle will effect the comfort of mandibular dentures

Biochemistry/Physiology
Zinc is essential to carbonic anhydrase
For swallowing to begin, the mucosal mechanoreceptors must indicate the
consistency of the bolus
Saliva provides calcium and phosphate for remineralization of teeth
o Bicarbonate is secreted into saliva to serve as a buffer
Smooth muscle lacks troponin
o It does have actin, myosin, calmodulin and tropomyosin
Platelets are prevented from aggregating by prostacyclin
o Thromboxane A2 promotes their aggregation
The pars nervosa is the region of the posterior pituitary where oxytocin is released
o ADH is released from the
Bile is released from the gall bladder in response to increasing levels of CCK
The binding of ATP to the myosin head dissociates actin from myosin
Atropine prevents the secretion of saliva resulting from the stimulation of the chorda
typmani since it prevents the action of Ach on the secreting cells
Glucose cannot be made from acetyl CoA
o It can be made from lactate, glycerol, pyruvate, and fructose
The initiation of bone mineralization does not require the release of acid
phosphatase by osteocytes trapped in lacunae (osteocytes do not exist until bone
has formed around osteoblasts)

o The process does require

Pores in collagen fibers
Release of matrix vesicles by osteoblasts (containing alkaline
phosphatases)
Degradation of the matrix pyrophosphate to release inorganic
phosphate
Lactateglucose occurs in the liver in the Cori cycle
Urea formation is catalyzed by arginase
Atretic follicles are characteristic of the ovaries
Respiratory acidosis is induced when NO is given to a patient (NO>O)
Asthma does not result (immediately) in an increase in renal bicarbonate production
The insulin reaction (sudden fall in blood glucose) does not cause hyperventilation
o Does cause coma, dizziness, confusion, and convulsions
o Glucose transporters get glucose across the cell membranes
GLUT1: found in RBC and brain
GLUT2: found in liver, kidney, and pancreatic beta cells
GLUT3: found in neurons
GLUT4: found in adipose and skeletal muscles (responsive to insulin
levels)
GLUT5: fructose transporter
GLUT7: found in gluconeogenic tissues (liver)
When a fractured mandible regrows, new osteons are not found across the callus
o Blood clots form, a bridging (then periosteal) callus forms, and new
endochondral bone will result
Acetoacetate is considered a ketone body
Nucleotide synthesis requires folic acid
o Proper neural tube formation also requires this vitamin
The principal regulator of the fatty acid synthesis pathway is the step catalyzed by
acetyl CoA carboxylase
Glucose-6-phosphatase is associated with the kidneys and liver
o Converts G69glucose in gluconeogenic cells
o A deficiency in this is known as von Gierke disease
Restriction enzymes work as site-specific endonucleases
Calcium binds troponin C to allow for muscular contraction by moving the
tropomyosin complex off of the myosin binding site on actin
Type II pneumocytes produce surfactant
Bile salts = sodium salts of bile acid + taurine/glycine
The phosphorylation of phosphorylase ba works to breakdown glycogen in the
liver
Calcium metabolism is not effected by norepinephrine
Striated muscles has the least ability to regenerate when compared to bone, liver,
smooth muscle, and collagen
Gastric emptying is most decreased by the presence of fats in the duodenum
Thyroglobulin is likely to be secreted in response to an iodine deficiency

The SNS promotes mucous secretions by salivary gland, while the PNS promotes the
serous secretions
A-delta fibers are the neurons responsible for sending pain signals

Dental Anatomy
Oblique ridges are most likely to be found on the maxillary second molars
The primary mandibular second molar has more cusps than the primary mandibular
first molar
The lingual concavity of the maxillary anterior teeth and the groove direction of the
posterior teeth is influenced by the side shift of the mandible (Bennett movement)
On the primary maxillary first molar the mesial surface normally is larger than the
distal surface
o This tooth resembles a permanent premolar
The lingual embrasure is greater than the facial embrasure between the maxillary
central and lateral incisors
The amount of fibrous CT increases with age in the dental pulp
Mesial and distal pulp horns can be found in the maxillary central incisors
The ML cusp of the maxillary 1st molar moves through the lingual groove of the
mandibular 1st molar during a laterotrusive movement
The apex of the horizontal plane Gothic-arch tracing represents centric relation
The obtuse angles of the maxillary 1st molar are located at the MF and DL
o The oblique ridge runs from the DB to ML cusps
The DI aspect of the mandibular central incisors opposes the lingual fossa of the
maxillary centrals
The DL cusp of the maxillary 1st molars opposes the MMR of the mandibular 2nd
molar
The portion of dentin that is most highly mineralized is peritubular dentin
The least amount of collagen is found in enamel when compared to bone, dentin,
cementum, and mucosa
Maxillary 1st molars have a rhomboidal occlusal outline
At the CEJ, the mandibular canine shows an ovoid outline that is wider MD than at
the labial
The mandibular canine is the most likely anterior tooth to have a bifurcation, and
these roots are found on the facial and lingual aspects
o The maxillary central incisor is least likely to have a bifurcation in the root
On the labial surface of the canines, just mesial to the labial ridge, the ML
developmental groove is noted
The MR on the maxillary laterals are more prominent than on any other anterior
tooth
Mandibular 3rd molars are wider MD when compared to their BL dimension
7 year olds will not show a fully erupted mandibular central incisor with complete
root formation/closure at the apex
Mesiodens are small, calcified, radiopaque masses between teeth
When making a mesiotrusive movement it is possible to fracture off the lingual cusp
of the maxillary premolars

The lingual cusp of the maxillary 1st premolar is inclined mesially

Inorganic crystals of enamel have their long axes parallel to the rods in the body of
the rod and deviating increasingly in the tails
Between the DF cusp and D cusp of the mandibular 1st molar is the DF groove
The distal contact of the maxillary canines is not in the incisalmiddle 1/3 of
anterior teeth (the only one where this is true)
When compared to the mandibular lateral incisor, the maxillary counterpart has a
more prominent lingual fossa
The roots of a maxillary 2nd molar show a greater distal inclination than the
maxillary 1st molars
From a frontal view, the plane of occlusion of the mandibular arch is concave
The lingual cusp of the maxillary 1st premolar articulates with the distal fossa of the
mandibular 1st premolar
In a crossbite, the mandibular linguals and maxillary facial cusps contact each
other in MI
Mandibular canines show more incisal contacts then the maxillary canines
o The maxillary canines have sharper facial cusps, a more pronounced cingulum,
and a more convex mesial border
The MMR is more cervical than the DMR in the mandibular 1st premolar
Dentin in the roots has a decreased primary curvature in its tubules when compared
to coronal dentin
The maxillary 2nd premolar has a width where FL>MD
Protrusive movements would most likely cause a break in the mandibular central
incisors
In mandibular 1st molars the mesial root most likely has 2 canals and the distal
root has 1

Microbiology/Pathology
Calcium dipicolinate is present in large amounts in spores
Ewings sarcoma is a cancer that typically arises in teenagers/young adults
Interstitial pulmonary inflammation is a result of viral pneumonia
o Lobar pulmonary inflammation is a result of bacterial pneumonia
HPV16/18 commonly cause cervical cancer
Herpes zoster infections do not occur repeatedly in immunocompetent patients
o They are usually unilateral, involve 1-3 dermatomes, occur in individuals with
latent infections, and are more common in the immunocompromised
Capsular antigens are used in the vaccines for haemophilus influenzae
When periodontal disease becomes more severe, IgG production is increased
The picornaviruses do not cause cellular transformations
o Retroviruses, herpes, HBV, and HPV do
IL-1 is produced by macrophages
Immersion sterilants that are approved include glutaldehydes
Granulation tissue is not composed of plasma cells
o It does have fibroblasts, capillary buds, endothelial cells, and new collagen
Oral streptococci are alpha hemolytic

Semi-critical items should be reprocessed by heat stabilization if the material is

heat stable
Lymphocytes are not phagocytic cells
o Monocytes, macrophages, neutrophils, and histiocytes are
Inflammatory exudate is considered suppurative, purulent, fibrinous, and
pseudomembranous
o It is not fibrous
In external secretions, polymeric IgA is characteristic
A type of skin lesion that is typically precancerous is actinic keratosis
o Psoriasis, verruca vulgaris, intradermal nevus, and seborrheic keratosis are
usually not precancerous
Actinomyces naeslundii is a normal inhabitant of the gingival crevice and tonsillar
crypts
Hepatitis C is transported through blood
o HAV is done through oral/fecal routes, while HBV is spread through sexual
contact and blood
Tinea capitis is a fungal infections, and is therefore treated with anti-mycotic agents
Choriocarcinoma is discovered by detecting increased levels of hCG in the
blood/urine
Pernicious anemia is not characterized by microcytic hypochromic RBCs
o It does show atrophic glossitis/gastric mucosa, peripheral neuropathy, and
easy fatigability
Cigarette smoking is not linked to colon cancer
Rifampin is a drug that inhibits transcription
Asthma does not cause a decrease in surfactant production
o It does cause airway edema, bronchospasms, increased mucous secretions, and
increased airway resistance
o Multinucleated giant cells phagocytizing extrinsic antigens does not play a
role in this disorder
Diabetes (type I)
o Pancreatic carcinoma is not normally caused by uncontrolled type I diabetes
o Seizures are caused by the hypoglycemic state
Anemic people tend to have a normal oxygen tension, and reduced oxygen content
Mallory bodies do not result from hepatic failure
o Tremors, gynecomastia, hypoalbuminism, and spider telangiectasia do
Lead poisoning can result in abdominal pain, anemia, and wrist/foot drop
Infective endocarditis is most often associated with alpha-hemolytic streptococci
Droplets/Droplet sprays are not a method for the spread of condyloma acuminatum
o Whooping cough, meningitis, diphtheria, and pneumonia can spread this way
Bronchiolitis and pneumonia are most often caused by respiratory syncytial virus in
infants
Hepatitis D is only infective is with HBV
Endometrial carcinoma is more likely to occur in patients with hyperestrogenism
A TB like infection can be induced by the fungus histoplasma capsulatum
o Infections from this result from inhaling contaminated air

When a patient has a penicillin allergy, then azithromycin is prescribed

Hemodynamic disorders do not cause edema in the pancreas
o They can in the lungs, brain, subcutaneous tissue, and peritoneal cavity
Gingivitis is associated with gram negative anaerobic rods
Sickle cell anemia results in a decreased solubility of the deoxy form of
hemoglobin
Small cell carcinoma is associated with paraneoplastic syndrome
Hemophilia A is an X-linked recessive disorder
Exotoxin A from pseudomonas aeruginosa acts to inhibit protein synthesis
Type I hypersensitivities involve the binding of IgE and the eventual activation of
cytotoxic T cells to release their lymphokines
Before an atherosclerotic cerebral infarction, a transient ischemic attack is likely to
occur
Pathognomonic: characteristic of a single disease
Anthracosis (black lung) does not predispose people to cancer
o Asbestosis, HCV, ulcerative colitis, and Gardners syndrome do
Hyperparathyroidism does not result in titanic muscular convulsions
o Urolithiasis, elevated serum calcium, central giant-cell bone lesions, and the
loss of the lamina dura surrounding teeth
o The proliferative zone would most likely not be present in the TMJ with this
disorder
Acute lymphoblastic leukemia does not show multiple, acutely tender nodes due to
central node ischemic necrosis
o This is a myelophthisic anemia (severely anemia, normocytic, normochromic
RBCs)
o Thrombocytopenia results in increased bleeding in these patients
MI pain cannot be relived by vasodilators or nitroglycerins
Hypertrophy of the tunica intima is seen is atherosclerosis
o This is where the smooth muscle layer is located
Ischemic heart disease results from the occlusion of one or more coronary arteries
o Scarring of the left ventricle is usually noted
Strokes are prevented by the medication warfarin
HCV causes death due to inhibition of urea synthesis
o HCV can also lead to chronic hepatitis most of the times

1998 Released Exam

Anatomy
Microvilli are made of microfilaments
o Cilia has a microtubular arrangement of 9 + 2
The carotid triangle is bound by the superior omohyoid, SCM, and posterior
digastric
Triangle
Location

Triangle
Name

Boundaries

Floor

Roof

Posterior

Occipital

SCM, trapezius,
superior border of
the omohyoid

Splenius capitis,
levator scapulae,
scalene muscles

Investing
fascia

Organelles Found

Vessels
Found
Subclavian
artery/vein

Nerves
Found
Accessory
(XI), brachial
plexus (C5-

(prevertebral
fascia overlies
these)
Anterior scalene
muscle
(prevertebral
fascia overlies
these)

T1), cervical
plexus
(cutaneous)

Supraclavicular

SCM, middle 1/3

of the clavicle,
inferior border of
the omohyoid

Submandibular

Anterior/Posterior
bellies of the
digastric muscle,
mandible

Mylohyoid
muscle

Submandibular
gland,
submandibular
lymph nodes

Submental

Anterior bellies
of both digastric,
hyoid bone

Mylohyoid
muscle

Submental lymph
nodes

Anterior

Muscular

Median plane of
the neck, superior
belly of the
omohyoid, SCM

Carotid

Posterior belly of
the digastric
muscle, SCM,
superior belly of
the omohyoid

Infrahyoid muscle,
thyroid,
parathyroid,
pharynx,
esophagus,
trachea,
thyroid/cricoid
cartilage

Facial
artery/vein

Hypoglossal
(XII),
submandibular
ganglion,
lingual nerve

Carotid
sheath
vessels

Recurrent
laryngeal

Carotid
sheath
vessels,
external
carotid

Cervical
sympathetic
chain,
hypoglossal
(XII)

The thyroid gland originates from the foramen cecum

The blood testis barrier is maintained by the Sertoli cells
o Leydig cells are near the vasculature and secrete testosterone
The auriculotemporal and masseteric nerves are responsible for providing the TMJ
with sensation
By pushing a needle to far posteriorly during an inferior alveolar nerve block, you
may accidentally anesthetize the parotid gland
Meiosis occurs in the seminiferous tubules in males
Neoplasms in the angle of the mouth will pass through the submandibular lymph
nodes
Region/Structure
Drained By
Occipital
Occipital, posterior auricular nodes
Facial, submental, submandibular, parotid,
Face
preauricular nodes
Tip of tongue
Mandibular incisors/gingiva
Submental nodes
Anterior lower lip
Anterior floor of mouth
Anterior palate
Submandibular nodes
Lateral floor of mouth

Lateral lips
Anterior nasal cavity
All teeth/gingiva except mandibular
incisors
Anterior 2/3 of tongue
Posterior 1/3 of tongue
Lingual/Palatine tonsils
Pharyngeal tonsils
Nasal cavity
Paranasal sinus
Nasopharynx
Oropharynx
Posterior palate
Superficial anterior neck
Deep anterior neck

Submandibular and jugulo-omohyoid nodes

Jugulodigastric nodes

Retropharyngeal nodes

Retropharyngeal, jugulodigastric, and parotid

nodes
Anterior jugular nodes
Prelaryngeal, pretracheal, and paratracheal
nodes

SNS innervation in the head has the preganglionic fibers coming from the
intermediolateral horns of the thoracic spinal cord
o These cells synapse in the superior cervical ganglia and continue to the head
The thoracic duct lies posterior to the esophagus
The hamulus is an extension of the medial pterygoid plates of the sphenoid bone
Dermis is classified as dense irregular collagenous CT
The right vagus nerve travels just posterior to the azygous vein
The tempormandibular ligament helps resist posterior movements of the condyles
o Temporomandibular (lateral) ligament
Superficial layer comes from the articular tubercle and passes
obliquely (inferior and posterior) and inserts into the posterolateral
aspect of the mandibular neck (inferior to the lateral pole of the
condyle)
The medially situated portion comes from the crest of the eminence,
passing horizontally to insert into the lateral aspect of the condyle
In general the ligament allows for anteroinferior movement, and
prevents mediolateral movements
Superficial (outer oblique) portion prevents lateral movement,
and limits the rotation
o Restricts over-movement in posterior, lateral and
inferior directions
o Induces translation
Horizontal portion prevents posterior displacement of the
condyle
o This protects the retrodiscal tissue
There is no similar ligament on the medial side of the condyle within
the capsule

o Accessory ligaments
Sphenomandibular ligament
Remnant of Merkels cartilage
Goes from the spine of the sphenoidlingula (mandibular
foramen)
May assist in limiting lateral movement
Ringing in the ear may be associated with this
Stylomandibular ligament
Specialized deep cervical fascia
Goes from the styloid processposterior border of the
angle/ramus of the mandible
May assist in limiting anterior protrusion
o Medial/lateral collateral (discal) ligaments (collagenous CT)
Prevent the disc from leaving the condyle during translation/rotation,
allowing for the disc and condyle to move as a single unit
The pterygoid plexus is formed by veins that are tributaries of the maxillary vein
The primary supinator of the radio-ulnar joint is the biceps brachii
The diploic veins are found within the bones of the calvarium
Oxyphil cells are located in the parathyroid gland
o These are remnants of chief cells in this gland that make PTH
The most vascular portion of the TMJ is the bilaminar zone
o Superior posterior lamina (superior retordiscal lamina)
Made of elastic fibers and attaches to the temporal bone
Elastic fibers guide the condyle into the glenoid fossa during retraction
of the mandible
o Inferior posterior lamina (inferior retrodiscal lamina)
Made of collagenous fibers and attaches to the posterior aspect of the
neck of the condyle
o Between the laminae is the retrodiscal tissue
This is highly vascular (venous plexus), filling with blood during
opening of the jaw and pushing out blood during closure
Keeps a constant pressure within the joint
The right kidney is closest to the colon
The type of CT found in fetuses, but not adults is mesenchyme
The orbit is thinnest on the medial wall
The medial cord of the brachial plexus is formed by C8/T1
The only purely serous glands in the mouth are the parotid gland and the glands of
von Ebner (found on the lamina propria of the tongue)
The brachial artery runs adjacent and parallel to the median nerve in the arm
CT proper is noted as having more intercellular material than cells
Howships lacunae are formed by osteoclasts
The posterior limit of the vestibular side of the cheek is the pterygomandibular
raphe
The glossopharygneal nerve enters the pharynx between a gap in the
superior/middle constrictors

The pharyngeal tonsil is pseudostratified columnar ciliated epithelium

Zonula occludens make the greatest resistance to substances moving between cells
o Gap junctions allow communication directly between neighboring cells
o Desmosomes join cells to resist shearing forces
o The zonula adherens is just basal to the ZO
Veins have a more prominent tunica adventitia

Fibers from the thalamus to the cortex are found within the internal capsule of the
brain
The mimetic muscles are supplied by the facial nerve
As pulp ages, the amount of collagenous material increases and its size decreases
The prochordal plate is made of endoderm of the roof of the yolk sac and
embryonic ectoderm
The palatine gland is purely mucous
The submandibular duct is just deep to the mucous membrane of the oral cavity
Accessory root canals are formed as a result of a break in the epithelial root sheath
prior to dentin formation
The stratum basale is just deep to the stratum spinosum
The vertebral artery passes through the foramen magnum
Bone and cellular cementum are similar in that they contain cells in lacunae with
canaliculi that extend towards the nutritional source
o They are also similarly calcified
Gnarled enamel is found in the cusps of teeth
As enamel matures, the inorganic content increases, the water content decreases,
and the organic content decreases
Para-keratinized oral mucosa is found in the attached gingiva
o Mucosas
Masticatory
Stratified, squamous, (para) keratinized epithelium
o Has a well developed RA
Underlying connective tissue
Found in the gingiva, hard palatte, and dorsum of the tongue
(lots of friction in these areas)
Lining
Stratified, squamous, nonkeratinized epithelium
o Average RA to none
Underlying connective tissue
Found in any non-masticatory tissue
Specialized
Determined by the presence of taste buds and is located within
the lining epithelium
This tissue CANNOT be stratified or keratinized
Dentin is made primarily of type I collagen

Biochemistry/Physiology
G-actin is converted to F-actin due to the action of ATP
ADH increases the permeability of the CD and DCT to water
Insulin is created as a larger peptide, and needs to be cleaved prior to activation
GABA increases the permeability of postsynaptic membranes to chloride
Calcium is transported across membranes via a sodium countertransporter
Citrate catalyzes the rate-limiting step of fatty acid synthesis
o Is regulated by a positive modulator (allosterically)

In animal cell membranes, linoleic acid is commonly found

The presence of ATP tends to inhibit catabolic pathways
Systemic and pulmonary circulation have the same flow rate
A longer loop of Henle allows for a more concentrated urine to form
Steroid hormones are not found in the same concentration in glomerular filtrate as
plasma
o Urea, glucose, amino acids, and plasma electrolytes are
If the membrane of an axon became very permeable to sodium, the membrane
potential would approach +60mV
Niacin deficiency results in pellagra (dementia, diarrhea, and dermatitis)
Streptomycin inhibits prokaryotic translation
Insulin will increase the activity of phosphofructokinase when administered
Emphysema results in an increased functional residual capacity and increased
compliance
Cholesterol in the liver is converted into cholic acid
Dentin is made of noncollagenous protein components (osteonectin) and collagen
type I
Increased vagal activity will result in a decreased cardiac oxygen consumption
Coenzyme A participates in the activation of carboxyl groups
The catabolism of amino acids begins with the transamination of the alpha amino
to a keto acid
Both elastin and collagen are made of ~1/3 glycine
Chief cells do not secrete bicarbonate into the GI tract
o Colon mucosa, salivary glands, and the stomach mucosa do
Without pulmonary surfactant, there is a decrease in lung compliance and decrease
in vital capacity
A 23 year old man would have a hematocrit of 45%
Plasmid vectors have 2 genes conferring resistance to different antibiotics to show
that the vector has been taken up (one will be whole, one will be disrupted)
During an isotonic contraction the length of the A band does not change
During an insulin insufficiency, acetyl CoA is channeled to ketone-body formation
In prolonged acidosis, ammonia is found in high concentrations in the urine
Sodium fluoride inhibits enolase
With an increase in arterial pressure, the baroreceptors cause an inhibition of SNS
and excitation of PNS
In a denervated heart, adjustments to workload are mediated by the end diastolic
volume
o An increase in this will increase workload according to the Frank Starling law
of the heart
1 anomeric carbon is present in fructose

Dental Anatomy
The maxillary 2nd premolar has a width that is greater in the FL than the MD and
has 2, equal height cusps

The lingual cusps of the mandibular 1st premolar does not occlude with any
maxillary tooth in MI
From the labial aspect, the canines resemble a pentagon
The height of contours on the maxillary canine are in the cervical 1/3 in the labial
and lingual
The mandibular cusps trace a line towards the mesial on the maxillary teeth
The nonworking path of the maxillary teeth on the mandibular posterior teeth is
towards the distofacial
The mandibular posterior teeth have a straight line tracing their alignment
The articular disc is thickest in the posterior border from a sagittal view
The oblique fibers provide the support to the teeth during function
The maxillary first premolar is most difficult to perform root canal
therapy/extractions on
o Due to the bifurcated roots, with potential for multiple canals
The MF cusp of the maxillary 1st molar opposes the MF groove of the mandibular
1st molar
The primate space is between the canine and 1st molar in the primary dentition
The distal contact of the mandibular lateral incisor is in the incisal 1/3
The mandibular canine is most likely to have a bifurcated root in the anterior teeth
The occlusal table makes up 55-65% of the BL width of teeth
Pit and fissures caries is most likely to occur on the lingual of maxillary molars than
any other permanent tooth
The epithelial attachment is part of the periodontium
A 6 year old child will have 18 primary teeth and 6 permanent teeth (4 1st
molars and 2 mandibular central incisors)
The maxillary 1st primary molar has a crown resembling the premolars
Anterior guidance plays a major role is disoccluding the posterior teeth in a
lateroprotrusive movement
The occlusal aspect of the mandibular 2nd molar is pentagonal
The cervical line on the mandibular lateral incisor is more apical on the distal than
the mesial
The maxillary lateral incisor can be peg-shaped at times
Both maxillary premolars have a lingual cusp offset to the mesial
Root canals join the pulp chamber just apical to the CEJ
The mandibular 1st molar has a lingual surface of each cusp possessing a slightly
convex shape in the occlusal 1/3
For a mandibular 1st premolar, a second root canal is likely to be found in the lingual
aspect of the root
The mandibular 1st premolar has an occlusal pit extending to proximal as a ML
developmental groove
When the muscles of mastication are in equilibrium the physiologic rest of the
mandible is established
The horizontal and vertical overlap of the teeth protects the lips, cheeks, and
tongue
In anterior teeth, the incisal ridge calcifies first

The posterior temporal fibers retrude the mandible

The mesial mandibular 1st molar root is the largest root of all 1st molars
The primary mandibular 1st molar normally has a distal triangular fossa
The canine erupts before the fourth tooth from the midline in the mandibular arch of
the permanent dentition
During protrusion, the condyles move forwards and downwards
The root length of both maxillary incisors are equal (maxillary lateral may be
slightly greater)

Microbiology/Pathology
On the dorsum of the tongue there are commonly streptococcus salivarius
A heterophile antibody test is found with infections of EBV
Allergies to penicillin can be overcome by prescribing erythromycin
Over the past 30 years there has been an increase in mortality in women from lung
cancer
Normal clotting and normal platelet levels, along with increased bleeding time is a
result of excessive aspirin ingestion
Hereditary angioedema is a result of deficiency in C1 esterase inhibitor
Karolysis (along with other nucleus changes) represent irreversible damage
Infants in developed countries can get viral birth defects from infections with
cytomegalovirus
Rabies has the longest incubation period when compared to the common cold,
influenza, measles, and herpetic gingivostomatitis
In an uncomplicated healing process by secondary intention there would be noted
ulceration on the epithelial surface at day 3
Chronic hyperplastic candidiasis produces a firmly adherent white plaque on the
oral mucosa
Anasarca is not associated with congestive heart failure (dyspnea, cyanosis, ankle
edema, and passive liver congestion are noted)
Neuroblastomas originate primarily in the adrenal glands
In apoptosis, lysosomal enzymes function to autolyse necrotic cells
Pseudoarthritis results from an inadequate immobilization after bone fracture
Phage conversion can be responsible for the production of pyrogenic toxins in
bacteria
Blastomycosis is characterized by hyphae growing in/around vessels
Bacterial pili allow bacteria to adhere to human cells
Rickettsial diseases produce illness in humans since they are destructive to
endothelial cells
The uptake of naked DNA by bacteria is known as transformation
The capsule of streptococcus mutans enhances the oral accumulation of the
bacteria
Glutaraldehyde has the broadest antimicrobial spectrum
Cor pulmonale is a direct result of resistance of blood flow through the lungs
Glioblastoma mutliforme has a more favorable prognosis than Grade I
astrocytoma

Enterotoxin from staphylococcus aureus causes food poisoning

Endotoxins are made of somatic O polysaccharide, core polysaccharide, and lipid
A
Acute appendicitis would not have a differential diagnosis of duodenal peptic ulcers
o Crohns disease, Meckels diverticulitis, pelvic inflammatory disease, and
gastroenteritis with mesenteric adenitis are
Dimorphism in fungi means it can produce yeast and mycelial phases
The destruction of glomerular basement membranes in glomerulonephritis is due to
PMNs

Anatomy
The parafollicular cells of the thyroid gland secrete calcitonin
o This counteracts the action of PTH
Lesions of the lower motor neurons of VII will cause an ipsilateral flaccid paralysis
of the facial musculature
o A lesion of the upper motor neurons of VII would cause a contralateral flaccid
paralysis of the lower facial muscles only
The temporalis inserts into the coronoid process
Without secretions from the hypophysis there is a lack of bone growth
Just deep to the oral mucosa of the floor of the mouth, there is the sublingual gland,
lingual nerve, and submandibular duct
Blood passes through the hepatic sinusoids and towards the central veins
In a mid-humeral shaft fracture, the radial nerve would be injured
Simple columnar epithelium is suited for secretions and absorption
The spleen does not develop from an outpouching of the gut
o The lung, liver, pancreas, and gallbladder are
The geniohyoid does not receive innervation from the ansa cervicalis
o It receives innervation from C1 (so does the thyrohyoid)
Tendons are dense regular CT
o Dermis is dense irregular CT
The facial canal does not open into the pterygopalatine fossa
o The pterygoid canal, pharyngeal canal, sphenopalatine foramen, and
pterygomaxillary fissure do
The hepatic vein drains into the inferior vena cava
Calcium ions are sequestered by the sarcoplasmic reticulum
Bone can be distinguished from osteoid since bone has a mineralized matrix
Barr bodies differentiate the sexes in certain epithelial cells
The vagus nerve supplies the GI tract with PNS up to the level of the ascending
colon
o The rest of the tract is supplied by the sacral PNS
The dental arches are drained by the submandibular lymph nodes
The ventral surface of the tongue/floor of the mouth, is covered by thin
nonkeratinized stratified squamous epithelium with a thin lamina propria
The least differentiated layer of the epidermis is the stratum basale

Damage to the right hypoglossal nerve will deviate the tongue to the right
o Damage to the right lateral pterygoid muscle will cause a deviation of the jaw
to the right also
o The contractile muscle for the tongue and jaw move the unit towards the
contralateral side
Smooth muscle in the vasculature is thickest in the arterioles since these are the
resistance vessels
The superior laryngeal artery and internal laryngeal nerve pierce the thyrohyoid
membrane
o The external laryngeal nerve runs with the superior thyroid artery
o The inferior laryngeal nerve runs with the inferior thyroid artery
The vertebral artery branches from the subclavian artery
o The thyrocervical trunk (also a subclavian branch) are the supraclavicular,
inferior thyroid, and transverse cervical arteries
The lingual nerve, sublingual gland, submandibular duct, and hypoglossal nerve are
found between the hyoglossus and mylohyoid muscles
o The lingual artery is not
The buccinator receives its motor innervation from the facial nerve
o Its sensory innervation comes from the buccal branch of V
Submucosa is not found in the gallbladder but is present throughout the rest of the
GI tract
The thoracic duct empties into the junction of the left internal jugular and
subclavian veins
Cilium are composed of microtubules
o Microvilli are composed of microfilaments
The superior orbital fissure allows for the passage of III, IV, V1, and VI but not the
ophthalmic artery
The right lung is made of 3 lobes while the left is 2 lobes
Peritubular dentin has a greater content of inorganic salts than intertubular dentin
Enamel tufts extend into the enamel from the DEJ in a hypocalcified fan shaped
manner
Pain fibers associated with IX have their cell bodies in the superior ganglion of IX
o They extend to the descending nucleus of V
The lingula on the mandible is the attachment site for the sphenomandibular
ligament
The alveolar mucous membrane is highly vascular and has a thin epithelium
The tongue is developed from the 1st, 2nd, and 3rd brachial arches
On the apical end of serous glandular cells (proteins secretions) there are a large
amount of zymogen granules
The S-shape of dentinal tubules result from odontoblastic crowding
A fracture of the hamulus effects the action of the tensor veli palatini since it serves
as a region where the muscle wraps around
Demilunes of the mucous alveoli are composed of serous cells

Biochemistry/Physiology

Vitamin B1 is least likely to be involved in tooth development, while A, C, and D are

Vitamin C, alpha ketoglutarate, and oxygen are required for the hydroxylation of
proline in collagen
When there is excess NE in the presynaptic neuron, it is deaminated by monoamine
oxidase
Osteonectin has a high affinity for binding calcium and collagen
In the presence of adenosine vascular smooth muscle relaxes
Enamel is harder than bone since its crystals are larger and more firmly packed
Matrix proteins of enamel are known as amelogenins
The hydrolysis of lecithin results in phosphoric acid, glycerol, fatty acids, and
choline
Vitamin K is a coenzyme for the carboxylation of glutamate side chains
Enterokinase activates trypsinogen (to trypsin)
Unsaturated fatty acids are oleate
o Cholesterol, palmitate, stearate, and choline are saturated fatty acids
The branching of glucose is a alpha 1-6 linkage
o Joining glucose in a chain is a alpha 1-4 linkage
Glucokinase is found in the liver only, and performs a similar function to hexokinase
in other cells
You will not find triglycerides in lipid membranes
o There will be cholesterol, gangliosides, sphingomyelin, and
phosphatidylocholine
The amplitude of an AP can be increased easily by increasing the concentration of
extracellular sodium
Somatostatin is also known as growth hormone inhibiting hormone to inhibit the
release of GH from the anterior pituitary
Gastrin will activate the pyloric pump, relax the pylorus, and contract the LES
Negative nitrogen balance means that the nitrogen output > intake
When the clearance of a substance by the kidneys is completely removed from one
pass of blood then it equals the renal plasma flow
25-hydroxycholecaliferol is derived directly from 7-dehyrdo-cholesterol

Dental Anatomy
The incisal angle with the greatest convexity in maxillary teeth is the MI of the
lateral
The DL cusp of the maxillary molars are not part of the primary cusp triangle
The contacts between the maxillary lateral and central incisors are centered
faciolingually
The maxillary lateral incisor has a distal contact in the middle third
The mesial surface of the maxillary 1st premolar and distal surface of the 1st
molar have concavities in them
The maxillary 1st molar does not contact the mandibular 2nd molar
The root of the mandibular canine is flattened in a MD direction
Prominent cervical ridges are found on the F/L of the primary maxillary central
incisors

The largest incisal embrasure is between the maxillary canine and lateral incisor
o The widest incisal embrasure is between the maxillary canine and 1st premolar
During protrusion, the mandibular 1st molar can contact the maxillary 1st molar and
2nd premolar
A concavity on the lingual surface is noted on the maxillary lateral incisor
The greatest incisal curvature is on the mesial of the maxillary central incisor
The styloglossus muscle retracts the tongue
The maxillary 2nd molar has shorter developmental groove and many
supplementary grooves compared to the 1st premolar
At age 9, 12 primary teeth remain in the mouth
Centric supporting cusps do not occlude in embrasures
During protrusion the mandible translates (not rotates)
Crescent shaped central developmental grooves are on the mandibular 2nd molar
The maxillary 3rd molar may only have 3 cusps
The oblique ridge of the maxillary 1st molar opposes the groove between the DF and
D cusps of the mandibular 1st molar
A Bennett movement occurs during the earliest stages of lateral movements
In the primary mandibular 1st molar there is a transverse ridge separating the
mesial portion of the tooth from the rest of the occlusal table
The maxillary canine exhibits a distal portion that displays some concavity in its
facial outline
A proximal view of mandibular posterior teeth is rhomboidal and encourages cusp
fracture
Canines are pentagonal from the lingual
In a class II occlusion, protrusion will place the mandibular canines contacting the
maxillary lateral incisors and canines
Curve of Spee has an anterior-posterior curvature of the occlusal surfaces of teeth
as seen from the facial
The pulp cavity of the maxillary canine is pointed in the incisal limit
Primary molars lack identifiable root trunks
Mandibular 1st premolars function similarly to the mandibular canine
THERE IS A DISTAL CONCAVITY ON THE MAXILLARY 1ST MOLAR
AND MESIAL CONCAVITY ON THE MAXILLARY 1ST PREMOLAR

Microbiology/Pathology
Obligate anaerobes in the oral cavity are opportunistic and found in the normal
flora
o Facultative streptococci are the most numerous microbe in the oral cavity
Malignant epithelial cells have an increased number of laminins for invasive
properties
An autosomal dominant trait with 50% penetrance will occur in 25% of the offspring
Pulmonary emboli are most commonly caused by thrombophlebitis
Aflatoxin is produced by aspergillus
Chronic bronchitis will predispose people to lung cancer by causing squamous
metaplasia of the bronchial epithelium

Meningitis is caused by neisseria meningitidis and streptococcus pneumoniae

Carbon monoxide poisoning causes cherry red blood
o Has a200 times higher affinity for binding to hemoglobin than oxygen
In males, mumps can cause orchitis
Bacillary dysentery is most likely caused by shigella
In children < 2 years, gastroenteritis is caused mainly by rotavirus
Alcoholics commonly have esophageal varices cause massive hematemesis
Left ventricular heart failure is indicated by chronic passive congestion of the lungs
Palpable breast masses in women are commonly caused by fibrocystic disease
Rubella and toxoplasmosis are similar in that they are potentially teratogenic
Peptidoglycans are not synthesized in the presence of penicillin
o This only works against growing cells, and therefore cannot be given with
erythromycin
Sudden heart failure is commonly caused by cardiac tamponade
A DNA gyrase inhibitor is ciprofloxacin and serves a broad spectrum
The HBV vaccine makes us generate Anti-HBsAg
All types of muscle have a limited capacity to regenerate
A lack of T cells will allow for candidiasis to run wild in the mouth
If there is a cerebral embolism with a MI then it signifies a mural thrombosis
NK cells are activated by IL-2
Myasthenia gravis is an autoimmune disease where antibodies are directed against
Ach receptors
Adenovirus conjunctivitis is not a common opportunistic infection of HIV
o Candidiasis, hairy leukoplakia, pneumocytsic carinii pneumonia, and
cryptosporidium entercolitis are
Acute bilary obstruction causes a rise in conjugated bilirubin in the serum
Chronic pyelonephritis is usually caused by an infection from urinary influx
Antibodies directed against bacteria in adult periodontitis are IgG
Ethylene oxide inactivates cellular DNA and is therefore a good antimicrobial agent
Drug-induced anemias result in normochromic, normocytic RBCs, but reduced
levels of them
Renal insufficiency does not result in hemorrhagic tendency
o Scurvy, acute leukemia, hepatic insufficiency, and secondary
thrombocytopenia do
Bacterial conjugation transfers the most amount of genetic information between
bacteria
Congestion early on in inflammation is caused by active hyperemia
Transitions are a type of mutation that are caused by base analogues
The arthus reaction is a necrotizing reaction that occurs in response to a second
injection of a foreign material
T helper cells are not antigen specific
o B cells, macrophages, langerhan cells, and dendritic cells are
Immunologic differences in the M protein differentiate streptococcus pyogenese
group A

Nodular prostatic hyperplasia rarely results in the development of carcinomas

o Can cause dysuria, hydronephrosis, pyelonephritis, and urinary tract
obstructions
Myxomas are tumors of CT origin
o Benign (-oma)
Do not penetrate adjacent tissue borders or spread to distant sites
Remain as localized overgrowths in the area of origin
Differentiated tumors (resemble tissue of origin)
Examples
Chondroma = benign chondrocyte tumor
Adenoma = benign glandular epithelium tumor
Teratoma = benign germ cell tumor (with differentiated
structureshair, teeth, skin, etc.)
Hamartoma = disorganized caricature of normal tissue
components
o Malignant (-carcinoma)
Invaded contiguous tissue and metastasize
At distant sites, subpopulations take up residence, grow, and spread
again
Examples
Squamous cell carcinoma = invasive tumor of the skin
Transitional cell carcinoma = malignancy of the bladder
Some historical terms are also used
Hepatoma = malignancy of the liver
Melanoma = malignancy of the skin
Lymphoma = malignancy of the lymphoid tissues
Hemopoietic malignancies are -emia (leukemia)
Secondary descriptors are also used to refer to a
morphological/functional characteristic
Papillary = frond-like structure
Medullary = soft, cellular tumor with little CT
Scirrhous/Desmoplastic = dense, fibrous stroma
Colloid = secrete lots of mucus
Comedocarcinoma = intraductal neoplasm with necrotic
material in the ducts
Some malignancies are a poor histological understanding and are
given their own names (Hodgkins disease, Ewing, sarcoma, etc.)
A chronic ulcer near the inner canthus (corner of the eye) can be diagnosed as basal
cell carcinoma
Multiple myeloma causes bone pain, osteolytic lesions, plasma cell infarctions, and
synthesis of abnormal Igs
Pharyngitis is commonly caused by viruses
The risk for osteosarcomas are increased by osteitis deformans
The protein A of staphylococcus is antiphagocytic, elicits hypersensitivity, and
causes platelet injury

Malignant growth is not characterized by aplasia (lack of cells)

o Anaplasia = things becoming less differentiated (as in malignancies)

The pulp cavity of a permanent mandibular central incisor is flattened mesiodistally

(the canal seems to be pushed from the mesial and distal)
Protrusive pathways of mandibular cusps are towards the mesial
o Working side pathways are towards the facial
o Nonworking side pathways are towards the mesiolingual
The DL cusp of the permanent maxillary 1st molar opposes the MMR area of the
mandibular 2nd molar
The facial cusp of the mandibular 1st premolar opposes the MMR area of the
maxillary 1st premolar
The MF cusp of the mandibular 1st molar contacts the MMR area of the maxillary
1st molar
The axial inclination of the roots of the maxillary 1st premolar are nearly vertical
with the arch
The highest/sharpest cusp of the primary mandibular 1st molar is the ML cusp
The tooth with the greatest axial inclination to the occlusal plane is the maxillary
central incisor
All permanent incisors show from a proximal view that the incisal edge lingual to
the long axis of the root
The maxillary lateral incisors commonly have a lingual groove extend from the
enamel onto the cemental area of the root
Transverse ridges are found on the mandibular 1st molars and mandibular 1st
premolar (most prominently, but to some extent on the other premolars)
The distal contact of the maxillary canine is in the middle 1/3
The wear patterns created by proximal contacts on posterior teeth cause a reduction
in interproximal embrasure spaces
The mesial surface of the mandibular canine is almost parallel to the long axis of the
root
On the mandibular canine FL>MD
The posterior fibers of the temporalis muscle work to retrude the mandible
The cross section of the mandibular canine shows a irregularly oval shape
Dentin is 20-30% organic
The central developmental grooves of maxillary 2nd premolars are shorter and with
more supplementary grooves than the maxillary 1st premolars
The acute angles of the maxillary 1st molar (occlusal surface) are the MF and DL
o The oblique ridge runs from the DB to the ML
The alveolar process is thinnest in facial to the mandibular incisors
In a Class II preparation for the maxillary 1st molar, you must be careful to expose the
MF and ML pulp horns
Calcification of the roots of the primary dentition begin at ages 3-4 years
No teeth contact the maxillary central incisors during retrusion
Proximal contacts function to prevent food impaction, stabilize the dental arch,
and protect the periodontium

The root of mandibular 1st premolars are broader on the facial, lack a marked
distal curvature, and are seen with a slight concave area on the mesial/distal
Pronounced developmental grooves are seen between the embrasures of the
maxillary canines and 1st premolars AND mandibular canines and 1st premolars
The tooth least likely to have a divided pulp canal is the maxillary central incisor
Transseptal fibers are gingival, not PDL fibers