Homeostasis

1. The regulation of the bodys internal environment (intracellular &

extracellular fluids) around set points.
2. Provides chemical reactions with a stable environment.: Maintains ratio of
products and reactions, avoiding consequences of the Law of Mass Action.
3. Regulated by negative feedback processes, compensatory processes.
4. Positive feedback loops are not homeostatic.: A stimulus leads to a response
that does not return the body to a set point. Unstable.
Ex: Childbirth, clot formation, ovulation, immune responses
Pathological examples of positive feedback
i.

Some immune responses

ii.

Development of neural conditions including depression,

schizophrenia

Control Systems & Homeostasis: Local control refers to responses that do not
include the brain. Reflexes.
Set point / normal blood pH = 7.35-7.45 maintained through the use of
buffers, HCO3 ions are the main physiological buffer for acids.: Acidosis vs.
Alkalosis.
Nucleic Acids: Polymers of nucleotides, DNA, ATP.
Carbohydrates: Simple carbohydrates are monosaccharides such as fructose or
glucose or disaccharides such as sucrose (table sugar). Generally soluble in water.
An important source of energy. Forms components of other molecules and cell
membranes (structural function). Simple sugars can link together to form
polysaccharides which are sometimes known as complex carbohydrates.
Proteins: Composed of amino acids. Main source of N. Changing ionic environment
or temperature can alter protein secondary & tertiary shape. Generally soluble.
Most abundant biomolecule in body.
Lipids & Lipid Related Molecules: Hydrophobic, non-polar, not soluble in water.
Fatty acids in blood (free- fatty acids) or membranes. Triglycerides are the primary
form of stored energy (adipose).
Fatty Acids:
1. FAs are saturated or unsaturated.
a. Unsaturated FA increase flexibility of cell membranes, liquid at room
temperature, oils.
2. Unsaturated fats have less energy than saturated fats.
3. Omega 3 are UFAs

4. Trans fats are unsaturated but behave more like saturated fats in the body,
mostly man-made by hydrogenation.
Triglyceride: body fat. Glycerol (carbohydrate) + 3 fatty acids.
Cholesterol: Cholesterol is a steroid lipid, produced in the liver. Structural
component of cell membranes, contributes to membrane flexibility and prevents
water from crossing membranes.
Phospholipid: The major component of biological membranes. Slightly soluble in
water because
the glycerol-phosphate end is polar; the FAs are typically non-polar.
Biological Membranes
1. Cell membrane = plasmalemma = plasma membrane
a. ICF, intracellular fluid (ions, water, nutrients)
b. ECF, extracellular fluid (ions, water, nutrients)
Cell Membrane Structure
1. Membranes are mostly phospholipid & protein.
2. Phospholipid molecules form a bilayer, nonpolar tails on the inside of the cell
membrane, polar heads on surfaces of the cell membrane facing intracellular
fluid and extracellular fluid.
3. Transmembrane proteins span the membrane: Enzymes, Receptors,
Transporters or carriers for impermeable substances.
4. Peripheral proteins are on the intra/extracellular surface: Receptors, enzymes
5. Carbohydrates on membranes usually serve as cell identifiers: ABO blood
groups. Important component of glycoproteins & glycolipids.
6. Fluid Mosaic Model of Biological Membranes: Peripheral and Transmembrane
proteins are loosely associated with phospholipids. (Mobile, flip, change
shape).
Tissues
A. Tissues are collections of one or more types of cells
1. Most are joined with cell junctions: Blood is an exception. It is a
connective tissue with no cell junctions.
2. Cells in a tissue work together to perform a function.
B. 4 tissues types: Muscle, Neural, Connective, Epithelial.
Neural Tissue: Conducts electrical signals for communication, control. Excitable
cells, tissues, due to ability to propagate electrical signals.

Muscle Tissue: Movement and contractions of glands. Excitable & Contractile.

Connective Tissue:
A.

Provides support, structure.

1. Characterized by few cells relative to the amount of matrix or ground
substance in ECF
2. Fibroblast cells secrete ground substance, collagen, and other proteins

B. Blood: Red cells (erythrocytes), White cells (leukocytes), Plasma (ions, water,
proteins).
C. Cartilage, tendons, ligaments, bone have dense matrix.
D. Adipose tissue, body fat, consists of adipocytes filled with triglyceride:
Energy storage, also cushions and protects internal organs.
Epithelia Provide Protection & Regulate Exchange
A. Epithelial tissues, epithelial membranes, separate the body from the external
environment.
1. Any substance entering or leaving the ECF must pass through an
epithelium
B. Five Types of Epithelia: Exchange, Transport, Ciliated, Protection, Secretion.
Exchange Epithelia
A. Exchange epithelia allow material to cross rapidly. Cells are thin & the
epithelium is 1 cell layer thick.
1. Gases CO2 and O2 cross phospholipid bilayers of any cell. Water, urea
usually can as well.
2. High cholesterol content prevents water from using the transcellular
pathway across an epithelium.
3. Leaky exchange epithelia allow larger molecules to pass using the
para-cellular pathway.
Transporting Epithelia
A. Transporting epithelia force material to use the transcellular pathway.
1.
2.
3.
4.

One cell layer thick

Tight junctions
Regulate the movement of impermeable material
Secretion: From the basolateral side of the cell, into ICF, across the apical side
of the cell then usually into a lumen of the digestive tract, kidney, or outside
the body
5. Absorption brings material in.

Protective Epithelium
Protective Epithelia are many layers thick: Skin. Desmosomes connect cells to keep
epithelium intact despite shear forces.
Integumentary System
A. Skin, hair, glands
Protection

Insulation

Water proofing

Temperature regulation

Excretion or Secretion
Cutaneous (skin) Sensory Cells
Metabolism (vit D, needed for calcium absorption)
A. Three regions
1. Epidermis
2. Dermis
3. Subcutaneous or Hypodermis
4. Includes accessory structures: hair, glands, nerves.
B. Epidermis is primarily protective.
1. The upper epidermal layer is composed of dead keratinocytes, filled
with keratin protein: Waterproofing to prevent water loss & Physical
protection.
2. Phospholipids of dead keratinocytes & in the matrix between cells also
provide waterproofing.
3. Living keratinocytes replace keratin layer from below.
4. Lower epidermal layer, near dermis, contains some nerve endings
which are sensory receptors for touch (touch receptors).
5. Lower epidermal layer, near dermis, also contains basal cells which are
stem cells that produce keratinocytes
6. Melanocytes
a. Produce melanin, pigment protein, which is deposited in
extensions off melanocyte that reach into epidermis.
b. Melanin absorbs light, protects DNA in skin cells.
C. The dermis is a thick, 4mm layer of loose connective tissue containing
1. Collagen & elastin fibers
2. Some blood vessels
3. Hair follicles
4. Nerves & sensory nerve endings

5. Exocrine glands: Sebaceous glands secrete lipids into hair follicles,

antibacterial, waterproofing. Apocrine glands release oily fluid into
hair follicle, becomes odiferous. Sweat or Eccrine glands release
hyposmotic fluid through pores, evaporation of the fluid cools
epidermis.
D. Hypodermis contains adipocytes and a high density of blood vessels.
1. Hypodermic injections
2. Adipose provides cushioning, protection, energy, insulation

Osmosis & Diffusion

1. Diffusion moves solute from regions of high concentration to low
concentration.
2. Osmosis is the movement of water from a region of low solute concentration
to a region of high solute concentration. Osmosis without diffusion of solute IF
membrane prevents diffusion.
3. Hyperosmotic vs. hyposmotic
4. Osmosis or diffusion occurs until regions are isosmotic, at equilibrium
5. At equilibrium, the solutions are isosmotic, the hyperosmotic side has gained
water.
Osmotic Pressure: is measured on the hyperosmotic side of a semipermeable
membrane. It is the pressure created as water enters a concentrated,
hyperosmotic solution (region of high osmotic pressure). An increase in blood
pressure in a blood vessel is due to, high osmotic pressure in blood, or high
osmolarity in blood.
Transport Processes: Cell Membranes are Selectively Permeable
1. A phospholipid bilayer is permeable to some small molecules, and to nonpolar (hydrophobic) molecules: Simple diffusion, the movement of substances
across a cell membrane using transient holes in bilayer (Rate increases with
steepness of gradient).
2. Water & urea are penetrating molecules. They are polar, but small: Small
molecules, even if polar, can fit between hydrophobic tails and avoid polar
heads (Urea is a waste product of protein breakdown. Nitrogenous waste).
3. Non-polar molecules are penetrating; membrane is permeable to these
1. Lipid soluble substances do not interact with the polar regions
1. Respiratory gases, oxygen, carbon dioxide
2. Steroid hormones, fatty acids, lipids

4. Cholesterol occupies the spaces between the hydrophobic tails, limiting

access to these spaces.
Review of Simple Diffusion
1) Simple diffusion does not use external energy. Non-polar or hydrophobic
substances, water, small polar molecules go in or out of a cell following
concentration gradients.
a) Passive
b) Passes across bilayer
2) Other processes are protein mediated transport, and can move any kind of
molecule.
Protein Mediated Transport
1. Membrane proteins assist in (mediate) the transport of substances across a
lipid bilayer.
a. Most molecules in body are non-penetrating: lipophobic, ions, charged,
large.
b. Channels (solutes move by diffusion)
c. Facilitated diffusion
d. Primary active transport (requires external source of energy, ATP)
e. Secondary active transport
Channel Proteins
1. Ions use membrane channels.
2. Channels proteins span a membrane, transmembrane, forming pores
a. Do NOT bind substance passing through
1. Channels still allow cell membranes to be selectively permeable.
a. Pore diameter can exclude substances.
b. Charge of amino acids lining the pore can inhibit like-charged ions.
c. Channels can be open or closed.
2. Channel gating is the regulation of channel opening: Does not control rate or
direction of solute movement, still follows concentration gradient
a. Gating stimuli
1. voltage gated channel, change in voltage
2. Chemically or ligand gated channel (change in pH or binding a
substance)

3. Mechanically gated channel (change in local temperature,

pressure
Carrier or Transporter Proteins
1. Uses membrane proteins which temporarily bind the transported substance
(ion, molecule).
a. Binding stimulates a conformational change
2. Co-transporters move more than one kind of ion or molecule at a time (vs.
uniport)
a. Symport: move two or more substances in same direction
b. Anti-port: move in opposite direction.
Facilitated Diffusion
1. Facilitated diffusion is diffusion that requires the help of a transporter.
a. Specificity, because substrate binds receptor.
2. Net transport stops at equilibrium, but substrate still binds and moves in both
directions

Primary Active Transport

1. Primary active transport uses bond energy released by the hydrolysis of ATP
to induce a conformational change in a transporter protein.
2. Moves substances against their concentration gradients (vs. channels or
facilitated diffusion)
Ex: Sodium-potassium ATPase, Na+ /K + ATPase (antiport pump).
Na+ /K + pump is continually working in all cells to keep K + high & Na + low in the ICF.
Homeostasis. Na + channels and K + channels continually allow some leak.
Secondary Active Transport
1. Uses two carrier proteins.
2. #1: primary active transport (using ATP) to create a concentration gradient
for an ion.
3. #2: symport or antiport of a ligand occurs as the ion moves DOWN its
concentration gradient. The transport of the target substrate generally is
moved UP its concentration gradient.
Ex: SGLT secondary active glucose transporter protein co-transports Glucose & Na+,
both into the cell.
1. Na+ in ECF > ICF, maintained by Na+ /K+ pump.

2. SGLT binds Glu & Na+ in ECF, releases them to ICF.

----------------------------------------------------------------------------------------------------------------------------------------Water Balance: Introduction
A. 50-60% total body weight, 30-42 L
B. 2.2 L/d enters from food & drink
C. Some loss is insensible (.9 L/d).
D. Most water is lost in urine: Osmosis at nephron is crucial for water balance.
Functions of the Kidney
A. Regulation of electrolyte balance, osmoregulation
1. Electrolytes ions: Na+, K+, Cl-, HCO3-, PO432. 290-300 mOsM set point
B. Acid/base balance, pH of plasma
C. Works with cardiovascular system to regulate blood pressure & volume of the
ECF
D. Hormone production
1. Erythropoietin (EPO) for red blood cell production.
E. Removal of metabolic waste & drugs
1. xenobiotics
2. Urobilinogen from hemoglobin breakdown in bile by bacteria in the
digestive tract, reabsorbed to plasma, excreted by kidney.
3. Nitrogenous waste.
A. Protein catabolism leaves NH3+, toxic.
B. Enzymes of the Urea Cycle in the liver convert N waste into
urea, blood transports it to the kidney, which excretes it in urine.
Intro: Renal or Urinary System
A. Nephrons process or handle plasma.
B. Renal handling: a description of what the nephron does with molecules found
in plasma or filtrate
Nephron Regions
A. Bowmans capsule

1. Glomerulus from afferent renal arteriole

2. Renal corpuscle
B. Proximal tubule
C. Loop of Henle
D. Distal tubule
E. Collecting duct
F. Blood flow: Renal artery -> Afferent arteriole -> Glomerulus -> Efferent
arteriole -> Peritubular capillaries -> Vasa recta -> Renal vein.
Renal Exchange
A. Filtration moves material from blood to lumen at renal corpuscle, glomerular
filtration rate
B. Reabsorption moves material from filtrate in lumen back to ECF & blood
C. Secretion moves material from blood into tubule, Proximal & Distal tubules
mostly
Glomerular Filtration
A. Blood from the renal artery is filtered at the Bowmans capsule. After
processing, the (usually) hyperosmotic fluid is called urine, and passes to the
ureter and then the bladder.
B. Some of the blood from the renal artery splits into numerous afferent
arterioles.
C. 20% of the blood in a renal arteriole is filtered into the Bowmans capsule by
hydrostatic pressure. This is the filtration fraction.
D. Hydrostatic pressure of fluid (blood) pushes water, ions, nutrients, drugs
through filtration barrier into the capsular space.
A. Cells & proteins remain in blood
B. Filtration is otherwise non-selective.
Diabetes & Renal Function
A. Hyperglycemia, high blood glucose
B. One of the symptoms of nephropathy due to high blood glucose is glycosuria
& proteinuria (albumin).
C. Excess Glu injures epithelia in the renal corpuscle, GFR (glomerular filtration
rate) increases. In late stages of renal failure, GFR decreases.
D. GFR, 125 mL/min, 180 L/day

1. average urine production 1.5 L/d

2. bladder capacity 0.5 L
3. Total plasma volume 3 L
Autoregulation of GFR
A. Autoregulation, intrinsic or contained within the organ.
1. Usually refers to negative feedback responses, reflexes
B. Goal of renal autoregulation of GFR is to maintain constant GFR
1. Too high: poor reabsorption, damage to filtration membranes in renal
corpuscle
2. Too low: poor waste removal, low O2 supply to nephron cells
C. Myogenic response of smooth muscle surrounding the afferent arteriole keeps
GFR constant.
1. Increased blood volume / blood pressure stretches smooth muscle
stimulating reflexive contraction (vasoconstriction).
2. Vasoconstriction if BP above 80mmHg.
3. Dilate if BP less than 70 mmHg.
D. Tubuloglomerular feedback, NaCl in filtrate influences GFR.
1. Macula densa cells of the juxtaglomerular apparatus respond to
increased NaCl
A. Releases a signaling molecule which stimulates vasoconstriction
in afferent arteriole.
B. Increased NaCl indicates high GFR (due to high BP)
C. Vasoconstriction lowers GFR
2. Macula densa cells also respond to decreased NaCl
A. Stimulate granular cells of the juxtaglomerular apparatus to
release renin.
B. Renin is an enzyme that leads to the production of Angiotensin
II.
C. Angiotensin II is a strong vasoconstrictor.
D. Efferent arteriole now constricts, lowering flow out of the
glomerulus, increasing hydrostatic pressure in the glomerulus,
so GFR increases.
Nephron Modifies Filtrate Volume & Osmolarity

A. Hydrostatic pressure filters 180L filtrate

B. Proximal tubule recaptures (reabsorbs) key nutrients, glucose, electrolytes
into peritubular capillaries, osmosis follows, 70% filtrate is reabsorbed.
Reabsorption at the Proximal Tubule
1) Filtrate in Bowmans Capsule through Proximal Tubule is nearly isosmotic,300
mOsM
2) Basolateral side Na+ /K + pump drives reabsorption by lowering Na + in ICF.
a) Na + enters tubule cell through an apical ENaC (epithelial Na + channel).
b) Na+ enters tubule cell via apical co-transport with another molecule such as
Glucose which is undergoing secondary active transport. SGLT (apical side).
i) All Glu in filtrate is reabsorbed at the PCT.
ii) basolateral GLUT
iii) Simple diffusion into peritubular capillary, leaky epithelium
Secretion
A. Secretion moves molecules into the lumen of the nephron for excretion.
1. Secondary or primary active transport: Moving against gradients
2. Most secretion at Proximal Tubule
B. Secrete excess K+ for potassium ion balance
C. Secrete H + for acid / base balance
D. Secrete drugs
1. Most are anions, endogenous vs exogenous
2. Use organic ion transporter OAT

OATs
A. Organic Ion Transporters in PCT
1. Secretion of bile salts, benzoate from food, salicylate, saccharine,
antibiotics, antiviral drugs.
2. Secondary (tertiary) active transport driven by Na+/K+ pump
3. With filtration, contribute to Renal Clearance of xenobiotics, affects
working life of half-life for a drug.
4. Na/K pump keeps intracellular Na+ low

5. Apical Na + symport with a dicarboxylate such as aKG-, Na + down

concentration gradient, aKG- taken up its gradient.
6. High intracellular aKG- drives an OAT, a basolateral antiporter that
brings in an organic anion which exits the apical side through other
transporters
Interstitial fluid of Renal Medulla

A. Filtrate is isosmotic after reabsorption in the proximal tubule, but urine is

usually hyperosmotic.
1. Urine varies from 50-1200 mOsM
2. Diuresis, large quantities of hyposmotic urine.
B. Events in the Loop of Henle and Collecting Duct cause ISF of renal medulla to
vary from 300 mOsM near cortex to 1200 mOsM deep in medulla. This is the
cortico-medullary gradient.
C. Filtrate passing down collecting duct becomes concentrated
1. Osmotic pressure in ISF greater than filtrate
2. Water leaves
3. Filtrate OsM increased
4. Filtrate moves down, encounters ISF of greater osmotic pressure.
D. Aquaporin, water channels, on apical and basolateral membrane of collecting
duct cells.
1. Present, osmosis occurs, filtrate loses water to ISF

E. Presence of aquaporin due to hormone, vasopressin

1. ADH, antidiuretic hormone.
2. ADH increases number of aquaporin (AQP-2) on apical membranes of
collecting duct.
F. ADH released into blood from Posterior Pituitary
1. Reaches receptor on basolateral membrane
2. Stimulates upregulation of AQP-2
Fluid and electrolyte homeostasis
A. Water Balance
1. Intake, L/d
a. Food, drink 2.2: Thirst, main response for water intake
b. Metabolism .3
2. Loss, L/d
a. Insensible, .9
b. Urine 1.5: Renal responses, main solution to decrease loss.
c. Feces .1
B. The function of the kidney is to regulate excretion, usually by conserving
water.
1. Osmosis from the collecting duct
2. Regulation of GFR
C. ADH, anti-diuretic hormone
1. posterior pituitary
2. increases production & insertion of aquaporin in apical membrane of
collecting duct, allows more osmosis & water reabsorption
D. Osmosis relies on ionic gradients. The regulation of ion and electrolytes
affects water balance as well as ionic balance
1. K+ in ICF affects excitable cell function
2. Na+ in ECF affects osmolarity, 300 mOsM set point.
E. Respiratory, cardiovascular, renal systems are most affected by fluid and ion
balance
1. CV system monitors blood pressure, ECF volume

Blood volume and osmolarity activate osmoreceptors

A. Osmoreceptors are neurons that are sensitive to changes in cell volume
1. Neuron is a single cell
2. Change in plasma membrane alters ion flux
3. Current hypothesis: shrinking opens cation channels
B. Example: Hyperosmolarity due to water loss or increased salt intake
stimulates osmoreceptors in the forebrain and hypothalamus
1. Hypothalamic osmoreceptors
2. Monitor blood plasma osmolarity
3. Stimulates AVT release & feelings of thirst
4. Hypothalamic osmoreceptors stimulate ADH release from posterior
pituitary at plasma osmolarity > 280 mOsm
A. Always some ADH in blood
B. Some osmoreceptors respond to low plasma osmolarity
C. Baroreceptors are stretch receptors (& shrink) in locations that detect
changes in blood volume or blood pressure.
1. Lower blood pressure in the heart or in main arteries leaving heart
(carotid, aortic) stimulate baroreceptors
2. Baroreceptor activation leads to hypothalamic stimulation
A. Hypothalmic stimulation leads to AVP release from posterior
pituitary.
3. Baroreceptors also stimulate the diencephalon
A. which activates sympathetic nerves
B. which increases heart rate, contraction strength of heart
A. leading to an increase in blood pressure
A.

ADH release

Low BP stimulates carotid

& aortic baroreceptors

Low blood volume

stimulates atrial stretch
receptors

High plasma osmolarity

stimulates hypothalamic
osmoreceptors

B. Plasma osmolarity increases due

to

High salt intake

Dehydration

C. Hypovolemia, low blood volume

(usually also means low blood
pressure).

Stretch receptors in atrium

of heart

LACK of stretch will

stimulate hypothalamus

D. Low blood pressure

Stimulates carotid & aortic

baroreceptors
o

Increase cardiac

output, senstive
o

Increase ADH release if BP or blood volume drops approx. 10%,

L

Normally, only hypothalamic osmoreceptors control ADH.

A. Ingest salt, ECF osmolarity increases

B. Hypothalamic osmoreceptors shrink,

stimulates release of AVT from posterior
pituitary into blood.
C. AVT leads to increased water reabsorption
D. Hypothamic osmoreceptors also stimulate
thirst by activating the anterior cingulate
cortex.
a. increases water intake which
increases ECF volume.
E. Blood pressure increases
a. Carotid, aortic, atrial baroreceptors
decrease ADH release
b. Baroreceptors decrease cardiac function to lower BP (cardiovascular
reflex)
F. Filtration eventually removes excess Na+. Osmolarity and blood pressure
return to normal
Behavioral mechanisms in salt and water balance
A. Thirst, conscious sensation of the need for water, homeostatic drive.
1. Increased plasma osmolarity
2. Decrease blood volume
3. Dry mouth
4. Increase ANG II
B. Oropharynx receptors initiate AND terminate drinking
1. Increase thirst
2. Decrease thirst
3. Decrease ADH secretion
4. Fluid, especially cold.
Low Na+ stimulates salt appetite
C. Low Na+ in filtrate and low plasma osmolarity will lead to the release of a
hormone, ANG II
1. Increased salt appetite by stimulating brain regions including
hypothalamus, amygdala, brainstem.
2. Increased ADH
3. Increased blood pressure, hypertension

Aldosterone controls sodium balance

A. Steroid hormone from adrenal cortex.
B. Increases in response to hyperkalemia, hypotension.
C. Acts on Principal (P) cells of renal distal tubule & upper region of collecting
duct

increases Na+ reabsorption (increases osmotic

gradient)

increases K+ secretion

Aldosterone
1. Basolateral Na+ /K + ATPase works faster
2. Upregulation of Na+ /K+ pumps & Na+ & K+ channels
3. Pumps bring more K+ into the cell from interstitium
(so more leaves plasma).
4. K+ & Na+ channels on luminal side for K+ efflux, Na+
influx
5. Increased K+ secretion resolves hyperkalemia
6. Increased Na+ reabsorption
D. Aldosterone alone does not lead to osmotic water reabsorption
7. Collecting duct permeability, due to ADH, allows osmosis to respond to
increased osmotic pressure
E. High plasma osmolarity will inhibit aldosterone release from the adrenal
cortex
Low blood pressure activates RAS pathway
F. Low blood pressure in afferent arteriole, (uncorrected by autoregulation)
stimulates granular cells of juxtaglomerular apparatus
G. Renin-Angiontensin (RAS) Pathway
a. Granular cells of the juxtaglomerular apparatus secrete renin in
response to low blood pressure in afferent arteriole
b. Renin converts Angiotensinogen, an inactive plasma protein, into
Angiotensin I.
c. Angiotensin-converting enzyme (ACE) in the endothelial lining of most
blood vessels, converts ANG-I to ANG -II.
d. ANG- II stimulates adrenal gland to release aldosterone.
Angiotensin II has many effects: ANG II increases blood pressure

1. Stimulates vasoconstriction in vessels which increases blood pressure

2. Stimulates brain regions which control cardiovascular system leading
to further vasoconstriction, increased heart rate, and increased
strength of heart contractions.
3. Stimulates Hypothalamus to release ADH: Increases ADH, osmotic
water reabsorption from collecting duct, blood volume, blood pressure.
4. Stimulates hypothalamic thirst centers: Increases water intake, blood
volume, blood
5. Stimulates aldosterone release from adrenal cortex (main function):
Increases K+ secretion BUT ALSO Na+ reabsorption, osmotic water gain
IF ADH present.

Natriuretic peptide promotes Na+ and water excretion

1) ANP, atrial natriuretic peptide

2) Stretch receptor in atria of heart releases
ANP when blood volume increases
a) ANP binds ANP receptors on
hypothalamus, inhibits ADH release
b) Blocks renal receptors for ADH
i) Fewer aquaporin, lowers osmotic
water reabsorption
c) Inhibits aldosterone release, binds
receptors on adrenal cortex.
i) decreases Na+ reabsorption
d) Strong vasodilator
i) lowers systemic BP
ii) inhibits renin (& aldosterone)
secretion by lowering BP in afferent
arteriole
(1) Less ANG II
(2) Less renal Na+ reabsorption
iii) lower systemic BP may lower GFR, but the dilation affects afferent
arteriole so ultimately, GFR increases, excretion increases.
----------------------------------------------------------------------------------------------------------------------------------------Resting Membrane Potential
A. The uneven distribution of charged particles between ECF and ICF creates a
membrane potential, or potential difference
1. Assign ECF as ground, 0 volts
2. Because there are more (-) charges, and fewer (+) charges in the ICF, the ICF is
relatively negative
B. K+ is the main intracellular cation & it is more concentrated in the ICF
C. Phosphate and proteins are the main intracellular anions.
D. Na+ and Ca2+ are the main extracellular cations, and are more concentrated in
the ECF than ICF
E. Cl is the main extracellular anion.
F. Because of the distribution of charges, cells maintain a constant potential
difference, voltage difference, membrane potential.

G. Some cells (neurons, muscle) are excitable, able to change Vm as a way to send
electrical signals.
Cause of the Resting Membrane Potential
A. Resting membrane potential is the result of
1. Fixed anions : Phosphate, proteins, Glucose, ATP are trapped in the ICF
2. K+ distribution
a. The cell membranes selective permeability to ions
b. Na+/K+ pump activity: leave ICF relatively negative (3 Na out/2 K in).
Resting Membrane Potential
A. The distributions of cations and anions across a cell membrane are determined
by the net electrochemical gradient for the ions, the Na+/K+ pump and selective
membrane permeability
1. Chemical gradient = concentration gradient
2. Electrical gradient: Cations (+) attracted to (-) regions & Anions (-) attracted to
(+) regions
A. An electrochemical equilibrium determines K+ distribution.
1. Electrical: Large anions trapped in ICF and activity of the Na+/K+ pump makes
the ICF (-), so K+ is attracted to the ICF
2. Chemical: The Na+/K+ pump also creates a concentration gradient favoring K+
efflux, K+ is drawn to the ECF.
A. An electrochemical equilibrium determines Na+ distribution.
1. Electrical: Large anions trapped in ICF and activity of the Na+/K+ pump makes
the ICF (-), so Na+ is attracted to the ICF
2. Chemical: The Na+/K+ pump also creates a concentration gradient favoring Na+
influx, Na+ is drawn to the ICF by this too
Equilibrium Potential
A. The equilibrium potential for an ion is the membrane potential (Vm) that would
be measured if that one ion were allowed to come to equilibrium across the
membrane, while all others are held constant
B. The equilibrium potential for K+ is -90mV
1. The K+ concentration gradient favors K+ leaving the cell. It leaves through leak
channels.
2. But, K+ feels an electrical gradient pulling it back in, -70mV (anions, pump)
3. Also, as K+ leaves, the ICF becomes more negative.

1. End net K+ efflux, leaving cell more negative than resting, -70 mV to -90 mV
2. The K+ eq is the point at which the electrical and chemical gradients acting on
K+ are equal.
C. The equilibrium potential for Na+ is +60mV
1. Both electrical and chemical gradients acting on Na+ favor Na+ entry into ICF
2. Na+ influx through leak channels
D. The Na+ eq is the point at which the electrical and chemical gradients acting on
Na+ are equal
Changing Membrane Potentials
A. Resting Vm is polarized, not 0.
B. Depolarizing changes make the membrane less polarized, less negative, closer to
0 from -70mV, Vm decreases.
C. Repolarization, return to resting.
D. Hyperpolarization, more negative than resting
E. Overshoot above 0
Neurons Carry Electrical Signals
A. Single cell, functional unit of the nervous system.
1. Function is to conduct electrical signals.
B. The axon conducts action potentials. APs are triggered when the axon hillock
(trigger zone) is depolarized enough to reach threshold.
1. Only axons conduct action potentials.
Graded Potentials Reflect Stimulus Strength
A. Observed in most cells.
1. depolarizations or hyperpolarizations
2. Graded
a. Amplitude proportional to signal
b. Signal is influx Na+ or efflux of K+
c. Return to resting Vm due to cation leak
d. Na+/K+ pump restores resting ion concentrations
B. like repels like, Na+ entry repels all intracellular cations (mostly K +), a wave
of depolarizing + charges from site of Na+ influx

C. At any point in a membrane, a voltmeter will measure a depolarization (rise

in Vm) peak, and repolarization to resting.
D. Key features of graded potentials
1. A greater stimulus (more Na+ influx) creates a larger depolarization
2. The larger depolarization travels farther from the point of origin so the
graded potential will be detectable over longer distances but constant
K+ leak and Na+/K+ pump activity, the depolarization dissipates over
distance and time.
Action Potentials Travel Long Distances
A. A single stimulus triggers a series of changes in Vm that does not dissipate
over distance.
1. all-or-none event unlike graded potential.
2. Change in membrane voltage that has the same size and shape each
time it is triggered, unlike graded potentials.
3. Seen in axons, where voltage gated channels are found
Action Potentials
A. If a graded potential reaches the axon hillock, some voltage gated Na +
channels open
1. Na+ VGC threshold for opening, -55 mV
B. Na+ influx depolarizes the cell, reaching threshold for more Na + VGC. Positive
feedback.
C. A spike, rapid depolarization. Na + influx brings the cell towards ENa+
D. After a few milliseconds, Na+ channels close, Vm at +30mV.
E. Falling phase of the spike of the action potential is due to K + efflux through
voltage gated K+ channels, very slow to open after threshold is reached.
F. Vm hyperpolarized due to continued K+ efflux, Vm heads towards EK+.
G. When all voltage gated channels are closed, Na + leak (influx) and Na+/K+
pump activity restores Vm & ion distributions to resting.
H. Very few ions move, thousands of action potentials can be generated in an
axon even if Na+/K+ pumps are disabled.
Refractory Periods
A. No action potentials during the Absolute Refractory Period
1. Lasts the duration of the spike, voltage gated Na + channels are
refractory.

2. Time required for these to reset, return to resting state.

B. Relative Refractory Period, an action potential can occur if stimulus is larger
than normal.
1. Na+VGCs that have not returned to resting require a greater
depolarization.
2. K+ channels are open, counteracting Na + entry during stimulus.
Action Potentials are Conducted
A. Na+ influx due to an AP spike
B. Na+ pushes K+ away, K+ spreads to adjacent regions of the axon, collect under
a spot, causes depolarization.
C. Na+ influx at site of action potential moves K+ in both directions, toward cell
body and toward axon terminal.
D. The only side that can generate an action potential is the side that is not
refractory
Conduction Velocity
A. Myelin provides insulation or high resistance to the loss of cations from the
cell. This improves axonal movement of cations.
1. Na+ VGCs concentrated at Nodes of Ranvier, APs leap from node to
node, saltatory conduction.
2. Thin, unmyelinated neuron speed 1.0m/s
3. Thick, myelinated neuron speed 100m/s
Synaptic Communication
A. The junction between a neuron & another cell.
B. When an action potential reaches axon terminal of presynaptic cell,
neurocrine neurotransmitters are released, cross synaptic cleft, alter ion
permeability in the postsynaptic cell resulting in a graded potential.
Neurotransmitter Release
A. Neurotransmitter (NT) is stored in vesicles in presynaptic axon terminal
B. Na+ influx during action potential opens voltage gated Ca 2+ channels on
terminal membrane, Ca2+ enters cell: Electrochemical gradient for Ca2+ favors
influx.
C. Ca2+in the presynaptic axon terminal activates intracellular proteins which
move vesicles to presynaptic membrane and cause exocytosis of NT.

D. NT diffuses across the synaptic cleft & may bind with receptors (R) on
postsynaptic membrane.
E. The consequence of NT binding receptors depends on the receptor.
F. K+ efflux repolarizes terminal, closing VG-Ca2+channels
G. NT release continues as long as enough presynaptic Ca 2+ is present. A pump
continually works to remove Ca2+
Fast and Slow Postsynaptic Responses
A. The consequence of NT binding postsynaptic receptors depends on the
receptor.
B. Binding may open or close ion channels (ionotropic receptors) on
postsynaptic membrane
C. Ionotropic receptors are ligand or chemically gated channels. Fast response
because neurotransmitter immediately alters ion flux
D. Binding may activate metabotropic receptors such as G-proteins.
A. Slow.
B. The neurotransmitter binds a G-protein coupled receptor.
C. Receptor activates a G-protein (intracellular, peripheral).
D. G-protein activates, a 2nd messenger system, an intracellular signal
molecule, cAMP
E. cAMP acts as a ligand for a chemically gated channel OR modifies an
intracellular protein, a slow process
Response to NT
A. In the nervous system, G proteins usually open ion channels
B. Ion channel receptors
1. Excitatory post synaptic potentials
a. EPSP
b. Depolarizing
2. Inhibitory post synaptic potentials
a. IPSP
b. hyperpolarizing
Nicotinic AChR
A. Ligand gated channels, common in neuromuscular junctions.

B. Excitatory, binding ACh opens Na+ channel, depolarizes dendrite/cell

1. Nicotine is an agonist.
C. Somatic nervous system, controlling muscle contraction. Always excitatory.
Peripheral Muscarinic AChR (not CNS)
A. Glands and smooth & cardiac muscle cells.
1. Inhibitory.
2. ACh activates G-protein, G binds & opens K+ channel
Termination of Neurotransmitter Activity
A. Neural signals are brief, allowing them to adjust rapidly to changing
conditions.
1. At any point, some neurotransmitters are binding receptors, some
being terminated.
2. After binding, some rebind, some terminated.
3. Reuptake
4. Inactivate
5.

Diffusion away from synapse

Reuptake
A. All or part of the NT can return to the presynaptic cell
1. NE, norepinephrine, an amine NT uses Na+ symport for reuptake, MAT,
mono-amine transporter.
a. Repacked into vesicle
b. Mono-amine Oxidase MAO in mitochondria can break down
amine NT: NE, dopamine, serotonin
NT Inactivation
A. Acetylcholine, ACh, inactivated by Acetylcholinesterase (AChE), enzyme on
postsynaptic membrane of a cholinergic cell
A. Choline taken into presynaptic cell, joins new Acetate produced in the
presynaptic terminal & reforms ACh
Acetylcholine
Cholinergic synapses
a. Nicotinic, ion channels. Nicotine is an agonist, supports activity of receptor.
b. Muscarinic, muscarine agonist. G protein receptors.

c. AChE inactivation followed by reuptake

Amine or mono-amine neurotransmitters
A. Derived from tryptophan or tyrosine.
B. Common in CNS (central nervous system, brain & spinal cord)
C. Serotonin, tryptophan.
D. Dopamine, norepinephrine (NE), epinephrine (Epi) from tyrosine
E. Epi / NE in adrenergic, noradrenergic neurons.
1. Adrenergic receptors are G proteins, open an ion channel.
2. All or part of the NT can return to the presynaptic cell using Na+ symport on the
MAT, mono-amine transporter.
a. Repacked into vesicle
b. Mono-amine Oxidase MAO on mitochondria break down amine neurotransmitters
in the axon terminal
F. Serotonin NT in synapses that regulate mood.
G. Dopamine NT for synapses regulating motor control & emotional reward.
H. Norepinephrine found in the heart, smooth muscles, leads to increased blood
pressure by causing vasoconstriction.
Amino acids
A. Glutamate, main excitatory NT in the CNS
1. Some receptors are ionotropic some metabotropic
B. GABA, gamma-aminobutyric acid, main inhibitory NT in the CNS
1. Receptor is a Cl- channel
Stronger stimuli release more neurotransmitter
A. Action potentials are all or none, so size of AP cannot carry information about
signal strength.
B. Frequency of APs reflect stimulus strength / size, and stimulus duration
1. If GP is still above threshold at hillock, when the hillock reaches relative refractory
period or leaves RRP, another AP will be generated.
a. Larger stimuli will keep GP above threshold longer, more AP per time
Integration of neural information transfer
A. Most neurons interact with more than one pre or post synaptic cell.

B. Divergence
1. Axons of a presynaptic cell branch, forming collaterals that synapse onto more
postsynaptic cells.
2. Divergence allows one signal to contribute to many different effects
C. Convergence is more integrative; one cell receives input from many others
Summation: Integration of Synaptic Signaling
A. Each action potential releases a fixed amount of transmitter. In many synapses,
one action potential is NOT sufficient to generate an action potential in a
postsynaptic cell. How do you build a stronger graded potential at the hillock?
1. Summation. Adding the effects of multiple APs at one or multiple synapses
B. Spatial summation: postsynaptic cell receives input from more than one neuron
1. Sum of EPSPs & IPSPSs affect the graded potential reaching trigger zone.
2. Synapses closer to hillock may dominate
B. Temporal summation: postsynaptic cell receives input from one synapse that is
itself firing many APs, thus many quanta of NT are released: EPSP or IPSP
Synaptic Modulation
A. Postsynaptic modulation
1. Change number of receptors, due to infrequent use or due to stimulation
2. Up-regulation, increase postsynaptic receptors
3. Down-regulation, decrease postsynaptic receptors
4. Learning is an example of Postsynaptic modulation and Long-Term Potentiation
Long-Term Potentiation
A. Learning increases the size of an EPSP when the transmitter Glutamate binds 2
receptors.
1. NMDA-R
2. AMPA-R
B. Glutamate binds AMPA-R, Na+ influx, EPSP
C. Glutamate binds NMDA-R. If the membrane has been slightly depolarized by the
Na+ influx at the AMPA-R, get Ca2+ influx at the NMDA-R
D. Ca2+ leads to upregulation of AMPA-Rs, an increase in AMPA-R function, and
presynaptic modulation to increase glutamate release.
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Central Nervous System

A. brain & spinal cord
B. General functions
1. Homeostasis.
2. Combining and interpreting sensory input, origin of voluntary responses.
3. Motor control. Directs activity of motor neurons controlling skeletal muscles,
endocrine & exocrine glands.
C. Neurons of the brain are surrounded by cerebrospinal fluid (CSF) secreted by
chloroid plexus
1. ECF of CNS
2. Protective cushioning
3. Nutrient & waste exchange, absorbs nutrients from blood, drains into blood.
Blood-Brain Barrier
A. Astrocytes are the most abundant glial cell, and more than 50% of the cells in the
CNS are glial cells.
1. Regulate synapse function by taking up neurotransmitter that has diffused out of
the synapse and/or transporting transmitter and precursors back into neuron
2. Astrocytes also induce endothelial cells to form tight junctions forming the bloodbrain barrier.
B. Endothelial cells of capillaries form tight junctions (vs leaky endothelium).
1. Regulates exchange between plasma, neurons & CSF by sealing off the
paracellular pathway for molecular transport from blood to ISF.
2. Barrier to bacteria, large & polar molecules including antibodies, many drugs.
Metabolic requirements of neurons
A. All neurons require substrate for aerobic metabolism to make ATP
1. Glucose, oxygen
a. O2 & CO2 easily pass through blood brain barrier.
b. Astrocytes provide glucose and glycogen
c. SGLT & GLUTs on cells of the blood-brain barrier
Brainstem
A. Controls autonomic or involuntary functions (below consciousness) & homeostatic
functions

1. Influenced by higher centers in the cerebral cortex and hypothalamus.

2. Visceral reflexes, muscle & gland activity, micturition, respiration, vomiting,
swallowing, digestion.
Cerebellum
A. Processes sensory information relating to movement and the position of the body
1. Sensory input from receptors of equilibrium in inner ear
2. Integrates sensory information with proprioceptors (receptors in joints and
muscles that monitor position)
Diencephalon
A. Thalamus & hypothalamus
B. Thalamus first site of processing for visual and auditory senses, sends
information to other regions.
C. Hypothalamus is the center for homeostasis, master gland for autonomic
functions.
1. Thermoregulation, plasma osmolality, reproduction, hunger / satiety behavior
2. Regulates hormone release as well as neural responses to stimuli.
D. Pituitary & Pineal glands are endocrine glands of diencephalon
Cerebral cortex
A. The centers or regions include
1. Cerebral cortex, location of higher brain functions, integration, thinking,
reasoning.
2. Limbic system, near brainstem, primitive.
Limbic System
1. Amygdala of limbic system, associated with physiological responses to emotions,
especially fear.
2. Hippocampus of limbic system regulates learning in higher centers.
Overview of NS structure
A. Central Nervous System
B. Peripheral Nervous system
1. Afferent division: Sensory input sent to CNS
2. Efferent division
a. Somatic division, controls skeletal muscle: voluntary, motor control.

b. Autonomic division, below the level of consciousness, visceral functions:

involuntary, controls smooth & cardiac muscle, glands, viscera.

Sympathetic fight or flight: Circulatory adjustments during normal or

stressful times, adrenergic synapse at target cell.
Parasympathetic rest & digest: cholinergic synapse at target cell.