RAKESH SHARMA, BAMS, MS-Ph.

Biochemistry and Biomedical Science

http://myprofile.cos.com/rakesh

Course material: BME 4004c

Florida State University, Tallahassee, Florida 32304

 Unit I
Membrane Dynamics
&
Body Fluid Compartments
 Membrane Dynamics
• Membranes in The Body
– The cell Membrane or Plasma Membrane
• Phospholipid Bilayer
Glycoproetins (Carbo)

ECF Fig 1
Membrane Spanning
( Integral) Protein

Hydrophobic
Tails

Fatty Acid Tail

Hydrophilic Heads (Non Polar)
ICF
Phospholipid Head
Polar
 The Cell Membrane
The Cell Membrane, is the
Membrane That Surrounds The Cell.
Membrane Lipids Form a Barrier Between
The ICF and The ECF
Regulation of Exchange with The
Environment
Communication Between The Cell and its
Environment
 Membrane Proteins
Function as:
Structural
Enzymes
Receptors (Cell Signaling)
Transporters
• Channel Proteins
• Carrier Proteins
 Membrane Proteins
“Receptors are Part of The Cell Signaling System”

Fig 2
 Transporters
“Channel Proteins”

Phospholipid

Fig 3

Membrane Protein
 Membrane Proteins
Transporters

• Channel Proteins
Water Filled Channels
(Aquaporins)

Fig 4

Channel Proteins

Named after substance they allow to pass Na+ K+

Maybeopen (leakChannels) or gated(Voltage)

 Gating of
Channel Proteins
Closed ECF Open

ICF

Chemically, Voltage or Mechanically Gated Fig 5

 Membrane Proteins
Transporters

Carrier Proteins
Never a direct
Connection between
ICF and ECF

Substrate

Fig 6
 Body Fluid Compartments

ECF ICF

Blood Instfl

Fig 7 Cell Membrane

 Movement Across Membranes
• Diffusion
• Osmosis
• Carrier-Mediated Transport
Movement Across Membranes
“Diffusion”

High Low
Concentration Concentration
Movement Across Membranes
“Osmosis”

H2O

High Low
Concentration Concentration

Semi Permeable
Membrane
 Movement Across Membranes
“Carrier-Mediated Transport”

• Mediated Transport

Substance A
+Carrier Protein
Semi permeable
Membrane
– Facilitated Diffusion
• Passive (Moves down Concentration Gradient)

– Active Transport
• Active (Moves against Concentration Gradient)
– ATP ADP + E
 Carrier-Mediated
Transport
• Carrier Proteins
1. Specificity
• GLUT Transporters

2. Competition
3. Saturation
Fig 8
 Carrier Mediated Transport
“Uniport”

Energy

Carrier

Concentration
Gradient (active) Concentration
Gradient (Passive)
Fig 10 Carrier Mediated Transport
 Carrier Mediated Transport
“Symport Cotransporters”
Energy

Co transport
Carrier

Concentration
Concentration
Gradient (Passive)
Gradient
Carrier Mediated Transport Fig 11
 Carrier Mediated Transport
“Antiport Cotransporters”
Energy

Co transport
Carrier
Concentration
Gradient
Carrier Mediated Transport
Fig 12
 Facilitated Diffusion
“Down The Diffusion Gradient”

GLUT

Fig 9
 Active Transport
“Requires The Input of Energy From ATP”

• Primary Active Transport

– ATP ADP + E
• Secondary Active Transport
– Kinetic Energy

ATP ADP
Active Transport
“Primary Active Transport”

Energy Source

Fig 13

3Na+ - 2K+ - ATPase Pump

 Active Transport
“Secondary Active Transport”

Kinetic E ( down Concentration Gradient )

Na+ High
Glu Low Na+ Low
Glu High

Na-Glucose Symporter

Fig 14
Transepithelial Transport
Glu Na+
What is this

What is this

Glu Na+
What is this

Glu Na+ K+ = Low

= High

Glu Na+ K+

How Well Do You Understand This ?

 Calcium Is the Signal for Exocytosis

Action
Potential

Axon Terminal
Action Potential
Depolarizes Axon Terminal
Synaptic
Voltage Gated Ca2+
Vesicles
Channels Open

Calcium Induced
Exocytosis
Voltage Gated
Ca2+ Neurotransmitter binds
Channels With receptor
Receptor
Response
 Unit II
Electrical Signals and The Cell
Membrane
“ Lets Get It Right”
 The Cell Membrane Allows
Separation of Electrical Charges

Cell Membrane

Fig 1

Cell and Solution are at Electrical, Osmotic and Chemical Equilibrium

 The Cell Membrane Allows
Separation of Electrical Charges

Resting membrane
Cell Membrane -1 Potential
+1
Fig 2

Cell and Solution are Electrically and Chemically at Disquilibrium

Measuring Membrane Potential
Differences

This is the Membrane

Potential Difference
ICF Fig 3
ECF -40 and - 90mV

But Why ?
The Resting Membrane Potential is
Due Mostly to Potassium

Fig 4

Cell and Solution are Electrically Neutral

The Resting Membrane Potential is
Due Mostly to Potassium

Fig 5

Potassium Follows Concentration Gradient

The Resting Membrane Potential is
Due Mostly to Potassium
K+ out

Concentration Gradient

Electrical Gradient
+1

-1

So….. Equilibrium Potential is………… Fig 6

EIon or EK Concentration Gradient = Electrical Gradient

The Resting Membrane Potential is
Due Mostly to Potassium
• The Nernst equation
– Eion= 61/z log [ion]out/[ion]in
• Z = Charge on the Ion
• [ion] are the ion concentrations inside/outside
the cell
• Here 150 mM K+ in and 5 mM K+ out @37 C
• Ek = -90mV
The Resting Membrane Potential is
Due Mostly to Potassium

Fig 7
 The Resting Membrane Potential is Due
Mostly to Potassium
• The Nernst equation
– Eion = 61/z log [ion] out/[ion] in
• Z = Charge on the Ion
• [ion] are the ion concentrations inside/outside the cell
• Here 150 mM Na+out and 5 mM Na+in @37 C
• ENA=+60mV
• EK=-90mV
• But the Cell would have a resting membrane potential of – 70mV
( Goldman Equation)
 Ion Movement Across the Cell
Membrane Creates Electrical Signals
• Resting Membrane
Potential (-70mV)

Concentration Grad
ECF

Elect- Grad

ICF
0 mV Fig 8

K+ is the Key Player Here

Changes in Ion Permeability Change the
Membrane Potential
• Depolarization
-10mV
Na +
Cl -

Fast Slow
ECF

K+ ICF

Fig 9
Voltage Gated Na+ Channels Open
Na+ is The Key Player Here
Entry of Cl- Ions would Hyperpolarize
Changes in Ion Permeability Change the
Membrane Potential
• Repolarization
+30mV
Na+
Close
ECF

K+ ICF

Fig 10
Changes in Ion Permeability Change the
Membrane Potential
• Repolarization
-70mV
Na+

K+

K+

Fig 11
 Ion Movement Across the Cell
Membrane Creates Electrical Signals
• Resting Membrane
Potential (-70mV)

ICF

ECF

Na+ ---- K+ ATPase Pump Returns Proper

Concentration Gradient
Fig 12
 Ion Movement Across the Cell Membrane
Creates Electrical Signals
Na+ Channels Close
K+ Channels Open

K+ Channels Remain Open

Na+ Channels
Open
Return to Normal Ion
Conc. 3Na+ -2K+ Pump
Resting

Fig 13
K+ Channels Close
 Unit III A
Cell-to Cell Communication
Signal Pathways and Chemical
Messengers
 Cell To Cell Communication
” How Does The Body Control 75 Trillion Cells?”

• Gap Junctions
• Local Communication
• Autocrines and Paracrines
• Long Distance Communication
• Neurocrine
• Neurotransmitter
• Neuromodulators
• Neurohormone
• Cytokines (Regulatory Peptides/ May be Local or Long Distance )

• Hormones
 Gap Junctions
“Transfer Chemical and Electrical Signals Directly
Between Cells”
Protein Channels
(Connexon)

Membrane
Spanning Protein

Fig 1 Cytoplasmic Bridges

 Autocrines and Paracrines
“Local Calls Only”

Diffusion
Autocrines and Paracrines

Target

Fig 2
Chemical Signals Distributed by Diffusion
 Hormones
“Long Distance Please”

Blood
Hormone

Fig 3
Neurotransmitter/Neuromodulator
“Long Distance Please”

Neurotransmitter/
Synapse
Neuromodulator

Fig 4
 Neurohormone
“Long Distance Please”

Neurohormone Ligand
Blood

Fig 5
 Signal Pathways
“A cell cannot respond to a chemical signal if it lacks the appropriate
receptors for that signal”

1 Signal Ligand First messenger

Target
Directs the cellular
Receptor response
2
Activation Effectors (Last intracellular signal molecule)
4
3
Synthesis of or modification
Intracellular signal of target protein
molecule

Response
 Signal Pathways
Receptors
“Inside the cell or on the Cell Membrane”

mRNA

Fig 6
 Signal Pathways
“There are Four Major Categories of Membrane Receptors”

• Types of Receptors
• Ion-Gated
• Receptor-Enzymes
• G-Protein Coupled
• Integrin receptor
 Signal Pathways
Ion-Gated membrane Receptor

Ligand

Ion Gated Channel ECF

Alters Ion Flow
ICF

Ligand Binding opens or closes the channel

Fig 7
 Signal Pathways
Receptor-Enzyme Membrane Receptor

Ligand

Receptor Region

ECF
Activation of an
Enzyme
ICF

Fig 8
Enzyme Region
Ligand Binding to a receptor-enzyme activates an
Intracellular enzyme
 Signal Pathways
Integrin Receptor

Integrin

ECF

ICF

Fig 9 Cyctoskeleton

Ligand Binding to Integrin receptors alters

the cytoskeleton
 Signal Pathways
G-Protein Coupled Membrane Receptor

Ligand

G Protein Receptor ECF

ICF

Fig 10
G Protein

Ligand Binding to a G protein-coupled receptor opens

an ion channel or alters enzyme activity
 Signal Pathways
“Membrane Proteins Facilitate Signal Transduction”
Signal Molecule
1
ECF
Receptor
First Messenger ICF
Amplification
2
Enzymes
Signal Transduction
By
Effector Proteins

4
3
Second Messenger Opens Ca Ion
Protein Kinases
Channel

5
Cellular Response
Increase Intracellular
Fig 11 Ca++
 Signal Pathways
Ions
Signal Molecule

Ion Channel

Ions Create Electrical

Signals

-
Na+ , K+ , Cl
Creates Electrical Signal

Voltage Sensitive Cellular Response

Fig 12 Proteins
 Calcium
An Intracellular Messenger
Ca2+
1 Chemical or
ECF
Electrical Signal

ICF

3 Ca2+
ER Ca2+

Ca2+ Binds to Proteins 4

Fig 16
Cellular Response 5
Enzyme Activity Exocytosis Movement
Calcium Is an Important Intracellular Signal
 Signal Pathways
“Not ALL Ion Channels are Receptors”

ECF
1 2

3
Intracellular signal Molecules
Ions Create Electrical
Signals

ICF

Fig 13
 Signal Pathways
“Tyrosine kinase, an example of a Receptor Enzyme”

Ligand
1
Receptor

ECF
2
Tyrosine-Kinase
ICF
3
ATP + protein ADP + Protein-P

Guanylate Cyclase GTP cyclic GMP (cGMP)

Activation of an
Enzyme
Fig 14
 Signal Pathways
G-Protein Coupled Receptors
“Most Signal Transduction Uses G Proteins”

Signal Molecule
First Messenger (Phospholipase C)
Adenylate cyclase
1
Receptor Inostisol PPP
IP3

3 ATP Ca++
Fig 15 2
G-Protein Second Messenger
cAMP
4
5
Protein Phosphorylation Protein Kinase A

G-Protein-coupled adenylyl cyclase- cAMP system

 Modulation of Signal Pathways
• Receptors Exhibit
– Saturation
– Specificity
– Competition
β 2

Epinephrine
α and β Adrenergic Receptors β 1

Norepinephrine

α
 Target Response
Target Response depends on the Target Receptor

Receptor Isoforms
Vessel Constricts
α -Receptor Intestinal Blood Vessel

Epinephrine

Vessel Dilates
β -Receptor
Skeletal Muscle Blood Vessel

Fig 17
 Up and Down Regulation
• UP-and-Down-
Regulation of
Receptors Enables
Cells to Modulate
Cellular Response

Fig 18
Unit III B
G Proteins
G Proteins

Adenylate
Cyclase
Cell Signaling and Signal Pathways

Binds To Activates Alters Creates

Signal Intracellular Target

Receptor Response
Molecule Sig Molecule Protein

G Proteins
 Signal Transduction
Signal Molecule

Receptor

Cell Membrane

Phosopholipid
Bilayer
 G Proteins Act as Signal
Transducers
Signal Molecule

1 (GPCR)
Effector molecule
(Enzyme)

Adenylate
Cyclase
ATP 4
GTP
Gα
3
cAMP Second Messenger

Gβ
2 Gγ 5
GDP Response

G proteins are so-called because they bind the guanine nucleotides:

GDP and GTP
G Proteins Act as Signal
Transducers
Signal Molecule

Effector molecule
(GPCR)
1 (Enzyme)

Guanylate
Cyclase GTP

3 4
cGMP Second Messenger

2
5
Response
 G Proteins Act as Signal
Transducers
Signal Molecule

Effector molecule
1 (GPCR)
(Enzyme)

Phospholipase
C

3 4
Second Messenger

2 Ca2+

5
Response
 G Proteins and The Activity of
Epinephrine/Norepinephrine
Hormone
E/NE

GPCR GPCR
I Gα A Gα

Effects on cAMP Levels Effects on Ca2+ Levels

 G Proteins and The Activity of Epinephrine and
Norepinephrine on Beta1 Receptors of Cardiac Contractile
Cells
Hormone
E/NE ECF
β β 1
I Gα A Gα
1
Adenylate ICF
ATP Cyclase

cAMP “Second Messenger"

PO4 PO4
Opens Ca2+ Kinase Activation Phospholamban
Channels RP

ER Ca2+ ATP ase

More Forceful Contraction
Shorter Duration of Contraction
G Proteins and The Activity of Epinephrine and
Norepinephrine on Alpha1 Receptors
Hormone
E/NE Ca2+

α 1 PLC Via DA
G
Gα
PK
A Via IP3 C

Release of Ca2+ Second Messenger

Stored Calcium Ca2+
Ca2+
PLC = Phospholipase C
Calmodulin
PKC = Protein kinase C
DAG= Diaclyglycerol
IP3 = inositol triphosphate Myosin light chain kinase

Contraction of Vascular Smooth Muscle

in arterioles BP
 Unit IV Part I
The Autonomic Nervous
System
 The Nervous system
(an overview)
• Organization of the Nervous System
• Central nervous system (CNS)
• Peripheral nervous system (PNS)
• Sensory-somatic nervous system
• Efferent Motor
• Somatic Motor
Autonomic nervous system
Sympathetic
Parasympathetic
 Organization of
The Nervous
System
CNS

Spinal
Signal Cord
Efferent
Afferent
Neurons
Neurons

Stimulate Autonomic Somatic

Neurons Motor Neurons
Sensory
Receptors
Sympathetic Parasympathetic Control
Communicate Control
with
Smooth Muscle Skeletal
Stimulate
Exocrine Glands Muscles
Feedback Some Endocrine Glands
Control Cardiac Muscle

Enteric
Signal Nervous
System Response
 Autonomic Nervous System
”The Sympathetic and Parasympathetic Systems Maintain Homestasis”

• The Autonomic Nervous System (ANS)

• Controls the Body's Internal Environment
(heart rate, blood pressure, digestion,
respiration, blood pH and other bodily
functions through a series of complex reflex
actions

Think Homeostasis !!!!

 Autonomic Nervous System
”The Sympathetic and Parasympathetic Systems Maintain Homestasis

Properties of Homeostatic Control

1. Maintenance of The “Fitness” of Internal

Environment
2. Tonic “Up-Down” Regulation
3. Antagonistic Control
4. Variable Tissue Response (Receptors)
 Autonomic Nervous System
”The Sympathetic and Parasympathetic Systems Maintain Homestasis”

SETPOINT

Fig 2
 Control Pathways
Homeostasis May be Maintained by Local or
Long-Distance Pathways
Local
Autocrines
Paracrines
Reflex Control
Response Loop
Feedback Loop
 Negative
 Positive
 Response Loop
1 2
3

4

Feedback loop

5

6
Fig 3
 Feedback Loop
Negative Feedback Positive Feedback

Fig 4
Autonomic Nervous System
“The Hypothalamus and Brain Stem initiate Autonomic
responses”

Cerebral Cortex
Limbic System
Hypothalamus Pons

Medulla Oblongata

Parasympathetic

Sympathetic
 Autonomic Reflexes
“The Hypothalamus ,Pons and Medulla initiate Autonomic responses”

BRAIN Endocrine

Hypothalamus
Pons
Autonomic Function
Medulla Heart Rate, BP Temp Regulation
Osmolarity, CO2

Bypass the Brain

Limbic System Cerebral

Cortex Autonomic Spinal Reflexes
(Urination, Penile Erection, Defecation)
 Autonomic Spinal Reflexes

• Visceral Reflexes
– Short reflexes
• Bypass the CNS and involve sensory neurons and
Interneurons whose cell bodies are located
within Autonomic Ganglia.
– Long reflexes
• Are more-complex and are coordinated by
processing centers in the medulla oblongata.
 Autonomic Spinal Reflexes
(Short and Long Reflexes)

Medulla

Stimulus

Long
Reflex
Short Reflex

Response

Fig 5
 Autonomic Nervous System
”The Autonomic Division Consists of Two Efferent Neurons in Series”

• The Autonomic Pathway

Fig 6
 Autonomic Nervous System
”Sympathetic and Parasympathetic Branches Exit The Spinal Cord at
Different Regions”

Sympathetic
Arise from the Thoracic and Lumbar regions of
the spinal cord
The pre ganglionic nerves are short and synapse
in paired ganglia adjacent to the spinal cord
Parasympathetic
Arise from the Cranial and Sacral regions of the
CNS.
They have long preganglionic nerves which
synapse at ganglia near or on the organ
innervated
 Autonomic Nervous System
“The Sympathetic and Parasympathetic Systems use a Variety of
Neurotransmitters”

Neurotransmitter
Neurotransmitter
PreGN PostGN

CNS Autonomic Ganglion Target

Fig 7
 Autonomic Nervous System
“The Sympathetic and Parasympathetic Systems use a Variety of
Neurotransmitters”

• Pre Ganglionic Neurons of the PNS and SNS use the

same transmitter, Acetylcholine (ACh), at the
Autonomic ganglia (1).
• At the “Target” (2) different transmitters are used
(1) (2)
– Parasympathetic ACh ACh
– Sympathetic ACh NE E
Dopamine NO
Ganglia Target
 Autonomic Nervous System
“The Sympathetic and Parasympathetic Systems use a Variety of
Neurotransmitters”

Cholinergic

Adrenergic Catecholamines

Fig 8
Parasympathetic Nervous System
“Acetylcholine onto Muscarinic Receptors”

• All Parasympathetic synapse suse the same transmitter, Ach

– There are two types of ACh receptors membranes
• Nicotinic (pre Synaptic)
Exposure to ACh always causes excitation of the
ganglionic neuron or muscle fiber by the opening chemically
gated channels in the postsynaptic membrane.
• Muscarinic (post Synaptic)
The response, is determined by the activation
(phosphorulation) or inactivation of enzymes, and can be
excitatory or inhibitory.
Parasympathetic Nervous System
“Acetylcholine onto Muscarinic Receptors”

Membrane Receptors

Pre ganglionic Neuron Cholinergic Cholinergic

Nicotinic Muscarinic

ACh
ACh
Target

CNS
ACh-ase Post
ganglionic
Neuron

Fig 9
Parasympathetic Nervous System
“Acetylcholine onto Muscarinic Receptors”

Cholinergic Cholinergic
Nicotinic Muscarinic

ACh
ACh
Target

CNS G-proteins-coupled
ACh-ase

Fig 10 Gated Ca2+ Channels

Second Messengers
cAMP
Muscle contraction
 Parasympathetic Nervous System
“Acetylcholine onto Nicotinic/ Muscarinic Receptors”

Action
Potential

Axon
Terminal
Action Potential
Depolarizes Axon Terminal
Synaptic
Voltage Gated Ca2+
Vesicles
Channels Open

Calcium Induced
Voltage Exocytosis
Gated
Acetylcholine binds
Ca2+
With receptor
Channels
Receptor
Response
Parasympathetic Nervous System
“Acetylcholine onto Nicotinic / Muscarinic Receptors”

Acetylcholine
Acetyl CoA
Choline + Acetyl CoA
CoA

E Acetylcholine
Ch Acetylcholinesterase
Synaptic Breaks down
Vesicles Acetylcholine

Ch Choline is transported
Back into cell

Acetylcholinesterase Receptor
 Sympathetic Nervous System
“Norepinephrine onto Adrenergic Receptors”
Most sympathetic post ganglionic neurons release the Transmitter
Norepinephrine
There are two classes of sympathetic receptors:
(1) Alpha receptors
alpha-1 α 1 NE
The stimulation of a1 receptors leads to an increase in
activity
alpha-2 α 2 NE
The stimulation of a2 receptors leads to a decrease or
inhibition activity
(2) Beta receptors
beta-1 β 1 NE E
The stimulation of β 1 receptors leads to an increase in
activity
beta-2 β 2 Non innervated E
The stimulation of β 2 receptors leads to an decrease in
activity
 Sympathetic Nervous System
“Norepinephrine onto Adrenergic Receptors”

Membrane Receptor
Most Symp.
Pre ganglionic Neuron Adrenergic α 1 Target
Cholinergic Tissues
Nicotinic
α 2 GI Tract
ACh NE
CNS
β 1 Heart/
TARGET Kidney
ACh-ase Post ganglionic β Certain
Neuron Blood
2
Norepinephrine Vessels
Smooth
Fig 12 Epinephrine Muscle
(Adrenal Medulla)
 Sympathetic Nervous System
“Norepinephrine onto Adrenergic Receptors”

Pre ganglionic Neuron Cholinergic Adrenergic

Nicotinic Activates
α 1

Phospholipase C
ACh NE α 2 Decreases
CNS cAMP
TARGET
β Increases
1

ACh-ase Post ganglionic cAMP

Neuron
β Decreases
2
Norepinephrine cAMP
Epinephrine
(Adrenal Medulla)
Fig 13
 Sympathetic Nervous System
“Norepinephrine onto Adrenergic Receptors”

Axon Varicosity
MAO
Tyrosine 1) Action Potential
Ribosome
2) VG Ca2+ Channel
3) Exocytosis
Action Potential 4) NE bind to
receptor
5) NE Diffusion
Exocytosis 6) Reuptake Channel
Ca2+ Reuptake Channel 7) NE Reabsorption
NE Diffusion 8) NE Metabolized by
NE MAO at Ribosome

Response
Adrenergic Receptor
 “Most Internal Organs are Innervated by
Both Autonomic Branches”

• Dual Innervations (Antagonistic Control)

Most organs receive instructions from

both divisions usually with opposing
results
However
Vascular System notable exception which
is Innervated only by the Sympathetic
Branch
 Dual Innervations
“Most Internal Organs are Innervated by Both Autonomic Branches”
G H

A
F

I
D E
C
β 1

α Autonomic Effectors Muscarinic

Smooth Muscle
Cardiac Muscle
Endocrine Glands
β
2 Lets Practice
Fig 15
 Dual Innervations
“Most Internal Organs are Innervated by Both Autonomic Branches”

Fig 15
 Autonomic Tone
“Allows for very fine tuning of organ function”

• Autonomic Tone
– Stimulation of the Autonomic Nervous
system under resting conditions.
• sympathetic or parasympathetic tone.
– In general there is Sympathetic tone
within the blood vessels while there is
Parasympathetic tone in the heart.
 Eyeview of Brain and Senses
• Introduction to Nerves and Sensory
System
• Individual senses and physiology in detail
 Mid
Brain
&
Cranial
Nerves
Mid Brain (Posterior View)
 Nerve Tissue
• Brain is made of Neurons (Axon+cell body)
 Peripheral
Nervous
System
• Cranial and
Spinal nerves
innervate with
target organs
in the body
 Motor Cortex and Corticospinal
Tract Controls Motor Function
• Primary Motor Cortex(movements): Hand, leg, jaw
• Broca Area: Speech
• Somatosensory Feedback to Motor Cortex: Muscle
contraction

• Pyramidal Tracts (Direct Pyramidal and Extrapyramidal)

pass the stimuli to brain by
(a) Ascending; and (b) Descending pathways.
• NEURAL PATHWAYS(in January 2006)

GH 686-687
• Disorders: Spinal cord Paralysis,
Poliomyelitis, Amyotrophic Lateral
Sclerosis
• Lumber Puncture and CSF drainage

• Biomedical Engineering applications:

Nerve stem cells
 Processing the
nerve stimulus
Level of propagation:
Receptor(Nerve
ending,Muscle spindle,
kinesthetic receptor)
Circuits(spinal
cord,medulla,Pons,Reticular
formation/cerebellum->
Thalamus)
Perceptual(Thalamus,Motor
and somatosensory cortex),
 Review: Nervous System
• Nerve:soma cells, ganglia, receptor,dendrites, axon
– Somatic(efferent and afferent branches) or
– Somato-Motor, Somato-Sensory
– Sensory(5 senses):Smell,Taste,Vision,Hearing,Position
– Motor
– Visceral
• Divisions: CNS(brain)
ANS(spinal cord nerves, ganglia, synapse),
PNS(hind brain, spinal nerve plexus, remi, reflex arc)
VNS(cervical and pelvic afferent ramus communications)
 Special Senses
• Five receptor cell types are responsible for
5 special senses (Smell, taste, vision,
hearing and equilibrium)
Taste: Tongue in Buccal Cavity
• The basal cells differentiate into Taste
buds:
• In buccal cavity, fungiform papillae and
vallate papillae (V) make Gustatory cells
with hair cells (receptor afferent fibers)
connected with brain
 Pathway for taste
receptor
• Gustatory Hair fibers connected with
brain
• Main taste receptors:
Sweet, sour, salty, bitter &
delicious/steak
• Activation of Receptors:
• Taste  depolarized gustatory
receptor  neurotransmitter
potential Ion channelsSalt(Na+),
Sweet(K+), sour(H+),bitter (G-protein-
Ca++ ) gustatory afferent stimulus
(facial VII,Glassopharyngeal IX, Vagus
X)Medulla Ob.-Thalamus-
CortexSalivary and digestive reflex
Tongue Anatomy: Fungiform papillae, Circumvallate papillae,
Tonsils, Taste fibers, Gustatory receptor cells
 Smell(Olfactory Receptor)

• At the superior nasal choncha, olfactory columnar cells

have Olfactory fixed cilia.
• Receptors form nacked axon filament of Olfactory
nerve(I) entering in ethmoid bone (cribriform plate).
• Pathway: Odor  O receptor proteinNa+ channel
potentialG-protein/cAMPdepolarized Olfactory
nerveimpulse transmitted(Olfactory bulb-mitral cells
-glomeruli(GABA) dendrodendritic synapse)-Tracts to:
(a) Thalamus/ frontal lobe-cortex;
(b) Hypothalamus, amygdala, limbic system, leads to
Odor Reflex.
• Disorders: Ansomia-Zinc, Uncinate and Auras fits
Eye Orbit and Nasal Cavity
Eye: Gross Anatomy

•Eye(Opical or Ocular Cavity)

•Eye lid and eye brow
•Eye ball, Eye cornea
•Ocular muscles
 Vision and Eye
• Eye brows have Orbicularis
oculi and Corrugator muscles.
• Eyelids have:
– Levator pulpebrae,
– angled by flesh(caruncle and canthus) and
– connected with Orbicularis oculi and levator
pulpibrae superioris muscles.
• Meibomian glands (Sty and Chalazion)
• Eyelashes have Ciliary Glands and Hair follicle
 Conjunctiva and Lacrimal
Apparatus
• Transverse mucus
membrane (ocular
bulbar conjunctiva)
covers eye ball white to
make ocular sac.
• Lacrimal Apparatus:
Canaliculi, Sac, Duct
• Lysozyme release and
tears from gland
Eye ball
page 565
Sclera
Cornea
Choroid
Iris
Pupil
Retina
Lens
 Ocular Muscles
• Sup/Inf rectus (III) & oblique/lateral/medial rectus(VI,III),
Sup.oblique/trochlea muscles(IV)
• Disorders: Diplopia and Strasbismus
 Retina
• Coroid
• Pigmented layer
• Neural layer:
– Photoreceptors: Rods(dark) and
Cones(light)
– Bipolar, Amacrine cells and
M and P Ganglionic cells
• Optic Disc (Blind spot)
• Yellow spot (fovea centralis) allows
light to reach cones
• Central artery/vein
Eye Chambers and Fluid
• Vitreous humor in
posterior segment
• Aquous humor in anterior
segment divided by iris,
lens
• Glaucoma is increased
pressure on optic nerve
and retina
• Crystallins, fibers and
epithelium form Lens
• Cataract is hardening,
clauding of lens
• Sight: Myopia, Hyperopia,
Astigmatism
 Photoreceptors
• 3 Rod types: Formation of
Rhodopsin <-> Opsin +
retinal(11 cis -> all trans
retinol (in light)
• Vitamin A activation
• 3 Cone types: Rhodopsin
breaks down to opsin and
11 cis retinal (Bleaching)
 Visual Pigments
• Outer layer:
• Basal lamina,melanin,
pigment disc, Rods/cones
have Photopigments (outer
layer) for dark/light
wavelengths &
• Inner layer:
– Mitochondria
• Cell body and synapse
endings
 Light and Dark Phases of Vision
• Rhodopsin
• Retinol isomerism
• Vitamin A
• Retinol Binding Protein

Light frequency controls

Physiology & Propagation
Glutamate neurotransmitter-> Rhodopsin-transducin (cGMP
Phosphodiesterase) creates hyperpolarization potential->
adaptation
•Optic nerve axon pass: Optic
chiasma -> Optic tract->Sup.
Colliculi & Ipsi/contralateral
fibers in thalamus ganiculate
body-> Occipital lobe
•Bipolar neurons decifer
 Lens Focusing and Depth
Resolution
• Convex lense
• Monotonous eye vision
• Bifocal and multifocal vision in birds and
rodents
 Ear
Anatomy
•Outer ear
•Middle ear
(Ossicles)
Incus
Stapes
Malleus, Drum
•Inner ear
Labyrinth
(Cochlea,canals,
duct)
 Middle ear is controlled by
Tympani Muscle
• Drum vibrates
Fluid in tympanic
cavity propagates
sound waves to
tune with Cochlea
(spring) strain
• Cochlear and
Vestibular nerves
pick up the strain
amplitude
• Disorder: Otitis
Media
 Ear and Hearing
page 582-585
• Auricle and auditory canal constitute the ear (Outer-
tympanic vibrating membrane-inner ear).
• Middle ear is box (temporal bone) and joins with
naso-pharynx
• Ossicles transmit sound ear drum to window
• Inner ear: labyrinth chamber( duct/ sac with
perilymph/endolymph) is bony & membranous,
Macula.
• Vestible: Saccule and Utricle.
• 3 sets of semicircular canals(ducts) come out
posteriorly.
• Cochlea: Cochlear duct (Scala media- Organ of Corti,
Hair cells-basilar nuclei and tactorial membrane)
Cochlea (Inner Ear): 3 ganglia, 3 canals,
3 nerves and Macula nodes
 Cochlea
• CN VIII
connects with
Spiral
ganglion &
lamina turns
• Organ of Corti in
center
• Scalae
– S.vestibule
– S.media
– S.tympani
Organ of Corti has
stereocilia and
supporting hair
Bath with
Perilymph and cells connected
Endolymph with afferent nerve
fibers
 Physiology :Hearing Across
Cochlea basilar membrane
(page 585-91)
•Sound->Frequency (Hz or pitch vs sine wave
length, amplitude, intensity(dB) -> Pressure waves
resonate with basilar fibers-> Organ of Corti hair
cells de-/hyperplorize by Glutamate /K+/Ca+->sense
it-> inner spiral ganglia cells --> medulla-> stem-
>thalamus geniculus->auditory cortex(brain)
EXCITATION OF ORGAN CORTI HAIR CELLS
•Tone, Pitch vs position of excited hair cells vs
time-intensity vs set of frequencies of transmitted
impulse vs localization
•Disorders:
–Tinnatus(sensory neurones)
–Meniere Syndrome (Vertigo, endolymph
accumulation in membrane labyrinth)
 Pathway of
auditary
stimulus
• Sound->Frequency (Hz or
pitch vs sine wave length,
amplitude, intensity(dB) ->
Pressure waves resonate
with basilar fibers-> Organ
of Corti hair cells
de-/hyperplorize by
Glutamate /K+/Ca+->sense
it-> inner spiral ganglia
cells --> medulla -> stem-
>thalamus geniculus-
>auditory cortex(brain)
 Ear and Hearing: Properties
• Auditory Processing:
– Perception of pitch
– Detection and analysis of sound loudness
– 3D spatial localization of sound

• Disorders: Deafness, Otosclerosis (ossicle

damage), sensoryneural (corti cells)
• Vestibular nucleus/receptor->Cerebellum-
> Neck movement & head rotation
 Orientation and
Gravity Balance (page
593-96)
• In Utricle, Maculae
receptors play:
– Otolith cover on top the
kinocilium (buds) and
stereocilium (base) of hair
cells sandwitched between
support cells.
– Hair cells propagate as
vestibular nerve fibers
– Depolarization->potential->
stimulus to brain
 G-Equilibrium: Crista Ampullaris

• Capula and
ampulla of
semicircular
canals bath
with
endolymph.
• Capula
change
orientation
and sensed by
Vestibular
nerve
 Unit V
Sensory Systems Function And
Physiology
Part IIA
The Ear: Hearing
 An Introduction to Sound
• Sound Waves Frequency = waves/sec
1 Wavelength Hz

1000-3000 Hz

Amplitude
db
Pressure

Fig 1
TIME
 Transduction of Sound Is a
Multistep Process

Mechanical Chemical Action

Fluid Waves Potentials
Vibrations Signals

Fig 2
 Anatomy of The Ear

External Inner
Middle Semicircular
Pinna
canals Oval Window
M I S
Vestibular apparatus
Cochlea

Bony
Canal Labyrinth

Tympanic
Membrane
Round To Pharynx
Fig 3 Window
Eustachian Tube
Sound Transmission Through The Ear
“The Middle Ear Transfers Sound from the Eardrum to the Cochlea”

Basilar Membrane
Cochlear Nerve
Incus Stapes
Oval 6
Malleus
Windo
Vestibular Duct
Canal w
(Perilymph)
3
Cochlear Duct
2 (Endolymph)
1 4
5
Tympanic Duct

Tympanic Membrane Round Window

Tectorial Membrane

Fig 4
 The Cochlea
“The Cochlea of the Inner Ear Is Filled with Fluid”

Oval Window Vestibular Duct

Cochlear Duct Organ of Corti

Perilymph

Endolymph Helicotrema

Round Window Basilar Membrane

Tympanic Duct

Fig 5
 The Cochlea
The Cochlea
Bony Labyrinth

Vestibular Duct

Cochlear Duct

Tectorial
Membran
e Cochlear
Nerve
Organ of
Corti
Basilar Tympanic Duct
Fig 6 Membrane
 The Organ of Corti

Tectorial Membrane

Hair Cell

Cochlear Nerve

Basilar Membrane

Fig 7
 Sound Transduction Through
The Cochlea
Perilymph

Vestibular Duct Sound Wave

Cochlear Duct

Tympanic Duct Endo-

lymph Hair Basilar Tectorial
Cell Membrane Membrane

Fig 8
Sound Transduction Through the Cochlea
“Depends on Movement of Hair Cell Stereocillium”

• Hair cells Stereocillium

– The sensory
receptors of the
inner ear are called
hair cells

Fig 9
 Hair Cells
“Sound Transduction”

AT REST
+ Tallest
Protein Bridge K Stereocilia

Stereocillium
Some Channels
Hair Cell Open

Sensory Neuron
Low Level Action
Potentials
(Tonic)
Fig 10
 Hair Cells
“Sound Transduction”

K+
Excitation
Tallest
Stereocilia
Stereocillium
More Channels Open
K+ K+ entry Depolarizes Cell

Fig 11 Action Potentials

 Hair Cells
“Sound Transduction”

INHIBITION K+
Channels Closed No
K+ Entry Cell
Hyperpolarizes

No Action Potentials
Fig 12
 How Do We Hear ?

M I S
Outer Ear Hair Cells

Mechanical Chemical Action

Fluid Waves Potentials
Vibrations Signals

Cochlea Medulla

Ipsilateral
Contralateral Auditory Cortex
Fig 13
 Sensory Coding for Pitch
STIFF FLEXIBLE
Man low pitch female high pitch

High Frequency Low Frequency

Fig 14

Basilar Membrane Helicotrema

 Unit V
Sensory Systems
Function And Physiology
Part IIIA
The Physics of Vision
 The Lens
• Posterior to the cornea
• Held in place by suspensory
ligaments called Zonules which are
in turn attached to the Ciliary
Muscles of the Eye
• Focuses visual image on the Retina
 The Lens

Ciliary Muscle

Lens Cornea

Zonules

Fig I
 Accommodation
“The Eye Adjusts The Shape of The Lens”

Ciliary Muscle

Lens

Zonules

Fig 2
The Lens Focuses Light on the
Retina
Parallel
Focal Point

20 ft + Light

Fig 3 Lens Flattened for distant Vision

The Lens Focuses Light on the
Retina
Non Parallel
Focal Point

< 20 ft

Object Object Image

Fig 4
 The Lens Focuses Light on the
Retina
The Rounder The Lens, the Greater the Refraction,
the Shorter the Focal Length

Fig 5
Lens Rounded for Close Vision
 Accommodation
“The Eye Adjusts The Shape of The Lens”

Ciliary Muscle
(relaxed)

Lens Cornea
(flattened)

Zonulas
(tight)

Fig 6
 Accommodation
“The Eye Adjusts The Shape of The Lens”

Ciliary Muscle
(contracted)

Lens
(rounded)

Zonulas
(slack)
Fig 7

The Loss of Accommodation is called Presbyopia

 Visual Defects
Hyperopia (Farsightedness)

Normal
(Emmetropia)

Focal Point Behind Retina

Fig 8
 Visual Defects
Myopia (Nearsightedness)

Normal
(Emmetropia)
Focal Point In Front of Retina
Fig 9
 Visual Defects
Astigmatism

Irregularities in cornea or lens

CORNEA

Fig 10
 Aqueous humor Trabecular meshwork
Canal of Schlemm

isual Disease Aqueous Flow

Angle Glaucoma/ Narrow Angle Glaucoma”
P

Fig 11
 Unit V
Sensory Systems
Function And Physiology
Part I
Olfaction and Gustation
 Sensory Physiology
• Sensory Stimuli That Reach The
Conscious level of Perception

Somatic Senses Special Senses

Temperature  Vision
Proprioception  Hearing
Nociception  Taste
Touch/Pressure  Smell
 Equilibrium
 General Properties of Sensory
Systems
• Receptors Are Sensitive To a Particular
Stimuli
• Sensory Transduction Converts Stimuli into
Graded Potentials
• Generator Potential (Action Potential)
• Receptor Potential ( Non-Neural Membrane
Potential)
• The CNS Integrates Sensory Information
• Coding and Processing Distinguish Stimulus
Modality (Labeled Line Coding), Location (Lateral Inhibition),
Intensity and Duration (Population and Frequency Coding)
General Properties of Sensory Systems
“Sensory Transduction Converts Stimuli into Graded Potentials”

1 Transducer
Sensory
Stimulus
Receptor

2 Electrical Graded Potentials

Sensory Afferent Neuron

3 4

CNS Cortex

Fig 1 ( Integration )
( Conscious Perception )
 Types of Receptors
“Receptors Are Transducers That Convert Stimuli into Electrical Signals”

 Photoreceptors (Vision)
– Photons
 Chemoreceptors
– CO2 O2, pH, various organic molecules (Taste and Smell)
 Mechanoreceptors (Hearing and Equilibrium)
– Tactile
– Baroreceptors
 The Special Senses
• Olfaction
• Vision
• Gustation
• Hearing
• Equilibrium
Sensory Transduction Converts Stimuli
into Graded Potentials

Threshold

Stimulus Receptor Receptor Potential

Generator Potential Neurotransmitter

Action Potential

CNS
Coding and Processing Distinguish
“Stimulus Modality, Location, Intensity and Location”

• Sensory Modality(nature)
– The Modality of a Signal is indicated by
which sensory neurons are activated and
where those Pathways Terminate in The
Brain. (Submodality means specific tastes-salt etc)
• Labeled Line Coding(receptors)
– The Association of a Receptor with a
Sensation
 Coding and Processing Distinguish
“Stimulus Modality ,Location, Intensity and Location”

• Location of a Stimulus
• Receptors Project to a Specific Region of
the Cortex
– Adjacent Sensory Receptors are
Processed in Adjacent Columns of the
Cortex (Topographical Arrangement)
– Lateral Inhibition
– If it is processed in brain. It must be
coming from…right or left side
 Coding and Processing Distinguish
“Stimulus Modality,Location,Intensity and Location”

• Lateral Inhibition
Primary Neuron Response
Is Proportional to
Intensity of Stimulus A B C

Pathway Closest to

- -
Stimulus Inhibits
Neighbors

Inhibition Enhances
Perception of
Stimulus In brain A B C
Coding and Processing Distinguish
“Stimulus Modality, Location, Intensity and Location”

Intensity and Duration of receptor

– Population Coding
• The Numbers/types of Receptors Activated
– Frequency Coding
• Stimulus Intensity
• The Frequency (per second) of Action Potentials
Coming from Receptors
– Duration
• How long a Series of Action Potentials Persist
– Tonic receptors (Slow but steady)
– Phasic receptors (Fast)
 CHEMORECEPTION
“Smell and Taste”

• Olfaction
– The sense of smell, called OLFACTION, is
provided by a pair of Olfactory organs
– These organs are located in the nasal cavity
on either side of the nasal septum.
 OLFACTION
Anatomy

Olfactory Bulb

Cribiform Plate

Olfactory Nasal Concha

Tract

Olfactory Organ

Fig 2
 Olfactory organs

• The olfactory organs contain the

following two layers
– Olfactory epithelium
• Olfactory receptors
– Lamina propria
• Olfactory glands ( Bowman's Glands )
 OLFACTION
The Olfactory cells Synapse with Secondary Sensory Neurons in The
Olfactory Bulb synapse
connections
20Receptor Neuron Olfactory Bulb

Olfactory tract

Lamina propria
10Receptor Neuron
Olfactory
epithelium Mucus Layer

Fig 3 Olfactory Cilia

 OLFACTION
Olfactory Cells are Neurons

• Smells are detected in the nose by

specialized receptor cells called
olfactory receptor cells.

Basal Cell

Support cell Receptor Cell

Cilia Mucous Layer

Fig 4
 OLFACTION
Odorant Receptors are G protein-cAMP linked Receptors

cyclic-nucleotide Ca
gated (CNG) Adenylate cyclase
channels Na

CNG

Cell Depolarizes

Action Potential / Fig 5

Population Coding
 OLFACTORY PATHWAYS

Olfactory epithelium

Olfactory bulbs

Olfactory tract

olfactory cortex hippocampus amygdala

Limbic System
 GUSTATION
“Taste Is a Combination of Five Basic Sensations”

• Sweet
• Sour
• Salty
• Bitter
• Umami (monosodium glutamate)
 Gustation
• The superior surface of the tongue
bears epithelial projections called
lingual papillae
FRICTION
– filiform papillae
– fungiform papillae CONTAIN TASTE BUDS

– circumvallate papillae
 Taste Buds
Why did I put this Here?

Bitter

Sour

Sweet

Salty
Fig 6
 Taste Cells
“Taste Cells are Non-Neural Polarized Epithelial Cells”

• Each taste bud Taste pore

contains receptors
called Gustatory
(sensory) cells Gustatory
cell

Support
cell

Basal cell

Sensory neuron
Fig 7
 Taste ligand
Membrane channel or
receptor

Taste Ligands bind to Tight junction

Receptors and Create Ca++
Signals

Ca+

Neurotransmitter

Sensory neuron

Fig 8 Action potential

Receptor Potential
 Summary of Taste Transduction

1 Ligands Activate the Taste Cell

2 Intracellular Pathways are Activated
3 Ca Signal Triggers Exocytosis
++

4 Neurotransmitter Released and

Primary Sensory Neuron Fires
5 Action Potential is sent to the Brain
 Bitter Sweet Sour Salt

G protein Umami 1 Leak channel

Transduction 1 1
1

2 2
2
Taste
Transduction
3

4
Fig 9 5
To Brain
 Unit V
Sensory Systems
Function And Physiology
Part IIIB
The Physiology of Vision
 ANATOMY OF THE EYE
Aqueous Humor Fibrous Tunic
Vascular Tunic
Iris Cornea

Ciliary Body Sclera

Lens
Choroid

Zonulas

Vitreous Humor Visual Axis

The Neural Tunic

(Retina) Optic Disc Macula lutea

Neural

Pigmented Fovea

Optic Nerve Fig 1

 The Neural Tunic
“The Retina“

The Pigmented Part

 Absorbs light that passes through the neural part
and Important Biochemical reactions.
The Neural Part
 Contains light receptors and performs preliminary
processing and integration of visual information.
 The Neural Tunic
“Organization of the Retina”

Pigmented Layer
Optic Nerve Blood Vessels

Neural Layer

Photoreceptors

O NS
OT
PH
Optic Disc

Fig 2
 The Neural Tunic
“Organization of the Retina”
Pigmented Layer
Horizontal Cell
Amacrine

Photons

Cone

Rod

Ganglion Cell

Bipolar Cell
Fig 3
 The Neural Tunic
“Organization of the Retina”

• Photoreceptors
• Rods
• Cones
• Macula Lutea
• fovea
• Bipolar cells
– Regulate communication between photoreceptors
and ganglion cells
• Ganglion Cells
– The Axons of these cells form the Optic Nerve
• Horizontal and Amacrine Cells
– Facilitate or inhibit synaptic transmission
• Contrast
 VISUAL PHYSIOLOGY
“Phototransduction Occurs at The Retina”

• Photoreceptors
– Rods
– Presence or absence of photons
 Black and White
 Low Light Levels
 Low Acuity

– Cones
– Wavelength of arriving photons
• Color
• High Light Levels
• High Acuity
 Anatomy of Rods and Cones
“Photoreceptors Rods and Cones”

• Rods
– Outer segment
• discs
– Visual Pigments
• Opsin + Retinal
(Vitamin A)
– Inner segment
• cellular organelles
• neurotransmitters Rod

Fig 4
 Anatomy of Rods and Cones
“Photoreceptors Rods and Cones”

• Cones Disks
– Outer segment
• discs Mitochondria
– Visual Pigments
• Opsin (r,g,b) +
Retinal
– Inner segment
Cone
• cellular organelles
• neurotransmitters Synaptic Terminal

Fig 5 Bipolar Cell

 “Photoreceptors Rods and Cones”
OLD DISKS

Pigmented Layer

OUTER
SEGMENT

INNER
SEGMENT

Fig 6

SYNAPTIC TERMINAL P
Photoreceptors Rods and Cones
“Phototransduction Occurs at the Retina”

Rhodopsin
Molecule

Retinal Opsin

Fig 7 Cell Membrane

 Photoreception
“Dark Current”
Pigmented Layer
Rod in Darkness

cGMP
Inactive Rhodopsin
(Opsin+Retinal)

-40 mV This Membrane is

depolarized

Tonic Release of
Fig 8
Neurotransmitter(GPG)

Bipolar Neurons
 Photoreception
• Dark Current Outer Segment

– In darkness
• Gated Na+ channels are Na
kept open
C-GMP
-40 mV Na
Inner
Segment

Neurotransmitters
Bipolar cells
(G Protein glutamate) Na+
K+
The movement of Na+ from the outer segment, to the inner segment,
and out of the cell is known as the dark current
 Phototransduction
“Phototransduction Occurs at the Retina”

PHOTON

photon strikes the retinal portion

of a rhodopsin molecule.

Fig 9
 Phototransduction
“The Activation of Rhodopsin”
Activated
Photon

“A”Opsin Transducin

Opsin Phosphodiesterase
+
Cis-Retinal

Trans-Retinal Breakdown of cGMP

Rhodopsin Gated Na+

Close

Bleaching
Fig 10
 Photoreception
“Light adapted State” (RODS)
Activated Retinal
Activates Transducin
1
The Rod in Light
2

3 cGMP
-70 Mv

4
Fig 11 This Cell is
Hyperpolarized

Neurotransmitter release
Decreases/Light
 Photoreception
• Step 1: Opsin activation occurs
– When a photon of light strikes the rhodopsin molecule, the molecule
becomes active (cis to trans ) which activates the Opsin portion of the
molecule

• Step 2: Opsin activates a second enzyme

– Transducin, which in turn activates a third enzyme, Phosphodiesterase

• Step 3: Phosphodiesterase breaks down cGMP

– Cyclic-GMP levels decline, and gated sodium ion channels close..

• Step 4: The rate of neurotransmitter release declines

– Cellular Na+ levels drop the membrane hyperpolarizes. The rate
of neurotransmitter release decreases. This decrease indicates to the
adjacent bipolar cell that the photoreceptor has absorbed a photon
 Photoreception
“Recovery After Stimulation”
ADP
Trans Recovery From Bleaching
Cis
Opsin

ATP

After Image

Fig 12
 Light and Dark Adaptation
• Dark-adapted state
– all visual pigments (opsins) fully receptive

• Light-adapted state
– visual pigment breakdown is balanced by the
rate of reformation
 Stimulation in various combinations is
the basis for color vision
Color Vision
PHOTONS Opsin r

Retinal Opsin g
r
Brain
+
Opsin

Opsin b

Fig 13
 Convergence in The Retina
Rods

Horizontal Cells

Bipolar Neurons

Fig 14

Amacrine Cells
Ganglion Cell

To Optic Nerve
 Processing in The Retina
“Signal Processing Begins in the Retina”

OFF
Off Center Neurons

Visual Field
ON

On Center Neurons

Fig 15
Signal Processing Begins in the
Retina

Fig 16
 Convergence
• Cones show very little convergence
– Cones provide more-precise information
about a visual image than do rods.
 THE VISUAL PATHWAY
Left Right

• A partial crossover of
nerve fibers occurs at the
optic chiasm.
• Each hemisphere receives
visual information from
the medial half of the Optic Nerve
field of vision of the eye
on that side and from the
lateral half of the field Optic
of vision of the eye on Optic Tract chiasma
the opposite side.

Visual Cortex
Fig 17
 Unit VI The Heart
Part IA
Action Potentials and Calcium Induced Muscle
Contraction
 Cardiac muscle cells
• Two types of cardiac muscle cells are
involved in a normal heartbeat:
– (1) Contractile Cells, which produce the
powerful contractions that propel blood
– (2) Autorhythmic Cells ( Pacemakers)
which control and coordinate the activities
of the contractile cells.
 CONTRACTILE CELLS
• Contractile cells form the bulk of the Atrial
and Ventricular walls.
Two Different Action
Potentials !!!

SA Node
(Autorhythmic Cells)

Autorhythmic Myocardium
Cells

Intercalated Disc
Gap Junctions Fig 1
Action Potentials in Myocardial
Cells Vary According to Cell
Type
• Myocardial Autorhytmic Cells(MAC)
• Cardiac Contractile Cells(CCC)

• MAC GAP JUNCTION CCC

 Autorhythmic Cells
“ Cardiac Muscle Cells Contract Without Nervous Stimulation”

• Have the unique ability to generate

Action Potentials spontaneously !
– Unstable Membrane MAC potential
( Pacemaker Potential)
-60mV Then drifts upward
toward Threshold(slope)
 ACTION POTENTIALS IN CARDIAC
AUTORHYTHMIC CELLS
Ca2+ Channels Close

If Channels Close

Na+
K+

K+ Channels Close
If Channels Open

If Channels Open
“The Pacemaker Potential”
Fig 2
 MODULATION OF ACTION POTENTIALS IN
CARDIAC AUTORHYTHMIC CELLS
“ Alter The Permeability to Different Ions”

β 1
Receptors If Ca Na
Ach Muscarinic K Ca

Catecholamines β 1
cAMP If Opentime
Fig 3
MODULATION OF CARDIAC CONTRACTION

Fig 4
 CONTRACTILE CELLS
• In cardiac CONTRACTILE CELLS
– (1) An action potential propagation leads to
the appearance of Ca2+ among the myofibrils
– (2) The binding of Ca2+ to Troponin on the
thin Myosin filaments initiates the muscle
contraction
 The Action Potential in Cardiac Muscle
Cells
• STEP 1: Rapid depolarization.. Voltage-regulated
Fast sodium channels open and the membrane becomes
permeable to Na+. The result is rapid depolarization of the
sarcolemma.
• STEP 2: The plateau. Voltage-regulated fast sodium
channels close. As the fast sodium channels are closing, voltage-
regulated slow calcium channels are opening. As a result, the
transmembrane potential remains near 0 mV for an extended
period. This portion of the action potential curve is called the
plateau..
• STEP 3: Repolarization. As the plateau continues, Slow
calcium channels begin closing and Slow potassium channels
begin opening. The result is a period of rapid repolarization that
restores the resting potential.
 The Action Potential in Cardiac
Muscle Cells (NCK channel steps)
Fast Na+ Slow Ca2+
Channels close Channels open
#3 Slow Ca2+
#2 Channels close
#4
Slow K+
K+ChannelsClose Channels open
PNa
#1
Fast Na+
Channels open
#5

Resting
Potential
Fig 5
 “Calcium-Induced Calcium Release”

Ca2+ NaKATPase

Ryanodine
Receptor Channel

Calcium Spark
(Sum)
EC Coupling

Fig 6
 Cardiac Muscle Contraction Can
Be Graded
• NOT ALL-or-NONE
• Calcium Levels Determine The Force of
The Contraction
Ca2+ Summation of Ca2+ Spark

Troponin Tropomyosin (Cross Bridges)

SO
MODULATION OF CARDIAC CONTRACTION

FORCE and DURATION

Regulatory Protein

Fig 7
 The Refractory Period
 Refractory Period
That time after an action potential begins, during which the
membrane will not respond normally to a second stimulus

Absolute Refractory Period

The membrane cannot respond at all, because the sodium
channels are already open

Relative Refractory Period

The membrane will respond to a stronger-than-normal fast
twitch stimulus
The Refractory Period

Fig 8
The Cardiac Refractory Period
“The Refractory Period Last as Long as the Muscle Twitch”

2 3

Fig 9
The Cardiac Refractory Period

Fig 10
DIGITALIS
 The Endocrine System
Part I
“An Introduction to The Endocrine
System”
What Makes a Chemical a Hormone
a) Hormones Are Secreted by a Cell or Group
of Cells
b) Hormones Are Secreted into the Blood
c) Hormones Are Transported to a Distant
Target
d) Hormones Exert Their Effect at Very Low
Concentrations
e) Hormones Act by Binding to Receptors
f) Hormone Action Must be Terminated after
action is over(Half-life)
 What Makes a Chemical a
Hormone ?
Hormone
Blood

Target

Fig 1
Hormones are Chemical Messengers
Response
 What Makes a Chemical a
Hormone ?
Neurohormone Ligand
Blood

Fig 2

Hormones are Chemical Messengers

 What Makes a Chemical a
Hormone ?
Neurohormone Ligand
Blood

Fig 2

Hormones are Chemical Messengers

 AN OVERVIEW OF THE
ENDOCRINE SYSTEM
• CONTROL SYSTEMS
– Open loop
• Ballistic systems
– Closed loop
• Negative feedback systems
 Feedback Loop
Negative feedback Ballistic systems

Fig 3
Closed Loop Open Loop
 How Could We Classify
Hormones ?

• ACCORDING TO
• The ANATOMICAL SOURCE of The Hormone
• (Very traditional, but very boring)
• ACCORDING TO
• The CHEMICAL COMPOSITION of The
Hormone
 ACCORDING TO
 The SOLUBILITY of The Hormone IN WATER
OR FAT
ACCORDING TO ANATOMICAL SOURCE OF
THE HORMONE

Fig 4
 ACCORDING TO CHEMICAL
COMPOSITION
• PEPTIDE HORMONES
• Composed of Amino Acids
• STEROID HORMONES
• Derived from Cholesterol
• PEPTIDE AMINE HORMONES
• Derived from the amino acid:
– Tyrosine or Trytophan
 PEPTIDE HORMONES
“Most Hormones are Peptides or Proteins”

• Polypeptide hormones
– Most of the hormones from the anterior pituitary
gland.
– The hormones from the posterior pituitary
gland(oxytocin and ADH).
– All the hormones from the hypothalamus (except
dopamine)
– All the hormones from the stomach, duodenum,
pancreas and liver

• Glycoproteins
– Some of the stimulatory hormones from the anterior
pituitary gland. (TSH, FSH, LH)
– Parathyroid hormone
 AMINE HORMONES
Derived from the amino acids Tryptophan or Tyrosine

• Tryptophan
– Melatonin
• Tyrosine
• Thyroid hormones   (T3 and T4)
• Catecholamines
– Epinephrine
– Norepinephrine
– Dopamine
STEROID HORMONES
“are all derived from cholesterol”

• Sex hormones
– Gonads
• Estradiol
• Progesterone
• Androgen  
• All the hormones of the Adrenal cortex
• Aldosterone
• Cortisol
 ACCORDING TO SOLUBILITY
IN WATER OR FATS
Water soluble 
All peptide hormones. 
All amine hormones (except the Thyroid
hormones T3 T4).
Fat soluble
All steroid hormones. 
Both thyroid hormones (T3 and T4).
WATER SOLUBLE HORMONES
• THE HORMONES INVOLVED WITH
THE NEGATIVE FEEDBACK in
REGULATION OF THE INTERNAL
ENVIRONMENT
– Water soluble
– Absolutely essential for life
– Often work in counter regulatory
• (Rein Control) pairs:
 Rein Control
GLUCAGON
BLOOD GLUCOSE LEVELS

Fig 5

INSULIN
 Rein Control
• To rapidly reverse a particular action, it is
useful to have a Second hormone that has the
Opposite effect of the first, whose blood
concentration can be rapidly increased..
• It is the RATIO of the blood concentrations
of the two hormones, rather than the
absolute concentrations of either, that
determines the direction in which the
controlled variable response will change.
 CHARACTERISTICS OF THE
WATER SOLUBLE HORMONES
• True MESSENGERS (NEWS)
• Blood Hormone concentrations are highly variable (short Half life)
•  Are removed from the blood very quickly.
•  Changes in concentration convey the message.
  High concentrations in the blood have the opposite" meaning"
to low blood H concentrations. (different massage to cell)
•  Effects are completely reversible.(by Glucagon/Ins)
• These Bind to cell membrane receptor proteins (water soluble)
•  Effects seen very quickly, usually within seconds or minutes.
WATER SOLUBLE HORMONES FALL INTO
THREE FUNCTIONAL CATEGORIES

 I-REGULATORS OF THE INTERNAL

ENVIRONMENT
 II-BALLISTIC REGULATORS
impart messages whose effects are not
checked (Oxytocin, ADH)
 III-RELAY MESSENGERS for the
secretion of other hormones.
The Trophic Hormones (hypothalamus,
pitutary stimulating)
REGULATORS OF THE INTERNAL
ENVIRONMENT
Insulin and Glucagon
PTH and Calcitonin
• ADH and ANP
 BALLISTIC REGULATORS

• Epinephrine
• Oxytocin
• Prolactin (stimulate by sex hormones)
 The Trophic Hormones
• All the Hormones of the
Hypothalamic-Anterior Pituitary
Pathway (stored stimulatory hormones)
• Angiotensin II (kidney)
The Endocrine System
Part II
MECHANISMS OF ACTION
The Endocrine System
• MECHANISMS OF ACTION
HORMONE

WATER FAT SOLUABLE

SOLUABLE
Lipophilic
Lipophobic
A Simple Endocrine Reflex
Internal
Or External

Change

Sensory
Integration Endocrine

Efferent Hormone
Signal

Effector Sequence of molecular changes

Response
A Complex
Internal
Or External
Change

Neuroendocrine Receptor

Neuron
Reflex
Afferent Path

Sensory
Nervous
Integration

Efferent Neuron/
Signal Neurohormone

Sensory
Integration Endocrine

Efferent
Signal#2 Hormone

Effector

Response
 MECHANISMS OF ACTION
Water Soluble Hormones

• Hormone Binds to receptors on the

cell membrane
• Does not have direct effect on the
target cell
• The hormone-R acts only as a first
messengerCEG
cAMP Second Messenger

amplification

Response
 MECHANISMS OF ACTION
Water Soluble Hormones

H H Receptor Enzyme

Opens Ion Channel

cAMP
Fig 1

AE=Amplifier Enzyme
Cellular Response
 MECHANISMS OF ACTION
Water Soluble Hormones use G-Proteins

• G-Proteins
• The link between the Hormone and the second
messenger involves a G-protein

Hormone CELL
MEMBRANE

Fig 2
 MECHANISMS OF ACTION
Water Soluble Hormones

The entry The

The activation
and/or inhibition
of an AdCyclase
release of of
EnzymecAMP
calcium ions cellular
PK
activities.

Fig 3
 MECHANISMS OF ACTION
Water Soluble Hormones(E,

activation of β 1 receptors

Phosphodiesterase (PDE)
C-AMP AMP
Adenylate cyclase

ATP C-AMP KINASE

SECOND MESSENGER phosphorylation

MEMBRANE PROTEINS ENZYME ACTIVIATION

Fig 4 OPENS ION CHANNELS

Ca++
Na+ K+
 MECHANISMS OF ACTION
Water Soluble Hormones

activation of a1 receptors

phospholipase C (PLC).
PIP2

Diacylglycerol (DAG) Inositol triphosphate (IP3)

Fig 5 in membrane activates

protein kinase C (PKC) release of

Ca2+ second messengers
From ER
phosphorylation of calcium channel proteins
CALMODULIN
entry of extra cellular Ca2+.
RESPONSE
 MECHANISMS OF ACTION
Water Soluble Hormones(E NE)

activation of a2 receptors

inhibitory G-proteins

1 2
stimulates PDE
activity.
inhibits Adenylate cyclase activity
reduction in cAMP
levels
ATP

Fig 6
MECHANISMS OF ACTION
Water Soluble Hormones Synthesis, Storage and Release

Golgi
Post-Translational
Prohormone Modification

ER Hormone
Sig

Sig Seq

Preprohormone
MECHANISMS OF ACTION
Post-Translational Modification
 MECHANISMS OF ACTION
Lipid Soluble Hormones

(1) Diffusion through Cell Membrane

(2) Binding of messenger to cytoplasmic

Nuclear Receptors to form Hormone
Receptor Complex H-RC

(3) Binding of H-RC to DNA

(4) Gene
How? Why?
Activation

Transcription Translation Action

mRNA
MECHANISMS OF ACTION
LIPID SOLUABLE

Fig 7
The Endocrine System Part
III A
THE HORMONES INVOLVED
WITH THE NEGATIVE FEEDBACK
REGULATION OF THE INTERNAL
ENVIRONMENT
WATER SOLUBLE HORMONES FALL INTO
THREE FUNCTIONAL CATEGORIES

REGULATORS OF THE INTERNAL

ENVIRONMENT (Negative Feedback)
BALLISTIC REGULATORS
impart messages whose effects are not
checked
RELAY MESSENGERS for the secretion of
other hormones.
The Trophic Hormones
 NEGATIVE FEEDBACK
REGULATION
• Water soluble
• Absolutely essential for life
• Work in counter regulatory (Rein
control) pairs:
 NEGATIVE FEEDBACK
REGULATION
• Insulin : Glucagon
• Calcitonin: PTH (parathyroid hormone)
 INSULIN-GLUCAGON
The Insulin-to-Glucagon Ratio Regulates Metabolism

• REIN CONTROL OF THE BLOOD

GLUCOSE LEVEL

Fig 1
INSULIN
The Insulin-to-Glucagon Ratio Regulates Metabolism
 The Pancreas

Pancreatic Islets
“islets of “Langerhans”

Fig 3
 Pancreatic Islet

Fig 4
α Cell = Glucagon
β Cell = Insulin
 INSULIN SECRETION
Glucose

GLUT4 transporter

Metabolism

ATP
KATP
No
Secretion Open

Voltage Gated Ca -70 mV RMP

Channels Closed
Fig 5
 INSULIN SECRETION
Glucose

GLUT4 transporter

Metabolism

Ca2+
ATP
Exocytosis KATP
Ca2+ Closed

Ca+
Open
Cell K+
Depolarizes Fig 6
INCREASE OF BLOOD INSULIN
LEVEL
GENERAL
CIRCULATION

HEART

BETA CELLS
PORTAL
SYSTEM

Fig 7
 Insulin Activation of Tyrosine
Kinase
INSULIN INSULIN RECEPTOR
SUBSTRATE

ph o r yla ti o n
Phos
ECF
PI3-KINASE Phosophoinositide 3K
ICF

Phosphorylation (PDK)
(enzymes/membrane)
Increased Synthesis of (all target cells)
glycogen (in liver and muscles) 
Triglycerides in adipocytes 
VLDL (in liver) 
Increased Glucose
Fig 8 Cholesterol uptake and Utilization
 INSULIN BINDING TO ITS
RECEPTORS
Brings GluT4 glucose transporters in muscle and
fat tissue from endosomes to the cell membrane.
Promotes glucose uptake and utilization in cells

Phosphorylation of the enzymes of anabolic

metabolism
This causes synthesis of
glycogen (in liver and muscles) 
fat in adipocytes 
VLDL (in liver) 
Cholesterol
Insulin Activation of Tyrosine
Kinase
Glucose
Glucose
I-R

TK

ECF Facilitated
Exocytosis Diffusion

ICF
Transduction
Glut4

Glut4
Transporters
 “Down Regulation"
• When cell's food stores (especially
glycogen and triglyceride) are
saturated.
• A cell or tissue is not used (e.g.
immobilization of a muscle).
• Serious infections, cancer
 “Down Regulation"
• THE INSULIN RECEPTORS ARE
REMOVED FROM THE SURFACE OF
THE CELL (AND STORED IN
INTRACELLULAR ENDOSOMES).
 “Down Regulation"
• This is called "down regulation" of insulin
receptors.

Fig 9
 “Down Regulation"
ENDOCYTOSIS

Clathrin Pit

Fig 10
Glucagon
The Insulin-to-Glucagon Ratio Regulates Metabolism
 Pancreatic Islet

α Cell = Glucagon
Fig 11 β Cell = Insulin
 GLUCAGON SECRETION

Fig 12
 INCREASE OF BLOOD GLUCAGON
LEVEL

Alpha Cells

PORTAL
CIRULATION

Fig 13
 Glucagon Activation of Adenyl
Cyclase
GLUCAGON
GLUCAGON RECEPTOR
SUBSTRATE

adenylate cyclase

ATP C-AMP A-KINASE

SECOND MESSENGER

increases in glucose Phosphorylation

metabolism in skeletal (enzymes/membrane)
(adipocytes)
muscle (Glycogen) Liver
increases plasma
free fatty acid increases blood glucose
concentration concentration
Fig 14
(gluconeogenesis)
 GLUCAGON BINDING TO ITS
RECEPTORS
• cAMP mediated phosphorylation of
enzymes
– This causes
• (a) breakdown of
– glycogen in the liver 
– fat in adipocytes
• (b) Stimulates Glucose
– gluconeogenesis ( In The Liver)
 GLUCAGON BINDING TO ITS
RECEPTORS
• As a result, this increases the
Blood glucose concentration
Glycogen breakdown in skeletal Muscles Glucose
Stimulation of glucose production in the Liver
Plasma “free fatty acid” concentration
 REIN CONTROL OF THE
BLOOD GLUCOSE LEVEL

Set point Homeostatic balance

Fig 15
 Diabetes Mellitus
Diabetes Mellitus is a condition that
causes high blood glucose levels in the
blood. (Hyperglycemia)
 Diabetes
• Three possible reasons people develop
diabetes are:

Their bodies cannot make any insulin

Their bodies cannot make enough insulin
Their bodies cannot use insulin properly
 Diabetes Mellitus
• The two main types of diabetes mellitus
are:
type 1 diabetes (IDD)
type 2 diabetes (NIDD)
gestational diabetes (diabetes during
pregnancy)
(Diabetes Insipidus)
 Insulin-Dependent Diabetes
(IDD)
• IDD (also called Type 1 diabetes)
– characterized by little or no circulating
insulin
– most commonly appears in childhood.
– results from the destruction of the beta
cells by a cell-mediated auto immune
attack
 Type 1 Diabetes

TYPE ONE DIABETES

Fig 16
Non Insulin-Dependent Diabetes
(NIDD)
• In type 2 diabetes (non-insulin-
dependent diabetes NIDD)
– Failure to express a sufficient number of
glucose transporters in the plasma
membrane (and T-system) of the skeletal
muscles.
 Type 2 diabetes NIDD
• Normally when insulin binds to its
receptor on the cell surface, it initiates
a chain of events that leads to the
insertion in the plasma membrane of
increased numbers of a transmembrane
glucose transporter(GLUT-4)
• This transporter forms a channel that
permits the facilitated diffusion of
glucose into the cell.
Type 2 Diabetes

Genetic defect

Fig 17
 Type 2 Diabetes
• Mutant genes for one or another of the
transcription factors needed for transcription of
the insulin gene
• Mutations in one or both copies of the gene
encoding the insulin receptor
• Obesity
• Hormonal Imbalances
• Pregnancy
The Endocrine System (PTH)
Part III B
Endocrine Control of Calcium and
Phosphate Homeostasis

THE HORMONES INVOLVED

WITH THE NEGATIVE FEEDBACK
REGULATION OF THE INTERNAL
ENVIRONMENT
 PLASMA Ca ++
LEVEL
• Ca2+ is an Important Signal Molecule
• Initiate Exocytosis of Synaptic and (sense) Secretory
vessels
• Contraction of Muscle Fibers(striated)
• Enzyme Activity and Transporters

• Ca2+ is a Cofactor in the Coagulation

Cascade (factor V)
• Ca2+ concentrations affect the
excitability of Neurons
• Ca2+ Na+
Preventing Hypercalcemia and Hypocalcemia is
the result of Endocrine Control
• Calcium Deprivation Hypocalcemia refers
to low blood calcium concentration.
– increased neural excitability
– muscle spasms
– Tetany stiff muscle
– cardiac dysfunction.
• Calcium Loading Hypercalcemia blood
calcium higher than normal.
– Decreased neural excitability(depolarization)
– precipitation of Calcium phosphate in tissues,
leading to widespread organ dysfunction and
damage.
Body Distribution of Calcium and Phosphate” “total

body calcium = intake – output”

 Intracellular calcium:
0.001mM A large majority of calcium within cells is (maintained)
sequestered in mitochondria and Sarcoplasmic reticulum (other
is ER).

 Calcium in Extracellular fluid:

The concentration of ionized calcium in this compartment is
invariant at approximately 2.5mM. (The concentration of
phosphorus in blood is essentially identical to that of calcium.)

 Extracellular matrix (Bone)

The vast majority of body calcium is in bone. Within bone, 99% of
the calcium is tied up in the mineral phase, but the remaining
1% is in a pool that can rapidly exchange with Extracellular
calcium.
 Factors influencing Fluxes of
Calcium and Phosphate
absorbed.
The small intestine is the site where dietary calcium is
Importantly, efficient absorption of calcium in the
small intestine is dependent on expression of a calcium-binding
protein in epithelial cells.

resorption
Bone serves as a vast reservoir of calcium. Stimulating net
of bone mineral releases calcium and phosphate into
blood, and suppressing this effect allows calcium to be deposited
in bone.

homeostasis.
The kidney is critically important in calcium
Under normal blood calcium concentrations, almost
all of the calcium that enters glomerular filtrate is reabsorbed
from the tubular system back into blood.
Hormonal Control Systems
“ Three Hormones Control Calcium
Balance”
• Maintaining normal blood calcium and
phosphorus concentrations is managed
by the action of three hormones that
control fluxes of calcium in and out of
Bone and the Extracellular fluid
– Parathyroid hormone (PTH)
– Vitamin D (1,25Cholecalciferol/Calcitriol)
– Calcitonin
 ENDOCRINE CONTROL OF THE
PLASMA Ca2+ LEVEL
• PTH-CALCITONIN
• Vitamin D
Parathyroid
PTH

Thyroid Calcitonin

Fig 1
Fat Soluble Hormones
 Parathyroid Hormone
• Parathyroid hormone is the most
important endocrine regulator of
calcium and phosphorus concentration
in Extracellular fluid.
Physiologic Effects of Parathyroid
Hormone
Mobilization of calcium from bone:
Stimulates osteoclasts for resorption of bone mineral, liberating
calcium into blood.
H+ ATPase
Osteoblasts Bone Osteclasts
Enhancing absorption of calcium from the
small intestine:
Facilitating calcium absorption from the small intestine by
stimulating production of the active form of vitamin D in the
kidney.
Suppression of calcium loss in urine:
stimulating tubular reabsorption of calcium and phosphate ions in
urine (stimulates loss of phosphate ions )
 Low Plasma (Ca2+)

Parathyroid
Hormone
(PTH) Negative Feed Back

Another Example of a Simple

Endocrine Reflex

Fig 3
Plasma (Ca2+ )
Control of Parathyroid Hormone
Secretion
• Parathyroid hormone is released in response to low
Extracellular concentrations of free calcium

Fig 4
 Vitamin D (Cholecalciferol)
• Vitamin D acts to increase blood
concentrations of calcium.
– It is generated through the activity of
parathyroid hormone within the kidney.
– The most important effect of vitamin D is
to facilitate absorption of calcium from the
small intestine.
– In concert with parathyroid hormone,
vitamin D also enhances fluxes of calcium
out of bone.
Vitamin D (Cholecalciferol)

Vitamin D, as either D3
or D2, does not have
significant biological
activity. Rather, it
must be metabolized
within the body to the
hormonally-active form. PTH

Fig 5
To Small Intestine
 Endocrine Control of Calcium Balance
Endogenous
Precursors Diet

Sunlight Vit D

Liver(stored)

Kidney
+ PTH Plasma
Ca2+
-
Bone/
Intestine
+
Fig 6
Plasma
Ca2+
 Calcium Balance in The Body
Small Intestine

Dietary Calcium Ca2+ Calcium in

Feces
Calcitriol/PTH

Bone ECF
Kidney
Filtration
Calcitriol PTH Ca2+
Calcitonin Calcitonin

Active
Transport
Cell

Ca2+
Fig7
0.001mM Ca2+
Urine
Calcitonin
Decreases blood calcium levels

• Calcitonin
– Kidney: Calcitonin inhibits tubular
reabsorption of Calcium and phosphorus
– Bone: Calcitonin suppresses resorption of
bone by inhibiting the activity of
osteoclasts
– Although calcitonin has significant calcium-
lowing effects in some species, it appears
to have a minimal influence on blood calcium
levels in humans.
Control of Calcitonin Secretion
• The most prominent
factor controlling
calcitonin secretion
is the Extracellular
concentration of
ionized calcium.

Fig 8
 PTH-CALCITONIN

Homeostatic Balance

SETPOINT

Fig 9
 The Endocrine System
Part IV
The Hypothalamus and The
Anterior/Posterior Pituitary
 The Hypothalamus/Pituitary

Posterior Pituitary
(Neurohypophysis)

Fig 1 Anterior Pituitary

(Adenohypophysis)
 Control of Hormonal Activity
“Feedback loops Are Different in The Hypothalamic-Pituitary Pathway”

• Endocrine Reflexes
– Simple ( Short loop)
– Complex (Short and Long Loop)
• Regulatory Mechanisms of the Hypothalamus
(1) Regulatory Hormones
(2) Endocrine Control
(3) Direct Neural Control
 Endocrine Reflexes
Negative Feedback Loops in The Hypothalamic Anterior Pituitary Pathway

stimulation

inhibition Hypothalamus
IC1
Short Loop
Trophic Hormone
Negative
Hormone 1
Feedback
IC3
Endocrine organ Long Loop
IC2 Negative
Trophic Hormone2 Feedback
Short Loop
Negative Feedback
Target

Fig 2
 Regulatory Mechanisms of the
Hypothalamus
Regulatory Hormones Endocrine Control Direct Neural Control
Indirect Control Direct

Hypophyseal Travel along axons in Neuron

Portal System Infundibulum
“Trophic Hormones”

Anterior pituitary Posterior pituitary Adrenal

“Neurohypophysis” medulla
“Adenohypophysis”
acts by TH2
 Hypothalamus
Neurons synthesizing posterior
Pituitary Hormones
Neurons synthesizing
Trophic
Hormones

Capillaries
Portal Vessels
Endocrine cells

Axon Terminals

Posterior Pituitary
Fig 3
Anterior Pituitary
 Hypothalamus
“The Hypothalamic – Hypophyseal Portal System”

Neurons synthesizing
Trophic
Hormones

Capillaries
Portal Vessels
Endocrine cells

Fig 4

Anterior Pituitary
 Regulatory Hormones of the
Hypothalamus
Thyrotropin -releasing hormone (TRH)
Gonadotropin -releasing hormone (GnRH)
Growth hormone -releasing hormone (GHRH/GHIH Somatostatin )
Corticotropin -releasing hormone (CRH)
Prolactin-releasing hormone (PRH/PIH Dopamine)

Released into the blood, travel immediately to the

anterior lobe of the pituitary, where they exert their
effects

These are Trophic or (Releasing) Hormones !!!

 Regulatory Hormones of the
Hypothalamus
• All of these are released into
Hypophyseal Portal System, travel
immediately to the Anterior Lobe of
the Pituitary, where they exert their
effects

ACTH TSH GH ( PRL) FSH LH

The Anterior Pituitary Secretes Six Hormones

Trophic Regulatory Hormones

 Hormones of the Hypothalamic
Dopamine
Anterior Pituitary Pathway
Hypothalamus

PIH

PRH TRH CRH GHIH GnRH

GHRH
Anterior Pituitary

Prolactin TSH ACTH GH FSH LH

Endocrine Targets

Adrenal Gonads
Thyroid cortex Liver

Estrogens
T3/T4 Cortisol IGF’s Androgens Progesterone
Non Endocrine

Fig 5
Targets

Breast Tissues Gonads

Pathway of Growth Hormone Control
Cortisol Secretion
Is Controlled by ACTH
 Control Pathway for Cortisol
Secretion
stimulation

inhibition Hypothalamus
IC1
Short Loop
Negative
CRH Feedback

IC3
Adrenal Cortex
ACTH IC2
Cortisol
Long Loop
Negative
Target Tissue Feedback
Cortisol Secretion
Is Controlled by ACTH
 Endocrine Control (direct)
Posterior Pituitary by the Hypothalamus

• Two other hypothalamic hormones:

• Antidiuretic hormone ADH (Vasopressin)
• Oxytocin

Travel in neurons to the posterior lobe of the pituitary

where they are released into the circulation

ADH (Vasopressin) OXYTOCIN

 Endocrine Control (direct)
Posterior Pituitary by the Hypothalamus

Hormone is made in
Cell Body of Neuron

Hormones Travel Down The Axon

Vesicles Containing Hormones are stored

In Posterior Pituitary
Fig 6
Posterior Pituitary

Hormones are Released into Blood

Vein
 Endocrine Control (Direct)
Posterior Pituitary by the Hypothalamus

Indirect Control

Infundibulum
Anterior Pituitary
Posterior Pituitary

ADH (Vasopressin)
OXYTOCIN
Fig 7
ADH/Vasopressin

Afferent Afferent

Kidney
 Neural Control of the Adrenal Medulla
by the Hypothalamus
Catecholamines
NE
Epinephrine

Hypothalamus

Fig 8
The Endocrine System
Part V
BALLISTIC CONTROL SYSTEMS
 BALLISTIC CONTROL
SYSTEMS
Ballistic systems

Fig 1

Open Loop
 BALLISTIC CONTROL
SYSTEMS
• Epinephrine and Norepinephrine
– Ballistic control of blood sugar and blood
pressure.
• Oxytocin :
– Ballistic control of milk ejection and uterine
contractions.
• Prolactin :
– Ballistic control of fertility and (Negative feed
back control of lactation).
Epinephrine and Norepinephrine
The Catecholamines
THE BALLISTIC CONTROL of
BLOOD SUGAR
THE BALLISTIC CONTROL of
BLOOD PRESSURE
 The Alarm Phase
“Immediate Short-Term Response to Stress”

• Immediate response
to stress occurs.
• sympathetic
nervous system

Cerebral Cortex
Limbic
Hypothalamus
MONSTER

Fig 2
 The Alarm Phase

LIMBIC
SNAKE

AT FIRST
HYPOTHALAMUS

SYMPATHETIC NERVOUS
SYSTEM

ADRENAL MEDULLA

Fig 3
Norepinephrine/Epinephrine onto
α 1 β 1 Adrenergic Receptors
 Effects Of Epinephrine and
Norepinephrine
α 1 β 1 β 2

NE
E(80%)

Fig 4
 Effects Of Epinephrine and
Norepinephrine on α 1 β 1 β 2
Accelerates the utilization of cellular
energy and mobilization of energy
reserves
Adipose tissue ATP
α 1β 1
Liver Glycogen Glucose
In the Heart stimulation of β 1 increase in
Heart Rate and Force of Contraction BP
Vasodilatation of Blood vessels to Skeletal Muscle
β 2
Vasoconstriction of Blood vessels to Skin and
α 1
Gut
 PROLACTIN
• THE BALLISTIC CONTROL OF
FERTILITY
• MILK PRODUCTION
PROLACTIN
Hypothalamus

PIH

Fig 5
 PROLACTIN
“Ballistic and Non Ballistic Control”

Ballistic Control

Closed Loop
infertility

Fig 6
 OXYTOCIN
• THE BALLISTIC CONTROL OF MILK
EJECTION
• THE BALLISTIC CONTROL OF
CONTRACTIONS OF THE UTERUS
 OXYTOCIN

Release of Neurotransmitters

Posterior Pituitary

Fig 7
 OXYTOCIN
Suckling at Stretching of
Breast Cervix

Sexual Stimulation

Oxytocin
Fig 8
 OXYTOCIN

Contractions
Of The Uterus Milk Ejection

Fig 9
The Endocrine System
Part VI
FAT SOLUBLE
HORMONES
CHARACTERISTICS OF FAT SOLUBLE
HORMONES
Blood concentrations are highly predictable. The
"message" is kept constant or unchanging via negative
feedback
Work very slowly. (several days).
High blood concentrations DO NOT have the opposite
effect of low blood concentrations
Removed slowly from the blood
Bind to intracellular receptors (after penetrating the
cell membrane) and exert their effect in the cell
nucleus.
They stop production of … or initiate production of …
Transported in the plasma bound to carrier proteins
Often give the cell a new function or appearance.
Secretion is ALWAYS stimulated by a “TROPHIC"
RELAY MESSENGER
 THYROID HORMONES
• FAT SOLUBLE:
 Are transported on carrier proteins in the plasma.
 Intracellular receptors, which act on the cell nucleus.
 Influence which genes are transcribed, and which are not.
 Effects develop, therefore, very slowly.
 Many effects are irreversible.
 Prolonged absence of thyroid hormones is not fatal but,
instead, gives rise to peculiar appearance rather than death in
the short term.
 Secretion is stimulated by a relay messenger (or "trophic
stimulating hormone ") from the anterior pituitary gland
 THYROID HORMONES

T3
THYROXIN
T4

Fig 1
 THYROID HORMONES

hypothalamus

T3 and T4

FOLLICLE CELLS
IN THYROID

Fig 2
 THYROID HORMONES
Follicle Cells

Follicle Cavity

Fig 3
 THYROID HORMONES
Triiodothyronine T3
Follicle Cell
#3 THYROGLOBULIN
#1 #2
I 2

-T4
IODINE
+ T3 Thyroxime T4
2 TYROSINE
TSH
G cAMP
Endocytosis
#4
Capillary
T3-T4

T3&T4 Exocytosis
T3&T4
FOLLICLE CAVITY
LYSOSOMAL
DIGESTION
Bind with TBG or #5 Fig 4
Albumin #6
 THYROID HORMONES

FROM THYROID EQUILIBRIUM

FOLLICLES

TBG BOUND FREE

T3 T4 T3 T4 LIVER
0.3 0.03
T4 T3

AS FREE T3&T4 ARE TAKEN

INTO CELLS BOUND T3&T4
IS RELEASED FROM FOLLICLES
TO CELLS

Fig 5
 Thyroid Hormone Pathway
Tonic
Release

TRH

•Goiter Short Loop

•Hypothyroidism
•Hyperthyroidism
TSH
•Graves
•TSImm

Long Loop

T3-T4

Systemic Metabolic effects

T3 T4
I2
 THYROID HORMONES

Immediate effects Mediated

By Second Messenger
(Mitochondria ATP )
Thyroxin

ATPase
Fig 6
Regulation of
Cellular Metabolism
MECHANISMS OF ACTION
LIPID SOLUABLE H
Carrier Protein
(1) Diffusion through Cell Membrane

(2) Binding of messenger to cytoplasmic

Nuclear Receptors to form Hormone
Receptor Complex H-RC
Immediate effects May be
(3) Binding of H-RC to DNA Mediated By Second
Messenger System
(Mitochondria)
(4) Gene
Activation

Transcription Translation Enzyme Regulation of

mRNA Metabolism
Unit VII The Circulatory System
Blood Part I
Functions and Composition

Blood, a specialized fluid connective tissue that contains cells

suspended in a fluid matrix.
 Functions of blood
 The transportation of dissolved gases,
nutrients, hormones, and metabolic
wastes.
 The regulation of the pH and ion
composition of interstitial fluids.
 The restriction of fluid loss at injury
sites.
 Defense against toxins and pathogens.
 The stabilization of body temperature.
 Composition of Blood
• Plasma
– Plasma is the matrix in which the blood cells are
suspended.

• Formed elements
– Blood cells and cell fragments that are
suspended in plasma
– (1) Red blood cells
– (2)White blood cells
– (3) Platelets.
 Formed elements
• Red blood cells or Erythrocytes
• Platelets or Thrombocytes
• White blood cells or Leukocytes
• Three kinds of Granulocytes
• neutrophils
• eosinophils
• basophils
• Two kinds of Agranulocytes
• lymphocytes
• monocytes
 Plasma
• Composition of blood plasma
– Water 92%
– Plasma Proteins 7%
• Albumins
• Globulins
• Fibrinogen
– Other Solutes 1%
• Amino acids ,glucose, lipids, Ions, O2 and CO2
 Albumins
• Albumins
– The most abundant plasma proteins
– Major contributors to the osmotic
pressure of plasma.
– Transport of fatty acids, hormones,
steroids
 Globulins
• Globulins
– Antibodies (immunoglobulins)
– Transport globulins
• Thyroid-binding globulin and Transthyretin, which
transports thyroid hormones; Transcortin, which
transports ACTH; and transcalciferin, which
transports calcitriol.
• Metalloproteins, which transport metal ions.
• Apolipoproteins, which carry triglycerides and other
lipids
• Steroid-binding proteins, which transport steroid
hormones in blood.
 Fibrinogen
Functions in blood clotting
Hematopoiesis
“The Production of Blood Cells”

Pluripotent hematopoietic
Stem cell
Increasing
Specialization
HEMOCYTOBLAST
MYELOID STEM LYMPHOID STEM
CELLS CELLS

MYELOID PROGENITORS
LYMPHOCYTES
CELLS

Erythropoietin RBC

Thrombopoeitin MEGAKARYOCYTE
PLASMA
Cytokines PLATELETS
(Glycoprotein Hormone)

Colony Stimulating WBC

Fig 1 Factors BLOOD
Unit VII The Circulatory
System
Blood Part II
Red Blood Cells
Red Blood Cells (erythrocytes)
Structure of RBCs

 Each RBC is a biconcave disc with

a thin central region and a thicker
outer margin
 THIS gives each RBC a larger surface area
 THIS enables RBCs to form stacks, that
smooth the flow through narrow blood
vessels.
 THIS enables them to bend and flex when
entering small capillaries and branches.

Fig 1
 Red Blood Cells (erythrocytes)
• Loose most of their organelles, including nuclei;
these cells retain only the cytoskeleton (Hemoglobin).
• Because they lack nuclei and ribosome's, cannot
divide or synthesize structural proteins or
enzymes.
• Cannot perform repairs, and their life span is
relatively short--normally less than 120 days.
• In the absence of mitochondria, they obtain the
energy they need through the anaerobic
metabolism of glucose absorbed from the
surrounding plasma.
“The lack of mitochondria ensures that absorbed oxygen will be
carried to peripheral tissues, not "stolen" by mitochondria in
the cell “
 Red Blood Cells (erythrocytes)
• Red blood cells are responsible for the
Transport of oxygen and carbon dioxide
• Hb transports O2 and some CO2 from tissue
given away
Hb + O2 HbO2
CO2+ HbHb-CO2

• Temp, pH, metabolites effect Oxygen-Hb binding.

 Hemoglobin
“Hemoglobin Synthesis Requires Iron”

• Each Hemoglobin Can Bind Four O2 Molecules (100%

Saturation) through 4 sub-units.
• Hemoglobin is a protein molecule with 4 protein sub-units
(2 alphas and 2 betas) polypeptides.
• Each of the 4 sub-units contains a heme group which gives the
protein a red color
• Each heme has an iron atom in the center which can bind an oxygen
molecule (O2)
• The 4 hemes in a hemoglobin can carry a maximum of 4 oxygen
molecules
When hemoglobin is saturated with oxygen it has a bright red color; as it loses
oxygen it becomes bluish (cyanosis)
In Sickle Cell Anemia has two peptides Aug-Glu defect bend and twist Hb
molecule so cause flow obstruction
 Hemoglobin
“Hemoglobin Synthesis Requires Iron”

Fig 2
 Hematocrit
• The percentage of whole blood occupied
by cellular elements ( RBC S)
volume of packed red cells (VPRC) or
simply the packed cell volume (PCV).

The normal hematocrit in adult males averages

46 (range: 40–54); the average for adult
females is 42 (range: 37–47).
The Blood Count

Fig 3
 RBC Life Span
• In about 120 days
Rupture of the cell membrane
Damage is detected by phagocytic cells
(macrophages)
• RBC are replaced
Each day 1 percent of the circulating
RBCs, 3 million new RBCs enter the
bloodstream each second
The Blood Count
 Hemoglobin Conservation and Recycling
Intestine urobilins +sterobilins
(1) IRON

2 LIVER

Kidney AT
4 control RBC Bile
formn Transferin Ferritin
RBC
PRODUCTION Bilirubin 7
3 Metabolism
Fe
6 KIDNEY
RBC bilirubin
BONE MARROW
erytropoiesis
PLASMA biliverdin urobilins
EPO 8
Fe

Urine
OLD RBC
Fig 4 DESTROYED
5 Heme stripped
Erythropoietin Of Fe by
Macrophage
SPLEEN
Unit VII The Circulatory
System Blood Part III
Hemostasis
 PLATELETS
• Platelet Functions
– The transport of chemicals important to
the clotting process..
– The formation of a temporary patch in
the walls of damaged blood vessels..
– Active contraction after clot formation
has occurred.
 PLATELETS
• PlateletProduction (thrombocytopoiesis)
– megakaryocytes

Cellular Fragments

Fig 1
 Hemostasis
• The process of Hemostasis, the
cessation of bleeding
– Consists of three phases:
(1) vascular phase
(2) platelet phase
(3) coagulation phase.
 Hemostasis
“An Overview”

Platelet Phase Coagulation Phase

DAMAGE TO WALL OF BLOOD VESSEL

TISSUE FACTOR
COLLAGEN VASOCONSTRICTION
EXPOSED
EXPOSED 1

Formation of Loose Plug Coagulation Cascade

2 3

Fig 2
Exterinsic pathway Reinforced Platelet Plug Intrinsic pathway
 THE VASCULAR PHASE
• Vascular spasm
– Decreases the diameter of the vessel at
the injury site by Vasoconstrictive
Paracrines
– Changes occur in the vessel endothelium
 THE PLATELET PHASE
Formation of platelet plug/Begins the Clotting Process

DAMAGE TO WALL OF BLOOD VESSEL Intrinsic Pathway

To COLLAGEN
Common
EXPOSED
Pathway

PLATELETS ADHERE AND PLATELET

RELEASE PLATELET ACTIVATION
FACTOR

+
PLATELETS AGREGATE INTO COX
LOOSE PLUG PLATELET ACTIVATING
FACTOR (PAF)
Cytokines
Fig 3 Aspirin
Vasoconstriction
THE PLATELET PHASE
Formation of platelet plug

PAF

+NO
 THE COAGULATION PHASE
“Coverts the Platelet Plug into a More Stable Clot”

DAMAGE TO WALL OF BLOOD VESSEL

 FROM INTRINIC
TISSUE FACTOR III
PATHWAY TF XII
A EXPOSED B
TF VII
EXTRINSIC
COAGULATION CASCADE PATHWAY

C
+ THROBIN FORMATION
TF X
Loose Plug CONVERSION OF FIBRINOGEN
TO FIBRIN

Reinforced Plug
(clot)
COMMON PATHWAY
Fig 4
 The Extrinsic Pathway
• The Extrinsic Pathway begins with the
release of Tissue Factor III, also
known as Tissue Factor (TF), by
damaged endothelial cells
 The Intrinsic Pathway
• The Intrinsic Pathway begins with the
exposure of collagen fibers at the
injury site and the subsequent
activation of proenzymes (usually Factor
XII)
 The Common Pathway
The Common Pathway
Enzymes from the Extrinsic and Intrinsic
pathway activate Factor X
Prothrombinase

Starts Here

Prothrombin Thrombin

Ca+2
Fibrinogen Fibrin
Intrinsic Pathway Extrinsic Pathway
Collagen or other activators Damage Exposes Tissue Factor
III Van Willebrands
Tissue Factor
III & VII (a)

Positive Feedback

Hemophilia A

Common Pathway
Thrombin Prothrombin

Fibrinogen Fibrin

Positive Feedback Ca+2

Fig 5
Cross-Linked Fibrin
 Feedback Control of Blood Clotting

• Thrombin generated in the common

pathway stimulates blood clotting by
– (1) stimulating the formation of tissue
factor
– (2) stimulating the release of PAF-3 by
platelets. ( positive feedback loop)
accelerates the clotting process
Intrinsic Pathway PAF-3
THROMBIN
Extrinsic Pathway Tissue Factor
From Common
Pathway Positive Feedback
Intrinsic Pathway Extrinsic Pathway

Common Pathway

Fig 6
 Calcium Ions, Vitamin K, and
Blood Clotting
• Calcium ions and vitamin K (Cofactor)
affect almost every aspect of the
clotting process. All three pathways
(intrinsic, extrinsic, and common)
require Ca2+.
 CLOT RETRACTION
• CLOT RETRACTION
– The platelets then contract, and the entire
clot begins to undergo clot retraction
• (1) pulls the torn edges of the vessel closer
together,
• (2) reduces the size of the damaged area,
making it easier for fibroblasts, smooth
muscle cells, and endothelial cells to complete
repairs.
 FIBRINOLYSIS
The clot gradually dissolves

Plasminogen

Fig 7
 Anticoagulants Prevent
Coagulation
• Blood clotting is restricted by factors that
inactivate or remove clotting factors
– Anticoagulants IX,X,XI,XII
(intrinsic)

Heparin Antithrombin-III
(activates)
Inactivates Thrombin

Thrombomodulin Binds to Thrombin

Converts
Protein C
Inactivates clotting

Anticoagulant Drugs (Coumarin)

Warfarin (Coumadin)
Vitamin K (cofactor) II,VII,IX,X (extrinsic)
 Unit VII The Circulatory System
Part IIA Cardiovascular Physiology I
Blood Flow and Blood Pressure

Objectives:
(1)To Describe the factors that influence Blood pressure and how
Blood pressure is regulated
(2)The mechanisms that regulate blood flow through Arteries,
Capillaries, and veins

The Goal of Cardiovascular regulation is The Maintenance of

adequate blood flow through peripheral tissues and organs
 An Overview of Cardiovascular
Physiology
Neural(neurotransmitter)
and
Hormonal(catecholamine) Homeostatic Balances

Regulation

Afterload

Arterial Peripheral Capillary

Cardiac Venous
Blood Resistance Pressure
Output Pressure
Pressure

Capillary
Exchange
Interstitial
Fluid
Fig 1
 PRESSURE
• Circulatory Pressure (Pressure Gradient)

– Blood pressure refers to arterial

pressure (BP)
– Capillary hydrostatic pressure (CHP), or
capillary pressure is the pressure
within capillary beds.
– Venous pressure is the pressure within
the venous system.
• Blood Flow (F) The volume of blood
flowing per unit of time
 RESISTANCE
“A Force That Opposes Movement”

• The resistance of the cardiovascular system

opposes the movement of blood. The greater
the resistance, the slower the blood flow.
– Peripheral resistance (PR)
• The resistance of the arterial system
– F Pressure Gradient/R
– In Other Words
– (Flow is directly proportional to the pressure
gradient P, and inversely proportional to the
resistance, R.
 Factors Affecting Peripheral
Resistance
TOTAL PERIPHERAL
RESISTANCE

Peripheral Resistance (PR) (arterial resistance)

Vascular Resistance Viscosity Turbulence

(bruit)
Length Diameter

X 2 X 16

R α 1/r4

Fig 2
 ARTERIAL BLOOD PRESSURE

• Circulatory Pressure
– Systolic pressure
• The peak blood pressure measured during L ventricular systole

– Diastolic pressure
• The minimum blood pressure at the end of L ventricular diastole
– Pulse pressure
• The difference between the systolic and diastolic pressures

• Mean Arterial Pressure (MAP) mean driving force

– Calculated by adding one third of the pulse pressure to the

diastolic pressure MAP = DP +pp/3
 ARTERIAL BLOOD PRESSURE
“Ventricular Contraction”

Ventricular Contraction

Semilunar Valves 3 Arteries Expand and

open Store energy

Fig 4
 ARTERIAL BLOOD PRESSURE

Elastic Rebound sends

Isovolumic Ventricular Blood forward
Relaxation

1 3

Semilunar Valves
shut

Fig 5
 Systemic Pressures
Systolic Pressure

Pulse Pressure

Diastolic
Pressure
Mean Pressure
MAP = dp +pp/3

Fig 6
 Mean Arterial Pressure
“ is a Function of Cardiac Output and
Resistance in The Arterioles”
MAP = DP +pp/3
Mean Arterial Pressure
Cardiac Output Variable Resistance

Left Ventricle Arterioles

MAP CO x P.RESISTANCE
Fig 7
MEAN ARTERIAL BLOOD PRESSURE
“The Driving Pressure for Blood Flow”

Is determined by

60% Resistance 60% Blood

Volume

Fig 8
 ARTERIAL BLOOD PRESSURE
Ventricular ejectionPeak
(120 Systolic
mmHg) Pressure
B C

dicrotic notch
MAP isovolumetric
S valves close D
Diastolic Pressure

E
A

EDV;bicuspid V close

Fig 9
 ARTERIAL BLOOD PRESSURE
“Is Estimated by Sphygmomanometry”

Sphygmomanometer
Brachial Artery

> 120 mmHg

Fig 10
 ARTERIAL BLOOD PRESSURE
Sounds of Korotkoff are Created
By Pulsatile Blood Flow (SBP)

80 -120mmHg

Systolic Pressure

Fig 11
 Hypertension and Hypotension
• Hypertension (High Blood Pressure)
– Over 150/90
• Leading to Coronary ischemia
• Hypotension (Low Blood Pressure)
• Orthostatic Hypotension
 Unit VII The Circulatory System
Part IIB Cardiovascular Physiology II
The Regulation of Blood Pressure, Blood Volume and
Blood Flow

MAP

Blood Volume Cardiac Output Resistance Distribution

Diameter of Diameter of
Fluid In Fluid Out
Arterioles Veins

Kidneys

Changes in Blood Volume Affect Blood Pressure

 The Regulation of Blood Pressure and
Blood Volume

Homeostasis

Homeostasis Disturbed
Autoregulation
(Autoregulation Ineffective)
(Local)

Neural
(Short Term) Fast

Kidney Slow
Fig 1 (Endocrine/Long Term
The Regulation of Blood Pressure, Blood
Volume and Blood Flow

Local Control/Autoregulation

Myogenic Paracrines

Metabolic Signal Molecules

Vasoconstriction
O2 CO2 NO Histamines

Vasodilate Vasodilate

Fig 2
The Regulation of Blood Pressure, Blood
Volume and Blood Flow

“Local Control matches tissue blood flow

to the metabolic needs of the tissue”
 Myogenic Autoregulation
• The ability of smooth muscle to
regulate its own state of contraction

Release of endothelins

Ca+ Vasoconstriction
BP stretches
vessel

Fig 3
 Paracrines Alter Vascular Smooth
Muscle Contraction

Paracrines

Metabolic Signal Molecules

O2, CO2 H+ NO, Histamines, Adenosine
Seratonin

Vasodilation Vasodilation

Think Homeostatic Balances !!!

Fig 4
 Paracrines Alter Vascular Smooth
Muscle Contraction
Active Hyperemia Tissue Metabolism
(dilation)
O2 CO2

Wash Away

Fig 5
 Paracrines Alter Vascular Smooth
Muscle Contraction
Tissue Blood Flow Due To
Occlusion

CO2 H+

Reactive Hyperemia Increased Blood Flow

Following a Period of
Low Perfusion

Fig 6
 Cardiovascular Regulation
“Neural”

Tonic
Autonomic Reflex Control
Sympathetic Parasympathetic

NE on α Epinephrine on β 2 ACh/NO
1
Receptors Cholinergic Receptors
Receptors
Vasodilation Vasodilation
Vasoconstriction

Vascular Smooth Heart

Muscle Liver
BP
Skeletal Muscle
BP
Fig 7
Reflex Control of Cardiovascular
Function ( Blood Pressure)

• Cardiovascular centers detect changes

in tissue demand of arterial blood, with
respect to
– Blood pressure
– pH
– Dissolved gas concentrations.
 Baroreceptor reflexes
Chemoreceptor reflexes

The Baroreceptor reflexes

• respond to changes in blood pressure
• The Chemoreceptor reflexes
– monitor changes in the chemical
composition of arterial blood
 Components of The Baroreceptor
Reflex Carotid sinuses
Medullary CV Center
Acceleratory
Inhibitory
Vasomotor (Autonomic)
vasoconstriction
vasodilatation

Atrial Baroreceptors

Tonically active
Stretch
sensitive
receptors

Aortic sinuses
Fig 8
 Blood Pressure

Baroreceptor Reflex
“Is The Primary Homeostatic
Control for Blood Pressure”
-

β 1
α 1

Fig 9
 MAP ON STANDING

Baroreceptor Reflex
(Orthostatic Hypotension)
-

NE
?
? ? ?

Fig 10
 The Regulation of Blood Pressure and
Blood Volume
“ Long Term Endocrine Control byThe Kidney”

Decreased Blood Pressure and Volume

Kidney Sympathetic Stimulation

Erythropoietin Renin
(Short Term)

Long Term Angiotensin II

ADH
Heart Rate Increased Blood
Aldosterone Volume/Pressure
Fig 11
Thirst
 The Regulation of
Blood Pressure and Blood Volume
Blood Volume

Cardiovascular Renal
(Short Term)
Blood Pressure (Long Term)

Slow
Fast

Fig 12
 The Regulation of Blood Pressure and
Blood Volume
“Endocrine Control The Heart”

Increased Blood Pressure and Volume

Stretching of Heart
Muscles
Release of Atrial Natriuretic
Peptides
Block Aldosterone /
Increased Na+ Loss in Urine
Reduced Blood
Block ADH/
Increased Water Loss in Urine Volume

Reduced Thirst

Block Renin
Fig 13 Peripheral Vasodilation
Reduced BP
 Circulatory shock
Homeostatic Failure 35% Blood Loss

BV
3 1
CO DAMAGE TO HEART
VESSEL CLOTTING
BP
2 Baroreceptor
DECREASE IN reflex
BLOOD TO TISSUES
ISCHEMIC RESPONSE

O2 TISSUE STARVATION
4
BRAIN

INCREASED CAPILLARY
PERMEABILITY FALLING ARTERIAL
PRESSURE

Fig 14 DEATH
 Unit VI
The Heart
Part IB
The Heart as a Pump
 Electrical Conduction in The Heart
“Electrical Conduction in The Heart Coordinates Contraction”

• The Sinoatrial (SA) node, located in the wall

of the right atrium.
• The Atrioventricular (AV) node, located at
the junction between the atria and ventricles.
• Conducting cells
– Internodal pathways ( Atria) SA
AV
– AV bundle, bundle branches, Purkinje
fibers (Ventricles)
 Electrical Conduction in The Heart
#1 Action Potential in Autorhytmic cells

#2 Depolarization Spreads Rapidly Through Gap Junctions

#3 Wave of Contraction from Atria to Ventricles
Electrical Conduction in The Heart
“THE CONDUCTING SYSTEM”

Fig 1
 Electrical Conduction in The Heart
“THE CONDUCTING SYSTEM”

• The path of an impulse from its

initiation at the SA node
ATRIAL CONTRACTION

(SA) Node moderator band

(AV) Node
AV Bundle (HIS) papillary
Bundle Branches muscles

Purkinje Fibers
Fig 2
VENTRICULAR CONTRACTION
Electrical Conduction in The Heart
“THE CONDUCTING SYSTEM”

SA Node Depolarizes

SA Node

AV Node

Fig 3
Electrical Conduction in The Heart
“THE CONDUCTING SYSTEM”

SA NODE Electrical activity goes

Rapidly to AV Node Via
Internodal Pathways

Bundle of HIS
AV NODE

Fig 4

Along the way, the conducting cells pass the stimulus to contractile cells
of both atria. The action potential then spreads across the atrial
surfaces by cell-to-cell contact
 Electrical Conduction in The Heart
“THE CONDUCTING SYSTEM”

Depolarization spreads more

Slowly across atria. Conduction
Fibrous
Slows through AV node
skeleton
Dense bands of
Very Important
elastic tissue
100 ms delay
Bundle of HIS

Fig 5

The stimulus affects only the atria, because the fibrous skeleton
isolates the atrial myocardium from the ventricular myocardium.
 Electrical Conduction in The Heart
“THE CONDUCTING SYSTEM”

Depolarization moves Rapidly

Through ventricular Conducting
AV NODE
system To the Apex of the
Heart

Chordae BUNDLE BRANCHES

tendineae
moderator band

APEX
Papillary
muscles
Fig 6
Electrical Conduction in The Heart
“THE CONDUCTING SYSTEM”

PURKINJE
Depolarization wave
FIBERS
Spreads upward from Apex

Fig 7
Electrical Conduction in The Heart
“Pacemakers Set The Heart Rate”
SA Node 70bpm

Extra fibrillation in the atria

SA node mesh is disrupted AV Node 35bpm

Fig 8
Unit VII The Circulatory System
The Heart
Part IC
THE
ELECTROCARDIOGRAM
“The Electrocardiogram Reflects the
Electrical Activity of the Heart”
THE ELECTROCARDIOGRAM
- +

-
-
Einthovens Triangle

Electrodes are attached

Forming a Triangle
Fig 1
+
+
THE ELECTROCARDIOGRAM
• ECG Fundamentals
 Equals the sum of all the electrical potentials
generated in the Heart
 Each component reflects depolarization or
repolarization of a Portion of the Heart
 Depolarization equals contraction
 Repolarization equals relaxation
 THE ELECTROCARDIOGRAM
“The Basics”

• There are Two Major Components of an

ECG
Waves
Deflections above or below Baseline
Segments
Sections of Baseline between Two Waves

(An Interval Contains Waves and

Segments)
 THE ELECTROCARDIOGRAM
“The Basics”

Waves

PR Segment Segment

Interval Fig 2
 THE ELECTROCARDIOGRAM
“The Basics”

• There are Three Major Waves on a

“Normal” ECG
The P wave
The QRS Complex
The T wave
 THE ELECTROCARDIOGRAM
“The Basics”

T
P

Fig 3
QRS COMPLEX
 P WAVE
The P wave represents the wave of depolarization that spreads from
the SA node throughout the atria

PR

The period of time from the onset of the P wave

to the beginning of the QRS complex is termed the
Fig 4 P-R interval AV NODE AV BUNDLE
Atria Contract
 QRS COMPLEX
WAVE OF VENTRICULAR DEPOLARIZATION

Fig 5
 QRS COMPLEX
WAVE OF VENTRICULAR DEPOLARIZATION

R
R
Ventricles Start
To Contract

Fig 6
 QRS COMPLEX
WAVE OF VENTRICULAR DEPOLARIZATION

R
S

Q
S

Fig 7
 ST Segment
The ST segment following the QRS is the time at which the entire
ventricle is depolarized (Ventricles Contract)

ST segment

S
Ventricles Contract

Fig 8
 T WAVE
The T wave represents ventricular repolarization

Fig 9 The Q-T interval represents the time for both

ventricular depolarization and repolarization to
occur.
 HEART RATE
“P WAVE TO P WAVE OR PEAK TO PEAK QRS”

Fig 10
http://www.britannica.com/nobel/cap/oelecar002a4.html
 THE ELECTROCARDIOGRAM
“ What are We Looking For? ”

1. What is the Heart rate ? (60-100 bpm)

A. Tachycardia
B. Brachycardia
2. Is the Rhythm regular ?
A. Arrhythmia
3. Are all the Waves Present in recognizable
form ?
A. Is there one QRS Complex for each P Wave.
B. Is The P-R segment constant in length ?
 Ischemia and Hypoxia
Ischemia is insufficient blood flow to provide adequate
oxygenation. This, in turn, leads to tissue hypoxia (reduced
oxygen) or anoxia (absence of oxygen).
• The most common causes of Ischemia are acute arterial
thrombus formation, chronic narrowing (stenosis) of a supply
artery that is often caused by atherosclerotic disease.   As
blood flow is reduced to an organ, oxygen within the tissue
falls (hypoxia) leading to a reduction in mitochondrial
respiration and oxidative metabolism.
Myocardial Infarction
Ischemic myocardial necrosis usually resulting from abrupt
reduction in coronary blood flow to a segment of myocardium
 Normal ECG
(First Degree Block)

Fig 11 First-degree AV nodal block - the conduction velocity is slowed

so that the P-R interval is increased.  Can be caused by enhanced
vagal tone, digitalis, beta-blockers, calcium channel blockers, or
ischemic damage
 Second-decree AV nodal block
Second-degree AV nodal block - the conduction velocity is slowed to the
point where some impulses from the atria cannot pass through the AV
node.  This can result in p-waves that are not followed by QRS complexes

Fig 12
 Third-decree AV nodal block
Conduction through the AV node is completely blocked so that no
impulses are able to be transmitted from the atria to the ventricles.
QRS complexes will still occur but they will originate from within the
AV node

Fig 13
 ATRIAL FIBRILLATION
Uncoordinated atrial depolarization

http://www.skillstat.com/ECG_Sim_demo.html
Fig 14 http://www.ecglibrary.com/ecghome.html?
http://sprojects.mmi.mcgill.ca/cardiophysio/arrythmiasintro.htm
 VENTRICULAR FIBRILLATION
Uncoordinated ventricular depolarization

Fig 15
 Pressure-Volume Changes During One Cardiac Cycle

LEFT VENTRICULAR
PRESSURE AORTIC VALVE Stroke Volume
CLOSES
ESV
D
A--------B
PASSIVE FILLING
AND ATRIAL CONTRACTION
AORTIC VALVE
B--------C
ISOVOLUMIC CONTRACTION
OPENS
C
C ------- D
VENTRICULAR EJECTION
D ------- A
ISOVOLUMIC RELAXATION

EDV = END DIASTOLIC MITRAL VALVE

CLOSES
VOLUME
MITRAL VALVE EDV
ESV = END SYSTOLIC
OPENS
VOLUME
A B
Fig 6 LEFT VENTRICULAR
VOLUME
 The Wiggers Diagram

Identify
Mitral valve opens
Mitral Valve closes
EDV
Aortic Valve opens
Aortic Valve closes
ESV

Fig 7
 Cardio Dynamics
• Cardiodynamics refers to the
movements and forces generated during
cardiac contractions
 End-diastolic volume (EDV) The amount of blood in each
ventricle at the end of ventricular diastole
 End-systolic volume (ESV) The amount of blood
remaining in each ventricle at the end of ventricular systole
 Stroke volume (SV) The amount of blood pumped out of
each ventricle during a single beat, which can be expressed as
EDV - ESV = SV
 Stroke volume/Cardiac Output
Cardiac Output Is a Measure of Cardiac Performance

CO = SV X HR
STROKE VOLUME HEART RATE

WHAT WOULD THE CO BE OF A PERSON WITH A

STROKE VOLUME OF 80ML/BEAT AND A HEART
RATE OF 75 ?

The Volume of Blood Pumped per Ventricle/Unit Time

Fig 8
 FACTORS AFFECTING THE
STROKE VOLUME
• EDV
(1) Filling time (Duration of Ventricular Diastole)
(2) Venous return (CO, BV, PphlCir, Skeletal & Muscular Activity)
• ESV
(1) Preload
The degree of stretching experienced during ventricular
diastole is called the preload.
The preload is directly proportional to the EDV: The
greater the EDV, the larger the preload
The greater the EDV, the larger the stroke volume

The Frank–Starling Principle

 The Frank–Starling Principle
Increasing the EDV results in a corresponding
increase in the stroke volume

FORCE RESTING VALUE 135ml

SV

Fig 9

STRETCH/ VENTRICULAR EDV

Length force relationship “ The Starling Curve”

 FACTORS AFFECTING THE
STROKE VOLUME
ESV Cont.
(2) Contractility The amount of force produced
during a contraction, at a given preload
Autonomic Activity (From Unit One)
Sympathetic (+ inotropic)
Parasympathetic (- inotropic)
Hormones
Epinephrine and Norepinephrine (+ inotropic)

(3) Afterload
The amount of tension the contracting ventricle must
produce to force open the semilunar valve and eject blood.
(As afterload increases the stroke volume decreases.)
 MODULATION OF CARDIAC CONTRACTION

Ca++ Ca++
β 1
Cardiac Muscle Cardiac Muscle
Cell Metabolism Cell Metabolism

Increase in force Decrease in force

Of Contraction/ Of Contraction
Rate
(Minimal)
Fig 10
MODULATION OF CARDIAC
CONTRACTION
 CARDIAC OUTPUT

Fig 11
 Factors Affecting
Bainbridge Reflex Cardiac Output

Fig 12
 Unit VIII
Part I
Respiratory Physiology
 The Respiratory System
• The respiratory system has five basic
functions
– To Provide an Extensive Area for Gas
exchange between air and circulating
blood
– Homeostatic regulation of pH/CO2
– Protecting respiratory surfaces (cilia)
– Producing sounds involved in speaking
– Providing olfactory sensations
 Respiratory Physiology
• External respiration
I. Exchange of oxygen and carbon dioxide between the
lungs and the air
II. Exchange of oxygen and carbon dioxide between the
lungs and the Blood
III. Transport by The Blood
IV. Exchange of oxygen and carbon dioxide between the
Blood and the Cells O2
O2

lungs cell

CO2 CO2
External Respiration
 Respiratory Physiology
Four integrated steps involved in External
respiration
(1) Pulmonary ventilation,
The physical movement of air into and out of the lungs.
(2) Gas diffusion,
Diffusion across the respiratory membrane (alveolar air spaces
and alveolar capillaries).
(3) The transport of oxygen and carbon dioxide
Between alveolar capillaries and capillary beds in other tissues.
(4) The Exchange of gases between blood and the
cells
 *Lung Compliance/Elastance
• The ability of the lung to stretch is
called compliance
– Fibrotic Lung Disease
– Surfactant insufficiency
• The ability of the lung to return to its
resting volume is called elastance
– Emphysema
 *Surfactant Decreases the
Work of Breathing
• Surfactants are molecules
that disrupt cohesive forces
between water molecules
– Type II alveolar cells
– NRDS Newborn
respiratory distress
syndrome(surfactant
deficiency)
Surfactant
 *Respiratory Physiology
“Gas Exchange Requires Pressure Gradients”
Alveoli

DR surface area X Conc. Gradient

Mem Thickness X Mem Resistance

Venous Circulation Arterial Circulation

Fig 1
XGas Composition in the Alveoli

At Rest
Equal to
Blood
Only 10%

During Exercise

Normal Fig 2
At Rest
Local Control Matches Ventilation
and Perfusion
Arteriole Bronchiole

Low O2
Blood

Pulmonary Capillaries
Fig 3
Local Control Matches Ventilation
and Perfusion
Restricted Ventilation

Fig 4
 Local Control Matches Ventilation
and Perfusion
Constriction of Arteriole
Due to Low O2

Blood Flow Diverted

To more(Better) Ventilated
Alveoli at high oxygen

Fig 5
 Gas Transport in The Blood
“Hemoglobin Transports Most Oxygen to the Tissues”
Hb+O2 HbO2
Hemoglobin Oxyhemoglobin

Total Blood Oxygen Content is =

Amount Dissolved in the Plasma + the
Amount Bound to Hemoglobin

2% in Plasma
98% Bound to Hemoglobin as
Oxyhemoglobin

Each Hemoglobin Molecule Binds Up to Four O2 Molecules

 Gas Transport in The Blood
“Hemoglobin Transports Most Oxygen to the Tissues”

Temperature, pH and
Metabolites Affect Oxygen-
Hemoglobin Binding
 *O2 LOADING
Factors Effecting The Solubility of a Gas in A Liquid

Dalton's Law of Partial Pressures

The partial pressure of a gas is the pressure contributed by a
single gas in a mixture of gases. The partial pressure is abbreviated by
the prefix P or p. All the partial pressures added together equal the
total pressure exerted by the gas mixture. High P more solubility.
Henry's Law
The solubility of a gas in a liquid depends on temperature, the
partial pressure of the gas over the liquid, the nature of the solvent
and the nature of the gas. The most common solvent is water. In
winter, oxygen diffuses fast(more soluble).
Bohr Effect
The solubility of a gas more on the basic Ph of the solvent.
Temp= K *O2 LOADING
“PO2 Determines Hemoglobin Binding of O2”

Fig 6

At Sea Level the Partial Pressure of O2 is High Enough to Give

Nearly 100% Saturation of Hemoglobin
 *O2 LOADING
• O2 Delivery in the Tissues is Promoted by Acid Conditions (Bohr
Effect)
• Muscle metabolism produces large amounts of acids: Ph
– Under Aerobic Conditions
• C6H12O6+02 CO2 +H2 (H2O) H2CO3 → HCO3- + H+
– bicarbonic Acid
– Under anaerobic conditions (maximal exercise)
– C6H12O6 CH3 CHOHCOOH H+
Acetic Acid
Both acids lower the pH

Low pH helps the unloading of O2 from hemoglobin(delivery in

tissue); normally only 25% is unloaded, but during exercise as
much as 75% may be unloaded
Temp= K
O2 UNLOADING
“The Effects of Ph”

Fig 7
 Gas Transport in The Blood
“Effects of Temperature”

Fig 8
 Gas Transport in The Blood
“The Effects of PCO2”

Fig 9
 Gas Transport in The Blood
“2,3-DPG alters Hemoglobin”

2,3 Diphosphoglycerate

Hypoxia
Fig 10
Anemia
High altitude
 Oxygen Transport

TISSUES LUNGS
O2

CO2
Hb+ CO2

CO2 ( Carbaminohemoglobin) Fig 11

Hb-CO2
 Gas Transport in The Blood
“Fetal Changes in Hemoglobin Structure”

Fig 12
 Gas Transport in The Blood
“Hemoglobin Transports Most Oxygen to the Tissues”
Total Arterial O2 Content
2% 98 %

Fig 13
 CO2 Transport
• Free 7% CO2 Remains in Plasma
• 93% of the free CO2 generated in the tissues
enters the red blood cells
• Bound CO2 Transport
– 23% Hb-CO2+ Carbaminohemoglobin
– 70% is converted to the bicarbonate ion and
travels back to the lungs in Plasma
The Transport of Carbon Dioxide
• Carbon Dioxide is Transported Three
Ways
– CO2 and Bicarbonate (70%)
– Hemoglobin and H+ ( 7 %)
– Hemoglobin and CO2 (23%)
 The Transport of Carbon Dioxide
CO2 and Bicarbonate

CO2 + H20 H2CO3 H+ + HCO3-

RBC

CARBONIC BICARBONATE
ANHYDRASE
(LUNGS)

AT CELL

AT LUNGS

Fig 14 Step One

 The Transport of Carbon Dioxide
Hemoglobin and H+

CO2 + H20 H2CO3 H+ + HCO3-

RBC

BUFFERS Cl-

Hb HB-H+ Plasma
pH 7.4

To Lungs

Fig15 Step Two

 The Transport of Carbon Dioxide
Hemoglobin and CO2

CO2 + Hb Hb-CO2
CARBAMINOHEMOGLOBIN

AT CELL

AT LUNGS

Fig 16
The Transport of Carbon Dioxide
“CO2 REMOVAL AT THE LUNGS”

Fig 17
Unit IX The Kidneys
Renal Physiology I
Basic Principles Of Urine
Formation
 Functions of The Kidneys

• Regulation of Extracellular Fluid Volume/blood

Pressure
• Regulation of Osmolarity 290mOsM/L across ICF/ECF
• Maintenance of Ion Balance: Na, K, Ca(muscle
contraction)
• Homeostatic Regulation of pH (H+ HCO3-)
• Excretion of Wastes ( Creatinine, Urea, Uric Acid)
• Production of Hormones (Renin-for BP,
Erythropoietin-for RBC)
• Urochrome pigment
 The Nephron Is the Functional Unit
of the Kidney
Tubular elements

The
Nephron

CORTEX

MEDULLA

Juxtamedullary
Nephrons

Fig 1
The Nephron Is the Functional Unit
of the Kidney

Fig 1

Vascular Elements

Each Nephron has Two Arterioles, Two Sets of Capillaries

and a Special Arteriole Called the VASA RECTA
 BASIC PRINCIPLES OF URINE
FORMATION
• Filtration
• Filtration occurs in the renal corpuscle as fluids move
across the wall of the glomerulus and into the capsular
space
• Reabsorption
• The removal of water and solutes from the filtrate,
across the tubular epithelium, and into the peritubular
fluid
• Secretion
• The transport of solutes from the peritubular fluid,
across the tubular epithelium, and into the tubular
fluid(distal tubule)
 BASIC STEPS OF URINE FORMATION
Filtration, Reabsorption, Secretion and Excretion
H2O and Na

Fig 2

FILTRATION B L
H2O and HCO3 (pH)
REABSORPTION L B

SECRETION B L
EXCRETION L
The Excretion of a Substance depends on the
Amount that was Filtered, Reabsorbed, and
Secreted

F R S E

F – R + S = E
Fig 3
 FILTRATION
• Filtration occurs in the renal corpuscle as fluids
move across the wall of the Glomerulus and into the
capsular space

Fig 4
 FILTRATION
“The Renal Corpuscle Consists of The Glomerulus and
Bowman's Capsule”

Fig 5
 FILTRATION
• Substances Leaving the Plasma Must
Pass Through Three Filtration Barriers
1 Fenestrated
Capillaries
- Glycoprotein

1/5 Plasma proteins 3

Capillary
Lumen
Lumen
-
2
Mesangial Cells

Glomerular Capillary Basal Lamina Podocyte

Endothelium (Epithelium of
Fig 6 Bowman's Capsule)
 FILTRATION
• Filtration Occurs Because of
Hydrostatic Pressure in The
Capillaries

• Movement of urine across the

glomerulus capillaries = BP
Filtration Hydrostatic Pressures
Glomerular hydrostatic pressure (GHP)
The blood pressure in the Glomerular capillaries
Capsular hydrostatic pressure (CsHP)
The pressure opposing the Glomerular hydrostatic
back pressure due to proximal convoluted tube.
Net hydrostatic pressure (NHP)
The difference between GHP and CsHP NHP = GHP -
CsHP
Blood colloid osmotic pressure (BCOP)
osmotic pressure resulting from the presence of
suspended proteins in Plasma.
Filtration pressure (FP) FP = NHP -
BCOP
the difference between the hydrostatic pressure
and the colloid osmotic pressure
 Filtration Pressures
(Capsular hydrostatic pressure)

CsHP
(Blood colloid osmotic pressure)
BCOP

(Glomerular hydrostatic pressure)

Fig 7 GHP

Filtration pressure (FP) FP = NHP - BCOP

 Glomerular Filtration Rate
Average is 180 L per Day
125 ml/min
• The Glomerular filtration rate (GFR) is the
amount of filtrate your kidneys produce each
minute

Fig 8
 Glomerular Filtration Rate
ml plasma cleared of solute/time

Creatinine Clearance Test (How we Measure GFR)

4mg/100ml

Creatinine
100ml/ 0ml Creatinine

4mg Creatinine clearance

Fig 9 100ml/min
GFR
 Glomerular Filtration Rate
ml plasma cleared of solute/time
Creatinine Clearance Test (How we Measure GFR)

What Would the GFR of a Person be Who Eliminates 84mg of Creatinine

per Hour and Has a Plasma Creatinine concentration of 1.4mg/dl ?

GFR= Cr Excretion Rate/Plasma Concentration (Plasma cleared)

GFR= 84mg/h/1.4mg/dl or GFR= 60 dl/hr = 60/60 ml/min

GFR= 100ml/min

Filtered Load (Excretion rate)= Plasma Concentration (X) * GFR (Clearance)

Now we can determine How the Kidney Handles any Solute

100mg glucose/100ml Plasma, GFR = 125 ml Plasma/Min

Filtered Load = 125 mg Glucose/Min

Unit IX The Kidneys
Renal Physiology II
Controlling the GFR
 Filtration Pressures
(Capsular hydrostatic pressure)

CsHP
(Blood colloid osmotic pressure)
BCOP

GHP (Glomerular hydrostatic pressure)

Fig 1

Filtration pressure (FP) FP = NHP - BCOP

 Filtration
“Controlling the GFR”
• Blood Pressure and Renal Blood Flow
Influence GFR
• The Control of GFR is Accomplished
Primarily by:
1. Regulating Blood Flow Through the
Renal Arterioles
2. Hormonal
 Controlling the GFR
“The GFR is Subject to Autoregulation”
Autoregulation of the GFR
The goal of autoregulation is to maintain an adequate
GFR despite changes in local blood pressure and blood
flow.
This goal is accomplished by changing the diameters of
the Afferent arterioles, the Efferent arterioles, and
the Glomerular capillaries

Fig 5 Autoregulation

Tubuloglomerular
Myogenic
feedback
 Controlling the GFR
(Myogenic)

Fig 2
 Controlling the GFR
“The Key is Where the Resistance Change
Takes Place”

Fig 3
GFR
 Controlling the GFR
“The Key is Where the Resistance Change
Takes Place”

Fig 4
 Controlling the GFR
“GFR Remains Constant When MAP Remains Between
80 and 180 mmHg”
GFR IS CONSTANT

WHILE

BLOOD PRESSURE

Fig 6
 “The GFR is Subject to Autoregulation”

Autoregulation
Afferent Blood Vessel

Tubuloglomerular
Myogenic
feedback

BP Tubular Pressure

Stretch-Sensitive ion Channels

Open

Fig 7 Muscles Depolarize Vasoconstriction

 Juxtaglomerular Apparatus

Distal Convoluted
Tubule

Macula Densa

Juxtaglomerular Cells

Afferent Arteriole
Fig 8
Juxtaglomerular apparatus (JGA). GFR

TUBULE FLOW

FLOW PAST
MACULA DENSA

Paracrines

Fig 9
Vasocontriction of
Juxtaglomerular Cells

GFR
Hormonal Regulation of the GFR
• The GFR is regulated by the hormones
of the “Renin – Angiotensin system”
and “Atrial Natriuretic Peptide”
(ANP).
Hormonal Regulation of the GFR
Second Way
• Atrial Natriuretic Peptide is released in response to the stretching of
the Atrial walls of the heart by increased blood volume or blood pressure

BV ANP BP

Hypothalamus Kidney Adrenal Cortex Medulla

Inhibits Inhibits
GFR
Vasopressin Aldosterone

NaCl and H20

Excretion

DECREASE BP AND BLOOD VOLUME

 Hormonal Regulation of the GFR
Juxtaglomerular apparatus
Renin
Renal blood flow declines as a
BP result of a decrease in blood
volume or fall in systemic
pressures

Angiotensinogen Angiotensin I
Lungs
Fig 10 Angiotensin II

Vasoconstriction Hypothalamus Adrenal glands Nephron

Arterioles &
Precapillary ADH Aldosterone Vasoconstriction of
Sphincters Afferent arterioles

Reabsorption of water DCT Sodium reabsorption in the DCT

 Angiotensin II

Adrenal glands

RENIN
Aldosterone
Angiotensin I
(lungs)

Angiotensin II CNS

Vasoconstriction
HYPOTHALMUS

Fig 11
Arterioles & Precapillary Sphincters PITUITARY
(ADH)
Hormonal Regulation of the GFR
• The final results are an increase in
systemic Blood volume and Blood
pressure and the restoration of
normal GFR by hormones

HOMEOSTASIS IS RESTORED
Unit IX The Kidneys
Renal Physiology III
Reabsorption and Secretion
Renal Review
 REABSORPTION AND SECRETION

“May be Active or Passive”

• Reabsorption and Secretion involves a
combination of diffusion, osmosis, and
carrier-mediated transport
– Carrier-Mediated Transport (ACTIVE OR
PASSIVE)
(1) Facilitated diffusion
(2) Active transport
cotransport
countertransport
A specific substrate binds to a carrier protein that facilitates
movement across the membrane
 Carrier-Mediated Transport
• A Specific Substrate Binds to a
Specific Carrier Protein
• A Given Carrier Works in One Direction
• The Membrane of a Tubular Cell
Contains Many Different Kinds of
Carriers
• Carrier Proteins can Become Saturated
The Tm and Renal Threshold
• For any Substance the Concentration at
Saturation is Called TRANSPORT
MAXIMUM Tm

Increasing Transport
Rate

RENAL THRESHOLD

Increasing Substrate Concentration

The Tm and Renal Threshold

Transport Rate at Saturation

Tm
Saturation

Renal Threshold
Plasma Concentration at Which
Fig 1 Saturation occurs
 The Tm and Renal Threshold
Renal Threshold

Amino acids and Carrier-Mediated Appears in urine

glucose Transport
(over)

transport maximum (Tm) transport maximum (Tm)

carrier protein carrier protein OVER
SATURATED SATURATED
 The Tm and Renal Threshold
“Glucose Handling in The Nephron”

What Happens Here ?

Tm

Normal Range

Fig 2
The Proximal Convoluted Tubule
ProximalCT
Reabsorption of organic nutrients Glu
Active reabsorption of ions (Na+ K+)
Reabsorption of water
• Secretion

Reabsorb 60–70 percent of the volume of

the filtrate produced in the renal corpuscle
LUMEN PERITUBULAR CAPPILLARY
 Sodium Reabsorption in the PCT

Glut4 facilitated diffusion

Glu low

Glu/Na symport ATPase

PCT Antiport
ECF

Fig 3

1 In Down Electrochemical Gradient

2 Out Na+-K=-ATPase
 Sodium Linked Glucose Reabsorption

Fig 4 1 In Symport Na+ Down Electrochemical Gradient

2 Out Glucose by simple diffusion
3 Na+ Na+ - K+ _ ATPase Pump
Reabsorption in The
Proximal Convoluted
Tubule “May be Very Important
Active or Passive

NaCl
Osmosis
Na+

The Passive Glucose

Reabsorption
H2O HERE
Of Urea
Urea
Fig 5

To Renal Medulla
Water Balance
Urine Concentration Is determined in the Loop of Henle
and the Collecting Ducts

Proximal Tubule Cortex

Distal Tubule

100mOsM
Isosmotic
300mOsM

Active
Reabsorption
CL
K Hormonal
Collecting
Na Regulation
H2O Duct
Variable H2O
Reabsorption
Loop
1200mOsM
Na
Medulla
Peritubular fluid
 The Loop of Henle and
Countercurrent Exchange
• Here half of the water and two-thirds
of the sodium and chloride ions
remaining in the tubular fluid are
reabsorbed
“The principle of countercurrent exchange “
 Countercurrent Exchange
Hyposmotic
Vasa Recta

Descending Ascending
Limb Limb

Lasix works here

Na

Hyperosmotic
 The Functions of The Vasa
Recta
• To Return Solutes
and Water
Reabsorbed Without
Disrupting The
Concentration
Gradient

Na+

H2O
Fig 11
The Distal Convoluted Tubule
• Selective Reabsorption and Secretion
make the Final Adjustments to the
Tubular Fluid.
– Water Balance
– Sodium Balance/ Potassium Balance
– Potassium Balance
– Acid Base Balance
 Water Balance/DCT
• Vassopressin and Aquaporins
 The Distal Convoluted Tubule /
The Collecting System
ADH/Vasopressin
ATRIAL NATRIURETIC
PEPTIDE
H 2O The Reabsorption of Water in the
ADH Collecting System
9L/Day

- FEEDBACK DCT

H 2O Water
17L/Day Channels

COLLECTING
TUBULE Osmolarity /Blood Volume/Low BP are the Key Fig 10
ADH/Vasopressin
ADH/Vasopressin
Sodium and Potassium Balance
• Aldosterone action on “principal cells in
the DCT controls Sodium Balance
 Reabsorption of Na +
at the DCT
K+
Aldosterone

ADRENAL CORTEX Na+ Cl-

Peritubular fluid
ANGII K+ OSMOLARITY

Fig 7
Reabsorption of Na+ at the DCT
 Reabsorption of Ca +
at the DCT
Parathyroid Hormone
And Calcitriol

Ca 2+

Fig 8
 Acid Base Balance
• Acidosis pH is Too Low
• Alkalosis pH is Too High

• Buffers
• Respiration
• Renal Regulation of H+ and HCO3-
 Secretion and Ph Homeostasis at
the DCT
Antibiotics Homeostasis
(Ph)

H+ HCO3-
Peritubular fluid

Fig 9
 Acid Base Balance
Acidosis Alkalosis

H+ is excreted HCO3-/K+ reabsorbed/ HCO3-/K+ excreted H+ reabsorbed

 Renal Summary
• Step One
– Filtration at the Renal Corpuscle
 Renal Summary
“PCT”

• Step Two
– In The PCT the Active removal of Ions
Producing a Continuous Osmotic Flow of
Water Out of The Tubular Fluid
– Obligatory Water Reabsorption
 Renal Summary
“Loop of Henle”

• Step 3
– Active Transport of K+ in while Na+ and
Cl- out of The Tubular Fluid Increasing
The Reabsorption of Water
 Renal Summary
“DCT/Collecting Ducts”

• Step Four
– The Final Adjustments in Volume and
Osmotic Concentration
• Facultative water Reabsorption
 Renal Summary
“The Vasa Recta”

• Step Five
– Absorption of Solutes and Water Which
Maintains the Concentration Gradient of
the Renal Medulla
 THE MICTURITION
REFLEX AND URINATION
 MICTURITION REFLEX
Bladder Stretch receptors
Afferent fibers

sacral spinal cord

Excites parasympathetic
interneurons
motor neurons

efferent fibers
thalamus
Smooth Muscle Fig 12
Bladder
Internal urethral sphincter Cerebral cortex
Relax (I have to Pee)
External urethral sphincter
 The Bladder at Rest
Bladder
Smooth Muscle
Higher CNS Input
Relaxed
Filling State

Motor Neuron Fires

Smooth Muscle

Internal Sphincter
Passively Contracted Skeletal Muscle
External Sphincter
Stays contracted

Fig 13
 MICTURITION REFLEX
1 I have to Pee
Stretch Receptors Fire CNS
Degree of Fullness
Sensory Neuron

2
Parasympathetic Neurons
Smooth Muscle
Fire
Contracts

2
Motor Neuron Stops Firing
3 Tonic Discharge
Internal Inhibited
Sphincter 3
Passively Pulled Open Fig 14
External Sphincter Relaxes
 Unit VIII
Part I
Respiratory Physiology
 The Respiratory System
• The respiratory system has five basic
functions
– To Provide an Extensive Area for Gas
exchange between air and circulating
blood
– Homeostatic regulation of pH/CO2
– Protecting respiratory surfaces (cilia)
– Producing sounds involved in speaking
– Providing olfactory sensations
 Respiratory Physiology
• External respiration
I. Exchange of oxygen and carbon dioxide between the
lungs and the air
II. Exchange of oxygen and carbon dioxide between the
lungs and the Blood
III. Transport by The Blood
IV. Exchange of oxygen and carbon dioxide between the
Blood and the Cells O2
O2

lungs cell

CO2 CO2
External Respiration
 Respiratory Physiology
Four integrated steps involved in External
respiration
(1) Pulmonary ventilation,
The physical movement of air into and out of the lungs.
(2) Gas diffusion,
Diffusion across the respiratory membrane (alveolar air spaces
and alveolar capillaries).
(3) The transport of oxygen and carbon dioxide
Between alveolar capillaries and capillary beds in other tissues.
(4) The Exchange of gases between blood and the
cells
 *Lung Compliance/Elastance
• The ability of the lung to stretch is
called compliance
– Fibrotic Lung Disease
– Surfactant insufficiency
• The ability of the lung to return to its
resting volume is called elastance
– Emphysema
 *Surfactant Decreases the
Work of Breathing
• Surfactants are molecules
that disrupt cohesive forces
between water molecules
– Type II alveolar cells
– NRDS Newborn
respiratory distress
syndrome(surfactant
deficiency)
Surfactant
 *Respiratory Physiology
“Gas Exchange Requires Pressure Gradients”
Alveoli

DR surface area X Conc. Gradient

Mem Thickness X Mem Resistance

Venous Circulation Arterial Circulation

Fig 1
XGas Composition in the Alveoli

At Rest
Equal to
Blood
Only 10%

During Exercise

Normal Fig 2
At Rest
Local Control Matches Ventilation
and Perfusion
Arteriole Bronchiole

Low O2
Blood

Pulmonary Capillaries
Fig 3
Local Control Matches Ventilation
and Perfusion
Restricted Ventilation

Fig 4
 Local Control Matches Ventilation
and Perfusion
Constriction of Arteriole
Due to Low O2

Blood Flow Diverted

To more(Better) Ventilated
Alveoli at high oxygen

Fig 5
 Gas Transport in The Blood
“Hemoglobin Transports Most Oxygen to the Tissues”
Hb+O2 HbO2
Hemoglobin Oxyhemoglobin

Total Blood Oxygen Content is =

Amount Dissolved in the Plasma + the
Amount Bound to Hemoglobin

2% in Plasma
98% Bound to Hemoglobin as
Oxyhemoglobin

Each Hemoglobin Molecule Binds Up to Four O2 Molecules

 Gas Transport in The Blood
“Hemoglobin Transports Most Oxygen to the Tissues”

Temperature, pH and
Metabolites Affect Oxygen-
Hemoglobin Binding
 *O2 LOADING
Factors Effecting The Solubility of a Gas in A Liquid

Dalton's Law of Partial Pressures

The partial pressure of a gas is the pressure contributed by a
single gas in a mixture of gases. The partial pressure is abbreviated by
the prefix P or p. All the partial pressures added together equal the
total pressure exerted by the gas mixture. High P more solubility.
Henry's Law
The solubility of a gas in a liquid depends on temperature, the
partial pressure of the gas over the liquid, the nature of the solvent
and the nature of the gas. The most common solvent is water. In
winter, oxygen diffuses fast(more soluble).
Bohr Effect
The solubility of a gas more on the basic Ph of the solvent.
Temp= K *O2 LOADING
“PO2 Determines Hemoglobin Binding of O2”

Fig 6

At Sea Level the Partial Pressure of O2 is High Enough to Give

Nearly 100% Saturation of Hemoglobin
 *O2 LOADING
• O2 Delivery in the Tissues is Promoted by Acid Conditions (Bohr
Effect)
• Muscle metabolism produces large amounts of acids: Ph
– Under Aerobic Conditions
• C6H12O6+02 CO2 +H2 (H2O) H2CO3 → HCO3- + H+
– bicarbonic Acid
– Under anaerobic conditions (maximal exercise)
– C6H12O6 CH3 CHOHCOOH H+
Acetic Acid
Both acids lower the pH

Low pH helps the unloading of O2 from hemoglobin(delivery in

tissue); normally only 25% is unloaded, but during exercise as
much as 75% may be unloaded
Temp= K
O2 UNLOADING
“The Effects of Ph”

Fig 7
 Gas Transport in The Blood
“Effects of Temperature”

Fig 8
 Gas Transport in The Blood
“The Effects of PCO2”

Fig 9
 Gas Transport in The Blood
“2,3-DPG alters Hemoglobin”

2,3 Diphosphoglycerate

Hypoxia
Fig 10
Anemia
High altitude
 Oxygen Transport

TISSUES LUNGS
O2

CO2
Hb+ CO2

CO2 ( Carbaminohemoglobin) Fig 11

Hb-CO2
 Gas Transport in The Blood
“Fetal Changes in Hemoglobin Structure”

Fig 12
 Gas Transport in The Blood
“Hemoglobin Transports Most Oxygen to the Tissues”
Total Arterial O2 Content
2% 98 %

Fig 13
 CO2 Transport
• Free 7% CO2 Remains in Plasma
• 93% of the free CO2 generated in the tissues
enters the red blood cells
• Bound CO2 Transport
– 23% Hb-CO2+ Carbaminohemoglobin
– 70% is converted to the bicarbonate ion and
travels back to the lungs in Plasma
The Transport of Carbon Dioxide
• Carbon Dioxide is Transported Three
Ways
– CO2 and Bicarbonate (70%)
– Hemoglobin and H+ ( 7 %)
– Hemoglobin and CO2 (23%)
 The Transport of Carbon Dioxide
CO2 and Bicarbonate

CO2 + H20 H2CO3 H+ + HCO3-

RBC

CARBONIC BICARBONATE
ANHYDRASE
(LUNGS)

AT CELL

AT LUNGS

Fig 14 Step One

 The Transport of Carbon Dioxide
Hemoglobin and H+

CO2 + H20 H2CO3 H+ + HCO3-

RBC

BUFFERS Cl-

Hb HB-H+ Plasma
pH 7.4

To Lungs

Fig15 Step Two

 The Transport of Carbon Dioxide
Hemoglobin and CO2

CO2 + Hb Hb-CO2
CARBAMINOHEMOGLOBIN

AT CELL

AT LUNGS

Fig 16
The Transport of Carbon Dioxide
“CO2 REMOVAL AT THE LUNGS”

Fig 17
 Not in Exam
Unit VIII Respiration
Part II
“The Regulation of Ventilation”
 Respiratory Physiology
• Passive Respiration (Tidal Volume)
• Active Respiration (Vital Capacity)
– Active (forced) Inhalation (IRV)
– Active (forced) exhalation (ERV)
• IRV +ERV = Vital Capacity
 Respiratory Physiology:CPG
“The Regulation of Ventilation by CPG”

• The Problem
– Skeletal muscles unlike Autorhythmic
cardiac muscles, are not able to contract
spontaneously
• The Solution
– A group of neurons that form a network
in the medulla oblongata that has
intrinsic rhythmic activity called the
“Central pattern generator”
 Respiratory Physiology
Respiratory Control

• THE RESPIRATORY CENTERS OF THE

BRAIN
– Medulla Oblongata Inhalation and Exhalation
• Dorsal respiratory group (DRG)
• Ventral respiratory group (VRG).
– Pons Respiration Rate and Depth
• Apneustic centers
• Pneumotaxic centers
 Respiratory Physiology
“Neurons in the Medulla Control Breathing”

Sensory Input Central Pattern Generator

Medulla Oblongata
Dorsal Ventral
Pons Respiratory Respiratory
Group Group

Fig 1
 Dorsal Respiratory Group
(DRG)

• The DRG's inspiratory center contains

INSPIRATORY NEURONS (I neurons)
that control the External intercostals
and the diaphragm.
 DRG
( Inhalation )
• Activity in the DRG increases for 2 seconds
(Ramping), stimulating inspiratory muscles. Inhalation
occurs.
• After 2 seconds, the DRG neurons become inactive.
remain quiet for 3 seconds allowing inspiratory
muscles to relax. Passive exhalation occurs
Inhalation Exhalation P
P

2 sec 3sec

Fig 2
Atmospheric Pressure
 DRG
“Rhythmic Breathing”
Ramping Inspiration Shuts
Off

Rapid Positive
Feedback

Inspiration Passive Expiration Inspiration

Fig 3 2 sec 3 sec 2 sec
TIME
 Ventral Respiratory Group
VRG
• The VRG contains Neurons that control
muscles used for active expiration and
greater than normal inspiration
E NEURONS used for active
expiration and I+ Neurons that control
the muscles for greater-than-normal
inspiration.
 Ventral Respiratory Group
Input from DRG VRG

Inspiratory center Expiratory center

I + Neurons E Neurons

RECIPTRICAL INNERVATION

Fig 4
 INTINISIC RYTHMIC ACTIVITY
(Autorythmic cells)
Other
mitigating ACTIVE
factors

Passive
Fig 5
E neuron

Sternocleidomastoid

Inhalation forceful They exhalate

 The Apneustic and
Pneumotaxic centers

• The Apneustic and the Pneumotaxic

centers of the Pons adjust the output
of the respiratory rhythmic centers
– Rate
– Depth
The Apneustic and Pneumotaxic
centers
• Apneustic Center
– Increases Intensity of Inhalation
• Pneumotaxic Center
– Inhibits the Apneustic center
 The Apneustic and Pneumotaxic
centers
Fine Tuning Rate and
PNTC Depth
APNC

CPG DRG RAMPING

2 SEC

MECHANICS

APNEUSTIC AND PNEUMOTAXIC CENTERS ARE

Fig 6 RECIPROCALLY INNERVATED
 Respiratory Physiology
Respiratory Control

• Factors Influencing Reparatory Rate

– Carbon Dioxide CSF
– Oxygen in atery
– pH in CSF
 Respiratory Physiology
Respiratory Control and Respiratory Reflexes
low levels
(CO2)

central or medullary Peripheral

R
chemoreceptor
CSF O2 increase

Apneustic Center
Pneumotaxic Center

Fig 7

Sternocleidomastoid
 Respiratory Reflexes
Factors affecting the respiratory Rate

Chemoreceptors sensitive to the pH, PO2 and

PCO2 of the blood or cerebrospinal fluid.
• Blood pressure in the aortic or carotid sinuses.
(Baroreceptors)
• Stretch receptors that respond to changes in the
volume of the lungs.
• Physical or chemical stimuli in the nasal cavity,
larynx, or bronchial tree.
• Pain, changes in body temperature, and abnormal
visceral sensations.
 The Chemoreceptor Reflexes
Carbon Dioxide, Oxygen, and pH Regulate Ventilation

• Peripheral chemoreceptors
– Carotid and Aortic Bodies
Respond only to the PCO2, PO2 and pH of the Plasma

• Central chemoreceptors (medulla)

– Respond only to the PCO2 concentration of the Cerebrospinal fluid

- pH of CNS
CO2 + H2O H+ + HCO3 means
 The Carotid and Aortic Bodies
• The Carotid and Aortic Bodies are
sensitive to The PO2,PCo2 and Ph
contained in the Plasma of Arterial
Blood.
 Translation of PO2 Levels
To Action Potentials
(PCO2, PO2 and Ph)

At 60 eV,
High O2 opens K channel

CAROTID BODY Glomus cells(carotid/aorta)

O2 (peripheral chemoreceptors
SENSOR
Cell depolarized(positive)
Ca channel open

<60mmHg

Fig 8
 Central Chemoreceptors
• Central chemoreceptors monitor
cerebrospinal fluid (CSF) and respond to
changes in the PCO2

CO2 H2O H+ + HCO3-

Lowers Ph

Blood Brain Barrier

The Most Important Chemical Controller of Ventilation Mediated Through

CCR
 The Hering – Breuer Reflexes
“Mechanical Reflexes Protect the Lungs”

• Inflation reflex
– prevents overexpansion of the lungs during
forced breathing.( Over 1Liter)

• Deflation reflex
– inhibits the expiratory centers and stimulates
the inspiratory centers when the lungs are
deflating
 CENTRAL CHEMORECEPTOR

Translation of PCO2 Levels

Fig 9 To Action Potentials
 The Chemoreceptor Reflex
Primary:
Hypercapnia

Hypercapnia(CO2 high)plsma & CSF H3Olow pH stimulates central chemo

R Rate of ventillation low O2—negative feed back(homeostasis)

High CO2 leads to Emphysema

On right: Peripheral: Inf amount of O2

is 60% H3O+

CCR—CPG-PRG glomus
Fig 10 cells

CPG-DRG

\
Hypocapnia
 VOLUNTARY CONTROL OF
RESPIRATION
• The cerebral cortex can have a direct
or indirect effect on your respiratory
centers
• Conscious thought processes tied to strong
emotions
• Emotional states (Limbic)
• Conscious control over our respiratory
activities
– Speech
– Holding your breath
Carotid and Aortic Bodies
PCO2, PO2 and Ph of the Plasma
APNC
PONS
PNTC DRG
PChR

CPG SOMATIC MOTOR RESPIRATORY

NEURONS RATE

Fig 11

VRG How Can Oxygen Kill Your Patient ?

Watch what you do!!!
CChR

medulla –PCO2 concentration of the Cerebrospinal fluid

(Ph)
 Unit X
Reproduction
Male and Female
Hormonal Control Pathways And
The Production of Gametes
• Control Pathways for Sex Steroids Are
Similar in Males and Females
• Feedback Pathways Include Both Long
and Short Loop Feedback
• The Hypothalamus Releases
Gonadotropin in Small Pulses
 Hormonal Control Pathways
CNS

HYPOTHALAMUS

ANTERIOR
PITUITARY

Fig 1
The Reproductive System
Part I

Male
 The Male Reproductive System

Pecker

Fig 2
The Male Reproductive System
• Male Gonads
• Paired testes are suspended in The Scrotum
– The Word Testes Come from Latin and Means
“Witness”
• The Testes Produce Sperm and Testosterone
 THE TESTES

Spermatogenesis

Interstitial Cells
(Leydig)

Fig 3 Sperm Mature and

Are Stored Here
Spermiogenesis
Spermatogenesis
Interstitial Cells
( Leydig Cells )

Basement Membrane

Lumen
Spermiogenisis

Sertoli Cells
(Sustentacular cells)
Fig 4

XS SEMINIFEROUS TUBULES
 Hormonal Control of
Spermatogenesis
• Spermatogenesis Requires
Gonadotrophins and Testosterone
 HYPOTHALAMUS
GnRH
ANTERIOR PITUITARY
LH FSH
(3-4 Pulses/1.5hrs)

Interstitial Cells
(Leydig) Inhibin
Fig 5
2nd Messenger
Seminiferous Tubules
-
Testosterone Sertoli Cells
1.CNS
(Libido) Paracrines
2.Bone and
Binds To Spermatogonium
Muscle Growth

3.Male 2ndary Sexual

Androgen Spermatogenesis
Characteristics
Binding Protein Spermiogenesis
 The Male Sexual Response
“Anatomy of An Erection”

2ndMessenger
guanosine monophosphate (cGMP)

Nitric oxide

Vasocoagulation

Fig 6
 VIAGRA
“ What About Us Old Guys ? ”
VIAGRA inhibits
phosphodiesterase
type 5 (PDE5) BRAIN Sexual arousal

Parasympathetic nonadrenergic-noncholinergic neurons

Nitric oxide

Nitric oxide diffuses into corpus cavernosal smooth-muscle

guanosine monophosphate (cGMP) 2ndMessenger

phosphodiesterase type 5 Not enough

Vasodilation of Penile Arterioles

Erection
 BRAIN

Ejaculation/Orgasm
Sympathetic

Orgasm
Emission. Muscles Tighten

epididymis and vasa deferens

ALL Muscles Relax contract

sperm enter ejaculatory

Expulsion duct
Muscular contractions at base of
penis expel semen
(ischiocavernosus and secretions from seminal
bulbospongiosus muscles)) vesicles, prostate gland,
and bulbourethral glands
Pre emission Adjust Ph

Urethra and Female

 The Male Sexual Response

SYMPATHETIC
Muscles tighten

Sexual Stimulation Sex Act

Real or imagined
PARASYMPATHETIC
Erection

Fig 7
 What Makes a Male a Male
Anyway?
SRY FACTOR

Testis Determining
Factor Bipotential Gonadal Tissue

Mullerian Ducts Wolffian Ducts

Vagina uterus,
MIF fallopian tubes,
testosterone causes each wolffian
Testosterone duct to develop into epididymis,
Testis (DHT) vas deferens, and seminal vesicles
Leydig

Fig 8
The Reproductive System

Female
 The Ovary Produces Eggs
and Hormones

Fig 9
 The Menstrual Cycles
“The Menstrual Cycle Lasts About One Month”

Uterine Cycle Ovarian Cycle

Prepares One Oocyte Per

Prepares Uterus
Month
To Receive Fertilized
Oocyte

Fig 10

PROCREATION
 The Ovarian Cycle
• Follicular Phase
• Period of Follicular Growth 10 Days to 3 Weeks
• Ovulation
• Release of The Oocyte (Ova)
• Luteal Phase
• Transformation of Follicular Remains into The
Corpus Luteum
 Uterine Cycle
• Menses (Corresponds to Day One Follicular Phase)

• Menstrual Discharge Days 1 - 7

• Proliferative Phase (Estrogen)
• Thickening of Endometrium Days 7-14
• Secretory Phase (Progesterone) Days 14-28
• Conversion of Endometrium to Secretory
Structure
– Lipids and Glycogen into cell cytoplasm
– Mucous
– Increased vascularization
 Follicular Phase
Antrum

Theca

Granulosa

Ovulation

Luteal Phase
Fig 11

The Ovarian Cycle

 The Ovarian Cycle
“Hormonal Control of the Menstrual Cycle is Complex”
FOLLICULAR PHASE
Hypothalamus LUTEAL PHASE
GnRH
Pituitary
Gland
FSH

- /+
LH
follicle

Estrogen
Corpus
-/ +
luteum
Ovary

Fig 12 Progesterone
 Early to Mid Follicular Phase
“The First Day of Menstruation is Day One of the Cycle”

Hypothalamus

GnRH WHY?

- FSH
Pituitary

LH
FOLLICLE

+ Granulosa Thecal Cells

Fig 13
Cells
-
Estrogen Androgens

Endometrium
 Late Follicular Phase/Ovulation

Hypothalamus

GnRH

+
Surge in LH Levels
Pituitary
16-24 hrs after
FSH LH

-
FOLLICLE
Ovulation
Collagenase
Granulosa Thecal Cells
Cells

Inhibin Androgens
Fig 14 Small Amount of
Progesterone
High Estrogen Endometrium
 Collagenase

Ovulation

Fig 15
 EARLY TO MID LUTEAL PHASE

Hypothalamus

Pituitary

- FSH LH

Corpus Luteum
From Ovulated Follicle
(Thecal Cells)
Uterus
Secretes
Fig 16
Estrogen Progesterone Inhibin
 LATE LUTEAL PHASE
Tonic Secretions Resume
Negative Feedback Stops
Hypothalamus

Pituitary

- FSH LH

Corpus Luteum
Disintegrates into
(12 Days)
Corpus albicans

Fig 17
Estrogen Progesterone
 The Menstrual Cycle
“The Menstrual Cycle Lasts About One Month”

Fig 18
 How A Woman Achieves Orgasm?
Unlike the male of the species ,orgasm in the female is the result of a vast
range of physical, emotional ,and mental stimulation, and at its peak is
affected by the synchronicity of all these elements.
Touch/visual/olfactory

Sexual Arousal

Parasympathetic Sympathetic

Clitoral erection/ Peristaltic contraction of Uterus/Vagina

Cervical mucous glands And
Contraction of Bulbospongiosus and
ischiocavernosus Muscles
Fig 19

ORGASM
 Unit X
Reproduction
Male and Female
Hormonal Control Pathways And
The Production of Gametes
• Control Pathways for Sex Steroids Are
Similar in Males and Females
• Feedback Pathways Include Both Long
and Short Loop Feedback
• The Hypothalamus Releases
Gonadotropin in Small Pulses
 Hormonal Control Pathways
CNS

HYPOTHALAMUS

ANTERIOR
PITUITARY

Fig 1
The Reproductive System
Part I

Male
 The Male Reproductive System

Pecker

Fig 2
The Male Reproductive System
• Male Gonads
• Paired testes are suspended in The Scrotum
– The Word Testes Come from Latin and Means
“Witness”
• The Testes Produce Sperm and Testosterone
 THE TESTES

Spermatogenesis

Interstitial Cells
(Leydig)

Fig 3 Sperm Mature and

Are Stored Here
Spermiogenesis
Spermatogenesis
Interstitial Cells
( Leydig Cells )

Basement Membrane

Lumen
Spermiogenisis

Sertoli Cells
(Sustentacular cells)
Fig 4

XS SEMINIFEROUS TUBULES
 Hormonal Control of
Spermatogenesis
• Spermatogenesis Requires
Gonadotrophins and Testosterone
 HYPOTHALAMUS
GnRH
ANTERIOR PITUITARY
LH FSH
(3-4 Pulses/1.5hrs)

Interstitial Cells
(Leydig) Inhibin
Fig 5
2nd Messenger
Seminiferous Tubules
-
Testosterone Sertoli Cells
1.CNS
(Libido) Paracrines
2.Bone and
Binds To Spermatogonium
Muscle Growth

3.Male 2ndary Sexual

Androgen Spermatogenesis
Characteristics
Binding Protein Spermiogenesis
 The Male Sexual Response
“Anatomy of An Erection”

2ndMessenger
guanosine monophosphate (cGMP)

Nitric oxide

Vasocoagulation

Fig 6
 VIAGRA
“ What About Us Old Guys ? ”
VIAGRA inhibits
phosphodiesterase
type 5 (PDE5) BRAIN Sexual arousal

Parasympathetic nonadrenergic-noncholinergic neurons

Nitric oxide

Nitric oxide diffuses into corpus cavernosal smooth-muscle

guanosine monophosphate (cGMP) 2ndMessenger

phosphodiesterase type 5 Not enough

Vasodilation of Penile Arterioles

Erection
 BRAIN

Ejaculation/Orgasm
Sympathetic

Orgasm
Emission. Muscles Tighten

epididymis and vasa deferens

ALL Muscles Relax contract

sperm enter ejaculatory

Expulsion duct
Muscular contractions at base of
penis expel semen
(ischiocavernosus and secretions from seminal
bulbospongiosus muscles)) vesicles, prostate gland,
and bulbourethral glands
Pre emission Adjust Ph

Urethra and Female

 The Male Sexual Response

SYMPATHETIC
Muscles tighten

Sexual Stimulation Sex Act

Real or imagined
PARASYMPATHETIC
Erection

Fig 7
 What Makes a Male a Male
Anyway?
SRY FACTOR

Testis Determining
Factor Bipotential Gonadal Tissue

Mullerian Ducts Wolffian Ducts

Vagina uterus,
MIF fallopian tubes,
testosterone causes each wolffian
Testosterone duct to develop into epididymis,
Testis (DHT) vas deferens, and seminal vesicles
Leydig

Fig 8
The Reproductive System

Female
 The Ovary Produces Eggs
and Hormones

Fig 9
 The Menstrual Cycles
“The Menstrual Cycle Lasts About One Month”

Uterine Cycle Ovarian Cycle

Prepares One Oocyte Per

Prepares Uterus
Month
To Receive Fertilized
Oocyte

Fig 10

PROCREATION
 The Ovarian Cycle
• Follicular Phase
• Period of Follicular Growth 10 Days to 3 Weeks
• Ovulation
• Release of The Oocyte (Ova)
• Luteal Phase
• Transformation of Follicular Remains into The
Corpus Luteum
 Uterine Cycle
• Menses (Corresponds to Day One Follicular Phase)

• Menstrual Discharge Days 1 - 7

• Proliferative Phase (Estrogen)
• Thickening of Endometrium Days 7-14
• Secretory Phase (Progesterone) Days 14-28
• Conversion of Endometrium to Secretory
Structure
– Lipids and Glycogen into cell cytoplasm
– Mucous
– Increased vascularization
 Follicular Phase
Antrum

Theca

Granulosa

Ovulation

Luteal Phase
Fig 11

The Ovarian Cycle

 The Ovarian Cycle
“Hormonal Control of the Menstrual Cycle is Complex”
FOLLICULAR PHASE
Hypothalamus LUTEAL PHASE
GnRH
Pituitary
Gland
FSH

- /+
LH
follicle

Estrogen
Corpus
-/ +
luteum
Ovary

Fig 12 Progesterone
 Early to Mid Follicular Phase
“The First Day of Menstruation is Day One of the Cycle”

Hypothalamus

GnRH WHY?

- FSH
Pituitary

LH
FOLLICLE

+ Granulosa Thecal Cells

Fig 13
Cells
-
Estrogen Androgens

Endometrium
 Late Follicular Phase/Ovulation

Hypothalamus

GnRH

+
Surge in LH Levels
Pituitary
16-24 hrs after
FSH LH

-
FOLLICLE
Ovulation
Collagenase
Granulosa Thecal Cells
Cells

Inhibin Androgens
Fig 14 Small Amount of
Progesterone
High Estrogen Endometrium
 Collagenase

Ovulation

Fig 15
 EARLY TO MID LUTEAL PHASE

Hypothalamus

Pituitary

- FSH LH

Corpus Luteum
From Ovulated Follicle
(Thecal Cells)
Uterus
Secretes
Fig 16
Estrogen Progesterone Inhibin
 LATE LUTEAL PHASE
Tonic Secretions Resume
Negative Feedback Stops
Hypothalamus

Pituitary

- FSH LH

Corpus Luteum
Disintegrates into
(12 Days)
Corpus albicans

Fig 17
Estrogen Progesterone
 The Menstrual Cycle
“The Menstrual Cycle Lasts About One Month”

Fig 18
 How A Woman Achieves Orgasm?
Unlike the male of the species ,orgasm in the female is the result of a vast
range of physical, emotional ,and mental stimulation, and at its peak is
affected by the synchronicity of all these elements.
Touch/visual/olfactory

Sexual Arousal

Parasympathetic Sympathetic

Clitoral erection/ Peristaltic contraction of Uterus/Vagina

Cervical mucous glands And
Contraction of Bulbospongiosus and
ischiocavernosus Muscles
Fig 19

ORGASM
THANK YOU

GOOD LUCK