RAKESH SHARMA, BAMS, MS-Ph.D 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)

Membrane Spanning ( Integral) Protein Hydrophobic Tails

ECF

Fig 1

Hydrophilic Heads

Fatty Acid Tail

ICF

(Non Polar)

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

“Receptors are Part of The Cell Signaling System”

Membrane Proteins

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+
Myb o e (le kC a n ls o g te (Vlta e a e p n a hne ) r a d o g )

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 Concentration

Low Concentration

Movement Across Membranes
“Osmosis”
H2O

High Concentration

Low Concentration

Semi Permeable Membrane

Movement Across Membranes
“Carrier-Mediated Transport”

• Mediated Transport
Substance A +Carrier Protein Semi permeable Membrane

– Facilitated Diffusion – Active Transport

• Passive (Moves down Concentration Gradient) • Active (Moves against Concentration Gradient) ADP + E – ATP

Carrier-Mediated Transport
• Carrier Proteins
1. Specificity
• GLUT Transporters

2. Competition 3. Saturation
Fig 8

Carrier Mediated Transport
“Uniport”
Energy

Carrier Concentration Gradient (active) Fig 10 Concentration Gradient (Passive)

Carrier Mediated Transport

Carrier Mediated Transport
“Symport Cotransporters”
Energy

Co transport Carrier
Concentration Gradient Concentration Gradient (Passive)

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

“Requires The Input of Energy From ATP”

Active Transport
ADP + E

• Primary Active Transport
– ATP

• Secondary Active Transport
– Kinetic Energy

E 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-Glucose Symporter

Na+ Low Glu High

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 Voltage Gated Ca2+ Channels Open Calcium Induced Exocytosis Neurotransmitter binds With receptor Receptor Response

Synaptic Vesicles

Voltage Gated Ca2+ Channels

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

Cell Membrane

-1
+1

Resting membrane Potential

Fig 2

Cell and Solution are Electrically and Chemically at Disquilibrium

Measuring Membrane Potential Differences

This is the Membrane Potential Difference ICF ECF
Fig 3

-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 • EN =+60mV A • 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)
ECF
Concentration Grad

Elect- Grad

ICF

0 mV

Fig 8

K+ is the Key Player Here

Changes in Ion Permeability Change the Membrane Potential
• Depolarization
Na
Fast
+

Cl

-

-10mV Slow

ECF ICF

K+

Voltage Gated Na+ Channels Open

Fig 9

Na+ is The Key Player Here
Entry of Cl- Ions would Hyperpolarize

Changes in Ion Permeability Change the Membrane Potential
• Repolarization
Na+ Close ECF +30mV

K+

ICF

Fig 10

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

K+

Fig 11

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

ICF

ECF

Na+ ---- K+ ATPase Pump Returns Proper
Fig 12

Concentration Gradient

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 • Neurocrine

• Long Distance Communication
• Neurotransmitter • Neuromodulators • Neurohormone
(Regulatory Peptides/ May be Local or Long Distance )

• Cytokines • Hormones

“Transfer Chemical and Electrical Signals Directly Between Cells”
Protein Channels (Connexon)
Membrane Spanning Protein

Gap Junctions

Fig 1

Cytoplasmic Bridges

Autocrines and Paracrines
“Local Calls Only”
Autocrines and Paracrines Diffusion

Target

Fig 2 Chemical Signals Distributed by Diffusion

“Long Distance Please”
Blood Hormone

Hormones

Fig 3

Neurotransmitter/Neuromodulator
“Long Distance Please”

Synapse Fig 4

Neurotransmitter/ Neuromodulator

Neurohormone
“Long Distance Please”
Neurohormone
Ligand Blood

Fig 5

“A cell cannot respond to a chemical signal if it lacks the appropriate receptors for that signal” 1 Signal Ligand

Signal Pathways
First messenger
Target

Receptor
Activation 3 Intracellular signal molecule 2

Directs the cellular response Effectors (Last
4 Synthesis of or modification of target protein
intracellular signal molecule)

Response

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

Receptors

mRNA Fig 6

“There are Four Major Categories of Membrane Receptors”

Signal Pathways

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

Signal Pathways
Ion-Gated membrane Receptor Ligand

Ion Gated Channel Alters Ion Flow

ECF ICF

Ligand Binding opens or closes the channel
Fig 7

Receptor-Enzyme Membrane Receptor

Signal Pathways
Ligand

Receptor Region ECF ICF

Activation of an Enzyme

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

G-Protein Coupled Membrane Receptor

Signal Pathways
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

“Membrane Proteins Facilitate Signal Transduction”
Signal Molecule 1 Receptor ECF ICF Amplification Enzymes

Signal Pathways

First Messenger

2 Signal Transduction
By Effector Proteins

3 Protein Kinases 5

4 Second Messenger Opens Ca Ion Channel

Cellular Response Fig 11

Increase Intracellular Ca++

Signal Pathways
Ions
Signal Molecule

Ion Channel Ions Create Electrical Signals

Na+ , K+ , Cl

-

Creates Electrical Signal

Fig 12

Voltage Sensitive Proteins

Cellular Response

An Intracellular Messenger
Ca2+ 1 Chemical or Electrical Signal ECF ICF 2 3 Ca2+
ER

Calcium

Ca2+

Ca2+ Binds to Proteins 4
Fig 16 Cellular Response 5 Enzyme Activity Exocytosis Movement Calcium Is an Important Intracellular Signal

“Not ALL Ion Channels are Receptors” ECF 1 2

Signal Pathways

3 Ions Create Electrical Signals
Intracellular signal Molecules

ICF Fig 13

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

Ligand

1

Receptor

ECF ICF ATP + protein

2 Tyrosine-Kinase 3 ADP + Protein-P

Guanylate Cyclase GTP cyclic GMP (cGMP) Activation of an Enzyme Fig 14

G-Protein Coupled Receptors
“Most Signal Transduction Uses G Proteins” Signal Molecule Adenylate cyclase 1

Signal Pathways

First Messenger
Receptor

(Phospholipase C) Inostisol PPP IP3

Fig 15

G-Protein

2 cAMP 5

3 ATP

Ca++

Second Messenger
4

Protein Phosphorylation

Protein Kinase A

G-Protein-coupled adenylyl cyclase- cAMP system

Modulation of Signal Pathways
• Receptors Exhibit
– Saturation – Specificity – Competition
Epinephrine Norepinephrine

β β

2

α

and

Adrenergic Receptors

β

1

α

Target Response
Target Response depends on the Target Receptor

Receptor Isoforms

α

-Receptor

Intestinal Blood Vessel

Vessel Constricts

Epinephrine Vessel Dilates

β

-Receptor

Skeletal Muscle Blood Vessel

Fig 17

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

Fig 18

G Proteins

Unit III B

G Proteins
Adenylate Cyclase

Cell Signaling and Signal Pathways
Binds To Activates Alters Creates

Signal Molecule

Receptor

Intracellular Sig Molecule

Target Protein

Response

G Proteins

Signal Transduction
Signal Molecule Receptor Cell Membrane Phosopholipid Bilayer

G Proteins Act as Signal Transducers
Signal Molecule

1

(GPCR)
Adenylate Cyclase

Effector molecule (Enzyme)

GTP

ATP 4
Second Messenger


3

cAMP

2

GDP

Response

5

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

G Proteins Act as Signal Transducers
Signal Molecule

1

(GPCR) Guanylate Cyclase

Effector molecule (Enzyme)

GTP
Second Messenger

3 2

4

cGMP

Response

5

G Proteins Act as Signal Transducers
Signal Molecule

1

(GPCR)
Phospholipase C

Effector molecule (Enzyme)

3 2

4
Second Messenger

Ca2+
Response

5

G Proteins and The Activity of Epinephrine/Norepinephrine
Hormone E/NE
GPCR GPCR A Gα

I 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
1

I

β
ATP

A

1


Adenylate Cyclase cAMP

ICF

“Second Messenger" PO4

PO4 Opens Ca2+ Channels Kinase Activation

Phospholamban ER

RP

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
A

1

PLC Via IP3

Via DA G

PK C

Release of Stored Calcium
PLC = PKC = DAG= IP3 = Phospholipase C Protein kinase C Diaclyglycerol inositol triphosphate

Ca2+

Ca2+ Ca2+ Calmodulin

Second Messenger

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

CNS

Organization of The Nervous System

Signal Afferent Neurons

Spinal Cord

Efferent Neurons Autonomic Neurons Sympathetic Parasympathetic Somatic Motor Neurons Control

Stimulate
Sensory Receptors Communicate with Stimulate

Control Smooth Muscle Exocrine Glands Some Endocrine Glands Cardiac Muscle Skeletal Muscles

Feedback
Control Signal Enteric Nervous System

Response

”The Sympathetic and Parasympathetic Systems Maintain Homestasis”

Autonomic Nervous System

• 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 !!!!

”The Sympathetic and Parasympathetic Systems Maintain Homestasis

Autonomic Nervous System
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)

”The Sympathetic and Parasympathetic Systems Maintain Homestasis”

Autonomic Nervous System

SETPOINT

Fig 2

Control Pathways
Homeostasis May be Maintained by Local or Long-Distance Pathways

Local

Reflex Control
Response Loop
 Negative  Positive

Autocrines Paracrines

Feedback Loop

Response Loop
1
2 3

4
Feedback loop

5
7 6
Fig 3

Negative Feedback

Feedback Loop

Positive Feedback

X

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
BRAIN
Hypothalamus Pons Medulla
Endocrine

“The Hypothalamus ,Pons and Medulla initiate Autonomic responses”

Heart Rate, BP Temp Regulation Osmolarity, CO2

Autonomic Function

Bypass the Brain
Limbic System Cerebral Cortex

(Urination, Penile Erection, Defecation)

Autonomic Spinal Reflexes

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

Short Reflex

Long Reflex

Response
Fig 5

”The Autonomic Division Consists of Two Efferent Neurons in Series”

Autonomic Nervous System

• The Autonomic Pathway

Fig 6

”Sympathetic and Parasympathetic Branches Exit The Spinal Cord at Different Regions”

Autonomic Nervous System

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

Sympathetic

“The Sympathetic and Parasympathetic Systems use a Variety of Neurotransmitters”

Autonomic Nervous System

Neurotransmitter PreGN PostGN

Neurotransmitter

CNS

Autonomic Ganglion

Target

Fig 7

“The Sympathetic and Parasympathetic Systems use a Variety of Neurotransmitters”

Autonomic Nervous System

• 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) – Parasympathetic – Sympathetic ACh ACh Dopamine NO Ganglia (2) ACh NE E Target

“The Sympathetic and Parasympathetic Systems use a Variety of Neurotransmitters”

Autonomic Nervous System

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)

• Muscarinic (post Synaptic)

Exposure to ACh always causes excitation of the ganglionic neuron or muscle fiber by the opening chemically gated channels in the postsynaptic membrane. 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 Nicotinic ACh

Cholinergic Muscarinic ACh Target

CNS

ACh-ase

Post ganglionic Neuron Fig 9

Parasympathetic Nervous System
“Acetylcholine onto Muscarinic Receptors”

Cholinergic Nicotinic ACh

Cholinergic Muscarinic ACh

Target

CNS

ACh-ase

G-proteins-coupled Gated Ca2+ Channels Muscle contraction

Fig 10

Second Messengers cAMP

Parasympathetic Nervous System
“Acetylcholine onto Nicotinic/ Muscarinic Receptors” Action Potential Axon Terminal
Synaptic Vesicles

Action Potential Depolarizes Axon Terminal Voltage Gated Ca2+ Channels Open Calcium Induced Exocytosis Acetylcholine binds With receptor

Voltage Gated Ca2+ Channels

Receptor

Response

Parasympathetic Nervous System
“Acetylcholine onto Nicotinic / Muscarinic Receptors” Acetylcholine Choline + Acetyl CoA

Acetyl CoA

CoA E Acetylcholine Synaptic Vesicles

Ch

Acetylcholinesterase Breaks down Acetylcholine

Ch

Choline is transported Back into cell Receptor

Acetylcholinesterase

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 beta-1 β 1 NE E

(2) Beta receptors

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
Pre ganglionic Neuron Cholinergic Nicotinic ACh

Adrenergic
NE
TARGET

α 1 α 2 β 1 β 2

Most Symp. Target Tissues GI Tract

CNS

Heart/ Kidney
Certain Blood Vessels Smooth Muscle

ACh-ase

Post ganglionic Neuron
Norepinephrine Epinephrine (Adrenal Medulla)

Fig 12

Sympathetic Nervous System
“Norepinephrine onto Adrenergic Receptors”

Pre ganglionic Neuron

Cholinergic Nicotinic ACh

Adrenergic
NE
TARGET

CNS

Phospholipase C α 2 Decreases cAMP

α

Activates
1

ACh-ase

Post ganglionic Neuron
Norepinephrine Epinephrine (Adrenal Medulla)

β β

Increases cAMP
1

Decreases cAMP
2

Fig 13

Sympathetic Nervous System
“Norepinephrine onto Adrenergic Receptors”
Axon Varicosity
Tyrosine Action Potential

MAO Ribosome

1) 2) 3) 4) 5) 6) 7) 8)

Ca2+
NE Diffusion

Exocytosis

Reuptake Channel NE

Action Potential VG Ca2+ Channel Exocytosis NE bind to receptor NE Diffusion Reuptake Channel NE Reabsorption NE Metabolized by 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

“Most Internal Organs are Innervated by Both Autonomic Branches”

Dual Innervations
G F

H

A B

C
α
β 2

D
β 1

E

I

Autonomic Effectors Smooth Muscle Cardiac Muscle Endocrine Glands

Muscarinic

Fig 15

Lets Practice

“Most Internal Organs are Innervated by Both Autonomic Branches”

Dual Innervations

Fig 15

“Allows for very fine tuning of organ function”

Autonomic Tone

• 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-proteinCa++ ) gustatory afferent stimulus (facial VII,Glassopharyngeal IX, Vagus X)Medulla Ob.-ThalamusCortex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)

• 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

Middle ear is controlled by Tympani Muscle

Ear and Hearing
• Auricle and auditory canal constitute the ear (Outertympanic 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)
page 582-585

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
– S.vestibule – S.media – S.tympani

• Scalae Organ of Corti has stereocilia and supporting hair cells connected with afferent nerve fibers

Bath with Perilymph and Endolymph

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
1 Wavelength Frequency = waves/sec Hz 1000-3000 Hz

Amplitude db Pressure

Fig 1

TIME

Transduction of Sound Is a Multistep Process

Mechanical Vibrations

Fluid Waves

Chemical Signals

Action Potentials

Fig 2

Anatomy of The Ear
External
Pinna

Middle
M I S

Semicircular canals Oval Window

Inner

Vestibular apparatus Cochlea Bony Labyrinth

Canal

Tympanic Membrane

Fig 3

Round Window

To Pharynx Eustachian Tube

Sound Transmission Through The Ear
“The Middle Ear Transfers Sound from the Eardrum to the Cochlea”

Canal

Incus Stapes Oval Malleus Windo w

Basilar Membrane

Cochlear Nerve Vestibular Duct (Perilymph) Cochlear Duct (Endolymph)

6

3 1 2 5 4

Tympanic Duct Tympanic Membrane Round Window Tectorial Membrane

Fig 4

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

The Cochlea

Oval Window

Vestibular Duct

Cochlear Duct Organ of Corti Perilymph

Endolymph Round Window Basilar Membrane Tympanic Duct

Helicotrema

Fig 5

The Cochlea
The Cochlea Bony Labyrinth

Vestibular Duct Cochlear Duct Tectorial Membran e Organ of Corti

Cochlear Nerve

Fig 6

Basilar Membrane

Tympanic Duct

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 Endolymph

Hair Cell

Basilar Membrane

Tectorial Membrane

Fig 8

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

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

Stereocillium

Fig 9

“Sound Transduction”

Hair Cells
+

AT REST
Protein Bridge K

Tallest Stereocilia

Stereocillium Hair Cell

Some Channels Open

Sensory Neuron

Fig 10

Low Level Action Potentials (Tonic)

“Sound Transduction”

Hair Cells
K+

Excitation
Stereocillium

Tallest Stereocilia

K+

More Channels Open K+ entry Depolarizes Cell

Fig 11

Action Potentials

“Sound Transduction”

Hair Cells

INHIBITION

K+

Channels Closed No K+ Entry Cell Hyperpolarizes

Fig 12

No Action Potentials

How Do We Hear ?
Outer Ear M I S

Hair Cells
Fluid Waves Chemical Signals Action Potentials

Mechanical Vibrations

Cochlea
Fig 13
Ipsilateral Contralateral

Medulla

Auditory Cortex

Sensory Coding for Pitch
Man low pitch
STIFF

female high pitch

FLEXIBLE

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

“The Eye Adjusts The Shape of The Lens”

Accommodation

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

“The Eye Adjusts The Shape of The Lens”

Accommodation

Ciliary Muscle (relaxed)

Lens (flattened) Zonulas (tight) Fig 6

Cornea

“The Eye Adjusts The Shape of The Lens”

Accommodation
Ciliary Muscle (contracted)

Lens (rounded) Zonulas (slack)

Fig 7

The Loss of Accommodation is called Presbyopia

Hyperopia (Farsightedness)
Normal (Emmetropia)

Visual Defects

Fig 8

Focal Point Behind Retina

Visual Defects
Myopia (Nearsightedness)

Focal Point In Front of Retina Fig 9

Normal (Emmetropia)

Visual Defects
Astigmatism
Irregularities in cornea or lens

CORNEA Fig 10

Canal of Schlemm

Aqueous humor

Trabecular meshwork

isual Disease
P

Aqueous Flow

Angle Glaucoma/ Narrow Angle Glaucoma”

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
Temperature Proprioception Nociception Touch/Pressure

Special Senses

 Vision  Hearing  Taste  Smell  Equilibrium

• Receptors Are Sensitive To a Particular Stimuli • Sensory Transduction Converts Stimuli into
Graded Potentials

General Properties of Sensory Systems

• 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
Stimulus Sensory Receptor

Transducer

2 Electrical Graded Potentials
Sensory Afferent Neuron

3

4

CNS
Fig 1
( Integration )

Cortex
( Conscious Perception )

“Receptors Are Transducers That Convert Stimuli into Electrical Signals”

Types of Receptors

 Photoreceptors (Vision)  Chemoreceptors
– Tactile – Baroreceptors – Photons – CO2 O2, pH, various organic molecules (Taste and Smell)

 Mechanoreceptors (Hearing and Equilibrium)

The Special Senses
• • • • • Olfaction Vision Gustation Hearing Equilibrium

Sensory Transduction Converts Stimuli into Graded Potentials
Threshold Stimulus Receptor Receptor Potential

Generator Potential Action Potential

Neurotransmitter

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

A B

C

Inhibition Enhances Perception of Stimulus In brain

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

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

– Duration

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 Tract Olfactory Organ

Nasal Concha

Fig 2

Olfactory organs
• The olfactory organs contain the following two layers
– Olfactory epithelium
• Olfactory receptors

– Lamina propria
• Olfactory glands ( Bowman's Glands )

The Olfactory cells Synapse with Secondary Sensory Neurons in The Olfactory Bulb synapse

OLFACTION

connections

20Receptor Neuron Olfactory tract

Olfactory Bulb

Lamina propria
Olfactory epithelium

10Receptor Neuron Mucus Layer Olfactory Cilia

Fig 3

Olfactory Cells are Neurons

OLFACTION

• Smells are detected in the nose by specialized receptor cells called olfactory receptor cells.
Basal Cell Support cell Cilia Receptor Cell Mucous Layer

Fig 4

Odorant Receptors are G protein-cAMP linked Receptors

OLFACTION

cyclic-nucleotide gated (CNG) channels

Ca Na CNG
Adenylate cyclase

Cell Depolarizes Action Potential / Population Coding

Fig 5

OLFACTORY PATHWAYS
Olfactory epithelium Olfactory bulbs Olfactory tract olfactory cortex hippocampus amygdala

Limbic System

“Taste Is a Combination of Five Basic Sensations”

GUSTATION

• • • • •

Sweet Sour Salty Bitter Umami (monosodium glutamate)

Gustation
• The superior surface of the tongue bears epithelial projections called lingual papillae
– filiform papillae – fungiform papillae – circumvallate papillae
FRICTION CONTAIN TASTE BUDS

Taste Buds
Why did I put this Here?
Bitter

Sour

Sweet

Fig 6

Salty

“Taste Cells are Non-Neural Polarized Epithelial Cells”

Taste Cells

• Each taste bud contains receptors called Gustatory (sensory) cells

Taste pore

Gustatory cell Support cell Basal cell

Fig 7

Sensory neuron

Taste ligand

Membrane channel or receptor Tight junction

Taste Ligands bind to Receptors and Create Ca++ Signals

Ca+
Neurotransmitter Sensory neuron

Fig 8

Receptor Potential

Action 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 G protein Transduction

Sweet

Sour Umami

Salt

1

1 1 2 2

1

Leak channel

2

Taste Transduction

3

4 Fig 9
To Brain

5

Unit V Sensory Systems Function And Physiology
Part IIIB The Physiology of Vision

ANATOMY OF THE EYE
Vascular Tunic
Iris Ciliary Body Choroid Lens Zonulas Vitreous Humor The Neural Tunic (Retina) Visual Axis Aqueous Humor

Fibrous Tunic
Cornea Sclera

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” Optic Nerve Pigmented Layer Neural Layer Photoreceptors Blood Vessels

PH

O OT

NS

Optic Disc

Fig 2

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

Photons Cone Rod Ganglion Cell Fig 3 Bipolar Cell

The Neural Tunic
“Organization of the Retina”

• Photoreceptors
• Rods • Cones
• Macula Lutea • fovea

• Bipolar cells

• Ganglion Cells

– Regulate communication between photoreceptors and ganglion cells – The Axons of these cells form the Optic Nerve
– Facilitate or inhibit synaptic transmission • Contrast

• Horizontal and Amacrine Cells

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
Fig 4

Rod

Anatomy of Rods and Cones
“Photoreceptors Rods and Cones”

• Cones
– Outer segment
• discs
– Visual Pigments • Opsin (r,g,b) + Retinal

Disks Mitochondria

– Inner segment
• cellular organelles • neurotransmitters

Cone
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”

Rod in Darkness

Pigmented Layer

Inactive Rhodopsin (Opsin+Retinal)

cGMP

-40 mV

This Membrane is depolarized

Fig 8 Bipolar Neurons

Tonic Release of Neurotransmitter(GPG)

Photoreception
• Dark Current
– In darkness
• Gated Na+ channels are kept open C-GMP -40 mV Na Inner Segment Neurotransmitters (G Protein glutamate) Na+ Outer Segment Na

Bipolar cells

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 Occurs at the Retina” PHOTON photon strikes the retinal portion of a rhodopsin molecule.

Phototransduction

Fig 9

Phototransduction
“The Activation of Rhodopsin” Photon “A”Opsin Opsin + Cis-Retinal
Trans-Retinal Activated Transducin Phosphodiesterase

Breakdown of cGMP

Rhodopsin Bleaching
Fig 10

Gated Na+ Close

Photoreception
“Light adapted State” (RODS) Activated Retinal

The Rod in Light

1

Activates Transducin 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

“Recovery After Stimulation”
ADP Trans Cis Opsin

Photoreception

Recovery From Bleaching

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

Color Vision
PHOTONS

Stimulation in various combinations is the basis for color vision

Opsin r

Retinal + Opsin

Opsin g r

Brain

Opsin b Fig 13

Convergence in The Retina
Rods Horizontal Cells

Bipolar Neurons

Fig 14 Ganglion Cell Amacrine Cells

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

Optic Nerve
Optic chiasma

Optic Tract

Fig 17

Visual Cortex

Part IA Action Potentials and Calcium Induced Muscle Contraction

Unit VI The Heart

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 Cells

Myocardium

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

“ Cardiac Muscle Cells Contract Without Nervous Stimulation”

Autorhythmic Cells

• 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” Na Ach

β

1

Receptors If Ca

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 • STEP 2: The plateau. Voltage-regulated fast
Fast sodium channels open and the membrane becomes permeable to Na+. The result is rapid depolarization of the sarcolemma. sodium channels close. As the fast sodium channels are closing, voltageregulated 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+ Channels close #2 Slow Ca2+ Channels open #3 Slow Ca2+ Channels close #4 Slow K+ Channels open

PNa Fast Na+ Channels open #1

K+ChannelsClose

#5 Resting Potential

Fig 5

“Calcium-Induced Calcium Release”

Ca2+ Ryanodine Receptor Channel

N KA P s a Ta e

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+
Troponin
Summation of Ca2+ Spark

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

Absolute Refractory Period

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” 1 2 3

Fig 9

The Cardiac Refractory Period

Fig 10

DIGITALIS

Part I “An Introduction to The Endocrine System”

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)

Hormone

What Makes a Chemical a Hormone ?
Blood Target

Hormones are Chemical Messengers Response

Fig 1

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

X

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
• Polypeptide hormones
“Most Hormones are Peptides or Proteins”

– 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 – Some of the stimulatory hormones from the anterior pituitary gland. (TSH, FSH, LH) – Parathyroid hormone

• Glycoproteins

AMINE HORMONES
• Tryptophan
– Melatonin

Derived from the amino acids Tryptophan or Tyrosine

• Tyrosine

• Thyroid hormones   • Catecholamines
– Epinephrine – Norepinephrine – Dopamine

(T3 and T4)

STEROID HORMONES
“are all derived from cholesterol”

• Sex hormones
– Gonads
• Estradiol • Progesterone • Androgen   • Aldosterone • Cortisol

• All the hormones of the Adrenal cortex

ACCORDING TO SOLUBILITY
Water soluble 

IN WATER OR FATS

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 SOLUABLE

FAT SOLUABLE

Lipophobic

Lipophilic

A Simple Endocrine Reflex
Internal Or External

Change

Sensory Integration

Endocrine

Efferent Signal Effector Response

Hormone Sequence of molecular changes

A Complex Neuroendocrine Reflex

Internal Or External

Change Neuron

Receptor Afferent Path Sensory Integration Efferent Signal Sensory Integration Efferent Signal#2 Effector Response

Nervous Neuron/ Neurohormone Endocrine

Hormone

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 Fig 1 cAMP

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 activation of an AdCyclase EnzymecAMP PK
Fig 3

The entry and/or release of calcium ions

The inhibition of cellular activities.

MECHANISMS OF ACTION
Water Soluble Hormones(E, activation of β 1 receptors
Phosphodiesterase (PDE) C-AMP
Adenylate cyclase

AMP

ATP

C-AMP

KINASE

SECOND MESSENGER

phosphorylation
MEMBRANE PROTEINS ENZYME ACTIVIATION

Fig 4

OPENS ION CHANNELS

Na+ K+

Ca++

MECHANISMS OF ACTION
Water Soluble Hormones activation of a1 receptors

phospholipase C (PLC). Diacylglycerol (DAG) in membrane protein kinase C (PKC) phosphorylation of calcium channel proteins entry of extra cellular Ca2+.

PIP2

Fig 5

Inositol triphosphate (IP3) activates release of Ca2+ From ER CALMODULIN RESPONSE

second messengers

MECHANISMS OF ACTION
Water Soluble Hormones(E NE) activation of a2 receptors inhibitory G-proteins

1 inhibits Adenylate cyclase activity ATP

2 stimulates PDE activity. reduction in cAMP levels Fig 6

MECHANISMS OF ACTION
Golgi
Prohormone

Water Soluble Hormones Synthesis, Storage and Release

Post-Translational Modification

ER
Sig

Hormone

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 Activation Transcription mRNA Translation Action How? Why?

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
No Secretion

KATP Open

Voltage Gated Ca Channels Closed

-70 mV RMP Fig 5

INSULIN SECRETION
Glucose GLUT4 transporter

Metabolism

Ca2+ Exocytosis

ATP Ca2+

KATP

Closed

Ca+ Open

Cell Depolarizes

K+

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

ECF ICF

io n phorylat Phos
PI3-KINASE Phosophoinositide 3K

Phosphorylation (PDK)
Increased Synthesis of

(enzymes/membrane)

Fig 8

glycogen (in liver and muscles)  Triglycerides in adipocytes  VLDL (in liver)  Cholesterol

(all target cells)

Increased Glucose

uptake and Utilization

INSULIN BINDING TO ITS RECEPTORS
Brings GluT4 glucose transporters in muscle and
Promotes glucose uptake and utilization in cells
fat tissue from endosomes to the cell membrane.

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 TK ECF ICF
Glut4
Transduction Facilitated Diffusion

I-R

Glucose

Exocytosis

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).

• This is called "down regulation" of insulin receptors.

“Down Regulation"

Fig 9

“Down Regulation"
ENDOCYTOSIS

Clathrin Pit

Fig 10

Glucagon

The Insulin-to-Glucagon Ratio Regulates Metabolism

Pancreatic Islet

Fig 11

α Cell = Glucagon 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 metabolism in skeletal muscle (Glycogen) Fig 14

increases plasma free fatty acid concentration

(adipocytes)

Phosphorylation (enzymes/membrane) Liver
increases blood glucose concentration (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
– gluconeogenesis ( In The Liver)

Glucose

GLUCAGON BINDING TO ITS RECEPTORS
• As a result, this increases the

Blood glucose concentration

Glycogen breakdown in skeletal Muscles Stimulation of glucose production in the Liver

Glucose

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

β

Fig 16

• In type 2 diabetes (non-insulindependent diabetes NIDD)

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”
body calcium = intake – output”

“total

 Intracellular calcium:

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

 Calcium in Extracellular fluid:

 Extracellular matrix (Bone)

is the site where dietary calcium is The small intestineefficient absorption of calcium in the absorbed. Importantly,

Factors influencing Fluxes of Calcium and Phosphate

small intestine is dependent on expression of a calcium-binding protein in epithelial cells.

as vast reservoir of calcium. Stimulating Bone servesbonea mineral releases calcium and phosphatenet resorption of into

blood, and suppressing this effect allows calcium to be deposited in bone.

The kidney is critically important in calcium almost homeostasis. Under normal blood calcium concentrations,
all of the calcium that enters glomerular filtrate is reabsorbed from the tubular system back into blood.

Hormonal Control Systems
• 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
“ Three Hormones Control Calcium Balance”

ENDOCRINE CONTROL OF THE PLASMA Ca2+ LEVEL
• PTH-CALCITONIN • Vitamin D
Parathyroid PTH Calcitonin

Thyroid

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:

Enhancing

absorption of calcium from the small intestine:

Stimulates osteoclasts for resorption of bone mineral, liberating calcium into blood. H+ ATPase Osteoblasts Bone Osteclasts

Suppression of calcium loss in urine:

Facilitating calcium absorption from the small intestine by stimulating production of the active form of vitamin D in the kidney. stimulating tubular reabsorption of calcium and phosphate ions in urine (stimulates loss of phosphate ions )

Low Plasma (Ca2+)

Parathyroid Hormone (PTH)
Another Example of a Simple Endocrine Reflex

Negative Feed Back

Fig 3

Plasma (Ca2+ )

• Parathyroid hormone is released in response to low Extracellular concentrations of free calcium

Control of Parathyroid Hormone Secretion

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

Bone/ Intestine

+

-

Plasma Ca2+

Fig 6

Plasma Ca2+

Calcium Balance in The Body
Small Intestine Dietary Calcium
Calcitriol/PTH

Ca2+

Calcium in Feces

Bone
Calcitriol

ECF Filtration PTH
Calcitonin

Kidney Ca2+

Calcitonin

Active Transport Cell Fig7 Ca2+ 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 calciumlowing 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)

“Feedback loops Are Different in The Hypothalamic-Pituitary Pathway”

Control of Hormonal Activity

• 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

Negative Feedback Loops in The Hypothalamic Anterior Pituitary Pathway

Endocrine Reflexes

stimulation inhibition IC1 Hypothalamus Short Loop Negative Feedback Long Loop Negative Feedback
Short Loop Negative Feedback

Trophic Hormone Hormone 1 IC3 Endocrine organ

IC2 Trophic Hormone2 Target

Fig 2

Regulatory Mechanisms of the Hypothalamus
Regulatory Hormones
Indirect Control

Endocrine Control Direct

Direct Neural Control

Hypophyseal Portal System “Trophic Hormones” Anterior pituitary “Adenohypophysis” acts by TH2

Travel along axons in Infundibulum

Neuron

Posterior pituitary “Neurohypophysis”

Adrenal medulla

Hypothalamus
Neurons synthesizing posterior Pituitary Hormones Neurons synthesizing Trophic Hormones

Capillaries Endocrine cells Portal Vessels Axon Terminals Fig 3 Posterior Pituitary Anterior Pituitary

“The Hypothalamic – Hypophyseal Portal System”

Hypothalamus

Neurons synthesizing Trophic Hormones

Capillaries Endocrine cells Portal Vessels

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

Hypothalamus

Dopamine PIH PRH

Hormones of the Hypothalamic Anterior Pituitary Pathway
TRH CRH GHIH GHRH GnRH

Anterior Pituitary

Prolactin

TSH

ACTH

GH

FSH

LH

Endocrine Targets

Thyroid T3/T4

Adrenal cortex Cortisol

Liver IGF’s

Gonads

Androgens

Estrogens Progesterone

Non Endocrine Targets

Breast

Tissues

Gonads

Fig 5

Pathway of Growth Hormone Control

Cortisol Secretion
Is Controlled by ACTH

Control Pathway for Cortisol Secretion
stimulation inhibition IC1 CRH IC3 Adrenal Cortex Cortisol ACTH Hypothalamus Short Loop Negative Feedback

IC2 Long Loop Negative Feedback

Target Tissue

Cortisol Secretion
Is Controlled by ACTH

Posterior Pituitary by the Hypothalamus

Endocrine Control (direct)

• 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

Posterior Pituitary by the Hypothalamus
Hormone is made in Cell Body of Neuron

Endocrine Control (direct)

Hormones Travel Down The Axon Vesicles Containing Hormones are stored In Posterior Pituitary Fig 6 Posterior Pituitary Hormones are Released into Blood Vein

Posterior Pituitary by the Hypothalamus

Endocrine Control (Direct)

Indirect Control Infundibulum Posterior Pituitary

Anterior Pituitary

ADH (Vasopressin) OXYTOCIN Fig 7

ADH/Vasopressin

Afferent

Afferent

Kidney

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

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 • Oxytocin :
– Ballistic control of blood sugar and blood pressure. – Ballistic control of milk ejection and uterine contractions. – Ballistic control of fertility and (Negative feed back control of lactation).

• Prolactin :

Epinephrine and Norepinephrine
The Catecholamines THE BALLISTIC CONTROL of BLOOD SUGAR THE BALLISTIC CONTROL of BLOOD PRESSURE

“Immediate Short-Term Response to Stress”

The Alarm Phase

• Immediate response to stress occurs.
• sympathetic nervous system
Cerebral Cortex Limbic Hypothalamus MONSTER Fig 2

The Alarm Phase
SNAKE
AT FIRST

LIMBIC

HYPOTHALAMUS SYMPATHETIC NERVOUS SYSTEM

ADRENAL MEDULLA

Fig 3 α
1

β

1

Norepinephrine/Epinephrine onto Adrenergic Receptors

Effects Of Epinephrine and Norepinephrine
α
E(80%)
1

β
NE

1

β

2

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

β α

Vasodilatation of Blood vessels to Skeletal Muscle

Vasoconstriction of Blood vessels to Skin and 2 Gut 1

PROLACTIN
• THE BALLISTIC CONTROL OF FERTILITY • MILK PRODUCTION

PROLACTIN
Hypothalamus PIH

-

Fig 5

“Ballistic and Non Ballistic Control”
Ballistic Control

PROLACTIN

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 Breast Stretching of 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 T4 Fig 1

THYROXIN

THYROID HORMONES

hypothalamus

T3 and T4

FOLLICLE CELLS IN THYROID

Fig 2

THYROID HORMONES
Follicle Cells

Follicle Cavity

Fig 3

THYROID HORMONES
Follicle Cell
#1 Triiodothyronine T3 #2
IODINE 2 TYROSINE

#3 THYROGLOBULIN T3

I

2

+

TSH

-T4
#4 T3-T4

Thyroxime T4
Endocytosis

G cAMP

Capillary
T3&T4 LYSOSOMAL DIGESTION Bind with TBG or Albumin #6

T3&T4

Exocytosis

FOLLICLE CAVITY Fig 4

#5

THYROID HORMONES
FROM THYROID FOLLICLES TBG BOUND T3 T4 EQUILIBRIUM

FREE

T3

0.3

0.03

T4

LIVER

T4

T3

AS FREE T3&T4 ARE TAKEN INTO CELLS BOUND T3&T4 IS RELEASED FROM FOLLICLES Fig 5

TO CELLS

Thyroid Hormone Pathway
Tonic Release TRH •Goiter •Hypothyroidism •Hyperthyroidism •Graves •TSImm

Short Loop TSH

Long Loop

T3-T4 Systemic Metabolic effects

T3 T4 I2

THYROID HORMONES
Immediate effects Mediated By Second Messenger (Mitochondria ATP ) Thyroxin

ATPase Regulation of Cellular Metabolism Fig 6

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 Mediated By Second (3) Binding of H-RC to DNA Messenger System (4) Gene Activation Transcription mRNA Translation
(Mitochondria)

Enzyme Regulation of 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. – 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

Formed elements

• 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 CELLS LYMPHOID STEM CELLS LYMPHOCYTES

MYELOID PROGENITORS CELLS
Erythropoietin Thrombopoeitin

RBC MEGAKARYOCYTE

(Glycoprotein Hormone)

Cytokines

PLATELETS
WBC

PLASMA

Fig 1

Colony Stimulating Factors

BLOOD

Unit VII The Circulatory System
Red Blood Cells

Blood Part II

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 Synthesis Requires Iron”

Hemoglobin

• 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 Synthesis Requires Iron”

Hemoglobin

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
(1) IRON Kidney control RBC 4 formn
RBC PRODUCTION

Intestine 2
AT

urobilins +sterobilins

LIVER
Transferin Ferritin Bilirubin Metabolism

Bile 7

3 Fe RBC PLASMA Fe
bilirubin biliverdin

6

BONE MARROW erytropoiesis

KIDNEY urobilins 8
Urine

EPO

Fig 4 Erythropoietin

OLD RBC DESTROYED

5 SPLEEN

Heme stripped Of Fe by Macrophage

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
DAMAGE TO WALL OF BLOOD VESSEL

Coagulation Phase

COLLAGEN EXPOSED Formation of Loose Plug 2

VASOCONSTRICTION 1

TISSUE FACTOR EXPOSED

Coagulation Cascade 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

Common Pathway

To

COLLAGEN EXPOSED
PLATELET ACTIVATION

PLATELETS ADHERE AND RELEASE PLATELET FACTOR PLATELETS AGREGATE INTO LOOSE PLUG
COX

+
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 PATHWAY
TF XII

A

TISSUE FACTOR III EXPOSED
TF VII

B

COAGULATION CASCADE

EXTRINSIC
PATHWAY

+
Loose Plug

C
TF X

THROBIN FORMATION
CONVERSION OF FIBRINOGEN TO FIBRIN

COMMON PATHWAY

Reinforced Plug (clot)

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 Fibrinogen
Ca+2

Thrombin Fibrin

Intrinsic Pathway Collagen or other activators Tissue Factor III & VII (a)

Extrinsic Pathway Damage Exposes Tissue Factor III Van Willebrands

Positive Feedback
Hemophilia A

Common Pathway

Thrombin
Fibrinogen Fibrin

Prothrombin

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
THROMBIN From Common Pathway Intrinsic Pathway PAF-3 Extrinsic Pathway Positive Feedback Tissue Factor

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 IX,X,XI,XII – Anticoagulants Heparin Antithrombin-III Inactivates Thrombin
(intrinsic)
(activates)

Thrombomodulin

Binds to

Thrombin

Converts

Inactivates clotting

Protein C

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)
Regulation
Afterload

and Hormonal(catecholamine) Homeostatic Balances

Cardiac Output

Arterial Blood Pressure

Peripheral Resistance

Capillary Pressure

Venous Pressure Capillary Exchange
Fig 1

Interstitial Fluid

PRESSURE

– – –

Circulatory Pressure

(Pressure Gradient)

Blood Flow (F) The volume of blood flowing per unit of time

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.

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
Pressure Gradient/R – F – 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 X 2

Diameter 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 – Pulse pressure

• The minimum blood pressure at the end of L ventricular diastole The difference between the systolic and diastolic pressures mean driving force

• Mean Arterial Pressure (MAP)

diastolic pressure

Calculated by adding one third of the pulse pressure to the MAP = DP +pp/3

ARTERIAL BLOOD PRESSURE
“Ventricular Contraction”
Ventricular Contraction
1 2

Semilunar Valves open

3

Arteries Expand and Store energy

Fig 4

ARTERIAL BLOOD PRESSURE
Isovolumic Ventricular Relaxation

Elastic Rebound sends Blood forward

2 1 3

Semilunar Valves shut Fig 5

Systemic Pressures
Systolic Pressure

Pulse Pressure

Diastolic Pressure

Mean Pressure
MAP = dp +pp/3

Fig 6

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

Mean Arterial Pressure

Left Ventricle
Fig 7

Arterioles

MAP

CO x P.RESISTANCE

MEAN ARTERIAL BLOOD PRESSURE
“The Driving Pressure for Blood Flow”
Is determined by

60% Resistance

60% Blood Volume

Fig 8

ARTERIAL BLOOD PRESSURE
Ventricular ejection (120 Systolic Pressure Peak mmHg) B C dicrotic notch isovolumetric S valves close D Diastolic Pressure

MAP

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 Diameter of Arterioles Distribution

Fluid In

Fluid Out

Diameter of Veins

Kidneys

Changes in Blood Volume Affect Blood Pressure

The Regulation of Blood Pressure and Blood Volume
Homeostasis
Homeostasis Disturbed
Autoregulation (Local) (Autoregulation Ineffective) Neural (Short Term) Kidney (Endocrine/Long Term Fast Slow

Fig 1

The Regulation of Blood Pressure, Blood Volume and Blood Flow
Local Control/Autoregulation Myogenic
Vasoconstriction Metabolic O2 CO2

Paracrines
Signal Molecules 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

BP stretches vessel Fig 3

Ca+

Vasoconstriction

Paracrines Alter Vascular Smooth Muscle Contraction
Paracrines
Metabolic O2, CO2 H+ Vasodilation Signal Molecules NO, Histamines, Adenosine Seratonin Vasodilation

Think Homeostatic Balances !!! Fig 4

Paracrines Alter Vascular Smooth Muscle Contraction
Active Hyperemia (dilation)
O2 CO2

Tissue Metabolism

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
NE on

Parasympathetic

α

Receptors Vasoconstriction

1

Epinephrine on

β

Receptors Vasodilation

2

ACh/NO Cholinergic Receptors Vasodilation

Vascular Smooth Muscle

BP
Fig 7

Heart Liver Skeletal Muscle

BP

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
Medullary CV Center Acceleratory Inhibitory Vasomotor (Autonomic) vasoconstriction vasodilatation Atrial Baroreceptors

Carotid sinuses

Tonically active Stretch sensitive receptors
Fig 8

Aortic sinuses

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 Erythropoietin Renin Angiotensin II ADH Sympathetic Stimulation

(Short Term)

Long Term

Heart Rate Fig 11

Aldosterone Thirst

Increased Blood Volume/Pressure

The Regulation of Blood Pressure and Blood Volume

Blood Volume
Blood Pressure

Cardiovascular
(Short Term)

(Long Term)

Renal

Fast Fig 12

Slow

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
Increased Na+ Loss in Urine Increased Water Loss in Urine

Block Aldosterone / Block ADH/

Reduced Blood Volume

Reduced Thirst

Fig 13

Block Renin Peripheral Vasodilation

Reduced BP

Circulatory shock
Homeostatic Failure
BV CO VESSEL CLOTTING

35% Blood Loss

3 2

1
DAMAGE TO HEART Baroreceptor reflex ISCHEMIC RESPONSE BRAIN

BP

DECREASE IN BLOOD TO TISSUES O2 TISSUE STARVATION INCREASED CAPILLARY PERMEABILITY

4

FALLING ARTERIAL PRESSURE DEATH

Fig 14

Unit VI The Heart
The Heart as a Pump

Part IB

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 (AV) Node AV Bundle (HIS) Bundle Branches Purkinje Fibers
Fig 2

moderator band

papillary muscles

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 Slows through AV node
Very Important 100 ms delay

Dense bands of elastic tissue Bundle of HIS

Fibrous skeleton

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 system To the Apex of the Heart
BUNDLE BRANCHES moderator band APEX Fig 6

AV NODE

Chordae tendineae

Papillary muscles

Electrical Conduction in The Heart
“THE CONDUCTING SYSTEM”

PURKINJE FIBERS

Depolarization wave 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

“The Electrocardiogram Reflects the Electrical Activity of the Heart”

ELECTROCARDIOGRAM

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 Interval

Segment
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

The P wave represents the wave of depolarization that spreads from the SA node throughout the atria

P WAVE

P

PR

Fig 4

The period of time from the onset of the P wave to the beginning of the QRS complex is termed the P-R interval AV NODE AV BUNDLE Atria Contract

WAVE OF VENTRICULAR DEPOLARIZATION

QRS COMPLEX

Q

Q

Fig 5

WAVE OF VENTRICULAR DEPOLARIZATION

QRS COMPLEX

R

R
Ventricles Start To Contract

Q

Fig 6

WAVE OF VENTRICULAR DEPOLARIZATION

QRS COMPLEX

R

S

Q

S

Fig 7

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

ST Segment

ST segment

T

Ventricles Contract

S

Fig 8

The T wave represents ventricular repolarization

T WAVE

T
Q

Fig 9

The Q-T interval represents the time for both ventricular depolarization and repolarization to occur.

“P WAVE TO P WAVE OR PEAK TO PEAK QRS”

HEART RATE

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-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

Second-decree AV nodal block

Fig 12

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

Third-decree AV nodal block

Fig 13

ATRIAL FIBRILLATION
Uncoordinated atrial depolarization

Fig 14

http://www.skillstat.com/ECG_Sim_demo.html 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
A--------B PASSIVE FILLING AND ATRIAL CONTRACTION B--------C ISOVOLUMIC CONTRACTION C ------- D VENTRICULAR EJECTION D ------- A ISOVOLUMIC RELAXATION EDV = END DIASTOLIC VOLUME ESV = END SYSTOLIC VOLUME
AORTIC VALVE CLOSES

Stroke Volume

ESV

D
AORTIC VALVE OPENS

C

MITRAL VALVE CLOSES MITRAL VALVE OPENS

EDV

Fig 6

LEFT VENTRICULAR VOLUME

A

B

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

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

End-diastolic volume (EDV) The amount of blood in each

 

EDV - ESV = SV

Stroke volume/Cardiac Output
Cardiac Output Is a Measure of Cardiac Performance

CO = SV X
STROKE VOLUME

HR
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

• EDV • ESV

FACTORS AFFECTING THE STROKE VOLUME

(1) Filling time (Duration of Ventricular Diastole) (2) Venous return (CO, BV, PphlCir, Skeletal & Muscular Activity) (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 SV

RESTING VALUE 135ml

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)

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.)

Afterload

MODULATION OF CARDIAC CONTRACTION

Ca++ β 1
Cardiac Muscle Cell Metabolism

Ca++
Cardiac Muscle Cell Metabolism

Increase in force Of Contraction/ Rate

Decrease in force Of Contraction (Minimal)

Fig 10

MODULATION OF CARDIAC CONTRACTION

CARDIAC OUTPUT

Fig 11

Bainbridge Reflex

Factors Affecting 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

I.

External respiration
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 O2 Blood and the Cells
O2 lungs CO2 External Respiration cell CO2

Respiratory Physiology
Four integrated steps involved in External respiration (1) Pulmonary ventilation, (2) Gas diffusion,
The physical movement of air into and out of the lungs.

Diffusion across the respiratory membrane (alveolar air spaces and alveolar capillaries).

(3) The transport of oxygen and carbon dioxide

(4) The Exchange of gases between blood and the cells

Between alveolar capillaries and capillary beds in other tissues.

*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

“Gas Exchange Requires Pressure Gradients”
Alveoli

*Respiratory Physiology

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 Only 10% Blood

During Exercise

At Rest

Normal

Fig 2

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

“Hemoglobin Transports Most Oxygen to the Tissues” Hb+O2 HbO2

Gas Transport in The Blood
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

“Hemoglobin Transports Most Oxygen to the Tissues”

Gas Transport in The Blood
Temperature, pH and Metabolites Affect OxygenHemoglobin Binding

Factors Effecting The Solubility of a Gas in A Liquid

*O2 LOADING

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

“PO2 Determines Hemoglobin Binding of O2”

*O2 LOADING

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 – bicarbonic Acid – Under anaerobic conditions (maximal exercise) CH3 CHOHCOOH H+ – C6H12O6 Acetic Acid Both acids lower the pH
• C6H12O6+02 CO2 +H2 (H2O) H2CO3 → HCO3- + H+

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

Fig 10

Hypoxia Anemia High altitude

Oxygen Transport
TISSUES LUNGS

O2

CO2
Hb+ CO2

CO2

( Carbaminohemoglobin)
Hb-CO2

Fig 11

Gas Transport in The Blood
“Fetal Changes in Hemoglobin Structure”

Fig 12

“Hemoglobin Transports Most Oxygen to the Tissues”
Total Arterial O2 Content
2% 98 %

Gas Transport in The Blood

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

RBC

H+ + HCO3BICARBONATE (LUNGS)

CARBONIC ANHYDRASE

AT CELL AT LUNGS
Fig 14

Step One

The Transport of Carbon Dioxide
Hemoglobin and H+

CO2 + H20

H2CO3

H+ + HCO3RBC BUFFERS

Cl-

Hb To Lungs

HB-H+

Plasma
pH 7.4

Fig15

Step Two

The Transport of Carbon Dioxide
Hemoglobin and CO2

CO2 + Hb
AT CELL

CARBAMINOHEMOGLOBIN

Hb-CO2

AT LUNGS

Fig 16

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

Fig 17

Unit IX The Kidneys
Basic Principles Of Urine Formation

Renal Physiology I

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
The Nephron

Tubular elements

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 REABSORPTION L SECRETION EXCRETION B L

L

H2O and HCO3 (pH) B L

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

F

R

S

E

F – R + S
Fig 3

=

E

FILTRATION
• Filtration occurs in the renal corpuscle as fluids move across the wall of the Glomerulus and into the capsular space

Fig 4

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

FILTRATION

Fig 5

FILTRATION
• Substances Leaving the Plasma Must Pass Through Three Filtration Barriers - Glycoprotein Fenestrated 1 Capillaries
1/5 Capillary Lumen
Plasma proteins

3
Lumen

-

Mesangial Cells Glomerular Capillary Endothelium

2
Basal Lamina Fig 6

Podocyte (Epithelium of 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) Capsular hydrostatic pressure (CsHP) Net hydrostatic pressure (NHP)
The blood pressure in the Glomerular capillaries The pressure opposing the Glomerular hydrostatic back pressure due to proximal convoluted tube. The difference between GHP and CsHP NHP = GHP CsHP osmotic pressure resulting from the presence of suspended proteins in Plasma.

Blood colloid osmotic pressure (BCOP)

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

Fig 7

GHP

(Glomerular hydrostatic pressure)

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 100ml/min

Fig 9

GFR

Glomerular Filtration Rate
Creatinine Clearance Test
ml plasma cleared of solute/time (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

Fig 1

GHP

(Glomerular hydrostatic pressure)

Filtration pressure (FP) FP = NHP - BCOP

“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 •

Filtration

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

Myogenic

Tubuloglomerular feedback

Controlling the GFR
(Myogenic)

Fig 2

“The Key is Where the Resistance Change Takes Place”

Controlling the GFR

Fig 3

GFR

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

Fig 4

“GFR Remains Constant When MAP Remains Between 80 and 180 mmHg”
GFR IS CONSTANT

Controlling the GFR

WHILE

BLOOD PRESSURE Fig 6

“The GFR is Subject to Autoregulation”

Afferent Blood Vessel

Autoregulation

Myogenic BP

Tubuloglomerular feedback
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
Hypothalamus Inhibits Vasopressin Kidney

ANP

BP
Medulla

Adrenal Cortex Inhibits Aldosterone

GFR

NaCl and H20 Excretion DECREASE BP AND BLOOD VOLUME

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

Angiotensinogen
Fig 10

Angiotensin I
Lungs

Angiotensin II
Hypothalamus

Vasoconstriction Arterioles & Precapillary Sphincters

Adrenal glands

Nephron

ADH

Aldosterone

Vasoconstriction of 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 PITUITARY (ADH)

Arterioles & Precapillary Sphincters

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

Reabsorption and Secretion Renal Review

Unit IX The Kidneys Renal Physiology III

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
Increasing Transport Rate

Tm

RENAL THRESHOLD

Increasing Substrate Concentration

The Tm and Renal Threshold
Transport Rate at Saturation

Tm Saturation

Renal Threshold
Fig 1 Plasma Concentration at Which Saturation occurs

The Tm and Renal Threshold
Renal Threshold

Amino acids and glucose

Carrier-Mediated Transport

Appears in urine

(over)
transport maximum (Tm) carrier protein SATURATED transport maximum (Tm) carrier protein OVER SATURATED

The Tm and Renal Threshold
“Glucose Handling in The Nephron” What Happens Here ? Tm Normal Range

Fig 2

The Proximal Convoluted Tubule
Reabsorption of organic nutrients 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

ProximalCT
Glu

Sodium Reabsorption in the PCT
Glut4 facilitated diffusion Glu low

Glu/Na symport

ATPase Antiport

PCT

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 Active or Passive Osmosis The Passive Reabsorption Of Urea
Fig 5

Very Important

NaCl Na+ Glucose H2O HERE Urea
To Renal Medulla

Water Balance
Proximal Tubule

Urine Concentration Is determined in the Loop of Henle and the Collecting Ducts Distal Tubule
100mOsM

Cortex
Isosmotic

300mOsM

H2O

CL K Na

Active Reabsorption Collecting Duct Hormonal Regulation Variable H2O Reabsorption

Loop
1200mOsM

Na Peritubular fluid

Medulla

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
Vasa Recta
Hyposmotic

Descending Limb

Ascending Limb
Lasix works here

Na Hyperosmotic

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

Fig 11

H2O

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

ADH

H 2O
9L/Day

The Reabsorption of Water in the Collecting System

- FEEDBACK
H 2O
17L/Day

DCT
Water Channels

COLLECTING Osmolarity /Blood Volume/Low BP are the Key TUBULE

Fig 10

ADH/Vasopressin

ADH/Vasopressin

Sodium and Potassium Balance
• Aldosterone action on “principal cells in the DCT controls Sodium Balance

Reabsorption of Na
Aldosterone
ADRENAL CORTEX ANGII K+ OSMOLARITY

+

at the DCT

K+

Na+ ClPeritubular fluid

Fig 7

Reabsorption of Na+ at the DCT

Reabsorption of Ca
Parathyroid Hormone And Calcitriol

+

at the DCT

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)

Peritubular fluid

H+ HCO3-

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

“DCT/Collecting Ducts”

Renal Summary

• 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 motor neurons efferent fibers Bladder Relax Smooth Muscle

interneurons

thalamus Fig 12 Cerebral cortex (I have to Pee)

Internal urethral sphincter External urethral sphincter

The Bladder at Rest
Bladder Smooth Muscle Relaxed Filling State Smooth Muscle Internal Sphincter Passively Contracted Motor Neuron Fires

Higher CNS Input

External Sphincter
Stays contracted Fig 13

Skeletal Muscle

1

MICTURITION REFLEX

I have to Pee

Stretch Receptors Fire
Degree of Fullness

CNS

Sensory Neuron 2
Smooth Muscle Contracts Parasympathetic Neurons Fire

3 2 3
Internal Sphincter Passively Pulled Open Motor Neuron Stops Firing

Tonic Discharge Inhibited
Fig 14

3 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

I.

External respiration
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 O2 Blood and the Cells
O2 lungs CO2 External Respiration cell CO2

Respiratory Physiology
Four integrated steps involved in External respiration (1) Pulmonary ventilation, (2) Gas diffusion,
The physical movement of air into and out of the lungs.

Diffusion across the respiratory membrane (alveolar air spaces and alveolar capillaries).

(3) The transport of oxygen and carbon dioxide

(4) The Exchange of gases between blood and the cells

Between alveolar capillaries and capillary beds in other tissues.

*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

“Gas Exchange Requires Pressure Gradients”
Alveoli

*Respiratory Physiology

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 Only 10% Blood

During Exercise

At Rest

Normal

Fig 2

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

“Hemoglobin Transports Most Oxygen to the Tissues” Hb+O2 HbO2

Gas Transport in The Blood
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

“Hemoglobin Transports Most Oxygen to the Tissues”

Gas Transport in The Blood
Temperature, pH and Metabolites Affect OxygenHemoglobin Binding

Factors Effecting The Solubility of a Gas in A Liquid

*O2 LOADING

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

“PO2 Determines Hemoglobin Binding of O2”

*O2 LOADING

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 – bicarbonic Acid – Under anaerobic conditions (maximal exercise) CH3 CHOHCOOH H+ – C6H12O6 Acetic Acid Both acids lower the pH
• C6H12O6+02 CO2 +H2 (H2O) H2CO3 → HCO3- + H+

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

Fig 10

Hypoxia Anemia High altitude

Oxygen Transport
TISSUES LUNGS

O2

CO2
Hb+ CO2

CO2

( Carbaminohemoglobin)
Hb-CO2

Fig 11

Gas Transport in The Blood
“Fetal Changes in Hemoglobin Structure”

Fig 12

“Hemoglobin Transports Most Oxygen to the Tissues”
Total Arterial O2 Content
2% 98 %

Gas Transport in The Blood

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

RBC

H+ + HCO3BICARBONATE (LUNGS)

CARBONIC ANHYDRASE

AT CELL AT LUNGS
Fig 14

Step One

The Transport of Carbon Dioxide
Hemoglobin and H+

CO2 + H20

H2CO3

H+ + HCO3RBC BUFFERS

Cl-

Hb To Lungs

HB-H+

Plasma
pH 7.4

Fig15

Step Two

The Transport of Carbon Dioxide
Hemoglobin and CO2

CO2 + Hb
AT CELL

CARBAMINOHEMOGLOBIN

Hb-CO2

AT LUNGS

Fig 16

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

Fig 17

“The Regulation of Ventilation”

Not in Exam Unit VIII Respiration Part II

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 – Pons
• Dorsal respiratory group (DRG) • Ventral respiratory group (VRG).
Respiration Rate and Depth

• Apneustic centers • Pneumotaxic centers

“Neurons in the Medulla Control Breathing”
Sensory Input

Respiratory Physiology
Central Pattern Generator

Medulla Oblongata Pons
Dorsal Respiratory Group Ventral Respiratory 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
P Inhalation Exhalation P

2 sec

3sec

Fig 2

Atmospheric Pressure

“Rhythmic Breathing”
Ramping
Inspiration Shuts Off

DRG

Rapid Positive Feedback

Fig 3

Inspiration 2 sec

Passive Expiration 3 sec

Inspiration 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
I + Neurons

Expiratory center
E Neurons

RECIPTRICAL INNERVATION

Fig 4

INTINISIC RYTHMIC ACTIVITY
(Autorythmic cells)

Other mitigating factors

ACTIVE

Fig 5

Passive
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
PNTC APNC

Rate and Depth

CPG

DRG
2 SEC MECHANICS

RAMPING

Fig 6

APNEUSTIC AND PNEUMOTAXIC CENTERS ARE 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 R chemoreceptor CSF O2 increase Apneustic Center Pneumotaxic Center

Peripheral

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.

Carbon Dioxide, Oxygen, and pH Regulate Ventilation

The Chemoreceptor Reflexes

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

• Central chemoreceptors
CO2 + H2O

(medulla)

– Respond only to the PCO2 concentration of the Cerebrospinal fluid H+ + HCO3

-

means

pH of CNS

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 O2 SENSOR

Glomus cells(carotid/aorta) (peripheral chemoreceptors 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+ + HCO3Lowers 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 To Action Potentials

Fig 9

Primary: Hypercapnia

The Chemoreceptor Reflex

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 Fig 10 glomus 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
PONS PChR APNC PNTC

PCO2, PO2 and Ph of the Plasma

DRG

CPG
Fig 11 VRG CChR

SOMATIC MOTOR NEURONS

RESPIRATORY RATE

How Can Oxygen Kill Your Patient ? Watch what you do!!!

medulla –PCO2 concentration of the Cerebrospinal fluid
(Ph)

Reproduction Male and Female

Unit X

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

Fig 4

Sertoli Cells (Sustentacular cells)

XS SEMINIFEROUS TUBULES

Hormonal Control of Spermatogenesis
• Spermatogenesis Requires Gonadotrophins and Testosterone

HYPOTHALAMUS GnRH ANTERIOR PITUITARY LH FSH Interstitial Cells
Fig 5 (Leydig) (3-4 Pulses/1.5hrs)

Inhibin
2nd Messenger

Seminiferous Tubules

-

1.CNS (Libido) 2.Bone and Muscle Growth 3.Male 2ndary Sexual Characteristics

Testosterone

Sertoli Cells
Paracrines

Binds To

Spermatogonium Androgen Binding Protein Spermatogenesis Spermiogenesis

The Male Sexual Response
“Anatomy of An Erection”
e 2ndMssenger

guanosine monophosphate (cGMP) Nitric oxide

Vasocoagulation

Fig 6

VIAGRA inhibits phosphodiesterase type 5 (PDE5)

“ What About Us Old Guys ? ” BRAIN
Nitric oxide Sexual arousal

VIAGRA

Parasympathetic

nonadrenergic-noncholinergic neurons

Nitric oxide diffuses into corpus cavernosal smooth-muscle

guanosine monophosphate (cGMP) phosphodiesterase type 5 Vasodilation of Penile Arterioles

e 2ndMssenger

Not enough

Erection

Ejaculation/Orgasm
Orgasm
ALL Muscles Relax

BRAIN

Sympathetic

Emission.

Muscles Tighten

epididymis and vasa deferens contract sperm enter ejaculatory duct secretions from seminal vesicles, prostate gland, and bulbourethral glands Adjust Ph Urethra and Female

Muscular contractions at base of penis expel semen (ischiocavernosus and bulbospongiosus muscles)) Pre emission

Expulsion

The Male Sexual Response
SYMPATHETIC Muscles tighten

Sexual Stimulation Real or imagined

Sex Act
PARASYMPATHETIC Erection

Fig 7

What Makes a Male a Male Anyway?
SRY FACTOR
Testis Determining Factor

Bipotential Gonadal Tissue
Mullerian Ducts MIF
Vagina uterus, fallopian tubes,

Wolffian Ducts

Testis

Testosterone (DHT) Leydig Fig 8

testosterone causes each wolffian duct to develop into epididymis, vas deferens, and seminal vesicles

The Reproductive System
Female

The Ovary Produces Eggs and Hormones

Fig 9

“The Menstrual Cycle Lasts About One Month”

The Menstrual Cycles
Ovarian Cycle

Uterine Cycle
Prepares Uterus To Receive Fertilized Oocyte

Prepares One Oocyte Per Month

Fig 10

PROCREATION

The Ovarian Cycle
• Follicular Phase • Ovulation
• Period of Follicular Growth 10 Days to 3 Weeks • Release of The Oocyte (Ova) • Transformation of Follicular Remains into The Corpus Luteum

• Luteal Phase

Uterine Cycle
• Menses
(Corresponds to Day One Follicular Phase)

• Menstrual Discharge Days 1 - 7

• Proliferative Phase • Secretory Phase

(Estrogen)

• Thickening of Endometrium Days 7-14 (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

The Ovarian Cycle

Fig 11

“Hormonal Control of the Menstrual Cycle is Complex”

The Ovarian Cycle
Hypothalamus Pituitary Gland
GnRH

FOLLICULAR PHASE

LUTEAL PHASE

- /+
Estrogen
Ovary
Fig 12

FSH follicle

LH

Corpus luteum

-/ +
Progesterone

“The First Day of Menstruation is Day One of the Cycle”
Hypothalamus

Early to Mid Follicular Phase

+
Fig 13 Endometrium

GnRH

WHY?

Pituitary
FSH FOLLICLE Granulosa Cells Thecal Cells LH

-

Estrogen

Androgens

Late Follicular Phase/Ovulation
Hypothalamus

+ Fig 14 Inhibin

GnRH

Surge in LH Levels

Pituitary FSH FOLLICLE Granulosa Cells Thecal Cells
Androgens Endometrium

LH

16-24 hrs after

Ovulation

Collagenase

High Estrogen

Small Amount of Progesterone

Collagenase

Ovulation

Fig 15

EARLY TO MID LUTEAL PHASE
Hypothalamus

-

Pituitary FSH Corpus Luteum From Ovulated Follicle
(Thecal Cells)

LH

Uterus
Inhibin Fig 16

Secretes
Estrogen

Progesterone

LATE LUTEAL PHASE
Tonic Secretions Resume
Negative Feedback Stops

Hypothalamus

-

Pituitary FSH
(12 Days)

LH Corpus Luteum Disintegrates into 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

Fig 19

Peristaltic contraction of Uterus/Vagina Clitoral erection/ And Cervical mucous glands Contraction of Bulbospongiosus and ischiocavernosus Muscles

ORGASM

Reproduction Male and Female

Unit X

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

Fig 4

Sertoli Cells (Sustentacular cells)

XS SEMINIFEROUS TUBULES

Hormonal Control of Spermatogenesis
• Spermatogenesis Requires Gonadotrophins and Testosterone

HYPOTHALAMUS GnRH ANTERIOR PITUITARY LH FSH Interstitial Cells
Fig 5 (Leydig) (3-4 Pulses/1.5hrs)

Inhibin
2nd Messenger

Seminiferous Tubules

-

1.CNS (Libido) 2.Bone and Muscle Growth 3.Male 2ndary Sexual Characteristics

Testosterone

Sertoli Cells
Paracrines

Binds To

Spermatogonium Androgen Binding Protein Spermatogenesis Spermiogenesis

The Male Sexual Response
“Anatomy of An Erection”
e 2ndMssenger

guanosine monophosphate (cGMP) Nitric oxide

Vasocoagulation

Fig 6

VIAGRA inhibits phosphodiesterase type 5 (PDE5)

“ What About Us Old Guys ? ” BRAIN
Nitric oxide Sexual arousal

VIAGRA

Parasympathetic

nonadrenergic-noncholinergic neurons

Nitric oxide diffuses into corpus cavernosal smooth-muscle

guanosine monophosphate (cGMP) phosphodiesterase type 5 Vasodilation of Penile Arterioles

e 2ndMssenger

Not enough

Erection

Ejaculation/Orgasm
Orgasm
ALL Muscles Relax

BRAIN

Sympathetic

Emission.

Muscles Tighten

epididymis and vasa deferens contract sperm enter ejaculatory duct secretions from seminal vesicles, prostate gland, and bulbourethral glands Adjust Ph Urethra and Female

Muscular contractions at base of penis expel semen (ischiocavernosus and bulbospongiosus muscles)) Pre emission

Expulsion

The Male Sexual Response
SYMPATHETIC Muscles tighten

Sexual Stimulation Real or imagined

Sex Act
PARASYMPATHETIC Erection

Fig 7

What Makes a Male a Male Anyway?
SRY FACTOR
Testis Determining Factor

Bipotential Gonadal Tissue
Mullerian Ducts MIF
Vagina uterus, fallopian tubes,

Wolffian Ducts

Testis

Testosterone (DHT) Leydig Fig 8

testosterone causes each wolffian duct to develop into epididymis, vas deferens, and seminal vesicles

The Reproductive System
Female

The Ovary Produces Eggs and Hormones

Fig 9

“The Menstrual Cycle Lasts About One Month”

The Menstrual Cycles
Ovarian Cycle

Uterine Cycle
Prepares Uterus To Receive Fertilized Oocyte

Prepares One Oocyte Per Month

Fig 10

PROCREATION

The Ovarian Cycle
• Follicular Phase • Ovulation
• Period of Follicular Growth 10 Days to 3 Weeks • Release of The Oocyte (Ova) • Transformation of Follicular Remains into The Corpus Luteum

• Luteal Phase

Uterine Cycle
• Menses
(Corresponds to Day One Follicular Phase)

• Menstrual Discharge Days 1 - 7

• Proliferative Phase • Secretory Phase

(Estrogen)

• Thickening of Endometrium Days 7-14 (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

The Ovarian Cycle

Fig 11

“Hormonal Control of the Menstrual Cycle is Complex”

The Ovarian Cycle
Hypothalamus Pituitary Gland
GnRH

FOLLICULAR PHASE

LUTEAL PHASE

- /+
Estrogen
Ovary
Fig 12

FSH follicle

LH

Corpus luteum

-/ +
Progesterone

“The First Day of Menstruation is Day One of the Cycle”
Hypothalamus

Early to Mid Follicular Phase

+
Fig 13 Endometrium

GnRH

WHY?

Pituitary
FSH FOLLICLE Granulosa Cells Thecal Cells LH

-

Estrogen

Androgens

Late Follicular Phase/Ovulation
Hypothalamus

+ Fig 14 Inhibin

GnRH

Surge in LH Levels

Pituitary FSH FOLLICLE Granulosa Cells Thecal Cells
Androgens Endometrium

LH

16-24 hrs after

Ovulation

Collagenase

High Estrogen

Small Amount of Progesterone

Collagenase

Ovulation

Fig 15

EARLY TO MID LUTEAL PHASE
Hypothalamus

-

Pituitary FSH Corpus Luteum From Ovulated Follicle
(Thecal Cells)

LH

Uterus
Inhibin Fig 16

Secretes
Estrogen

Progesterone

LATE LUTEAL PHASE
Tonic Secretions Resume
Negative Feedback Stops

Hypothalamus

-

Pituitary FSH
(12 Days)

LH Corpus Luteum Disintegrates into 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

Fig 19

Peristaltic contraction of Uterus/Vagina Clitoral erection/ And Cervical mucous glands Contraction of Bulbospongiosus and ischiocavernosus Muscles

ORGASM

THANK YOU

GOOD LUCK

Master your semester with Scribd & The New York Times

Special offer for students: Only $4.99/month.

Master your semester with Scribd & The New York Times

Cancel anytime.