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ECF Fig 1
Membrane Spanning
( Integral) Protein
Hydrophobic
Tails
Fig 2
Transporters
“Channel Proteins”
Phospholipid
Fig 3
Membrane Protein
Membrane Proteins
Transporters
• Channel Proteins
Water Filled Channels
(Aquaporins)
Fig 4
Channel Proteins
ICF
Carrier Proteins
Never a direct
Connection between
ICF and ECF
Substrate
Fig 6
Body Fluid Compartments
ECF ICF
Blood Instfl
High Low
Concentration Concentration
Movement Across Membranes
“Osmosis”
H2O
High Low
Concentration Concentration
Semi Permeable
Membrane
Movement Across Membranes
“Carrier-Mediated Transport”
• Mediated Transport
Substance A
+Carrier Protein
Semi permeable
Membrane
– Facilitated Diffusion
• Passive (Moves down Concentration Gradient)
– Active Transport
• Active (Moves against Concentration Gradient)
– ATP ADP + E
Carrier-Mediated
Transport
• Carrier Proteins
1. Specificity
• GLUT Transporters
2. Competition
3. Saturation
Fig 8
Carrier Mediated Transport
“Uniport”
Energy
Carrier
Concentration
Gradient (active) Concentration
Gradient (Passive)
Fig 10 Carrier Mediated Transport
Carrier Mediated Transport
“Symport Cotransporters”
Energy
Co transport
Carrier
Concentration
Concentration
Gradient (Passive)
Gradient
Carrier Mediated Transport Fig 11
Carrier Mediated Transport
“Antiport Cotransporters”
Energy
Co transport
Carrier
Concentration
Gradient
Carrier Mediated Transport
Fig 12
Facilitated Diffusion
“Down The Diffusion Gradient”
GLUT
Fig 9
Active Transport
“Requires The Input of Energy From ATP”
ATP ADP
Active Transport
“Primary Active Transport”
Energy Source
Fig 13
Na+ High
Glu Low Na+ Low
Glu High
Na-Glucose Symporter
Fig 14
Transepithelial Transport
Glu Na+
What is this
What is this
Glu Na+
What is this
= High
Glu Na+ K+
Action
Potential
Axon Terminal
Action Potential
Depolarizes Axon Terminal
Synaptic
Voltage Gated Ca2+
Vesicles
Channels Open
Calcium Induced
Exocytosis
Voltage Gated
Ca2+ Neurotransmitter binds
Channels With receptor
Receptor
Response
Unit II
Electrical Signals and The Cell
Membrane
“ Lets Get It Right”
The Cell Membrane Allows
Separation of Electrical Charges
Cell Membrane
Fig 1
Resting membrane
Cell Membrane -1 Potential
+1
Fig 2
But Why ?
The Resting Membrane Potential is
Due Mostly to Potassium
Fig 4
Fig 5
Concentration Gradient
Electrical Gradient
+1
-1
Fig 7
The Resting Membrane Potential is Due
Mostly to Potassium
• The Nernst equation
– Eion = 61/z log [ion] out/[ion] in
• Z = Charge on the Ion
• [ion] are the ion concentrations inside/outside the cell
• Here 150 mM Na+out and 5 mM Na+in @37 C
• ENA=+60mV
• EK=-90mV
• But the Cell would have a resting membrane potential of – 70mV
( Goldman Equation)
Ion Movement Across the Cell
Membrane Creates Electrical Signals
• Resting Membrane
Potential (-70mV)
Concentration Grad
ECF
Elect- Grad
ICF
0 mV Fig 8
Fast Slow
ECF
K+ ICF
Fig 9
Voltage Gated Na+ Channels Open
Na+ is The Key Player Here
Entry of Cl- Ions would Hyperpolarize
Changes in Ion Permeability Change the
Membrane Potential
• Repolarization
+30mV
Na+
Close
ECF
K+ ICF
Fig 10
Changes in Ion Permeability Change the
Membrane Potential
• Repolarization
-70mV
Na+
K+
K+
Fig 11
Ion Movement Across the Cell
Membrane Creates Electrical Signals
• Resting Membrane
Potential (-70mV)
ICF
ECF
Na+ Channels
Open
Return to Normal Ion
Conc. 3Na+ -2K+ Pump
Resting
Fig 13
K+ Channels Close
Unit III A
Cell-to Cell Communication
Signal Pathways and Chemical
Messengers
Cell To Cell Communication
” How Does The Body Control 75 Trillion Cells?”
• Gap Junctions
• Local Communication
• Autocrines and Paracrines
• Long Distance Communication
• Neurocrine
• Neurotransmitter
• Neuromodulators
• Neurohormone
• Cytokines (Regulatory Peptides/ May be Local or Long Distance )
• Hormones
Gap Junctions
“Transfer Chemical and Electrical Signals Directly
Between Cells”
Protein Channels
(Connexon)
Membrane
Spanning Protein
Diffusion
Autocrines and Paracrines
Target
Fig 2
Chemical Signals Distributed by Diffusion
Hormones
“Long Distance Please”
Blood
Hormone
Fig 3
Neurotransmitter/Neuromodulator
“Long Distance Please”
Neurotransmitter/
Synapse
Neuromodulator
Fig 4
Neurohormone
“Long Distance Please”
Neurohormone Ligand
Blood
Fig 5
Signal Pathways
“A cell cannot respond to a chemical signal if it lacks the appropriate
receptors for that signal”
Target
Directs the cellular
Receptor response
2
Activation Effectors (Last intracellular signal molecule)
4
3
Synthesis of or modification
Intracellular signal of target protein
molecule
Response
Signal Pathways
Receptors
“Inside the cell or on the Cell Membrane”
mRNA
Fig 6
Signal Pathways
“There are Four Major Categories of Membrane Receptors”
• Types of Receptors
• Ion-Gated
• Receptor-Enzymes
• G-Protein Coupled
• Integrin receptor
Signal Pathways
Ion-Gated membrane Receptor
Ligand
Fig 7
Signal Pathways
Receptor-Enzyme Membrane Receptor
Ligand
Receptor Region
ECF
Activation of an
Enzyme
ICF
Fig 8
Enzyme Region
Ligand Binding to a receptor-enzyme activates an
Intracellular enzyme
Signal Pathways
Integrin Receptor
Integrin
ECF
ICF
Fig 9 Cyctoskeleton
Ligand
ICF
Fig 10
G Protein
4
3
Second Messenger Opens Ca Ion
Protein Kinases
Channel
5
Cellular Response
Increase Intracellular
Fig 11 Ca++
Signal Pathways
Ions
Signal Molecule
Ion Channel
-
Na+ , K+ , Cl
Creates Electrical Signal
ICF
3 Ca2+
ER Ca2+
Fig 16
Cellular Response 5
Enzyme Activity Exocytosis Movement
Calcium Is an Important Intracellular Signal
Signal Pathways
“Not ALL Ion Channels are Receptors”
ECF
1 2
3
Intracellular signal Molecules
Ions Create Electrical
Signals
ICF
Fig 13
Signal Pathways
“Tyrosine kinase, an example of a Receptor Enzyme”
Ligand
1
Receptor
ECF
2
Tyrosine-Kinase
ICF
3
ATP + protein ADP + Protein-P
Signal Molecule
First Messenger (Phospholipase C)
Adenylate cyclase
1
Receptor Inostisol PPP
IP3
3 ATP Ca++
Fig 15 2
G-Protein Second Messenger
cAMP
4
5
Protein Phosphorylation Protein Kinase A
Epinephrine
α and β Adrenergic Receptors β 1
Norepinephrine
α
Target Response
Target Response depends on the Target Receptor
Receptor Isoforms
Vessel Constricts
α -Receptor Intestinal Blood Vessel
Epinephrine
Vessel Dilates
β -Receptor
Skeletal Muscle Blood Vessel
Fig 17
Up and Down Regulation
• UP-and-Down-
Regulation of
Receptors Enables
Cells to Modulate
Cellular Response
Fig 18
Unit III B
G Proteins
G Proteins
Adenylate
Cyclase
Cell Signaling and Signal Pathways
G Proteins
Signal Transduction
Signal Molecule
Receptor
Cell Membrane
Phosopholipid
Bilayer
G Proteins Act as Signal
Transducers
Signal Molecule
1 (GPCR)
Effector molecule
(Enzyme)
Adenylate
Cyclase
ATP 4
GTP
Gα
3
cAMP Second Messenger
Gβ
2 Gγ 5
GDP Response
Effector molecule
(GPCR)
1 (Enzyme)
Guanylate
Cyclase GTP
3 4
cGMP Second Messenger
2
5
Response
G Proteins Act as Signal
Transducers
Signal Molecule
Effector molecule
1 (GPCR)
(Enzyme)
Phospholipase
C
3 4
Second Messenger
2 Ca2+
5
Response
G Proteins and The Activity of
Epinephrine/Norepinephrine
Hormone
E/NE
GPCR GPCR
I Gα A Gα
PO4 PO4
Opens Ca2+ Kinase Activation Phospholamban
Channels RP
α 1 PLC Via DA
G
Gα
PK
A Via IP3 C
Spinal
Signal Cord
Efferent
Afferent
Neurons
Neurons
Enteric
Signal Nervous
System Response
Autonomic Nervous System
”The Sympathetic and Parasympathetic Systems Maintain Homestasis”
SETPOINT
Fig 2
Control Pathways
Homeostasis May be Maintained by Local or
Long-Distance Pathways
Local
Autocrines
Paracrines
Reflex Control
Response Loop
Feedback Loop
Negative
Positive
Response Loop
1 2
3
4
Feedback loop
5
6
Fig 3
Feedback Loop
Negative Feedback Positive Feedback
Fig 4
Autonomic Nervous System
“The Hypothalamus and Brain Stem initiate Autonomic
responses”
Cerebral Cortex
Limbic System
Hypothalamus Pons
Medulla Oblongata
Parasympathetic
Sympathetic
Autonomic Reflexes
“The Hypothalamus ,Pons and Medulla initiate Autonomic responses”
BRAIN Endocrine
Hypothalamus
Pons
Autonomic Function
Medulla Heart Rate, BP Temp Regulation
Osmolarity, CO2
• Visceral Reflexes
– Short reflexes
• Bypass the CNS and involve sensory neurons and
Interneurons whose cell bodies are located
within Autonomic Ganglia.
– Long reflexes
• Are more-complex and are coordinated by
processing centers in the medulla oblongata.
Autonomic Spinal Reflexes
(Short and Long Reflexes)
Medulla
Stimulus
Long
Reflex
Short Reflex
Response
Fig 5
Autonomic Nervous System
”The Autonomic Division Consists of Two Efferent Neurons in Series”
Fig 6
Autonomic Nervous System
”Sympathetic and Parasympathetic Branches Exit The Spinal Cord at
Different Regions”
Sympathetic
Arise from the Thoracic and Lumbar regions of
the spinal cord
The pre ganglionic nerves are short and synapse
in paired ganglia adjacent to the spinal cord
Parasympathetic
Arise from the Cranial and Sacral regions of the
CNS.
They have long preganglionic nerves which
synapse at ganglia near or on the organ
innervated
Autonomic Nervous System
“The Sympathetic and Parasympathetic Systems use a Variety of
Neurotransmitters”
Neurotransmitter
Neurotransmitter
PreGN PostGN
Fig 7
Autonomic Nervous System
“The Sympathetic and Parasympathetic Systems use a Variety of
Neurotransmitters”
Cholinergic
Adrenergic Catecholamines
Fig 8
Parasympathetic Nervous System
“Acetylcholine onto Muscarinic Receptors”
Membrane Receptors
ACh
ACh
Target
CNS
ACh-ase Post
ganglionic
Neuron
Fig 9
Parasympathetic Nervous System
“Acetylcholine onto Muscarinic Receptors”
Cholinergic Cholinergic
Nicotinic Muscarinic
ACh
ACh
Target
CNS G-proteins-coupled
ACh-ase
Action
Potential
Axon
Terminal
Action Potential
Depolarizes Axon Terminal
Synaptic
Voltage Gated Ca2+
Vesicles
Channels Open
Calcium Induced
Voltage Exocytosis
Gated
Acetylcholine binds
Ca2+
With receptor
Channels
Receptor
Response
Parasympathetic Nervous System
“Acetylcholine onto Nicotinic / Muscarinic Receptors”
Acetylcholine
Acetyl CoA
Choline + Acetyl CoA
CoA
E Acetylcholine
Ch Acetylcholinesterase
Synaptic Breaks down
Vesicles Acetylcholine
Ch Choline is transported
Back into cell
Acetylcholinesterase Receptor
Sympathetic Nervous System
“Norepinephrine onto Adrenergic Receptors”
Most sympathetic post ganglionic neurons release the Transmitter
Norepinephrine
There are two classes of sympathetic receptors:
(1) Alpha receptors
alpha-1 α 1 NE
The stimulation of a1 receptors leads to an increase in
activity
alpha-2 α 2 NE
The stimulation of a2 receptors leads to a decrease or
inhibition activity
(2) Beta receptors
beta-1 β 1 NE E
The stimulation of β 1 receptors leads to an increase in
activity
beta-2 β 2 Non innervated E
The stimulation of β 2 receptors leads to an decrease in
activity
Sympathetic Nervous System
“Norepinephrine onto Adrenergic Receptors”
Membrane Receptor
Most Symp.
Pre ganglionic Neuron Adrenergic α 1 Target
Cholinergic Tissues
Nicotinic
α 2 GI Tract
ACh NE
CNS
β 1 Heart/
TARGET Kidney
ACh-ase Post ganglionic β Certain
Neuron Blood
2
Norepinephrine Vessels
Smooth
Fig 12 Epinephrine Muscle
(Adrenal Medulla)
Sympathetic Nervous System
“Norepinephrine onto Adrenergic Receptors”
Phospholipase C
ACh NE α 2 Decreases
CNS cAMP
TARGET
β Increases
1
Axon Varicosity
MAO
Tyrosine 1) Action Potential
Ribosome
2) VG Ca2+ Channel
3) Exocytosis
Action Potential 4) NE bind to
receptor
5) NE Diffusion
Exocytosis 6) Reuptake Channel
Ca2+ Reuptake Channel 7) NE Reabsorption
NE Diffusion 8) NE Metabolized by
NE MAO at Ribosome
Response
Adrenergic Receptor
“Most Internal Organs are Innervated by
Both Autonomic Branches”
A
F
I
D E
C
β 1
Fig 15
Autonomic Tone
“Allows for very fine tuning of organ function”
• Autonomic Tone
– Stimulation of the Autonomic Nervous
system under resting conditions.
• sympathetic or parasympathetic tone.
– In general there is Sympathetic tone
within the blood vessels while there is
Parasympathetic tone in the heart.
Eyeview of Brain and Senses
• Introduction to Nerves and Sensory
System
• Individual senses and physiology in detail
Mid
Brain
&
Cranial
Nerves
Mid Brain (Posterior View)
Nerve Tissue
• Brain is made of Neurons (Axon+cell body)
Peripheral
Nervous
System
• Cranial and
Spinal nerves
innervate with
target organs
in the body
Motor Cortex and Corticospinal
Tract Controls Motor Function
• Primary Motor Cortex(movements): Hand, leg, jaw
• Broca Area: Speech
• Somatosensory Feedback to Motor Cortex: Muscle
contraction
GH 686-687
• Disorders: Spinal cord Paralysis,
Poliomyelitis, Amyotrophic Lateral
Sclerosis
• Lumber Puncture and CSF drainage
• Capula and
ampulla of
semicircular
canals bath
with
endolymph.
• Capula
change
orientation
and sensed by
Vestibular
nerve
Unit V
Sensory Systems Function And
Physiology
Part IIA
The Ear: Hearing
An Introduction to Sound
• Sound Waves Frequency = waves/sec
1 Wavelength Hz
1000-3000 Hz
Amplitude
db
Pressure
Fig 1
TIME
Transduction of Sound Is a
Multistep Process
Fig 2
Anatomy of The Ear
External Inner
Middle Semicircular
Pinna
canals Oval Window
M I S
Vestibular apparatus
Cochlea
Bony
Canal Labyrinth
Tympanic
Membrane
Round To Pharynx
Fig 3 Window
Eustachian Tube
Sound Transmission Through The Ear
“The Middle Ear Transfers Sound from the Eardrum to the Cochlea”
Basilar Membrane
Cochlear Nerve
Incus Stapes
Oval 6
Malleus
Windo
Vestibular Duct
Canal w
(Perilymph)
3
Cochlear Duct
2 (Endolymph)
1 4
5
Tympanic Duct
Fig 4
The Cochlea
“The Cochlea of the Inner Ear Is Filled with Fluid”
Perilymph
Endolymph Helicotrema
Fig 5
The Cochlea
The Cochlea
Bony Labyrinth
Vestibular Duct
Cochlear Duct
Tectorial
Membran
e Cochlear
Nerve
Organ of
Corti
Basilar Tympanic Duct
Fig 6 Membrane
The Organ of Corti
Tectorial Membrane
Hair Cell
Cochlear Nerve
Basilar Membrane
Fig 7
Sound Transduction Through
The Cochlea
Perilymph
Cochlear Duct
Fig 8
Sound Transduction Through the Cochlea
“Depends on Movement of Hair Cell Stereocillium”
Fig 9
Hair Cells
“Sound Transduction”
AT REST
+ Tallest
Protein Bridge K Stereocilia
Stereocillium
Some Channels
Hair Cell Open
Sensory Neuron
Low Level Action
Potentials
(Tonic)
Fig 10
Hair Cells
“Sound Transduction”
K+
Excitation
Tallest
Stereocilia
Stereocillium
More Channels Open
K+ K+ entry Depolarizes Cell
INHIBITION K+
Channels Closed No
K+ Entry Cell
Hyperpolarizes
No Action Potentials
Fig 12
How Do We Hear ?
M I S
Outer Ear Hair Cells
Cochlea Medulla
Ipsilateral
Contralateral Auditory Cortex
Fig 13
Sensory Coding for Pitch
STIFF FLEXIBLE
Man low pitch female high pitch
Fig 14
Ciliary Muscle
Lens Cornea
Zonules
Fig I
Accommodation
“The Eye Adjusts The Shape of The Lens”
Ciliary Muscle
Lens
Zonules
Fig 2
The Lens Focuses Light on the
Retina
Parallel
Focal Point
20 ft + Light
< 20 ft
Fig 4
The Lens Focuses Light on the
Retina
The Rounder The Lens, the Greater the Refraction,
the Shorter the Focal Length
Fig 5
Lens Rounded for Close Vision
Accommodation
“The Eye Adjusts The Shape of The Lens”
Ciliary Muscle
(relaxed)
Lens Cornea
(flattened)
Zonulas
(tight)
Fig 6
Accommodation
“The Eye Adjusts The Shape of The Lens”
Ciliary Muscle
(contracted)
Lens
(rounded)
Zonulas
(slack)
Fig 7
Normal
(Emmetropia)
Normal
(Emmetropia)
Focal Point In Front of Retina
Fig 9
Visual Defects
Astigmatism
CORNEA
Fig 10
Aqueous humor Trabecular meshwork
Canal of Schlemm
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
1 Transducer
Sensory
Stimulus
Receptor
3 4
CNS Cortex
Fig 1 ( Integration )
( Conscious Perception )
Types of Receptors
“Receptors Are Transducers That Convert Stimuli into Electrical Signals”
Photoreceptors (Vision)
– Photons
Chemoreceptors
– CO2 O2, pH, various organic molecules (Taste and Smell)
Mechanoreceptors (Hearing and Equilibrium)
– Tactile
– Baroreceptors
The Special Senses
• Olfaction
• Vision
• Gustation
• Hearing
• Equilibrium
Sensory Transduction Converts Stimuli
into Graded Potentials
Threshold
Action Potential
CNS
Coding and Processing Distinguish
“Stimulus Modality, Location, Intensity and Location”
• Sensory Modality(nature)
– The Modality of a Signal is indicated by
which sensory neurons are activated and
where those Pathways Terminate in The
Brain. (Submodality means specific tastes-salt etc)
• Labeled Line Coding(receptors)
– The Association of a Receptor with a
Sensation
Coding and Processing Distinguish
“Stimulus Modality ,Location, Intensity and Location”
• Location of a Stimulus
• Receptors Project to a Specific Region of
the Cortex
– Adjacent Sensory Receptors are
Processed in Adjacent Columns of the
Cortex (Topographical Arrangement)
– Lateral Inhibition
– If it is processed in brain. It must be
coming from…right or left side
Coding and Processing Distinguish
“Stimulus Modality,Location,Intensity and Location”
• Lateral Inhibition
Primary Neuron Response
Is Proportional to
Intensity of Stimulus A B C
Pathway Closest to
- -
Stimulus Inhibits
Neighbors
Inhibition Enhances
Perception of
Stimulus In brain A B C
Coding and Processing Distinguish
“Stimulus Modality, Location, Intensity and Location”
• 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 Organ
Fig 2
Olfactory organs
Olfactory tract
Lamina propria
10Receptor Neuron
Olfactory
epithelium Mucus Layer
Basal Cell
Fig 4
OLFACTION
Odorant Receptors are G protein-cAMP linked Receptors
cyclic-nucleotide Ca
gated (CNG) Adenylate cyclase
channels Na
CNG
Cell Depolarizes
Olfactory epithelium
Olfactory bulbs
Olfactory tract
Limbic System
GUSTATION
“Taste Is a Combination of Five Basic Sensations”
• Sweet
• Sour
• Salty
• Bitter
• Umami (monosodium glutamate)
Gustation
• The superior surface of the tongue
bears epithelial projections called
lingual papillae
FRICTION
– filiform papillae
– fungiform papillae CONTAIN TASTE BUDS
– circumvallate papillae
Taste Buds
Why did I put this Here?
Bitter
Sour
Sweet
Salty
Fig 6
Taste Cells
“Taste Cells are Non-Neural Polarized Epithelial Cells”
contains receptors
called Gustatory
(sensory) cells Gustatory
cell
Support
cell
Basal cell
Sensory neuron
Fig 7
Taste ligand
Membrane channel or
receptor
Ca+
Neurotransmitter
Sensory neuron
2 2
2
Taste
Transduction
3
4
Fig 9 5
To Brain
Unit V
Sensory Systems
Function And Physiology
Part IIIB
The Physiology of Vision
ANATOMY OF THE EYE
Aqueous Humor Fibrous Tunic
Vascular Tunic
Iris Cornea
Zonulas
Neural
Pigmented Fovea
Pigmented Layer
Optic Nerve Blood Vessels
Neural Layer
Photoreceptors
O NS
OT
PH
Optic Disc
Fig 2
The Neural Tunic
“Organization of the Retina”
Pigmented Layer
Horizontal Cell
Amacrine
Photons
Cone
Rod
Ganglion Cell
Bipolar Cell
Fig 3
The Neural Tunic
“Organization of the Retina”
• Photoreceptors
• Rods
• Cones
• Macula Lutea
• fovea
• Bipolar cells
– Regulate communication between photoreceptors
and ganglion cells
• Ganglion Cells
– The Axons of these cells form the Optic Nerve
• Horizontal and Amacrine Cells
– Facilitate or inhibit synaptic transmission
• Contrast
VISUAL PHYSIOLOGY
“Phototransduction Occurs at The Retina”
• Photoreceptors
– Rods
– Presence or absence of photons
Black and White
Low Light Levels
Low Acuity
– Cones
– Wavelength of arriving photons
• Color
• High Light Levels
• High Acuity
Anatomy of Rods and Cones
“Photoreceptors Rods and Cones”
• Rods
– Outer segment
• discs
– Visual Pigments
• Opsin + Retinal
(Vitamin A)
– Inner segment
• cellular organelles
• neurotransmitters Rod
Fig 4
Anatomy of Rods and Cones
“Photoreceptors Rods and Cones”
• Cones Disks
– Outer segment
• discs Mitochondria
– Visual Pigments
• Opsin (r,g,b) +
Retinal
– Inner segment
Cone
• cellular organelles
• neurotransmitters Synaptic Terminal
Pigmented Layer
OUTER
SEGMENT
INNER
SEGMENT
Fig 6
SYNAPTIC TERMINAL P
Photoreceptors Rods and Cones
“Phototransduction Occurs at the Retina”
Rhodopsin
Molecule
Retinal Opsin
cGMP
Inactive Rhodopsin
(Opsin+Retinal)
Tonic Release of
Fig 8
Neurotransmitter(GPG)
Bipolar Neurons
Photoreception
• Dark Current Outer Segment
– In darkness
• Gated Na+ channels are Na
kept open
C-GMP
-40 mV Na
Inner
Segment
Neurotransmitters
Bipolar cells
(G Protein glutamate) Na+
K+
The movement of Na+ from the outer segment, to the inner segment,
and out of the cell is known as the dark current
Phototransduction
“Phototransduction Occurs at the Retina”
PHOTON
Fig 9
Phototransduction
“The Activation of Rhodopsin”
Activated
Photon
“A”Opsin Transducin
Opsin Phosphodiesterase
+
Cis-Retinal
Bleaching
Fig 10
Photoreception
“Light adapted State” (RODS)
Activated Retinal
Activates Transducin
1
The Rod in Light
2
3 cGMP
-70 Mv
4
Fig 11 This Cell is
Hyperpolarized
Neurotransmitter release
Decreases/Light
Photoreception
• Step 1: Opsin activation occurs
– When a photon of light strikes the rhodopsin molecule, the molecule
becomes active (cis to trans ) which activates the Opsin portion of the
molecule
ATP
After Image
Fig 12
Light and Dark Adaptation
• Dark-adapted state
– all visual pigments (opsins) fully receptive
• Light-adapted state
– visual pigment breakdown is balanced by the
rate of reformation
Stimulation in various combinations is
the basis for color vision
Color Vision
PHOTONS Opsin r
Retinal Opsin g
r
Brain
+
Opsin
Opsin b
Fig 13
Convergence in The Retina
Rods
Horizontal Cells
Bipolar Neurons
Fig 14
Amacrine Cells
Ganglion Cell
To Optic Nerve
Processing in The Retina
“Signal Processing Begins in the Retina”
OFF
Off Center Neurons
Visual Field
ON
On Center Neurons
Fig 15
Signal Processing Begins in the
Retina
Fig 16
Convergence
• Cones show very little convergence
– Cones provide more-precise information
about a visual image than do rods.
THE VISUAL PATHWAY
Left Right
• A partial crossover of
nerve fibers occurs at the
optic chiasm.
• Each hemisphere receives
visual information from
the medial half of the Optic Nerve
field of vision of the eye
on that side and from the
lateral half of the field Optic
of vision of the eye on Optic Tract chiasma
the opposite side.
Visual Cortex
Fig 17
Unit VI The Heart
Part IA
Action Potentials and Calcium Induced Muscle
Contraction
Cardiac muscle cells
• Two types of cardiac muscle cells are
involved in a normal heartbeat:
– (1) Contractile Cells, which produce the
powerful contractions that propel blood
– (2) Autorhythmic Cells ( Pacemakers)
which control and coordinate the activities
of the contractile cells.
CONTRACTILE CELLS
• Contractile cells form the bulk of the Atrial
and Ventricular walls.
Two Different Action
Potentials !!!
SA Node
(Autorhythmic Cells)
Autorhythmic Myocardium
Cells
Intercalated Disc
Gap Junctions Fig 1
Action Potentials in Myocardial
Cells Vary According to Cell
Type
• Myocardial Autorhytmic Cells(MAC)
• Cardiac Contractile Cells(CCC)
If Channels Close
Na+
K+
K+ Channels Close
If Channels Open
If Channels Open
“The Pacemaker Potential”
Fig 2
MODULATION OF ACTION POTENTIALS IN
CARDIAC AUTORHYTHMIC CELLS
“ Alter The Permeability to Different Ions”
β 1
Receptors If Ca Na
Ach Muscarinic K Ca
Catecholamines β 1
cAMP If Opentime
Fig 3
MODULATION OF CARDIAC CONTRACTION
Fig 4
CONTRACTILE CELLS
• In cardiac CONTRACTILE CELLS
– (1) An action potential propagation leads to
the appearance of Ca2+ among the myofibrils
– (2) The binding of Ca2+ to Troponin on the
thin Myosin filaments initiates the muscle
contraction
The Action Potential in Cardiac Muscle
Cells
• STEP 1: Rapid depolarization.. Voltage-regulated
Fast sodium channels open and the membrane becomes
permeable to Na+. The result is rapid depolarization of the
sarcolemma.
• STEP 2: The plateau. Voltage-regulated fast sodium
channels close. As the fast sodium channels are closing, voltage-
regulated slow calcium channels are opening. As a result, the
transmembrane potential remains near 0 mV for an extended
period. This portion of the action potential curve is called the
plateau..
• STEP 3: Repolarization. As the plateau continues, Slow
calcium channels begin closing and Slow potassium channels
begin opening. The result is a period of rapid repolarization that
restores the resting potential.
The Action Potential in Cardiac
Muscle Cells (NCK channel steps)
Fast Na+ Slow Ca2+
Channels close Channels open
#3 Slow Ca2+
#2 Channels close
#4
Slow K+
K+ChannelsClose Channels open
PNa
#1
Fast Na+
Channels open
#5
Resting
Potential
Fig 5
“Calcium-Induced Calcium Release”
Ca2+ NaKATPase
Ryanodine
Receptor Channel
Calcium Spark
(Sum)
EC Coupling
Fig 6
Cardiac Muscle Contraction Can
Be Graded
• NOT ALL-or-NONE
• Calcium Levels Determine The Force of
The Contraction
Ca2+ Summation of Ca2+ Spark
SO
MODULATION OF CARDIAC CONTRACTION
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
Fig 8
The Cardiac Refractory Period
“The Refractory Period Last as Long as the Muscle Twitch”
2 3
Fig 9
The Cardiac Refractory Period
Fig 10
DIGITALIS
The Endocrine System
Part I
“An Introduction to The Endocrine
System”
What Makes a Chemical a Hormone
a) Hormones Are Secreted by a Cell or Group
of Cells
b) Hormones Are Secreted into the Blood
c) Hormones Are Transported to a Distant
Target
d) Hormones Exert Their Effect at Very Low
Concentrations
e) Hormones Act by Binding to Receptors
f) Hormone Action Must be Terminated after
action is over(Half-life)
What Makes a Chemical a
Hormone ?
Hormone
Blood
Target
Fig 1
Hormones are Chemical Messengers
Response
What Makes a Chemical a
Hormone ?
Neurohormone Ligand
Blood
Fig 2
Fig 2
Fig 3
Closed Loop Open Loop
How Could We Classify
Hormones ?
• ACCORDING TO
• The ANATOMICAL SOURCE of The Hormone
• (Very traditional, but very boring)
• ACCORDING TO
• The CHEMICAL COMPOSITION of The
Hormone
ACCORDING TO
The SOLUBILITY of The Hormone IN WATER
OR FAT
ACCORDING TO ANATOMICAL SOURCE OF
THE HORMONE
Fig 4
ACCORDING TO CHEMICAL
COMPOSITION
• PEPTIDE HORMONES
• Composed of Amino Acids
• STEROID HORMONES
• Derived from Cholesterol
• PEPTIDE AMINE HORMONES
• Derived from the amino acid:
– Tyrosine or Trytophan
PEPTIDE HORMONES
“Most Hormones are Peptides or Proteins”
• Polypeptide hormones
– Most of the hormones from the anterior pituitary
gland.
– The hormones from the posterior pituitary
gland(oxytocin and ADH).
– All the hormones from the hypothalamus (except
dopamine)
– All the hormones from the stomach, duodenum,
pancreas and liver
• Glycoproteins
– Some of the stimulatory hormones from the anterior
pituitary gland. (TSH, FSH, LH)
– Parathyroid hormone
AMINE HORMONES
Derived from the amino acids Tryptophan or Tyrosine
• Tryptophan
– Melatonin
• Tyrosine
• Thyroid hormones (T3 and T4)
• Catecholamines
– Epinephrine
– Norepinephrine
– Dopamine
STEROID HORMONES
“are all derived from cholesterol”
• Sex hormones
– Gonads
• Estradiol
• Progesterone
• Androgen
• All the hormones of the Adrenal cortex
• Aldosterone
• Cortisol
ACCORDING TO SOLUBILITY
IN WATER OR FATS
Water soluble
All peptide hormones.
All amine hormones (except the Thyroid
hormones T3 T4).
Fat soluble
All steroid hormones.
Both thyroid hormones (T3 and T4).
WATER SOLUBLE HORMONES
• THE HORMONES INVOLVED WITH
THE NEGATIVE FEEDBACK in
REGULATION OF THE INTERNAL
ENVIRONMENT
– Water soluble
– Absolutely essential for life
– Often work in counter regulatory
• (Rein Control) pairs:
Rein Control
GLUCAGON
BLOOD GLUCOSE LEVELS
Fig 5
INSULIN
Rein Control
• To rapidly reverse a particular action, it is
useful to have a Second hormone that has the
Opposite effect of the first, whose blood
concentration can be rapidly increased..
• It is the RATIO of the blood concentrations
of the two hormones, rather than the
absolute concentrations of either, that
determines the direction in which the
controlled variable response will change.
CHARACTERISTICS OF THE
WATER SOLUBLE HORMONES
• True MESSENGERS (NEWS)
• Blood Hormone concentrations are highly variable (short Half life)
• Are removed from the blood very quickly.
• Changes in concentration convey the message.
High concentrations in the blood have the opposite" meaning"
to low blood H concentrations. (different massage to cell)
• Effects are completely reversible.(by Glucagon/Ins)
• These Bind to cell membrane receptor proteins (water soluble)
• Effects seen very quickly, usually within seconds or minutes.
WATER SOLUBLE HORMONES FALL INTO
THREE FUNCTIONAL CATEGORIES
• 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
Change
Sensory
Integration Endocrine
Efferent Hormone
Signal
Response
A Complex
Internal
Or External
Change
Neuroendocrine Receptor
Neuron
Reflex
Afferent Path
Sensory
Nervous
Integration
Efferent Neuron/
Signal Neurohormone
Sensory
Integration Endocrine
Efferent
Signal#2 Hormone
Effector
Response
MECHANISMS OF ACTION
Water Soluble Hormones
amplification
Response
MECHANISMS OF ACTION
Water Soluble Hormones
H H Receptor Enzyme
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
Fig 3
MECHANISMS OF ACTION
Water Soluble Hormones(E,
activation of β 1 receptors
Phosphodiesterase (PDE)
C-AMP AMP
Adenylate cyclase
Ca++
Na+ K+
MECHANISMS OF ACTION
Water Soluble Hormones
activation of a1 receptors
phospholipase C (PLC).
PIP2
activation of a2 receptors
inhibitory G-proteins
1 2
stimulates PDE
activity.
inhibits Adenylate cyclase activity
reduction in cAMP
levels
ATP
Fig 6
MECHANISMS OF ACTION
Water Soluble Hormones Synthesis, Storage and Release
Golgi
Post-Translational
Prohormone Modification
ER Hormone
Sig
Sig Seq
Preprohormone
MECHANISMS OF ACTION
Post-Translational Modification
MECHANISMS OF ACTION
Lipid Soluble Hormones
(4) Gene
How? Why?
Activation
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
Fig 1
INSULIN
The Insulin-to-Glucagon Ratio Regulates Metabolism
The Pancreas
Pancreatic Islets
“islets of “Langerhans”
Fig 3
Pancreatic Islet
Fig 4
α Cell = Glucagon
β Cell = Insulin
INSULIN SECRETION
Glucose
GLUT4 transporter
Metabolism
ATP
KATP
No
Secretion Open
GLUT4 transporter
Metabolism
Ca2+
ATP
Exocytosis KATP
Ca2+ Closed
Ca+
Open
Cell K+
Depolarizes Fig 6
INCREASE OF BLOOD INSULIN
LEVEL
GENERAL
CIRCULATION
HEART
BETA CELLS
PORTAL
SYSTEM
Fig 7
Insulin Activation of Tyrosine
Kinase
INSULIN INSULIN RECEPTOR
SUBSTRATE
ph o r yla ti o n
Phos
ECF
PI3-KINASE Phosophoinositide 3K
ICF
Phosphorylation (PDK)
(enzymes/membrane)
Increased Synthesis of (all target cells)
glycogen (in liver and muscles)
Triglycerides in adipocytes
VLDL (in liver)
Increased Glucose
Fig 8 Cholesterol uptake and Utilization
INSULIN BINDING TO ITS
RECEPTORS
Brings GluT4 glucose transporters in muscle and
fat tissue from endosomes to the cell membrane.
Promotes glucose uptake and utilization in cells
TK
ECF Facilitated
Exocytosis Diffusion
ICF
Transduction
Glut4
Glut4
Transporters
“Down Regulation"
• When cell's food stores (especially
glycogen and triglyceride) are
saturated.
• A cell or tissue is not used (e.g.
immobilization of a muscle).
• Serious infections, cancer
“Down Regulation"
• THE INSULIN RECEPTORS ARE
REMOVED FROM THE SURFACE OF
THE CELL (AND STORED IN
INTRACELLULAR ENDOSOMES).
“Down Regulation"
• This is called "down regulation" of insulin
receptors.
Fig 9
“Down Regulation"
ENDOCYTOSIS
Clathrin Pit
Fig 10
Glucagon
The Insulin-to-Glucagon Ratio Regulates Metabolism
Pancreatic Islet
α Cell = Glucagon
Fig 11 β Cell = Insulin
GLUCAGON SECRETION
Fig 12
INCREASE OF BLOOD GLUCAGON
LEVEL
Alpha Cells
PORTAL
CIRULATION
Fig 13
Glucagon Activation of Adenyl
Cyclase
GLUCAGON
GLUCAGON RECEPTOR
SUBSTRATE
adenylate cyclase
SECOND MESSENGER
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:
Fig 16
Non Insulin-Dependent Diabetes
(NIDD)
• In type 2 diabetes (non-insulin-
dependent diabetes NIDD)
– Failure to express a sufficient number of
glucose transporters in the plasma
membrane (and T-system) of the skeletal
muscles.
Type 2 diabetes NIDD
• Normally when insulin binds to its
receptor on the cell surface, it initiates
a chain of events that leads to the
insertion in the plasma membrane of
increased numbers of a transmembrane
glucose transporter(GLUT-4)
• This transporter forms a channel that
permits the facilitated diffusion of
glucose into the cell.
Type 2 Diabetes
Genetic defect
Fig 17
Type 2 Diabetes
• Mutant genes for one or another of the
transcription factors needed for transcription of
the insulin gene
• Mutations in one or both copies of the gene
encoding the insulin receptor
• Obesity
• Hormonal Imbalances
• Pregnancy
The Endocrine System (PTH)
Part III B
Endocrine Control of Calcium and
Phosphate Homeostasis
Intracellular calcium:
0.001mM A large majority of calcium within cells is (maintained)
sequestered in mitochondria and Sarcoplasmic reticulum (other
is ER).
resorption
Bone serves as a vast reservoir of calcium. Stimulating net
of bone mineral releases calcium and phosphate into
blood, and suppressing this effect allows calcium to be deposited
in bone.
homeostasis.
The kidney is critically important in calcium
Under normal blood calcium concentrations, almost
all of the calcium that enters glomerular filtrate is reabsorbed
from the tubular system back into blood.
Hormonal Control Systems
“ Three Hormones Control Calcium
Balance”
• Maintaining normal blood calcium and
phosphorus concentrations is managed
by the action of three hormones that
control fluxes of calcium in and out of
Bone and the Extracellular fluid
– Parathyroid hormone (PTH)
– Vitamin D (1,25Cholecalciferol/Calcitriol)
– Calcitonin
ENDOCRINE CONTROL OF THE
PLASMA Ca2+ LEVEL
• PTH-CALCITONIN
• Vitamin D
Parathyroid
PTH
Thyroid Calcitonin
Fig 1
Fat Soluble Hormones
Parathyroid Hormone
• Parathyroid hormone is the most
important endocrine regulator of
calcium and phosphorus concentration
in Extracellular fluid.
Physiologic Effects of Parathyroid
Hormone
Mobilization of calcium from bone:
Stimulates osteoclasts for resorption of bone mineral, liberating
calcium into blood.
H+ ATPase
Osteoblasts Bone Osteclasts
Enhancing absorption of calcium from the
small intestine:
Facilitating calcium absorption from the small intestine by
stimulating production of the active form of vitamin D in the
kidney.
Suppression of calcium loss in urine:
stimulating tubular reabsorption of calcium and phosphate ions in
urine (stimulates loss of phosphate ions )
Low Plasma (Ca2+)
Parathyroid
Hormone
(PTH) Negative Feed Back
Fig 3
Plasma (Ca2+ )
Control of Parathyroid Hormone
Secretion
• Parathyroid hormone is released in response to low
Extracellular concentrations of free calcium
Fig 4
Vitamin D (Cholecalciferol)
• Vitamin D acts to increase blood
concentrations of calcium.
– It is generated through the activity of
parathyroid hormone within the kidney.
– The most important effect of vitamin D is
to facilitate absorption of calcium from the
small intestine.
– In concert with parathyroid hormone,
vitamin D also enhances fluxes of calcium
out of bone.
Vitamin D (Cholecalciferol)
Vitamin D, as either D3
or D2, does not have
significant biological
activity. Rather, it
must be metabolized
within the body to the
hormonally-active form. PTH
Fig 5
To Small Intestine
Endocrine Control of Calcium Balance
Endogenous
Precursors Diet
Sunlight Vit D
Liver(stored)
Kidney
+ PTH Plasma
Ca2+
-
Bone/
Intestine
+
Fig 6
Plasma
Ca2+
Calcium Balance in The Body
Small Intestine
Bone ECF
Kidney
Filtration
Calcitriol PTH Ca2+
Calcitonin Calcitonin
Active
Transport
Cell
Ca2+
Fig7
0.001mM Ca2+
Urine
Calcitonin
Decreases blood calcium levels
• Calcitonin
– Kidney: Calcitonin inhibits tubular
reabsorption of Calcium and phosphorus
– Bone: Calcitonin suppresses resorption of
bone by inhibiting the activity of
osteoclasts
– Although calcitonin has significant calcium-
lowing effects in some species, it appears
to have a minimal influence on blood calcium
levels in humans.
Control of Calcitonin Secretion
• The most prominent
factor controlling
calcitonin secretion
is the Extracellular
concentration of
ionized calcium.
Fig 8
PTH-CALCITONIN
Homeostatic Balance
SETPOINT
Fig 9
The Endocrine System
Part IV
The Hypothalamus and The
Anterior/Posterior Pituitary
The Hypothalamus/Pituitary
Posterior Pituitary
(Neurohypophysis)
• Endocrine Reflexes
– Simple ( Short loop)
– Complex (Short and Long Loop)
• Regulatory Mechanisms of the Hypothalamus
(1) Regulatory Hormones
(2) Endocrine Control
(3) Direct Neural Control
Endocrine Reflexes
Negative Feedback Loops in The Hypothalamic Anterior Pituitary Pathway
stimulation
inhibition Hypothalamus
IC1
Short Loop
Trophic Hormone
Negative
Hormone 1
Feedback
IC3
Endocrine organ Long Loop
IC2 Negative
Trophic Hormone2 Feedback
Short Loop
Negative Feedback
Target
Fig 2
Regulatory Mechanisms of the
Hypothalamus
Regulatory Hormones Endocrine Control Direct Neural Control
Indirect Control Direct
Capillaries
Portal Vessels
Endocrine cells
Axon Terminals
Posterior Pituitary
Fig 3
Anterior Pituitary
Hypothalamus
“The Hypothalamic – Hypophyseal Portal System”
Neurons synthesizing
Trophic
Hormones
Capillaries
Portal Vessels
Endocrine cells
Fig 4
Anterior Pituitary
Regulatory Hormones of the
Hypothalamus
Thyrotropin -releasing hormone (TRH)
Gonadotropin -releasing hormone (GnRH)
Growth hormone -releasing hormone (GHRH/GHIH Somatostatin )
Corticotropin -releasing hormone (CRH)
Prolactin-releasing hormone (PRH/PIH Dopamine)
PIH
GHRH
Anterior Pituitary
Adrenal Gonads
Thyroid cortex Liver
Estrogens
T3/T4 Cortisol IGF’s Androgens Progesterone
Non Endocrine
Fig 5
Targets
inhibition Hypothalamus
IC1
Short Loop
Negative
CRH Feedback
IC3
Adrenal Cortex
ACTH IC2
Cortisol
Long Loop
Negative
Target Tissue Feedback
Cortisol Secretion
Is Controlled by ACTH
Endocrine Control (direct)
Posterior Pituitary by the Hypothalamus
Hormone is made in
Cell Body of Neuron
Indirect Control
Infundibulum
Anterior Pituitary
Posterior Pituitary
ADH (Vasopressin)
OXYTOCIN
Fig 7
ADH/Vasopressin
Afferent Afferent
Kidney
Neural Control of the Adrenal Medulla
by the Hypothalamus
Catecholamines
NE
Epinephrine
Hypothalamus
Fig 8
The Endocrine System
Part V
BALLISTIC CONTROL SYSTEMS
BALLISTIC CONTROL
SYSTEMS
Ballistic systems
Fig 1
Open Loop
BALLISTIC CONTROL
SYSTEMS
• Epinephrine and Norepinephrine
– Ballistic control of blood sugar and blood
pressure.
• Oxytocin :
– Ballistic control of milk ejection and uterine
contractions.
• Prolactin :
– Ballistic control of fertility and (Negative feed
back control of lactation).
Epinephrine and Norepinephrine
The Catecholamines
THE BALLISTIC CONTROL of
BLOOD SUGAR
THE BALLISTIC CONTROL of
BLOOD PRESSURE
The Alarm Phase
“Immediate Short-Term Response to Stress”
• Immediate response
to stress occurs.
• sympathetic
nervous system
Cerebral Cortex
Limbic
Hypothalamus
MONSTER
Fig 2
The Alarm Phase
LIMBIC
SNAKE
AT FIRST
HYPOTHALAMUS
SYMPATHETIC NERVOUS
SYSTEM
ADRENAL MEDULLA
Fig 3
Norepinephrine/Epinephrine onto
α 1 β 1 Adrenergic Receptors
Effects Of Epinephrine and
Norepinephrine
α 1 β 1 β 2
NE
E(80%)
Fig 4
Effects Of Epinephrine and
Norepinephrine on α 1 β 1 β 2
Accelerates the utilization of cellular
energy and mobilization of energy
reserves
Adipose tissue ATP
α 1β 1
Liver Glycogen Glucose
In the Heart stimulation of β 1 increase in
Heart Rate and Force of Contraction BP
Vasodilatation of Blood vessels to Skeletal Muscle
β 2
Vasoconstriction of Blood vessels to Skin and
α 1
Gut
PROLACTIN
• THE BALLISTIC CONTROL OF
FERTILITY
• MILK PRODUCTION
PROLACTIN
Hypothalamus
PIH
Fig 5
PROLACTIN
“Ballistic and Non Ballistic Control”
Ballistic Control
Closed Loop
infertility
Fig 6
OXYTOCIN
• THE BALLISTIC CONTROL OF MILK
EJECTION
• THE BALLISTIC CONTROL OF
CONTRACTIONS OF THE UTERUS
OXYTOCIN
Release of Neurotransmitters
Posterior Pituitary
Fig 7
OXYTOCIN
Suckling at Stretching of
Breast Cervix
Sexual Stimulation
Oxytocin
Fig 8
OXYTOCIN
Contractions
Of The Uterus Milk Ejection
Fig 9
The Endocrine System
Part VI
FAT SOLUBLE
HORMONES
CHARACTERISTICS OF FAT SOLUBLE
HORMONES
Blood concentrations are highly predictable. The
"message" is kept constant or unchanging via negative
feedback
Work very slowly. (several days).
High blood concentrations DO NOT have the opposite
effect of low blood concentrations
Removed slowly from the blood
Bind to intracellular receptors (after penetrating the
cell membrane) and exert their effect in the cell
nucleus.
They stop production of … or initiate production of …
Transported in the plasma bound to carrier proteins
Often give the cell a new function or appearance.
Secretion is ALWAYS stimulated by a “TROPHIC"
RELAY MESSENGER
THYROID HORMONES
• FAT SOLUBLE:
Are transported on carrier proteins in the plasma.
Intracellular receptors, which act on the cell nucleus.
Influence which genes are transcribed, and which are not.
Effects develop, therefore, very slowly.
Many effects are irreversible.
Prolonged absence of thyroid hormones is not fatal but,
instead, gives rise to peculiar appearance rather than death in
the short term.
Secretion is stimulated by a relay messenger (or "trophic
stimulating hormone ") from the anterior pituitary gland
THYROID HORMONES
T3
THYROXIN
T4
Fig 1
THYROID HORMONES
hypothalamus
T3 and T4
FOLLICLE CELLS
IN THYROID
Fig 2
THYROID HORMONES
Follicle Cells
Follicle Cavity
Fig 3
THYROID HORMONES
Triiodothyronine T3
Follicle Cell
#3 THYROGLOBULIN
#1 #2
I 2
-T4
IODINE
+ T3 Thyroxime T4
2 TYROSINE
TSH
G cAMP
Endocytosis
#4
Capillary
T3-T4
T3&T4 Exocytosis
T3&T4
FOLLICLE CAVITY
LYSOSOMAL
DIGESTION
Bind with TBG or #5 Fig 4
Albumin #6
THYROID HORMONES
Fig 5
Thyroid Hormone Pathway
Tonic
Release
TRH
Long Loop
T3-T4
ATPase
Fig 6
Regulation of
Cellular Metabolism
MECHANISMS OF ACTION
LIPID SOLUABLE H
Carrier Protein
(1) Diffusion through Cell Membrane
• Formed elements
– Blood cells and cell fragments that are
suspended in plasma
– (1) Red blood cells
– (2)White blood cells
– (3) Platelets.
Formed elements
• Red blood cells or Erythrocytes
• Platelets or Thrombocytes
• White blood cells or Leukocytes
• Three kinds of Granulocytes
• neutrophils
• eosinophils
• basophils
• Two kinds of Agranulocytes
• lymphocytes
• monocytes
Plasma
• Composition of blood plasma
– Water 92%
– Plasma Proteins 7%
• Albumins
• Globulins
• Fibrinogen
– Other Solutes 1%
• Amino acids ,glucose, lipids, Ions, O2 and CO2
Albumins
• Albumins
– The most abundant plasma proteins
– Major contributors to the osmotic
pressure of plasma.
– Transport of fatty acids, hormones,
steroids
Globulins
• Globulins
– Antibodies (immunoglobulins)
– Transport globulins
• Thyroid-binding globulin and Transthyretin, which
transports thyroid hormones; Transcortin, which
transports ACTH; and transcalciferin, which
transports calcitriol.
• Metalloproteins, which transport metal ions.
• Apolipoproteins, which carry triglycerides and other
lipids
• Steroid-binding proteins, which transport steroid
hormones in blood.
Fibrinogen
Functions in blood clotting
Hematopoiesis
“The Production of Blood Cells”
Pluripotent hematopoietic
Stem cell
Increasing
Specialization
HEMOCYTOBLAST
MYELOID STEM LYMPHOID STEM
CELLS CELLS
MYELOID PROGENITORS
LYMPHOCYTES
CELLS
Erythropoietin RBC
Thrombopoeitin MEGAKARYOCYTE
PLASMA
Cytokines PLATELETS
(Glycoprotein Hormone)
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+ HbHb-CO2
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).
Fig 3
RBC Life Span
• In about 120 days
Rupture of the cell membrane
Damage is detected by phagocytic cells
(macrophages)
• RBC are replaced
Each day 1 percent of the circulating
RBCs, 3 million new RBCs enter the
bloodstream each second
The Blood Count
Hemoglobin Conservation and Recycling
Intestine urobilins +sterobilins
(1) IRON
2 LIVER
Kidney AT
4 control RBC Bile
formn Transferin Ferritin
RBC
PRODUCTION Bilirubin 7
3 Metabolism
Fe
6 KIDNEY
RBC bilirubin
BONE MARROW
erytropoiesis
PLASMA biliverdin urobilins
EPO 8
Fe
Urine
OLD RBC
Fig 4 DESTROYED
5 Heme stripped
Erythropoietin Of Fe by
Macrophage
SPLEEN
Unit VII The Circulatory
System Blood Part III
Hemostasis
PLATELETS
• Platelet Functions
– The transport of chemicals important to
the clotting process..
– The formation of a temporary patch in
the walls of damaged blood vessels..
– Active contraction after clot formation
has occurred.
PLATELETS
• PlateletProduction (thrombocytopoiesis)
– megakaryocytes
Cellular Fragments
Fig 1
Hemostasis
• The process of Hemostasis, the
cessation of bleeding
– Consists of three phases:
(1) vascular phase
(2) platelet phase
(3) coagulation phase.
Hemostasis
“An Overview”
TISSUE FACTOR
COLLAGEN VASOCONSTRICTION
EXPOSED
EXPOSED 1
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
To COLLAGEN
Common
EXPOSED
Pathway
+
PLATELETS AGREGATE INTO COX
LOOSE PLUG PLATELET ACTIVATING
FACTOR (PAF)
Cytokines
Fig 3 Aspirin
Vasoconstriction
THE PLATELET PHASE
Formation of platelet plug
PAF
+NO
THE COAGULATION PHASE
“Coverts the Platelet Plug into a More Stable Clot”
C
+ THROBIN FORMATION
TF X
Loose Plug CONVERSION OF FIBRINOGEN
TO FIBRIN
Reinforced Plug
(clot)
COMMON PATHWAY
Fig 4
The Extrinsic Pathway
• The Extrinsic Pathway begins with the
release of Tissue Factor III, also
known as Tissue Factor (TF), by
damaged endothelial cells
The Intrinsic Pathway
• The Intrinsic Pathway begins with the
exposure of collagen fibers at the
injury site and the subsequent
activation of proenzymes (usually Factor
XII)
The Common Pathway
The Common Pathway
Enzymes from the Extrinsic and Intrinsic
pathway activate Factor X
Prothrombinase
Starts Here
Prothrombin Thrombin
Ca+2
Fibrinogen Fibrin
Intrinsic Pathway Extrinsic Pathway
Collagen or other activators Damage Exposes Tissue Factor
III Van Willebrands
Tissue Factor
III & VII (a)
Positive Feedback
Hemophilia A
Common Pathway
Thrombin Prothrombin
Fibrinogen Fibrin
Common Pathway
Fig 6
Calcium Ions, Vitamin K, and
Blood Clotting
• Calcium ions and vitamin K (Cofactor)
affect almost every aspect of the
clotting process. All three pathways
(intrinsic, extrinsic, and common)
require Ca2+.
CLOT RETRACTION
• CLOT RETRACTION
– The platelets then contract, and the entire
clot begins to undergo clot retraction
• (1) pulls the torn edges of the vessel closer
together,
• (2) reduces the size of the damaged area,
making it easier for fibroblasts, smooth
muscle cells, and endothelial cells to complete
repairs.
FIBRINOLYSIS
The clot gradually dissolves
Plasminogen
Fig 7
Anticoagulants Prevent
Coagulation
• Blood clotting is restricted by factors that
inactivate or remove clotting factors
– Anticoagulants IX,X,XI,XII
(intrinsic)
Heparin Antithrombin-III
(activates)
Inactivates Thrombin
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
Regulation
Afterload
Capillary
Exchange
Interstitial
Fluid
Fig 1
PRESSURE
• Circulatory Pressure (Pressure Gradient)
X 2 X 16
R α 1/r4
Fig 2
ARTERIAL BLOOD PRESSURE
• Circulatory Pressure
– Systolic pressure
• The peak blood pressure measured during L ventricular systole
– Diastolic pressure
• The minimum blood pressure at the end of L ventricular diastole
– Pulse pressure
• The difference between the systolic and diastolic pressures
Ventricular Contraction
Fig 4
ARTERIAL BLOOD PRESSURE
1 3
Semilunar Valves
shut
Fig 5
Systemic Pressures
Systolic Pressure
Pulse Pressure
Diastolic
Pressure
Mean Pressure
MAP = dp +pp/3
Fig 6
Mean Arterial Pressure
“ is a Function of Cardiac Output and
Resistance in The Arterioles”
MAP = DP +pp/3
Mean Arterial Pressure
Cardiac Output Variable Resistance
MAP CO x P.RESISTANCE
Fig 7
MEAN ARTERIAL BLOOD PRESSURE
“The Driving Pressure for Blood Flow”
Is determined by
Fig 8
ARTERIAL BLOOD PRESSURE
Ventricular ejectionPeak
(120 Systolic
mmHg) Pressure
B C
dicrotic notch
MAP isovolumetric
S valves close D
Diastolic Pressure
E
A
EDV;bicuspid V close
Fig 9
ARTERIAL BLOOD PRESSURE
“Is Estimated by Sphygmomanometry”
Sphygmomanometer
Brachial Artery
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
Diameter of Diameter of
Fluid In Fluid Out
Arterioles Veins
Kidneys
Homeostasis
Homeostasis Disturbed
Autoregulation
(Autoregulation Ineffective)
(Local)
Neural
(Short Term) Fast
Kidney Slow
Fig 1 (Endocrine/Long Term
The Regulation of Blood Pressure, Blood
Volume and Blood Flow
Local Control/Autoregulation
Myogenic Paracrines
Vasodilate Vasodilate
Fig 2
The Regulation of Blood Pressure, Blood
Volume and Blood Flow
Release of endothelins
Ca+ Vasoconstriction
BP stretches
vessel
Fig 3
Paracrines Alter Vascular Smooth
Muscle Contraction
Paracrines
Vasodilation Vasodilation
Fig 4
Paracrines Alter Vascular Smooth
Muscle Contraction
Active Hyperemia Tissue Metabolism
(dilation)
O2 CO2
Wash Away
Fig 5
Paracrines Alter Vascular Smooth
Muscle Contraction
Tissue Blood Flow Due To
Occlusion
CO2 H+
Fig 6
Cardiovascular Regulation
“Neural”
Tonic
Autonomic Reflex Control
Sympathetic Parasympathetic
NE on α Epinephrine on β 2 ACh/NO
1
Receptors Cholinergic Receptors
Receptors
Vasodilation Vasodilation
Vasoconstriction
Atrial Baroreceptors
Tonically active
Stretch
sensitive
receptors
Aortic sinuses
Fig 8
Blood Pressure
Baroreceptor Reflex
“Is The Primary Homeostatic
Control for Blood Pressure”
-
β 1
α 1
Fig 9
MAP ON STANDING
Baroreceptor Reflex
(Orthostatic Hypotension)
-
NE
?
? ? ?
Fig 10
The Regulation of Blood Pressure and
Blood Volume
“ Long Term Endocrine Control byThe Kidney”
Erythropoietin Renin
(Short Term)
ADH
Heart Rate Increased Blood
Aldosterone Volume/Pressure
Fig 11
Thirst
The Regulation of
Blood Pressure and Blood Volume
Blood Volume
Cardiovascular Renal
(Short Term)
Blood Pressure (Long Term)
Slow
Fast
Fig 12
The Regulation of Blood Pressure and
Blood Volume
“Endocrine Control The Heart”
Reduced Thirst
Block Renin
Fig 13 Peripheral Vasodilation
Reduced BP
Circulatory shock
Homeostatic Failure 35% Blood Loss
BV
3 1
CO DAMAGE TO HEART
VESSEL CLOTTING
BP
2 Baroreceptor
DECREASE IN reflex
BLOOD TO TISSUES
ISCHEMIC RESPONSE
O2 TISSUE STARVATION
4
BRAIN
INCREASED CAPILLARY
PERMEABILITY FALLING ARTERIAL
PRESSURE
Fig 14 DEATH
Unit VI
The Heart
Part IB
The Heart as a Pump
Electrical Conduction in The Heart
“Electrical Conduction in The Heart Coordinates Contraction”
Fig 1
Electrical Conduction in The Heart
“THE CONDUCTING SYSTEM”
Purkinje Fibers
Fig 2
VENTRICULAR CONTRACTION
Electrical Conduction in The Heart
“THE CONDUCTING SYSTEM”
SA Node Depolarizes
SA Node
AV Node
Fig 3
Electrical Conduction in The Heart
“THE CONDUCTING SYSTEM”
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”
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”
APEX
Papillary
muscles
Fig 6
Electrical Conduction in The Heart
“THE CONDUCTING SYSTEM”
PURKINJE
Depolarization wave
FIBERS
Spreads upward from Apex
Fig 7
Electrical Conduction in The Heart
“Pacemakers Set The Heart Rate”
SA Node 70bpm
Fig 8
Unit VII The Circulatory System
The Heart
Part IC
THE
ELECTROCARDIOGRAM
“The Electrocardiogram Reflects the
Electrical Activity of the Heart”
THE ELECTROCARDIOGRAM
- +
-
-
Einthovens Triangle
Waves
PR Segment Segment
Interval Fig 2
THE ELECTROCARDIOGRAM
“The Basics”
T
P
Fig 3
QRS COMPLEX
P WAVE
The P wave represents the wave of depolarization that spreads from
the SA node throughout the atria
PR
Fig 5
QRS COMPLEX
WAVE OF VENTRICULAR DEPOLARIZATION
R
R
Ventricles Start
To Contract
Fig 6
QRS COMPLEX
WAVE OF VENTRICULAR DEPOLARIZATION
R
S
Q
S
Fig 7
ST Segment
The ST segment following the QRS is the time at which the entire
ventricle is depolarized (Ventricles Contract)
ST segment
S
Ventricles Contract
Fig 8
T WAVE
The T wave represents ventricular repolarization
Fig 10
http://www.britannica.com/nobel/cap/oelecar002a4.html
THE ELECTROCARDIOGRAM
“ What are We Looking For? ”
Fig 12
Third-decree AV nodal block
Conduction through the AV node is completely blocked so that no
impulses are able to be transmitted from the atria to the ventricles.
QRS complexes will still occur but they will originate from within the
AV node
Fig 13
ATRIAL FIBRILLATION
Uncoordinated atrial depolarization
http://www.skillstat.com/ECG_Sim_demo.html
Fig 14 http://www.ecglibrary.com/ecghome.html?
http://sprojects.mmi.mcgill.ca/cardiophysio/arrythmiasintro.htm
VENTRICULAR FIBRILLATION
Uncoordinated ventricular depolarization
Fig 15
Pressure-Volume Changes During One Cardiac Cycle
LEFT VENTRICULAR
PRESSURE AORTIC VALVE Stroke Volume
CLOSES
ESV
D
A--------B
PASSIVE FILLING
AND ATRIAL CONTRACTION
AORTIC VALVE
B--------C
ISOVOLUMIC CONTRACTION
OPENS
C
C ------- D
VENTRICULAR EJECTION
D ------- A
ISOVOLUMIC RELAXATION
Identify
Mitral valve opens
Mitral Valve closes
EDV
Aortic Valve opens
Aortic Valve closes
ESV
Fig 7
Cardio Dynamics
• Cardiodynamics refers to the
movements and forces generated during
cardiac contractions
End-diastolic volume (EDV) The amount of blood in each
ventricle at the end of ventricular diastole
End-systolic volume (ESV) The amount of blood
remaining in each ventricle at the end of ventricular systole
Stroke volume (SV) The amount of blood pumped out of
each ventricle during a single beat, which can be expressed as
EDV - ESV = SV
Stroke volume/Cardiac Output
Cardiac Output Is a Measure of Cardiac Performance
CO = SV X HR
STROKE VOLUME HEART RATE
Fig 8
FACTORS AFFECTING THE
STROKE VOLUME
• EDV
(1) Filling time (Duration of Ventricular Diastole)
(2) Venous return (CO, BV, PphlCir, Skeletal & Muscular Activity)
• ESV
(1) Preload
The degree of stretching experienced during ventricular
diastole is called the preload.
The preload is directly proportional to the EDV: The
greater the EDV, the larger the preload
The greater the EDV, the larger the stroke volume
Fig 9
(3) Afterload
The amount of tension the contracting ventricle must
produce to force open the semilunar valve and eject blood.
(As afterload increases the stroke volume decreases.)
MODULATION OF CARDIAC CONTRACTION
Ca++ Ca++
β 1
Cardiac Muscle Cardiac Muscle
Cell Metabolism Cell Metabolism
Fig 11
Factors Affecting
Bainbridge Reflex Cardiac Output
Fig 12
Unit VIII
Part I
Respiratory Physiology
The Respiratory System
• The respiratory system has five basic
functions
– To Provide an Extensive Area for Gas
exchange between air and circulating
blood
– Homeostatic regulation of pH/CO2
– Protecting respiratory surfaces (cilia)
– Producing sounds involved in speaking
– Providing olfactory sensations
Respiratory Physiology
• External respiration
I. Exchange of oxygen and carbon dioxide between the
lungs and the air
II. Exchange of oxygen and carbon dioxide between the
lungs and the Blood
III. Transport by The Blood
IV. Exchange of oxygen and carbon dioxide between the
Blood and the Cells O2
O2
lungs cell
CO2 CO2
External Respiration
Respiratory Physiology
Four integrated steps involved in External
respiration
(1) Pulmonary ventilation,
The physical movement of air into and out of the lungs.
(2) Gas diffusion,
Diffusion across the respiratory membrane (alveolar air spaces
and alveolar capillaries).
(3) The transport of oxygen and carbon dioxide
Between alveolar capillaries and capillary beds in other tissues.
(4) The Exchange of gases between blood and the
cells
*Lung Compliance/Elastance
• The ability of the lung to stretch is
called compliance
– Fibrotic Lung Disease
– Surfactant insufficiency
• The ability of the lung to return to its
resting volume is called elastance
– Emphysema
*Surfactant Decreases the
Work of Breathing
• Surfactants are molecules
that disrupt cohesive forces
between water molecules
– Type II alveolar cells
– NRDS Newborn
respiratory distress
syndrome(surfactant
deficiency)
Surfactant
*Respiratory Physiology
“Gas Exchange Requires Pressure Gradients”
Alveoli
Fig 1
XGas Composition in the Alveoli
At Rest
Equal to
Blood
Only 10%
During Exercise
Normal Fig 2
At Rest
Local Control Matches Ventilation
and Perfusion
Arteriole Bronchiole
Low O2
Blood
Pulmonary Capillaries
Fig 3
Local Control Matches Ventilation
and Perfusion
Restricted Ventilation
Fig 4
Local Control Matches Ventilation
and Perfusion
Constriction of Arteriole
Due to Low O2
Fig 5
Gas Transport in The Blood
“Hemoglobin Transports Most Oxygen to the Tissues”
Hb+O2 HbO2
Hemoglobin Oxyhemoglobin
2% in Plasma
98% Bound to Hemoglobin as
Oxyhemoglobin
Temperature, pH and
Metabolites Affect Oxygen-
Hemoglobin Binding
*O2 LOADING
Factors Effecting The Solubility of a Gas in A Liquid
Fig 6
Fig 7
Gas Transport in The Blood
“Effects of Temperature”
Fig 8
Gas Transport in The Blood
“The Effects of PCO2”
Fig 9
Gas Transport in The Blood
“2,3-DPG alters Hemoglobin”
2,3 Diphosphoglycerate
Hypoxia
Fig 10
Anemia
High altitude
Oxygen Transport
TISSUES LUNGS
O2
CO2
Hb+ CO2
Fig 12
Gas Transport in The Blood
“Hemoglobin Transports Most Oxygen to the Tissues”
Total Arterial O2 Content
2% 98 %
Fig 13
CO2 Transport
• Free 7% CO2 Remains in Plasma
• 93% of the free CO2 generated in the tissues
enters the red blood cells
• Bound CO2 Transport
– 23% Hb-CO2+ Carbaminohemoglobin
– 70% is converted to the bicarbonate ion and
travels back to the lungs in Plasma
The Transport of Carbon Dioxide
• Carbon Dioxide is Transported Three
Ways
– CO2 and Bicarbonate (70%)
– Hemoglobin and H+ ( 7 %)
– Hemoglobin and CO2 (23%)
The Transport of Carbon Dioxide
CO2 and Bicarbonate
CARBONIC BICARBONATE
ANHYDRASE
(LUNGS)
AT CELL
AT LUNGS
BUFFERS Cl-
Hb HB-H+ Plasma
pH 7.4
To Lungs
CO2 + Hb Hb-CO2
CARBAMINOHEMOGLOBIN
AT CELL
AT LUNGS
Fig 16
The Transport of Carbon Dioxide
“CO2 REMOVAL AT THE LUNGS”
Fig 17
Unit IX The Kidneys
Renal Physiology I
Basic Principles Of Urine
Formation
Functions of The Kidneys
The
Nephron
CORTEX
MEDULLA
Juxtamedullary
Nephrons
Fig 1
The Nephron Is the Functional Unit
of the Kidney
Fig 1
Vascular Elements
Fig 2
FILTRATION B L
H2O and HCO3 (pH)
REABSORPTION L B
SECRETION B L
EXCRETION L
The Excretion of a Substance depends on the
Amount that was Filtered, Reabsorbed, and
Secreted
F R S E
F – R + S = E
Fig 3
FILTRATION
• Filtration occurs in the renal corpuscle as fluids
move across the wall of the Glomerulus and into the
capsular space
Fig 4
FILTRATION
“The Renal Corpuscle Consists of The Glomerulus and
Bowman's Capsule”
Fig 5
FILTRATION
• Substances Leaving the Plasma Must
Pass Through Three Filtration Barriers
1 Fenestrated
Capillaries
- Glycoprotein
CsHP
(Blood colloid osmotic pressure)
BCOP
Fig 7 GHP
Fig 8
Glomerular Filtration Rate
ml plasma cleared of solute/time
4mg/100ml
Creatinine
100ml/ 0ml Creatinine
CsHP
(Blood colloid osmotic pressure)
BCOP
Fig 5 Autoregulation
Tubuloglomerular
Myogenic
feedback
Controlling the GFR
(Myogenic)
Fig 2
Controlling the GFR
“The Key is Where the Resistance Change
Takes Place”
Fig 3
GFR
Controlling the GFR
“The Key is Where the Resistance Change
Takes Place”
Fig 4
Controlling the GFR
“GFR Remains Constant When MAP Remains Between
80 and 180 mmHg”
GFR IS CONSTANT
WHILE
BLOOD PRESSURE
Fig 6
“The GFR is Subject to Autoregulation”
Autoregulation
Afferent Blood Vessel
Tubuloglomerular
Myogenic
feedback
BP Tubular Pressure
Distal Convoluted
Tubule
Macula Densa
Juxtaglomerular Cells
Afferent Arteriole
Fig 8
Juxtaglomerular apparatus (JGA). GFR
TUBULE FLOW
FLOW PAST
MACULA DENSA
Paracrines
Fig 9
Vasocontriction of
Juxtaglomerular Cells
GFR
Hormonal Regulation of the GFR
• The GFR is regulated by the hormones
of the “Renin – Angiotensin system”
and “Atrial Natriuretic Peptide”
(ANP).
Hormonal Regulation of the GFR
Second Way
• Atrial Natriuretic Peptide is released in response to the stretching of
the Atrial walls of the heart by increased blood volume or blood pressure
BV ANP BP
Inhibits Inhibits
GFR
Vasopressin Aldosterone
Angiotensinogen Angiotensin I
Lungs
Fig 10 Angiotensin II
Arterioles &
Precapillary ADH Aldosterone Vasoconstriction of
Sphincters Afferent arterioles
Adrenal glands
RENIN
Aldosterone
Angiotensin I
(lungs)
Angiotensin II CNS
Vasoconstriction
HYPOTHALMUS
Fig 11
Arterioles & Precapillary Sphincters PITUITARY
(ADH)
Hormonal Regulation of the GFR
• The final results are an increase in
systemic Blood volume and Blood
pressure and the restoration of
normal GFR by hormones
HOMEOSTASIS IS RESTORED
Unit IX The Kidneys
Renal Physiology III
Reabsorption and Secretion
Renal Review
REABSORPTION AND SECRETION
Increasing Transport
Rate
RENAL THRESHOLD
Tm
Saturation
Renal Threshold
Plasma Concentration at Which
Fig 1 Saturation occurs
The Tm and Renal Threshold
Renal Threshold
Normal Range
Fig 2
The Proximal Convoluted Tubule
ProximalCT
Reabsorption of organic nutrients Glu
Active reabsorption of ions (Na+ K+)
Reabsorption of water
• Secretion
PCT Antiport
ECF
Fig 3
NaCl
Osmosis
Na+
To Renal Medulla
Water Balance
Urine Concentration Is determined in the Loop of Henle
and the Collecting Ducts
100mOsM
Isosmotic
300mOsM
Active
Reabsorption
CL
K Hormonal
Collecting
Na Regulation
H2O Duct
Variable H2O
Reabsorption
Loop
1200mOsM
Na
Medulla
Peritubular fluid
The Loop of Henle and
Countercurrent Exchange
• Here half of the water and two-thirds
of the sodium and chloride ions
remaining in the tubular fluid are
reabsorbed
“The principle of countercurrent exchange “
Countercurrent Exchange
Hyposmotic
Vasa Recta
Descending Ascending
Limb Limb
Na
Hyperosmotic
The Functions of The Vasa
Recta
• To Return Solutes
and Water
Reabsorbed Without
Disrupting The
Concentration
Gradient
Na+
H2O
Fig 11
The Distal Convoluted Tubule
• Selective Reabsorption and Secretion
make the Final Adjustments to the
Tubular Fluid.
– Water Balance
– Sodium Balance/ Potassium Balance
– Potassium Balance
– Acid Base Balance
Water Balance/DCT
• Vassopressin and Aquaporins
The Distal Convoluted Tubule /
The Collecting System
ADH/Vasopressin
ATRIAL NATRIURETIC
PEPTIDE
H 2O The Reabsorption of Water in the
ADH Collecting System
9L/Day
- FEEDBACK DCT
H 2O Water
17L/Day Channels
COLLECTING
TUBULE Osmolarity /Blood Volume/Low BP are the Key Fig 10
ADH/Vasopressin
ADH/Vasopressin
Sodium and Potassium Balance
• Aldosterone action on “principal cells in
the DCT controls Sodium Balance
Reabsorption of Na +
at the DCT
K+
Aldosterone
Fig 7
Reabsorption of Na+ at the DCT
Reabsorption of Ca +
at the DCT
Parathyroid Hormone
And Calcitriol
Ca 2+
Fig 8
Acid Base Balance
• Acidosis pH is Too Low
• Alkalosis pH is Too High
• Buffers
• Respiration
• Renal Regulation of H+ and HCO3-
Secretion and Ph Homeostasis at
the DCT
Antibiotics Homeostasis
(Ph)
H+ HCO3-
Peritubular fluid
Fig 9
Acid Base Balance
Acidosis Alkalosis
• Step Two
– In The PCT the Active removal of Ions
Producing a Continuous Osmotic Flow of
Water Out of The Tubular Fluid
– Obligatory Water Reabsorption
Renal Summary
“Loop of Henle”
• Step 3
– Active Transport of K+ in while Na+ and
Cl- out of The Tubular Fluid Increasing
The Reabsorption of Water
Renal Summary
“DCT/Collecting Ducts”
• Step Four
– The Final Adjustments in Volume and
Osmotic Concentration
• Facultative water Reabsorption
Renal Summary
“The Vasa Recta”
• Step Five
– Absorption of Solutes and Water Which
Maintains the Concentration Gradient of
the Renal Medulla
THE MICTURITION
REFLEX AND URINATION
MICTURITION REFLEX
Bladder Stretch receptors
Afferent fibers
Excites parasympathetic
interneurons
motor neurons
efferent fibers
thalamus
Smooth Muscle Fig 12
Bladder
Internal urethral sphincter Cerebral cortex
Relax (I have to Pee)
External urethral sphincter
The Bladder at Rest
Bladder
Smooth Muscle
Higher CNS Input
Relaxed
Filling State
Internal Sphincter
Passively Contracted Skeletal Muscle
External Sphincter
Stays contracted
Fig 13
MICTURITION REFLEX
1 I have to Pee
Stretch Receptors Fire CNS
Degree of Fullness
Sensory Neuron
2
Parasympathetic Neurons
Smooth Muscle
Fire
Contracts
2
Motor Neuron Stops Firing
3 Tonic Discharge
Internal Inhibited
Sphincter 3
Passively Pulled Open Fig 14
External Sphincter Relaxes
Unit VIII
Part I
Respiratory Physiology
The Respiratory System
• The respiratory system has five basic
functions
– To Provide an Extensive Area for Gas
exchange between air and circulating
blood
– Homeostatic regulation of pH/CO2
– Protecting respiratory surfaces (cilia)
– Producing sounds involved in speaking
– Providing olfactory sensations
Respiratory Physiology
• External respiration
I. Exchange of oxygen and carbon dioxide between the
lungs and the air
II. Exchange of oxygen and carbon dioxide between the
lungs and the Blood
III. Transport by The Blood
IV. Exchange of oxygen and carbon dioxide between the
Blood and the Cells O2
O2
lungs cell
CO2 CO2
External Respiration
Respiratory Physiology
Four integrated steps involved in External
respiration
(1) Pulmonary ventilation,
The physical movement of air into and out of the lungs.
(2) Gas diffusion,
Diffusion across the respiratory membrane (alveolar air spaces
and alveolar capillaries).
(3) The transport of oxygen and carbon dioxide
Between alveolar capillaries and capillary beds in other tissues.
(4) The Exchange of gases between blood and the
cells
*Lung Compliance/Elastance
• The ability of the lung to stretch is
called compliance
– Fibrotic Lung Disease
– Surfactant insufficiency
• The ability of the lung to return to its
resting volume is called elastance
– Emphysema
*Surfactant Decreases the
Work of Breathing
• Surfactants are molecules
that disrupt cohesive forces
between water molecules
– Type II alveolar cells
– NRDS Newborn
respiratory distress
syndrome(surfactant
deficiency)
Surfactant
*Respiratory Physiology
“Gas Exchange Requires Pressure Gradients”
Alveoli
Fig 1
XGas Composition in the Alveoli
At Rest
Equal to
Blood
Only 10%
During Exercise
Normal Fig 2
At Rest
Local Control Matches Ventilation
and Perfusion
Arteriole Bronchiole
Low O2
Blood
Pulmonary Capillaries
Fig 3
Local Control Matches Ventilation
and Perfusion
Restricted Ventilation
Fig 4
Local Control Matches Ventilation
and Perfusion
Constriction of Arteriole
Due to Low O2
Fig 5
Gas Transport in The Blood
“Hemoglobin Transports Most Oxygen to the Tissues”
Hb+O2 HbO2
Hemoglobin Oxyhemoglobin
2% in Plasma
98% Bound to Hemoglobin as
Oxyhemoglobin
Temperature, pH and
Metabolites Affect Oxygen-
Hemoglobin Binding
*O2 LOADING
Factors Effecting The Solubility of a Gas in A Liquid
Fig 6
Fig 7
Gas Transport in The Blood
“Effects of Temperature”
Fig 8
Gas Transport in The Blood
“The Effects of PCO2”
Fig 9
Gas Transport in The Blood
“2,3-DPG alters Hemoglobin”
2,3 Diphosphoglycerate
Hypoxia
Fig 10
Anemia
High altitude
Oxygen Transport
TISSUES LUNGS
O2
CO2
Hb+ CO2
Fig 12
Gas Transport in The Blood
“Hemoglobin Transports Most Oxygen to the Tissues”
Total Arterial O2 Content
2% 98 %
Fig 13
CO2 Transport
• Free 7% CO2 Remains in Plasma
• 93% of the free CO2 generated in the tissues
enters the red blood cells
• Bound CO2 Transport
– 23% Hb-CO2+ Carbaminohemoglobin
– 70% is converted to the bicarbonate ion and
travels back to the lungs in Plasma
The Transport of Carbon Dioxide
• Carbon Dioxide is Transported Three
Ways
– CO2 and Bicarbonate (70%)
– Hemoglobin and H+ ( 7 %)
– Hemoglobin and CO2 (23%)
The Transport of Carbon Dioxide
CO2 and Bicarbonate
CARBONIC BICARBONATE
ANHYDRASE
(LUNGS)
AT CELL
AT LUNGS
BUFFERS Cl-
Hb HB-H+ Plasma
pH 7.4
To Lungs
CO2 + Hb Hb-CO2
CARBAMINOHEMOGLOBIN
AT CELL
AT LUNGS
Fig 16
The Transport of Carbon Dioxide
“CO2 REMOVAL AT THE LUNGS”
Fig 17
Not in Exam
Unit VIII Respiration
Part II
“The Regulation of Ventilation”
Respiratory Physiology
• Passive Respiration (Tidal Volume)
• Active Respiration (Vital Capacity)
– Active (forced) Inhalation (IRV)
– Active (forced) exhalation (ERV)
• IRV +ERV = Vital Capacity
Respiratory Physiology:CPG
“The Regulation of Ventilation by CPG”
• The Problem
– Skeletal muscles unlike Autorhythmic
cardiac muscles, are not able to contract
spontaneously
• The Solution
– A group of neurons that form a network
in the medulla oblongata that has
intrinsic rhythmic activity called the
“Central pattern generator”
Respiratory Physiology
Respiratory Control
Medulla Oblongata
Dorsal Ventral
Pons Respiratory Respiratory
Group Group
Fig 1
Dorsal Respiratory Group
(DRG)
2 sec 3sec
Fig 2
Atmospheric Pressure
DRG
“Rhythmic Breathing”
Ramping Inspiration Shuts
Off
Rapid Positive
Feedback
RECIPTRICAL INNERVATION
Fig 4
INTINISIC RYTHMIC ACTIVITY
(Autorythmic cells)
Other
mitigating ACTIVE
factors
Passive
Fig 5
E neuron
Sternocleidomastoid
MECHANICS
Apneustic Center
Pneumotaxic Center
Fig 7
Sternocleidomastoid
Respiratory Reflexes
Factors affecting the respiratory Rate
• Peripheral chemoreceptors
– Carotid and Aortic Bodies
Respond only to the PCO2, PO2 and pH of the Plasma
- pH of CNS
CO2 + H2O H+ + HCO3 means
The Carotid and Aortic Bodies
• The Carotid and Aortic Bodies are
sensitive to The PO2,PCo2 and Ph
contained in the Plasma of Arterial
Blood.
Translation of PO2 Levels
To Action Potentials
(PCO2, PO2 and Ph)
At 60 eV,
High O2 opens K channel
<60mmHg
Fig 8
Central Chemoreceptors
• Central chemoreceptors monitor
cerebrospinal fluid (CSF) and respond to
changes in the PCO2
• 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
is 60% H3O+
CCR—CPG-PRG glomus
Fig 10 cells
CPG-DRG
\
Hypocapnia
VOLUNTARY CONTROL OF
RESPIRATION
• The cerebral cortex can have a direct
or indirect effect on your respiratory
centers
• Conscious thought processes tied to strong
emotions
• Emotional states (Limbic)
• Conscious control over our respiratory
activities
– Speech
– Holding your breath
Carotid and Aortic Bodies
PCO2, PO2 and Ph of the Plasma
APNC
PONS
PNTC DRG
PChR
Fig 11
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)
Basement Membrane
Lumen
Spermiogenisis
Sertoli Cells
(Sustentacular cells)
Fig 4
XS SEMINIFEROUS TUBULES
Hormonal Control of
Spermatogenesis
• Spermatogenesis Requires
Gonadotrophins and Testosterone
HYPOTHALAMUS
GnRH
ANTERIOR PITUITARY
LH FSH
(3-4 Pulses/1.5hrs)
Interstitial Cells
(Leydig) Inhibin
Fig 5
2nd Messenger
Seminiferous Tubules
-
Testosterone Sertoli Cells
1.CNS
(Libido) Paracrines
2.Bone and
Binds To Spermatogonium
Muscle Growth
2ndMessenger
guanosine monophosphate (cGMP)
Nitric oxide
Vasocoagulation
Fig 6
VIAGRA
“ What About Us Old Guys ? ”
VIAGRA inhibits
phosphodiesterase
type 5 (PDE5) BRAIN Sexual arousal
Nitric oxide
Erection
BRAIN
Ejaculation/Orgasm
Sympathetic
Orgasm
Emission. Muscles Tighten
SYMPATHETIC
Muscles tighten
Fig 7
What Makes a Male a Male
Anyway?
SRY FACTOR
Testis Determining
Factor Bipotential Gonadal Tissue
Vagina uterus,
MIF fallopian tubes,
testosterone causes each wolffian
Testosterone duct to develop into epididymis,
Testis (DHT) vas deferens, and seminal vesicles
Leydig
Fig 8
The Reproductive System
Female
The Ovary Produces Eggs
and Hormones
Fig 9
The Menstrual Cycles
“The Menstrual Cycle Lasts About One Month”
Fig 10
PROCREATION
The Ovarian Cycle
• Follicular Phase
• Period of Follicular Growth 10 Days to 3 Weeks
• Ovulation
• Release of The Oocyte (Ova)
• Luteal Phase
• Transformation of Follicular Remains into The
Corpus Luteum
Uterine Cycle
• Menses (Corresponds to Day One Follicular Phase)
Theca
Granulosa
Ovulation
Luteal Phase
Fig 11
- /+
LH
follicle
Estrogen
Corpus
-/ +
luteum
Ovary
Fig 12 Progesterone
Early to Mid Follicular Phase
“The First Day of Menstruation is Day One of the Cycle”
Hypothalamus
GnRH WHY?
- FSH
Pituitary
LH
FOLLICLE
Fig 13
Cells
-
Estrogen Androgens
Endometrium
Late Follicular Phase/Ovulation
Hypothalamus
GnRH
+
Surge in LH Levels
Pituitary
16-24 hrs after
FSH LH
-
FOLLICLE
Ovulation
Collagenase
Granulosa Thecal Cells
Cells
Inhibin Androgens
Fig 14 Small Amount of
Progesterone
High Estrogen Endometrium
Collagenase
Ovulation
Fig 15
EARLY TO MID LUTEAL PHASE
Hypothalamus
Pituitary
- FSH LH
Corpus Luteum
From Ovulated Follicle
(Thecal Cells)
Uterus
Secretes
Fig 16
Estrogen Progesterone Inhibin
LATE LUTEAL PHASE
Tonic Secretions Resume
Negative Feedback Stops
Hypothalamus
Pituitary
- FSH LH
Corpus Luteum
Disintegrates into
(12 Days)
Corpus albicans
Fig 17
Estrogen Progesterone
The Menstrual Cycle
“The Menstrual Cycle Lasts About One Month”
Fig 18
How A Woman Achieves Orgasm?
Unlike the male of the species ,orgasm in the female is the result of a vast
range of physical, emotional ,and mental stimulation, and at its peak is
affected by the synchronicity of all these elements.
Touch/visual/olfactory
Sexual Arousal
Parasympathetic Sympathetic
ORGASM
Unit X
Reproduction
Male and Female
Hormonal Control Pathways And
The Production of Gametes
• Control Pathways for Sex Steroids Are
Similar in Males and Females
• Feedback Pathways Include Both Long
and Short Loop Feedback
• The Hypothalamus Releases
Gonadotropin in Small Pulses
Hormonal Control Pathways
CNS
HYPOTHALAMUS
ANTERIOR
PITUITARY
Fig 1
The Reproductive System
Part I
Male
The Male Reproductive System
Pecker
Fig 2
The Male Reproductive System
• Male Gonads
• Paired testes are suspended in The Scrotum
– The Word Testes Come from Latin and Means
“Witness”
• The Testes Produce Sperm and Testosterone
THE TESTES
Spermatogenesis
Interstitial Cells
(Leydig)
Basement Membrane
Lumen
Spermiogenisis
Sertoli Cells
(Sustentacular cells)
Fig 4
XS SEMINIFEROUS TUBULES
Hormonal Control of
Spermatogenesis
• Spermatogenesis Requires
Gonadotrophins and Testosterone
HYPOTHALAMUS
GnRH
ANTERIOR PITUITARY
LH FSH
(3-4 Pulses/1.5hrs)
Interstitial Cells
(Leydig) Inhibin
Fig 5
2nd Messenger
Seminiferous Tubules
-
Testosterone Sertoli Cells
1.CNS
(Libido) Paracrines
2.Bone and
Binds To Spermatogonium
Muscle Growth
2ndMessenger
guanosine monophosphate (cGMP)
Nitric oxide
Vasocoagulation
Fig 6
VIAGRA
“ What About Us Old Guys ? ”
VIAGRA inhibits
phosphodiesterase
type 5 (PDE5) BRAIN Sexual arousal
Nitric oxide
Erection
BRAIN
Ejaculation/Orgasm
Sympathetic
Orgasm
Emission. Muscles Tighten
SYMPATHETIC
Muscles tighten
Fig 7
What Makes a Male a Male
Anyway?
SRY FACTOR
Testis Determining
Factor Bipotential Gonadal Tissue
Vagina uterus,
MIF fallopian tubes,
testosterone causes each wolffian
Testosterone duct to develop into epididymis,
Testis (DHT) vas deferens, and seminal vesicles
Leydig
Fig 8
The Reproductive System
Female
The Ovary Produces Eggs
and Hormones
Fig 9
The Menstrual Cycles
“The Menstrual Cycle Lasts About One Month”
Fig 10
PROCREATION
The Ovarian Cycle
• Follicular Phase
• Period of Follicular Growth 10 Days to 3 Weeks
• Ovulation
• Release of The Oocyte (Ova)
• Luteal Phase
• Transformation of Follicular Remains into The
Corpus Luteum
Uterine Cycle
• Menses (Corresponds to Day One Follicular Phase)
Theca
Granulosa
Ovulation
Luteal Phase
Fig 11
- /+
LH
follicle
Estrogen
Corpus
-/ +
luteum
Ovary
Fig 12 Progesterone
Early to Mid Follicular Phase
“The First Day of Menstruation is Day One of the Cycle”
Hypothalamus
GnRH WHY?
- FSH
Pituitary
LH
FOLLICLE
Fig 13
Cells
-
Estrogen Androgens
Endometrium
Late Follicular Phase/Ovulation
Hypothalamus
GnRH
+
Surge in LH Levels
Pituitary
16-24 hrs after
FSH LH
-
FOLLICLE
Ovulation
Collagenase
Granulosa Thecal Cells
Cells
Inhibin Androgens
Fig 14 Small Amount of
Progesterone
High Estrogen Endometrium
Collagenase
Ovulation
Fig 15
EARLY TO MID LUTEAL PHASE
Hypothalamus
Pituitary
- FSH LH
Corpus Luteum
From Ovulated Follicle
(Thecal Cells)
Uterus
Secretes
Fig 16
Estrogen Progesterone Inhibin
LATE LUTEAL PHASE
Tonic Secretions Resume
Negative Feedback Stops
Hypothalamus
Pituitary
- FSH LH
Corpus Luteum
Disintegrates into
(12 Days)
Corpus albicans
Fig 17
Estrogen Progesterone
The Menstrual Cycle
“The Menstrual Cycle Lasts About One Month”
Fig 18
How A Woman Achieves Orgasm?
Unlike the male of the species ,orgasm in the female is the result of a vast
range of physical, emotional ,and mental stimulation, and at its peak is
affected by the synchronicity of all these elements.
Touch/visual/olfactory
Sexual Arousal
Parasympathetic Sympathetic
ORGASM
THANK YOU
GOOD LUCK