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Lecture 1 Spinal Cord Reflexes
Motor Functions are split into 2 ways
o Descending systems systems from above brain stem called
Upper Motor neuron systems
Basal Ganglia, cerebellum, motor cortex and brainstem centers
o The Lower motor neuron systems the motor neurons in the
ventral horn of the spinal cord
Form synapses at the neuromuscular junction and release AcH, thereby causing muscle contraction
These are the Piano Keys in order to get the Tune e.g. movement.. you must play the Piano keys activate
these motor neurons
Also called the Final common pathway
A Skeleton muscle cannot be inhibited- only the level of contraction
can change based on the concentration of acetylcholine
o To relax a muscle, you must inhibit the motor neuron.
Many different things can cause motor neuron excitation. All of these
things go to the spinal cord, which will then play the keys on the
piano
o Nociceptor Sensory Receptors in skin
o Skeletal muscle sensory receptors
o Receptors in tendons
Spinal cord is arranged by levels
o Cerivcal spinal cord =
hands/arms and chest, etc.
Spinal Cord has 2 colors
o Gray matter these are
neurons in the center
bowtie of the spinal cord
Dorsal Horn sensory input
Intermediate Regions Interneurons
Fingers on the keys of the piano
Ventral Horn The Motor Neurons reside here o White Matter These are the axons traveling up and down the
spinal cord. White due to some myelination
Antero - Lateral pain input
Ventral lateral motor function/ standing
Dorsal - touch/sensory input
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Dorso-lateral descending motor control
2 Major enlargements of the bowtie
o Cervical spinal cord
o Lumbar Spinal cord
o This is because this is where the most motor and sensory
information is needed hands and legs
Spinal cord is suspended in CSF Cerebral spinal cord
2 roots to the spinal cord
o Ventral Root
o Dorsal root
Contains the dorsal root ganglion cell body for sensory o These Roots combine to make up the peripheral nerve which
contains both motor and sensory axons
Some are myelinated, some arent.
Types of nerve fibers in peripheral nerves
o Somatic neurons
Muscle Spindles
Axon 1A tells spinal cord about length and movement
of the muscle.
This is parallel to the muscle fibers
Golgi Tendons provide info about muscle tension
Sits in series with the muscle fibers
Free nerve endings measure potential pain.. as well as temperature and crude touch
o Motor Neurons
Alpha Motor neuron this is the main one it synapses at the neuromuscular junction (NMJ)
Gamma Motor Neuron innervates a sensory receptor this is critical to the functioning of the Alpha motor neuron
Reflexes a sterotyped motor responses elicited by a defined sensory
stimulus
o Can be overridden if you think hard enough
Reflex Classifications
o Autonomic or somatic
o Where the reflex is integrated cranial or spinal cord
o When the reflex develop - learned or born with it?
o The Number of neurons in the reflex loop
Skeletal Muscle Sensory Receptor initiated reflex Muscle Stretch
Reflex patellar stretch reflex
o Muscle Spindle the sensory apparatus. Intrafusal Muscle Fiber
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This is in parallel with the muscle fibers. It detects how long the muscle is, and how its changing
o Afferent Sensory neuron inputs on the monosynaptic nerve
junction
o Motor neuron causes contraction (more Ach) for the quadriceps
muscle and relaxation (less Ach) for the hamstring muscle
Monosynaptic excitatory reflex
Polysynaptic inhibitory reflex o Ipsilateral (same side) and negative feedback. No afterdischarge
no sustained contraction
Alpha Gamma Co-activation occurs in the stretch reflex
o Alpha Motor Neuron actually causes the contraction
o Gamma motor neuron it targets the intrafusal muscle fiber and
innervates its contractile material to contract.
This is important because it keeps the muscle spinal taut so that the length of the muscle can be reported
Nociceptor Reflex ex. Ball of the foot crossed extensor/flexor
withdrawal reflex
o Lift foot when stepped on something sharp.. and kept it up..
also balanced the rest of body
o Polysynaptic pathway that is a protective reflex
o First, free endings detect pain and
transmit to the spinal cor dand
contract the quadriceps (flexors)
on the foot with pain.
o It does the opposite on the other
foot.
o Afterdischarge is active you
dont stop withdrawing your leg and
put it back down.
Golgi Tendon Reflex (Deep tendon reflex)
o The Golgi tendon organ is in series
with the muscle
It encodes info about tension o 1B Afferent axon
o It detects information about muscle contraction
o It prevents overstretching of the muscles tendon by causing
some inhibition of the muscle that was being contracted, and
contracts the antagonist muscles.
o Opposite of the myotatic reflex (stretch reflex)
Lecture 2: Sensory & Motor Pathways
Principles of sensory system organization
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o Specific sensory receptor types are sensitive to certain
modalities (like pain, light, etc.)
o Labeled lines a pathway codes for a particular modality
o Sensory info is processed by the opposite side of the brain
o Sensory pathways synapse in the thalamus on
their way to the cortex
Dermatome map (topographic organization)
Sensory input at different levels of spinal cord is
mapped out across the body
o Not precise for touch, pressure, vibration
o Accurate for pain and temperature
The body is mapped to the somatosensory cortex
o The cortical area is proportional to
sensory sensitivity
o Homunculus a representative body that is
made proportionate to the brains cortex.
Sensory Pathway
o 1st Order Neurons
Sensory, cell bodies in the PNS in the dorsal root ganglia and synapse in the dorsal horn
o 2nd order neurons
CNS neurons in the spinal cord or medulla o 3rd Order Neurons
Located in the contralateral (opposite side) of the brain in the thalamus
o All Ascending systems cross before the thalamus. The thalamic
projections to the cortex are the same side.
Mechanosensory system Dorsal Column medial lemniscal System
o Receptors in the skin touch pressure vibration, proprioception
(limb location)
o 1st Order neurons branch and
synapse in the dorsal horn, but
also send information to the brain
via the ipsilateral dorsal column
white matter.
Axons are organized such that the lower body is medially
organized, and upper body is
lateral in the white matter
somatotopical organization
o 1st order neuron terminates on the 2nd order neuron in the dorsal
column nuclei in the medulla
One nucleus for upper limb, one for lower o 2nd order medullary neurons project to the contralateral side of
the thalamus through a fiber called Medial Lemniscus
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o 3rd order neurons are in the thalamus. These project to the
cortex. This is also somatotopically organized.
Pain Pathway Spinothalamic/anterolateral pathway
o 1st Order sensory receptors free nerve endings detect pain
Different receptors from mechanosensory system
Bodies are located in the dorsal root ganglia
o 2nd order neurons are located in the
dorsal horn.
The axons from 2nd order neuron crosses the midline and travels in the anterolateral white
matter
These axons form the spinothalamic tract
2nd order axons synapse on the neurons at many different levels, ipsilaterally and contralatterally (for example,
the foot withdraw
reflex acts on both
sides)
Some axons go
direct to the
thalamus
contralaterally
3rd order neuron is in the thalamus and
goes to the cortex
o Mechanosensory (right) vs
pain (left) pathways:
Mechanosensory & Pain pathways
from the face via Cranial
nerve V Trigeminal nerve
Referred pain
o The somatosensory cortex is missing representations for things
such as the heart, lungs, etc. all visceral organs
o Visceral organs refer pain to specific sections of skin
o This probably because the organ also synapses on the same neuron
in the spinal cord
Phantom Limb Pain
o When someone loses a limb, central pathways can still be active
in the absence of stimuli
o People can still feel the missing limb and feel lots of pain
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o Difficult to treat destroying parts of pathway dont relieve
pain
Sensory Deficits after Spinal cord
injury Spinal Hemisection-
destruction half of the spinal
cord
o Spinal reflexes below the
lesion still work
Topic 3 CNS Motor
Interneurons are fingers on the
piano that cause the keys (motor
neurons) to play
The descending systems access these keys to cause tunes to be played
o Upper Motor Neurons
There are 2 types of pathways : Direct & Indirect
Direct Pathways Called Lateral Pathways
o Cortispinal tract/pathway
Originates from the cerebellar motor cortex
These go through the pyramidal system to the medulla
Crosses via pyramidal dissection while going through
the pyramidal tract
Synapses in the spinal cord and interneurons there. o Rubiospinal pathway
Originates from the red nucleus (Midbrain)
Synapse in the spinal cord and interneurons
o Both Pathways are still crossed
o They travel in the lateral white
matter on dorsal side
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The Spinal cord is somatotropically organized
o distal muscles are lateral and vice versa
o Lateral muscles synapse on lateral nuclei
Lesions of the motor cortex cause issues with
fine motor control but not all movements.
Lesions of the spinal cord causes inability to do
individual movements of limbs.. limb moves in
only one direction.
o Pitcher on a mound, but cant pitch the ball
Indirect (Extrapyramidal) pathways Brainstem/ventromedial Pathways
o Reticular Nuclei Posture & Walking
o Superior Colliculus vision & Vestibular nuclei balance
Tectospinal tract visual system
Vestibulospinal tract vestibular system o These innervate more of the proximal muscles
o Arise from Circuits originating in cortex, brainstem, cerebellum
o Synapse on neurons in the brainstem
o Brainstem neurons project into the spinal cord
o Really important in the maintenance of posture and coordinated
head/eye movements
Motor deficits after spinal
cord injury- spinal hemisection
o Flaccid paralysis on the
ipsilateral side
o Spastic Paralysis
reflexes are still
present, but no input from
the brain
o Clonus tap on the
patellar tendon, and itll
keep going up and down
instead of just doing it
once.
Descending input is needed to stop the oscillation.
Brown sequard Syndrome- Sensory & motor deficits following a
hemisection
Topic 4 Cerebral cortex and function
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3 types of cells in the CNS
o Neurons
o Glia (10x the amount of neurons)
Astrocytes
Oligodendrocytes myelin in the CNS
Microglia phagocytes. Immune system of brain o Ependymal cells line the Ventricles
Choroid plexus modified ependymal cells that produce CSF
CSF fills ventricles & subarachnoid space
o Produced 500 ml/ day. 150 ml in total. Turns over 3-4x / day.
o 2 foramens that let the CSF into the subarachnoid space
o Hydrocephalus the inability to absorb/drain CSF
A shunt is used to drain csf to the abdomen o CSF is chemically regulated
Important in chemosensory function
More acidic than blood
Due to the blood brain barrier
Meninges
o Dura Mater
2 Sinuss are created by folds of the dura mater and these drain the CSF from the brain.
Subdural space contains venous system o Arachnoid Mater
Subarachanoid space is between the arachnoid & Pia mater
The CSF resides here.
Contains arterial system
Arachnoid granulations arachnoid mater poking through the dura mater and drains csf into the venous sinus
o Pia mater
Subdural bleeding
o pushes the brain from the outside
Subarachnoid bleeding
o Bleeds into the brain and balloons inside the brain
Blood Brain Barrier
o Capillaries are one cell thick
o Astrocyte feet combine together to form the blood brain barrier
o Tight junctions restrict diffusional passage of large molecules
Prevents transport of everything not small, lipid soluble or gas
o Other molecules cross the barrier through many specific membrane
transporters
Cerebral Cortex
o Frontal cortex motor and function
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Personality and emotion
Orbital frontal cortex addictive behaviors o Parietal Cortex sensory functions & integration
Contralateral neglect syndrome if right side is damaged, you cant process some things from the left visual field
Occipital lobe primary visual cortex
o The brain processes the image upside down versus the visual
field and location of the brain
o The outer part of the cortex does more with macular (main part
of field) while inner parts do binocular parts
Temporal Lobe Audition learning, memory, facial recognition,
language
o If temporal lobe is damaged AGNOSIAS
Difficult recognizing, identifying and naming categories of objects
Right cortex unable to recognize faces
Separation of complex functions between cerebral hemispheres
o There is a lateralization (left/right)
o Wada Procedure disproved that left/right handedness indicated
which hemisphere of the brain was dominant
Injection of a fast acting barbiturate into the left/right carotid artery so that the hemisphere goes to sleep
Language repeating a spoken word
o Wernickes area processes the sound
from the auditory cortex, and passes
it through the angular gyrus
(yellow) to brocas area.
o Brocas area has to do with the
motor function for speech and
projects to the motor cortex
Repeating a written word
o Visual Cortex Angular Gyrus
wernickes area brocas area motor cortex
Corpus Callosum connects the two hemispheres - ~200 million axons
o Cutting the corpus callosum helps severe epileptic
o Its very difficult to figure out what the deficit of cutting
the corpus callosum was
o Sterognosis Experiment
Objects is held in the left hand (right hemisphere)
Object held in left hand cant be named
Object held in right hand can be named
The effects of stroke
o Aphasia change in expression or comprehension
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o Brocas Area unable to speak but can understand language
Motor or expressive aphasia o Wernickes Area unable to comprehend spoken or visual info
Sensory or receptive aphasia
Brain Death
o Patient came in a coma and its not medically induced
o Greatly reduced cerebral circulation
o No response to painful stimuli other than spinal reflexes
o Brainstem must be dead as well
Midbrain eyes, relays auditory and visual info, descending control of skeletal muscles
No pupillary light reflexes
Pons coordinates respiration, maintenance of upright posture, vestibular system induced eye movement
No eye movements with vestibular stimulation
Medulla blood pressure, heart rate, respiration, standing
Apnea w/ co2 level over 60 mmhg (very high)
Topic 5: Endocrine Thyroid & Glucose stuff
Hormone chemical messenger secreted by a cell that is transported
to a distant target where the hormone exerts its effects in low conc.
Mechanisms all work via 2nd messenger systems
o Hormones work by binding to ligand gated receptors and then:
o Alter membrane potentials/regular transport/cause exocytosis
Classes of hormones
o Peptides derived from amino acids. Ex. Insulin, TRH, TSH
o Amines derives from tyrosine. Ex. E, NE, thyroid hormones
o Steroids Derived from cholesterol. Ex. Cortisol, aldosterone
Thyroid hormones they are always required
o Required for normal maturation of the nervous system
o Required for normal bodily growth
o Required for normal alertness and reflexes
o Major determinate of the rate at which the body produces heat
o Facilitates the activity of the sympathetic nervous system by
stimulating the synthesis of Beta receptors for E & NE
Thyroid Hormone release can be controlled via hormones,
neurotransmitters or ion/nutrient changes
Release of T3/T4 (thyroid hormones)
o The Hypothalamus releases TRH (thyrotropin-releasing hormone)
that goes to the anterior pituitary via portal capillaries
o The TRH binds to the a G protein phospholipase C, IP3 DAG
receptor in the anterior pituitary.
Ip3 calcium release
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o The anterior pituitary releases TSH thyroid stimulating
hormone
o The TSH binds to a follicular cell in the thyroid to a G protein
coupled Adenylyl cyclase, cAMP second messenger pathway
This is a complex pathway
TSH pathway
o Enhances the transport of iodine into the follicular cell
o Iodination of tyrosine residues that is sitting in a long
peptide chains waiting.
This is why the hormones can be stored everything is stored on the thyro-globulin peptide chain in the colloid
o The protein can then be endocytosed to an endosome in the
follicular cell that chops up the thyroglobulin into T3 & T4
o TSH exerts a growth factor effect and causes hyperplasia of the
follicular cells as well.
T3 & T4 then bind to thyroxin binding protein which carries the
hormones through the blood stream.
o T4 = Thyroxin. 4 iodines
o T3 = more biologically active. 3 iodines.
o T3 is involved in negative feedback to regulate the levels of
TRH & TSH
Hypothyroidism 2 ways it can happen
o Follicular cells are making too little T3/T4. Because of this,
TSH & TRH are very high. This causes hyperplasia (TSH) Goiter
Hashimotos disease an autoimmune disorder o Secondary hypothyroidism too little T3/T4 due to too little
TRH/TSH.
No goiter because too little TSH
Hyperthyroidism
o Tumor Too much T3/T4 and low TRH/TSH no goiter
o Graves Disease due to TSI thyroid stimulating immunoglobin
is a TSH receptor antibody that stimulates TSH receptor
Causes goiter because of TSH like effects
Autoimmune disease
o Secondary hyperthyroidism too much TSH/TRH goiter o Hyperthyroidism affects B receptors and causes increased
contractility in the heart
Glucose Stuff
Increase in Plasma concentration of glucose causes the stimulation of
beta islet cells in the pancreas. >100 mg/dL is the threshold
o Glucose level rises in the B Cell
o ATP Production will increase due to the glucose increase
Closes a potassium ATP Channel
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o Membrane potential will depolarize
o Causes a voltage gated calcium to open calcium influx
Calcium induced calcium release o Calcium causes release of insulin vesicles
Increase levels of insulin
o Causes glucose uptake in muscles and fat cells
o Causes glucose release to stop in the liver and causes uptake
Increase in synthesis of glucagon and triglycerides
Insulin Receptor tyrosine kinase receptor
o Causes insertion of GLUT4 transporters in the cell.
o Brain, kidney and intestines arent insulin dependent they use
GLUT1 transporters instead
Glucose tolerance test a way to test for diabetes
o Can differentiate between non diabetic and type 1 & 2
o Oral Test
Fast overnight & glucose is measured in the blood
Drink a known Conc. Of glucose
Normal person sugar spikes and drop rapidly
Diabetic sugar spikes and goes down really slowly
Type 2 the insulin will still be made so youll see
it affect the curve, but you wont see it with type 1
Type 1 Diabetes Insulin Hyposecretion insulin dependent
o 10% of diabetics
o Autoimmune disease
o Glucosuria the kidneys cant reabsorb all glucose so its
excreted it.
Osmotic diuresis loss of lots of water due to glucose
Polyuria excessive urination
Polydipsia excessive thirst o Body will break down glycogen and fats for energy polyphagia
o Diabetic ketoacidosis build up of ketones from fat break down
will cause acidity in the blood and can lead to coma
Insulin Shock hypoglycemia
o Insulin excess
o Causes the body to take up too much glucose and reduces the
glucose available in the blood for the brain to use
Type 2 Diabetes
o Caused by genetics and being overweight
o Insulin resistance defect in the B cells ab ility to secrete
insulin
Gestational diabetes 4% of pregnancies
o Women can become diabetics due to insulin resistance
o Insulin resistance is connected to levels of progesterone and
cortisol
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o May be due to peptide hormone hPL (human placental lactogen)
o Problems go away after delivery
Topic 6: Cardiac Output and excitation coupling in vascular smooth muscle
Mean arterial pressure we cannot change this directly; it is
changed by cardiac output and stroke volume and peripheral resistance
Main features of the CV system
o Heart is a double pump and each side is equal volumes
o Arterial system is high pressure, venous is low pressure
o Right atrium Right ventricle lungs left atrium Left
Ventricle aorta (body)
Coordination of the heart beat
o SA Node (pacemaker) AV Node (delays contractions of ventricles
from atria) bundle of his purkinje fibers o ECG analysis
P wave = atrial depolarization
Q wave = depolarization through bundle of his
RS Wave = ventricular r depolarization
T Wave = ventricular repolarization o ECG Pathology
PR interval lengthening indicates 1st degree AV conduction block
QRS loss after P waves indicate 2nd degree AV block
Lengthening of QT interval indicates congenital defects in voltage gated Na+ or K+ channels.
A Singularly most important function of the CV system is to ensure
continuous system is to ensure adequate blood flow through
capillaries
Poiselles law
o P = F * R
Delta P = pressure gradient along the tube
F = flow of fluid
R = resistance to fluid flow
Mean Arterial Pressure (MAP) cardiac version of poiselles law
o MAP = CO * R
MAP = Mean pressure in aorta mean pressure at right atrium
CO = cardiac output - liters/min
CO = Heart Rate * Stroke Volume
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R = peripheral resistance (TPR or SVR)
SA Node Cell
o Able to be autorhythmic
o As the membrane repolarizes, an HCN non-specific cation channel
opens
This helps to depolarize the action potential o Nodal cells lack voltage gated Na+ channels. They use calcium
channels instead.
Heart Rate Control
o SA Node cells are pacemaker cells 100 bpm
o Av node cells are at lower rate 40-60 bpm
o Unregulated heart rate 100 bpm
o Decreasing heart rate
Increase parasympathetic activity. Muscarinic receptor causes K+ channel to open and hyperpolarize the potential.
Because of this, it takes longer for the pacemaker
potential to fire. (chronotropic effect)
Dromotropic (conduction) effect does the same o Increasing the heart rate
E & NE increase sympathetic activity via B receptors
Mechanical
events in the
cardiac cycle
o Systole
Period of
Contraction
o Diastole
period of
relaxation
The heart has
isovolumetric
contraction and
relaxation of
the ventricles
Stroke volume =
end diastolic
volume end
systolic
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Pressure Volume Loop for the left ventricle
Should be able to determine if stroke volume changed and whether it
was due to frank-starling
or due to change in
contractility
Regulating stroke volume
o Frank Starling law
o Increasing
Contracility
Frank-starling law
o Increasing sarcomere
length of muscle
fibers can increase
stroke volume
Increase EDV Increase SV
o Tension can be
increased rapidly as
the sarcomere length.
Skeletal muscle cant increase as
much
Cardiac Function curve is
the same as the frank
starling curve, just
different axes
o Increase in blood volume or venous
pressure, you will increase EDV
thereby stroke volume/ cardiac
output
Role of the veins
o Holds 60% of the blood of the body
o Increasing sympathetic nerve activity causes venoconstriction.
This causes more venous return to the heart
venous pressure venous return atrial pressure
EDV Stroke Volume Cardiac Output
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o This changes the pressure
volume loop preload increase
Contraction of ventricular muscle
o Gap junction depolarizes from
the action potential.
o A voltage gated L type Ca2+
channel in t tubule opens
Calcium induced calcium release
o Calcium released from SR binds
to troponin and allows the
actin/myosin to interact and
contract the sarcomere
o Changes in contractility is all about how the muscle is handling
calcium
Increasing contractility Increased Contracility Graph
o Increasing in developed
tension without changing
muscle length
o B adrenergic receptor
activates cAMP and
phosphorylates the L type
Ca2+ channel so it opens
longer
Ryanodine receptor (Ca channel in SR) also
phosphorylated
Ca transporter back into the SR is also
phosphorylated
o Ejection Fraction (EF) = SV/EDV
Normally 50% -75%
Contracility = Ejection Fraction
Frank-starling property represents changes due to increase in
EDV/venous return. Increasing contractility represents intrinsic
changes in the muscle performance
Another way to alter mean arterial pressure, you can change
peripheral resistance
o CV variables for resistance to blood flow
L = length of CV system (constant)
n = viscosity of the blood
r = radius of the blood vessel
Main thing that alters resistance
Smooth Muscles
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o Not striated
o Innervated by the autonomic nervous system sympathetic system
o Contains actin & myosin, tropomyosin, but NOT troponin
Troponin = calcium binding that causes tropomyosin shift o Can develop comparable max tension as striated muscle, but the
timing is different. Such as time taken to generate smooth
muscle
o Smooth muscle can be relaxed by neurotransmitter, unlike
skeletal muscle
o Smooth muscle lacks a specialized end plate/junction for
neurotransmitter release
o Contraction of smooth muscle can be initiated by hormones and
paracrines, unlike skeletal muscle
Ex. E, cortisol, angiotension II, nitric oxide, histamine o Unlike skeletal muscle, smooth muscle can be initiated by
mechanical stretch
o Actin and myosin are arranged in diagonal bundles and dont have
sarcomeres. Cross bridges are much slower
o Smooth muscle membrane is more complex.
Has voltage gated Ca2+ channel
Alpha receptors bind E or NE
G protein/phospholipase C / Ip3. IP3 opens Ca channel
in SR
Smooth Muscle Contraction
o Cytosol level of Calcium increases (IP3 of Ca induced Ca)
o No Troponin. Ca binds to calmodulin (CaM)
o CaM associates with MLCK. MLCK phosphorylates a protein in the
light chain in head of myosin
o Once myosin is phosphorylated, it binds actin and shortens.
o Relaxation is done via lowering calcium conc.
o Myosin phosphatase takes off the phosphate from the myosin
Topic 7: Vascular System
Most drop in blood pressure covers over the arterioles
o They are the primary determinant of blood flow resistance
o Determine the relative distribution of blood to body parts
This is done by changing radius. Radius flow
Control of the arteriolar radius
o Local control
Myogenic activity. Pressure Stretch
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Causes vasoconstriction
Paracrines from metabolism O2 Co2 H+, K+ Osmolarity
Causes vasodilation
Paracrine signal molecules
NO, histamine, adenosine - Vasodilation
Endothelin-1 Vasoconstriction
o Extrinsic control
Nervous - sympathetic input (NE alpha receptor)
Causes vasoconstriction
Neurons can release NO and cause vasodilation
Hormonal
Epinephrine
o Alpha 1 receptor vasoconstrict
o Beta 2 receptor vasodilation
o Different vessels have different receptors
Angiotensin II vasoconstriction
Arginine vasopressin (AVP) vasoconstriction
Cortisol vasoconstrict
Atrial natriuretic peptide (ANF) vasodilator
Local Control autoregulation
o Active hyperemia when organs increase activity
PO2 Arterioler radius Blood Flow o Flow Autoregulation due to drop in pressure (like bleeding)
Arterial pressure blood flow to organ PO2
metabolites Vessel wall stretch Arterioler radius Blood Flow
Doesnt have to be only drop in Pressure, also works
for increase in pressure
Autoregulation of Glomerular filtration rate(GFR) in kidney is an example of flow regulation
Capillary exchange and bulk flow
o Diffusion, facilitated diffusion and transcytosis
Bulk Flow
o Mass movement of water and dissolved solutes between and blood
and interstitial fluid
o Main function is to distribute the extracellular fluid
o Result of the balance between hydrostatic (blood pressure) and
osmatic pressures (due to conc. Gradients)
o Interstitial fluid can be thought of as a reservoir
Capillary wall is highly permeable to everything but large proteins
o This creates a osmotic pressure
o As you pass through a capillary, hydrostatic pressure decreases.
This is due to decreasing resistance.
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o Plasma osmotic (oncotic) inwards water movement
o NFP = net filtration pressure = filtration absorption
o NFP is usually positive more filtration than absorption
o Excess filtrate is taken up by the lymph system
o Pc= Hydrostatic pressure (out)
o Pif= interstitial fluid pressure
o if osmotic force due to if
fluid protein conc. (out of cap)
o c osmotic force due to protein conc in blood (into cap.)
Pulmonary capillaries capillary exchange processes are identical
except there is a small net filtration
o Pc is very low and large if
Vascular function curve
o Measures change in the
atrial pressure as cardiac
output changes
o No cardiac output central venous pressure (7mmhg) only
o As cardiac pressure
increases, atrial pressure
will decrease.
o Hypovolemia causes a
downward shift while
hypervolemia causes an
upward shift
Flipping the axes of the vascular
function curve and plotting cardiac
function leads to 2 intersecting
curves called the steady state point
o Transfusion vascular curve
moves to the right, steady state
point moves up
o Increase in contractility will
shift the cardiac curve up and
left
Lecture 8: Regulation of arterial blood pressure
Short Term regulation
o Baroreceptors blood pressure receptors in the aorta and in the
carotid arteries
One is located at the arch of the aorta and the other is in the carotid arteries
o Only variables heart rate, stroke volume and resistance
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Fixing high blood pressure
o Sympathetic outflow decreases. Less NE & excitation.
o Increase parasympathetic signals decrease heart rate
o Stroke volume cant change EDV, but you can change
contractility by reducing sympathetic outflow
Fixing Low Blood Drive
o More sympathetics More NE & E, increasing resistance and heart
rate and contractility.
o Withdraw parasympathetic brake and all activity
Long Term Regulation of high blood pressure decrease blood volume
o Kidneys will increase urinary loss of water and sodium
Lower activity of RAAS renin angiotensin-aldosterone system. Causes more Na+ excretion
Renin causes angiotensin II (by ACE enzyme) to go and produce aldosterone
Decrease Kidney tubular reabsorption of NA+ o If high Blood Volume is detected first
Activity of low pressure baroceptors detect blood volume and tells the medulla
AVP (anti diuretic hormone) secretion decreases causes more diuresis
Atrial natriuretic peptide (ANP) pathway
As plasma volume increases, atrial fibers release ANP
It decreases aldosterone
Afferent dilation and efferent constriction in kidney
arterioles Increase in GFR.
Decreases Na+ reabsorption
Regulation of aterial blood pressure
in shock
o Shock = sustained drop in mean
arterial blood pressure
Septic shock infection
Hypovolemic shock
o Hemorrhage 10%-20% rapid loss
of blood volume
o Short term regulation
Drop in blood volume
drop in EDV Drop in SV
Increase heart rate and contractility
Increase peripheral resistance baroreceptor reflex
Increase Sympathetic system, EDV rise in cardiac output
Reflex compensations work towards normalcy
Use the RAAS system
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o RAAS system
MAP GFR Renin Release
Renin converts angiotensinogen into angiotensin I
ACE converts Angiotensin I to angiotensin II
Angiotensin II goes to adrenal cortex and releases aldosterone
Aldosterone causes na+ and H20 to be retained
AVP cases vasoconstriction and aldosterone to be released
GFR wont be the same anymore because no auto regulation o Long term response
Drop in capillary hydrostatic pressure Increased fluid
absorption from interstitial compartment increase in
plasma volume restore MAP
Increase absorption because of starling forces in the
capillary more water leaves from interstitial fluid
(reservoir) and enters blood plasma
Called autotransfusion redistribution not replacement o Sometime after hemorrhage plasma rises back and beyond
original value, but erythrocyte cant regenerate.
o Red blood cell replacement can be done via erythropoietin
release by the kidney to stimulate more production, but takes
days to weeks for replacement.
Cardiogenic shock due to congestive heart failure
o Lower cardiac output
o Consequence of prolonged hypertension diastolic dysfunction
Serious hypertrophy and ventricular volume decreases o Systolic dysfunction consequence of damage to ventricular
tissue due to decreased coronary blood flow (heart attack)
o Coronary arteries provide the heart muscles with blood from the
base of the aorta
o Left anterior descending branch widowmaker can get blocked
left ventricle loses blood
Cardiovascular responses to cardiac failure / systolic dysfunction
o Decreased CO triggers baroreceptor reflex
Increases HR, SV, Contractility, and Resistance
Initially beneficial restoring CO & MAP
Long term leads to massive expansion of extracellular
fluid volume. RAAS Aldosterone AVP H20 retention
Causes EDV SV to increase CO
o This is bad because heart is damaged
o Frank starling curve is significantly lower
o Asking the heart to work harder
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o Cardiac function graph much lower due to
hypervolemia. More atrial pressure and less
cardiac output.
Ventricle muscles will start to tear
o EDV is too big.. tension needed is too much
Peripheral Edema(Swelling of the body) occurs
Pulmonary edema fluid build in the lungs
o Gas cant really diffuse well through the water
Increase in peripheral resistance more work load
Heart Failure Treatments
o Diuretics causes excretion of water
o Increase cardiac contractility - cardiac ionotropic drugs -
Digitalis (digoxin) poisons the Na/K ATPase pumps
Causes increase Ca+ in the cell o Inhibit AVP binding to receptors in kidney and vascular muscles
Increases excretion of water o Inhibit the RAAS system ACE inhibitors
ACE inhibitors block formation of angiotension II / aldosterone
o Vasodilators organic nitrates / nitroglycerin
Anaphylaxis an extreme allergic reaction
o A type of allergic response classified as immediate
hypersensitivity
o Rapid onset. Mediated by IgE immunoglobulins, mast cells, and
basophils
o Immunity stuff
Humoral immune response Memory B cells make antibodies
Cell mediated responses T cells cytotoxic T cells and helper T cells
Helper T cells when activated, make the humoral
response much larger and better. Cytotoxic not used.
Humoral response recognizes the antigen and makes antigens and the antigens wait for the next time.
Mast cell has IgE on its surface and binds to the allergen.
Releases histamine and other inflammatory mediators
Inflammatory response will divert more fluid away from
blood increase vascular permeability o Histamine will cause hypotension by binding to smooth vascular
muscles
o Swelling of the tissue around airways (Angio-edema)
o Bronchiolar smooth muscle contraction
o Epinephrine (epi-pen) is used to reverse anaphylaxis.
Vasoconstriction of the blood via A1 receptor
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Bronchodilation via B2 receptor
Hypertension
o Chronically increased MAP 140/90 +
o Major abnormality is increased peripheral resistance
o Baroreceptor reflexes reset to a different resting value
o Could also be due to kidney dysfunction in a small subset of the
population
o This will call diastolic dysfunction
o Hypertension will increases the chances of having a stroke
Treatments for hypertensive disease
o Diuretics
o B1 adrenergic blocks decrease CO, HR & SV. Decrease CO & MAP
o Calcium channel blocks decreases total peripheral resistance,
but can increase risk of heart attack (due to calcium channels
in the heart)
o ACE inhibitors
Renal hypertension is best treated with ACE inhibitors
Vasovagal syncope : emotional fainting
o Happens due to sudden drop in Blood pressure due to vasodilation
o Inhibition of smooth muscle & sympathetic innervation
o Baroreceptor reflex becomes uncoupled
Hyponatremia
o Occurred in 1% of new York marathoners in the past
o Cause by salt lost in sweat, though runners were hydrated
o Overhydration dilutes the plasmas Na+ content and blood flow to
kidneys is significantly lower
Interstitial Na content remains normal
Due to this imbalance, water flows into the interstitial space
Swelling of hands, feet, constriction of chest
People died due to brain swelling, fainting, coma, death o Treatment hypertonic saline IV
Ecstasy induced hyponatremia article key points
Due to genetic variation one can metabolize MDMA slower
MDMA forms inhibitor complexes with CYP2D6 an enzyme that is used
to breakdown MDMA. This can lead to acute toxicity
o CYP2D6 is also affected by other drugs as well
MDMA causes a lot of dehydration and fever.
Acute Kidney Injury can occur
o Dose dependent correlation of proximal tubule damage
Hyponatremia
o Excessive water intake is associated with MDMA use. People try
to hydrate to prevent fever
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o HMMA is a metabolite of MDMA that is a more potent inducer of
ADH (antidiuretic hormone (AVP) )
o Serum sodium conc. Drops, causing hyponatremia