Unit 7 - Autonomic Nervous System

7.1 - ANS Introduction

Overview

• ANS serves role in unconscious regulation in various organ systems such as cardiovascular,
respiratory, GI etc. Crucial in maintaining homeostasis.
• Internal —> Visceral Sensory Neurons —> CNS —> Somatic Motor Neurons —> External
• External—> Somatic/Special Sensory —> CNS —> Visceral Motor Neurons —> Internal
• Autonomic Nervous System (ANS): Involuntary control and regulation of visceral organs.
Innervates cardiac, smooth, endocrine, exocrine. Influences activity of most tissue and organ
systems. Regulates BP, GI, bladder. Effector organs not entirely dependent on ANS, but
instead ANS adjusts their tone. (Ex. ANS regulates heart pacemaker). Combination of Visceral
motor neurons and Visceral sensory neurons. Conduction velocity of ANS is slower in motor
neurons because they are thin and unmyelinated axons.
• Somatic Nervous System (SNS): Voluntary motor system under conscious control. Each
pathway consists of single motor neuron and muscle fibers it innervates. Soma located in CNS
(brain or spinal cord), axon synapses directly on skeletal muscle. Conscious sensory and
voluntary motor allow interaction with external environment. Combination of Somatic motor
neurons, and Somatic & Special sensory neurons.

Nervous System

• Sensory (afferent) division: Made up of Somatic & Visceral Sensory. PNS then CNS.
• Somatic Sensory: Touch, pain, pressure, vibration, temperature, proprioception in skin/body
wall/limbs. (Special: Hearing, equilibrium, vision, smell)
• Visceral Sensory: Stretch, pain, temperature, chemical changes and irritation in viscera,
nausea, hunger. (Special: Taste)

• Motor (efferent) division: Made up of Somatic & Visceral Motor. Leads to PNS then CNS
• Somatic Motor: Motor innervation of skeletal muscles. Generates voluntary movements
• Visceral Motor: Motor innervation of smooth, cardiac muscles, and secretory glands.
Equivalent to ANS. Contains parasympathetic and sympathetic divisions.

• Peripheral Nervous System (PNS): Cranial, and spinal nerves

• Central Nervous System (CNS): Brain and spinal cord. Processes information sent by PNS.




Autonomic reflexes: Visceral Sensation

• Visceral sensory neurons found in PNS and cranial sensory ganglia

• ANS nervous activity regulated by autonomic reflexes
• Sensory information transmitted to homeostatic control centers in the hypothalamus and
brain stem. Sensory input from thoracic and abdominal viscera transmitted by afferent fibers
present in cranial nerve 10 (vagus nerve) along with other cranial nerves
• Response carried out by nerve signals that modify pre-ganglionic autonomic neural activity.
• Many physiological variables monitored and regulated in the hypothalamus and brain
stem. Sensory neurons monitor levels of CO2, O2, sugar in the blood, arterial pressure,
chemical composition of stomach and gut.
• Afferent fibers transmitting visceral sensory information from internal organs back to CNS are
not divided into parasympathetic/sympathetic.
• Visceral afferent fibers: Class of axons that conducts autonomic sensory information.
Sensations are largely unconscious. Afferent components of visceral motor reflexes in hallow
organs/glands which are transmitted to CNS.
• Unconscious reflex arcs are normally undetectable, but they can send to pain to CNS
masked as referred pain (Ex. Myocardial infarction, pain in left arm or into jaw)
• Neural control centers may be influenced by higher brain areas (cerebral cortex, and limbic
system) ANS activities associated with emotional responses. (Ex. Blushing during
embarrassing moment. Originates in frontal association cortex and involves vasodilation in face)
• Some autonomic reflexes processed at spinal cord (micturition reflex, defecation reflex).
Although subject to influence from higher nervous centers, may occur without brain input
• Primary sensory neurons project (synapse) onto “second order” visceral sensory neurons
located in the medulla oblongata, forming the nucleus of the solitary tract (NTS), that
integrates all visceral information. The NTS also receives input from a nearby chemosensory
center, the area postrema, that detects toxins in the blood and the cerebrospinal fluid and is
essential for chemically induced vomiting or conditional taste aversion 

• All this visceral sensory information constantly and unconsciously modulates activity of the
motor neurons of the ANS, principally sympathetic and parasympathetic divisions.

Autonomic reflexes: Efferent pathways

• ANS encompasses three divisions which are sympathetic, parasympathetic, and enteric
• Sympathetic: Fight or flight; coordinates with parasympathetic division to maintain homeostasis
under normal conditions. Under emergency, it is activated to mobilize body for action.
• Parasympathetic: Rest and digest; coordinates with sympathetic division to maintain
homeostasis. Responsible for maintaining basal function (i.e heart rate, respiratory rate)
• Enteric: Both sensory and motor neuron plexus of the gut. Self-contained, minimal connections
to rest of nervous system. Responsible for mediating digestive reflexes.
• Sympathetic and Parasympathetic divisions complement each other. Both innervate
cardiac, smooth muscle, and exocrine gland tissue. Responsible for mediating visceral reflexes.
• Example: Experimental removal of sympathetic division. This requires organism to be
sheltered and unexposed to temperature changes, physical and emotional stress. Unable to
carry out strenuous work or fend for itself. Incapable of mobilizing blood sugar from glycogen
Terminology

• Adrenaline = Epinephrine (Epi)

• Noradrenaline = Norepinephrine (NE)
• Adrenergic neurons: Synthesize and release norepinephrine (NE)
Adrenergic receptors (adrenoreceptors) on effector organs. α and β forms.
Activated by NE from adrenergic neurons or Epinephrine from adrenal gland
• Cholinergic neurons: Synthesize and release acetylcholine (ACh)
Receptors for ACh are called cholinergic receptors. Nicotinic and muscarinic forms.


Organization

• Organization: Chain of two motor neurons

• First neuron: Pre-ganglionic neurons somas in CNS, axons leave and synapse on soma of
post-ganglionic neurons in autonomic ganglion which are outside of CNS. Myelinated.
• Ganglia/Ganglion: Structure containing multiple post-ganglionic somas. They are typically
linked by synapses, and form a swelling along nerve fiber
• Second neuron: Post-ganglionic axons extend to periphery where they synapse on effector
organs (muscle, heart, bladder, vascular smooth muscle). Unmyelinated
• Target cells of ANS do not have specialized end plate like in neuromuscular junction, instead
post-ganglionic neurons innervate target tissues in diffuse branching networks of axons. These
pre-synaptic fibers have several swelling (varicosities) along length.
• Varicosities: Bulbs where NT synthesis, storage and release occur. Analogous to pre-
synaptic nerve terminals of motor end plate
• Synaptic transmissions occurs at several sites along length of highly branched axons that
innervate target effector organs. Gives autonomic neurons more diffuse control, relatively few
highly branched axons regulate large masses of smooth muscle or glandular tissue.
7.2 - Sympathetic and Parasympathetic Divisions



Overview of Sympathetic Division

• Purpose of sympathetics is to mobilize body for fight or flight which includes increased Pa,
blood flow to skeletal muscles, metabolic rate, blood-glucose concentrations, and alertness.
• Sympathetic division rarely engages in full response of fight-or-flight, but instead maintains
ongoing tone and operates continuously to regulate function of organ systems.
• Sympathetic division also called thoracic lumbar system because pre-ganglionic neurons
originate within thoracic and lumbar regions of spinal column, their axons leave via ventral
motor routes and project either to paravertebral ganglia of sympathetic chain or to series of
prevertebral ganglia located on aorta.
• Somas of some post-ganglionic sympathetic neurons (lateral horn exiting T1 to L2) located
within paravertebral chain
• Most post-ganglionic axons are unmyelinated (gray rami communicantes)
• Sympathetic characterized by short pre-ganglionic axons and long post-ganglionic axons
• Sympathetic division innervates tissues throughout entire body.
• Pre-ganglionic origins are consistent with projection to periphery.
• Example: Sympathetic pathway to heart have origins in upper thoracic spinal cord while colon
or genitals have origins of lower lumbar spinal cord.
• Autonomic ganglia (paravertebral or prevertebral) of sympathetics are close to spinal cord
• Post-ganglionic origins (ganglia) are also consistent with projection
• Example: Superior cervical ganglion innervates head organs. Celiac ganglion innervate
stomach and small intestine. Superior mesenteric ganglion innervate to small/large intestines.
Inferior mesenteric ganglion innervate anus, bladder, and genitalia.

Adrenal Gland

• Adrenal gland sits on superior surface of kidney. Two components

1. Outer cortical region
2. Inner medullary region (adrenal medula)
• Adrenal medulla: Specialized sympathetic ganglia. Cells within it are called chromaffin cells.
• Pre-ganglionic neurons originate in thoracic spinal cord and pass through both sympathetic
chain, and celiac ganglia and synapse on adrenal medulla.
• Chromaffin cells: Modified neurons that do not have axons, but still capable of discharging
action potentials. When excited by pre-ganglionic activity, they secrete Epi and NE that are
taken up by capillaries. Allows for systemic delivery to help orchestrate full body-response.
Spinal Cord and Sympathetic Division (Thoracolumbar division)

• Important of sympathetic division of ANS that distinguishes it is that post-ganglion neurons

travel within each of 31 pairs of spinal nerves.
• 8% of axons constituting spinal nerve are sympathetic fibers which allows distribution to
effectors of skin like blood vessels and sweat glands.
• Highest innervated blood vessels in body, arterioles and veins, receive only sympathetic
fibers. No parasympathetic innervation of VSMC or sweat glands
• Pre-ganglionic cell bodies are located in lateral horn, and their axons exit T1-L2 sympathetic
paravertebral chain
• Short pre-ganglionic axons, long post-ganglionic axons
• Innervates tissues throughout the entire body. Head (eyes, salivary glands, mucous membrane
lining nasal cavity), thorax (heart and lungs), as well abdominal and pelvic cavities.
• Three main ganglia: Superior cervical ganglion, celiac ganglion, and inferior mesenteric
ganglion

Sympathetic and Parasympathetic Receptor Overview

• Pre-ganglionic neurons of both divisions use ACh which stimulate cholinergic receptors
• N2 type at autonomic ganglia cells.
• N1 type at neuromuscular junction are blocked by Curare, but N2 type is resistant to it
• Both activated N1 and N2 are permeable to Na+ and K+ with PNa dominating.
• Nicotinic stimulation of post-ganglionic neurons leads to rapid depolarization of post-ganglion
neuron which releases NE on to visceral target acting via adrenergic receptors.
• Exception is sweat glands uses ACh and express muscarinic receptors.
• All adrenergic receptors (𝛼 and 𝛽) are GPCR with second messenger systems
• 𝛼1 coupled with G𝛼q and act through PLC cascade (increased Ca2+)
• 𝛼2 coupled with G𝛼i and inhibit adenylyl cyclase (decreased cAMP)
• 𝛽1 and 𝛽2 coupled with G𝛼s and stimulate adenylyl cyclase.
• They have tissue-specific pattern of distribution.
• Example: 𝛽1 largely expressed by heart, 𝛽2 expressed on bronchial smooth muscle. Allows for
development of drugs that target specific tissue types to exert action. 𝛽2-agonists act on
broncho dilators without affecting heart.
• Adrenal medulla is homologous to sympathetic ganglia. Innervated by pre-ganglionic
sympathetic fibers that release ACh and chromaffin cells express N2 type receptor on surface
which release Epi of bloodstream (neuro-endocrine component), allows broadcast output.
Fight-or-Flight

• Sympathetic activation in extreme called Fight-or-Flight response when fully activated

• Whole body response which results in change of organ and tissue function in coordination

• Purpose: Well-oxygenated blood delivery to working skeletal muscle 

• Increased blood glucose from increased glycogenolysis (glycogen breakdown), and
gluconeogenesis (glucose formation) within liver. Necessary for brain and skeletal muscles
• Increased lipolysis (fat breakdown) in adipose tissue increases concentration of fatty acids
in blood. Skeletal muscles utilize glucose and fatty acids for metabolic energy in contraction

• Sweating enables thermoregulation of heightened physical activity and heat production
• Mass sympathetic discharge during fight-or-flight responses and exercise involve
simultaneous stimulation of organs and tissues, including adrenal medulla which releases
Epi and NE into blood. Indirect effects of these are similar to and reinforce sympathetics

Effects of Catecholamines

• Catecholamines circulating in blood are prolonged. This is due to their inactivation.

• NE is immediately removed from neuro-effector synapse by re-uptake. Limits duration.
• No blood enzymes to degrade catecholamines, instead enzyme in liver (COMT) does it.
Hepatic clearance requires several passes through circulation. Longer time (mins vs ms)
• Blood circulating catecholamines are capable of stimulating targets without directly
innervation. Therefore, wider activity. Airway smooth muscle, hepatocytes, and fat cells.

Catecholamines and the Heart

• NE and Epi have equal affinities for 𝛽1 receptors which are predominate on cardiac tissue
• NE has limited affinity for 𝛽2 receptors, therefore circulating Epi causes effects different
from direct sympathetic innervation including greater heart stimulation and VSMC relaxation.
• Heart contains small % of 𝛽2 receptors, which like 𝛽1, are excitatory and cause contraction
• Epi stimulates greater number of receptors and causes greater stimulation on myocardium
• Example: Heart rate and contractility increase so heart pumps more blood per minute. Wide-
spread vasoconstriction occurs to redirect blood away from organs and toward working muscles

Catecholamines and Skeletal Muscle

• 𝛽2 receptors found on smooth muscle, however they are inhibitory and cause relaxation
• Smooth muscle associated with skeletal muscle contains both 𝛼1 and 𝛽2 receptors
• NE, which stimulates only excitatory 𝛼1 receptor, causes strong vasoconstriction
• Epi stimulates both 𝛼1 and 𝛽2 and causes only weak vasoconstriction. Vasodilation from 𝛽2
receptor stimulation opposes vasoconstriction from 𝛼1 stimulation
• Since skeletal muscle accounts for 40% of body weight, potential difference in
vasoconstriction, blood pressure, and distribution of blood flow can be significant
• Example: Relaxation of VSMC in lungs by 𝛽2 stimulation. Bronchodilation facilitates airflow in
lungs. Any sympathetic innervation to lungs is irrelevant since only circulating Epi capable
Parasympathetic Division of the ANS

• Job is restorative. Conserves energy during times of no demand placed on organism.

• Central pre-ganglionic cells are located in several brain stem nuclei which are the nuclei of
cranial nerves III, VII, IX, and X and in the intermediolateral cell column of segments S2-S4 of
the sacral spinal cord
• Axons are long because their ganglia are close to or embedded in visceral target organs
• Long pre-ganglionic axons, and short post-ganglionic axons
• Pre-ganglionic origins are consistent with projection to effectors.
• Example: Parasympathetic innervation of heart, bronchioles, and GI tract originate in nuclei of
medulla and travel to periphery via CN X (Vagus nerve). Innervation of genitals originates in
sacral spinal cord and travels via pelvic nerves.
• Length of pre- and post-ganglionic axons is reverse of relative lengths in sympathetic.
Because parasympathetic ganglia are located on/in visceral target organs.

• Innervates tissues throughout the entire body

Rest-and-Digest

• Restorative and energy conservation 


• Decreases heart rate which helps to conserve energy during rest

• Enhanced salivary secretion to facilitate swallow, and stimulation of gastric and intestinal
motility for digestion and facilitate nutrient absorption

• Stimulates endocrine and exocrine secretions from pancreas. Enzymes from exocrine
contribute to breakdown of food in intestine as well as insulin from endocrine pancreas
promotes storage of nutrient molecule within tissues

• Example: Pupil constricts and lens adapts for near vision
• Example: Contraction of urinary bladder resulting in micturition/urination

Both Divisions of ANS Working Together

• In tissues receiving innervation from both sympathetic and parasympathetic divisions, both are
tonically active (they provide some degree of nervous input at all times). Therefore frequency
either increases or decreases. Without tonic activity, nervous input would only increase function.
• Most viscera receive both sympathetic and parasympathetic innervation, but not all
• Precise regulation of tissue function. Action potential discharge impacts organ/function
(enhanced or inhibited)
• Increasing one and decreasing the other produces rapid control of tissue function. Each
system is dominant under certain conditions
• Sympathetic during fight-or-flight and exercise to prepare body for strenuous physical activity.
It increases high oxygen and nutrient blood to effectors
• Parasympathetic during rest. Conserves and stores energy, regulate body functions.
• Although divisions have opposing effects, they are often work together to regulate organ
systems and coordinate physiological responses (Ex. Heart rate, GI tract, genitals)

Autonomic Control of the Iris

• Iris: Contractile structure of smooth muscle surrounding pupil. Colored portion of eye.
• Light enters eye through pupil and iris regulates light intake by controlling size of pupil
• Two groups of smooth muscle in eye:
1. Sphincter pupillae (constrictor muscles): Circular, inner layer.
2. Dilator pupillae (dilator muscles): Outer radial layer.
• When sphincter pupillae contracts, then iris decreases/pupil constriction
• Dilator pupillae causes pupil dilation when they contract (intrinsic eye muscles)
• Pupillae innervated by different division of ANS
• Parasympathetic from ciliary ganglion innervate circular muscles, constricts pupil
Used for close vision
• Sympathetic from superior cervical ganglion innervate radial muscles, dilates pupil
Used for distant vision
• Two influences are balanced, but shifts under arousal/alarm. One inhibited to allow the other.
• Atropine: Non-specific competitive antagonist for muscarinic ACh subtypes. Anti-
cholinergic drug. Causes dilation by blocking pupillary sphincter contraction, allowing
radial dilator muscles to contract unopposed causing pupil dilation. Used by optometrists.

Autonomic Control of the Bladder

• General theme in this unit: ANS is coordinating function within organ

• Detrusor muscle: 𝛽2 and M receptors
• Internal sphincter: 𝛼1 and M receptors
• External sphincter: Skeletal muscle
• Sympathetic activity dominates when bladder is filling, and this allows relaxation of
bladder wall and contraction of internal sphincter
• In urination, this reverses so parasympathetics dominate allowing activation of muscarinic
receptors causing contraction of detrusor muscle and relaxation of internal sphincter
• For final step of urination, body voluntarily allow external sphincter to relax

Sympathetic and Vasomotor Tone

• VSMC, adrenal medulla, erect pili, sweat glands innervated by only sympathetic division.
Therefore only way to adjust tension in them is to adjust sympathetic tone.
• Within sympathetic post-ganglionic axons innervating them, theres baseline firing frequency.
• Strong sympathetic (vasomotor) tone —> Smooth muscle contraction —> Vasoconstriction
• Weak sympathetic (vasomotor) tone —> Smooth muscle relaxation —> Vasodilation
• Shifting sympathetic activation of blood vessel beds shifts blood from one organ to another
• Sympathetics prioritizes blood vessels to skeletal muscles and heart in times of emergency.
• Example: Blood vessels in skin vasoconstrict to minimize bleeding if injury occurs during stress
7.3 - Receptors in ANS

Synaptic Physiology of the ANS

• Receptors are key targets for many pharmacology

• Somatic nervous system: Pre-ganglionic soma in CNS, extends axon to effector and releases
ACh. Skeletal muscle expresses N1 receptors
• All pre-ganglionic neurons release ACh and therefore are considered cholinergic neurons
• Autonomic nervous system: Post-ganglionic either adrenergic (NE) or cholinergic (ACh)
• Parasympathetics: Effector expresses only muscarinic receptors. Bodies of post-ganglionic
cells express N2 receptors including chromaffin cells.
• Sympathetics: Effector express multiple receptors. Including 𝛼1 𝛼2 𝛽1, 𝛽2.
• Among sympathetic adrenergic types, 𝛼1,2 receptors cause contraction of smooth muscle
while 𝛽1 involved in metabolic functions, 𝛽2 cause relaxation of smooth muscle

Cholinergic Receptors (Nicotinic and Muscarinic)

• Nicotinic: Ionotropic. Activated by ACh. Rapid opening of pore allows Na+, K+, and Ca2+
across membrane allowing Vm changes. Two main types (N1 and N2).
• N1 receptor: Peripheral muscle type found at neuromuscular junction.
• N2 receptor: Central neuronal type found at post-ganglionic synapses in ANS
• Curare: Blocks nicotinic acetylcholine receptors (nAChR) at the neuromuscular junction (N1)
by competing with ACh for binding site. Elicits paralysis of skeletal muscle
• α-bungarotoxin: Binds to post-synaptic receptors at NMJ (N1) and interferes with ACh 

• β and γ -bungarotoxin: Acts pre-synaptically to reduce ACh release

• Muscarinic: Metabotropic. Activated by ACh. Interaction with muscarine, water-soluble toxin.

• Five subtypes in CNS, M1-M4 are also found in peripheral tissues
• M1 receptor: Secretory glands
• M2 receptor : Cardiac tissue. Closes Ca2+ channels to reduce force and rate of contraction.
• M3 receptor : Smooth muscle and secretory glands
• Stimulatory: M1, M3, M5. Use G𝛼q to stimulate PLC resulting in IP3 and increased [Ca2+]i
• Inhibitory: M2, M4. Use G𝛼i to inhibit AC leading to reduced cAMP
• Divided by patterns of tissue-specific expression
• Coupled to signal transduction cascades in cells
• Each receptor activated or inhibited by specific drugs that have therapeutic uses
Cholinergic Receptors Specific Drugs and Therapeutic Uses

• Nicotinic receptor agonists: Nicotine. No important role in therapeutics. Recreational

stimulant. No effect on peripheral nicotinic synapses. General sympathetic effect in small
doses, result of release of CNS NT. Reversed in higher doses. Peripheral effects include
tachycardia, increased BP, and reduced GI motility. Light headed feeling due to stimulation of
nicotinic receptors on sensory nerve fibers (chemoreceptors responsible for modulating BP)
• Nicotinic receptor antagonists: Curare, Hexamethonium. Hexamethonium is an autonomic
ganglia blocker, acts on both parasympathetic and sympathetic ganglia. Treats chronic
hypertension, but it has poor specificity. Parasympathetic action
• Muscarinic receptor agonists: Bethanechol. Mimic actions of parasympathetic nervous
system. Decreased heart rate, indirect vasodilation due to NO production from vascular
endothelial cells. ACh on it’s own does not have a therapeutic use due to breakdown from ACh
esterase and ability to stimulate all cholinergic subtypes. Bethanechol is specific to M3 and not
susceptible to hydrolysis by cholinesterase. Used to stimulate GI motility, induce bladder
emptying, Pupil constriction, decrease interocular pressure.
• Examples: Contraction of smooth muscle in GI tract and relaxation of sphincters. Stimulation of
exocrine glands lead to gastric acid secretion, salivation, tearing and sweating. Contraction of
detrusor muscle and relaxation of sphincters lead to urination. Constriction of pupil and ciliary
muscle of eye lead to miosis and decreased interocular pressure.
• Muscarinic receptor antagonists: Atropine, Scopolamine. Oppose actions of parasympathetic
division. Sympathetic action. Cause range of peripheral effects like flushing, dry mouth, blurred
vision, dilated pupils, tachycardia, urinary retention, constipation, hypothermia, and central
effects like confusion, hallucinations, coma, and convulsions. Uses are pupillary dilation
(atropine), relaxation of bronchial smooth muscles, decreased gastric motility and bladder
emptying.

Pharmacology of Cholinergic Transmission

• Acetylcholinesterase enzymes terminate ACh activity rapidly present in cholinergic neuron-

effectors, synaptic junctions, and cholinergic nerve terminals.
• Butyrylcholinesterase is a related enzyme found in plasma which has broader substrate
specificity and involved in metabolism of therapeutics including suxamethonium.
• Produced by organophosphate nerve gases, and insecticides.
• Absence (excess cholinergic) induces DUMBBELS = Diarrhea, Urination, Miosis (muscle
weakness), Bradycardia, Bronchoconstriction, Emesis, Lacrimation, Salivation/Sweating
• Inhibition of cholinesterase enzymes account for effects of organophosphate nerve gases
like Serine and insecticides. Symptoms include overstimulation of parasympathetics
• Cholinesterase inhibitors: Anti-cholinesterases. Used therapeutically
Different durations of activation Long & irreversible, Medium (physostigmine), Short

• Clinical uses of anti-cholinesterases

Diagnosis and treatment of myasthenia gravis (reduced functional nicotinic receptors)
Neostigmine, physostigmine, pyridostigmine 

Slowing the progression of Alzheimer’s Disease (reduced cholinergic neurons in CNS)
Donepezil, rivastigmine 

Glaucoma (reduce pressure within eye)

Ecothioate, physostigmine
Adrenergic Receptors

• Activated by catecholamines
• 𝛼 and 𝛽 subtypes

𝛼1 Receptors

• α1 receptor: VSMC, GI sphincters, bladder sphincters, radial muscle iris. Linked to G𝛼q which
activates PLC leading to muscle contraction

• α2 receptor: GI wall, presynaptic. Linked to G𝛼i. Decreases cAMP which causes muscle
relaxation. Presynaptic receptors inhibit release of NE, important feedback mechanism.

𝛼 Adrenergic Receptors Specific Drugs and Therapeutic Uses

• α1-receptor agonists (systemic vasoconstrictors): Nasal decongestants and pressor agents.

Induce contraction, leads to vasoconstriction (mimics sympathetic)
• Nasal decongestants: Vasoconstriction in nose. Oxymetazoline, Tetrahydrozoline,
Xylometazoline, Phenylephrine.
• Pressor agents: Blood vessel vasoconstriction which increases BP, treats hypotension/
shock. Methoxamine, Phenylephrine.
• α1-receptor antagonists: Phentolamine, vasodilation which treats hypertensive emergencies
(tumor of adrenal medulla)
• α2-receptor agonists (systemic vasodilators): Decreases cAMP. Leads to vasodilation, treats
hypertension. Clonidine, Guanfacine
• α2-receptor antagonists: Yohimbine. Leads to vasoconstriction. Used to reverse sedation.
• Sympathomimetics: Drugs that mimic sympathetic division, include both 𝛼 and 𝛽 agonist
properties, include catecholamines (epinephrine, norepinephrine and dopamine).

𝛽1 and 𝛽2 Receptors

• β1 receptor: Located in heart, salivary glands, adipose tissues, and kidneys.

• β2 receptor: Located in VSMC on skeletal muscle, GI wall, bladder wall, bronchioles.
• Both 𝛽 receptors are coupled to G𝛼s which activates AC forming cAMP which activates PKA
which phosphorylates L-type calcium channels and causes increase [Ca2+]i
𝛽 Adrenergic Receptors Specific Drugs and Therapeutic Uses

• β1-receptor agonists: Sympathetic. Increases CO, used in congestive heart failure.

• β1-receptor antagonists: Atenolol, Metoprolol. Parasympathetic. 𝛽-blockers decrease heart
rate, contractility, conduction velocity, and relaxation rate. Greater effect with sympathetic
activity. Used in hypertension, angina, and acute myocardial infarction. Does not interfere with
asthma drugs. Treats anxiety.
• β2-receptor agonists: Albuterol. Parasympathetic. Treats asthma and lung disease since they
relax smooth muscle in bronchioles. Relieves bronchospasm in asthma and COPD.
• β2-receptor antagonists: Sympathetic.

Multiple transmitters released from a Single Presynaptic Varicosity

• “One neuron, one transmitter” hypothesis is Dale’s Principle but it is wrong.

• Neuron were originally classified adrenergic or cholinergic based on NT released, however
some neurons are capable of releasing multiple NT. Therefore

• Co-transmission: Ability of neuron to release two or more NT.

Co-transmission in Varicosity of Sympathetic Axon

• Three neurotransmitters. ATP, NE, Neuropeptide Y co-localized in post-ganglionic

sympathetic vasoconstrictor neurons.
• ATP acts on P2X purinergic receptors on smooth muscle cells. Activation allows Ca2+ and
Na+ to enter, leads to depolarization and opens voltage-gated calcium channels. Causes rapid
increase in tension leading to rapid contraction of smooth muscle
• NE binds to 𝛼1 receptors leading to increased [Ca2+]i. Moderately fast speed increase
• If stimulation is intense enough, Neuropeptide Y released and acts on Y1 receptor which
leads increases [Ca2+]i. Slowest increase in tension



Co-transmission in Varicosity of Parasympathetic Axon

• Capillary endothelia expresses M3 receptor. Within it, there is also endothelial nitric oxide
synthase (eNOS). Found in pre- and post-ganglionic of both sympathetic and parasympathetic
• Pre-synaptic terminal varicosity activation activates neuronal nitric oxide synthase (nNOS).
When activated, utilizes Arg to synthesize NO.
• Within smooth muscle, VIP receptor which is GPCR. When activated it reduces of [Ca2+]i
• ACh in pre-synaptic terminal and co-transmission with VIP
• Vascular endothelium causes relaxation of smooth muscle via NO.
• Nitric oxide (NO): Short lived, highly diffusible gas from eNOS. Acts pre- and post-synaptically.
• NO, ACh, and VIP act to lower [Ca2+]i, causing VSMC relaxation leading to vasodilation.
• When M3 activated, and [Ca2+]i increases, then eNOS is stimulated, and NO produced, which
diffuses to smooth muscle and activates guanylyl cyclase forming cGMP causing relaxation
• ACh and NO produce rapid phase of relaxation, and VIP produces delayed relaxation
• Co-transmission of multiple NT leads to sustained relaxation or tension depending on which
NT are activating different receptors.

ANS Coordination

• Autonomic function coordinated by interconnected structures in periphery, brain stem,

and fore-brain. These combine to form central autonomic network.
• Nucleus of solitary tract receives visceral input from cranial nerves which uses sensory
information to modulate autonomic functions in two ways.
1. Project to neurons from brain stem and spinal circuits to control simple autonomic response
2. Sends collaterals into higher levels of brain (forebrain and hypothalamus) which permits
integration of autonomic function with endocrine and behavioral response

Central Control of Autonomic Function

• Hypothalamus located at base of forebrain. It is bound by optic chiasm rostrally and the mid-
brain tegmentum caudally. It forms the floor and wall of the third ventricle. It is continuous
through infundibular stalk with posterior pituitary gland.
• It integrates information from fore-brain, brain stem, spinal cord, and endocrine systems.
Important in central control of visceral motor functions
• Hypothalamus integrates autonomic and endocrine with behavior and emotions.
• Hypothalamus plays role in regulating fluid balance, body temperature, energy metabolism
blood pressure, and electrolyte composition, drinking behavior, salt appetite, blood osmolality,
vasomotor tone, food intake, feeding behavior, digestion, metabolic rate, reproduction, hormonal
control, pregnancy, lactation, and fight-or-flight response.
• Hypothalamus functions through three main mechanisms. 1. Access sensory information
from entire body, direct input from visceral sensory system, olfactory, and retina. Internal
sensors. 2. Compare sensory information with specific set points. 3. Issue commands that
adjust responses to restore homeostasis.
Learning objectives (Unit 7):

1. Describe each subdivision of the autonomic nervous system in terms of: Preganglionic
and postganglionic cell bodies locations

Sympathetic: Preganglionic are in thoracic and lumbar regions of spinal column.

Postganglionic are either on prevertebral (collateral ganglia) or paravertebral ganglia
(sympathetic chain)

Parasympathetic: Preganglionic are in brain stem with cranial nerves III, VII, IX, X and segments
S2-S4 of sacral spinal cord. Postganglionic are nearby or in effector organs. 


2. Compare and contrast the salient anatomical and physiological features of the
parasympathetic and sympathetic divisions of the ANS

Sympathetic: Fight-or-flight. Contains adrenal gland. Post-ganglionic neurons travel in each of

31 pairs of spinal nerves. Oxygenated blood delivery. Increased blood glucose from
glycogenolysis and gluconeogenesis. Increased lipolysis. Sweating. Pupil dilates and bladder
wall relaxes.

Parasympathetic: Rest-and-digest. Not capable of stimulating arterioles, veins, VSMC, and

sweat glands. Restorative and conserves energy. Decreased heart rate. Enhanced salivary
secretion, peristalsis, and gastric release. Pupil constricts and bladder wall contracts.

3. Describe each subdivision of the autonomic nervous system in terms of: Length of
axons

Sympathetic: Short pre-ganglionic axons, long post-ganglionic axons

Parasympathetic: Long pre-ganglionic axons, short post-ganglionic axons

4. Describe each subdivision of the autonomic nervous system in terms of:

Neurotransmitters used (Cholinergic & adrenergic)

Sympathetic: Post-ganglionic releases both catecholamines, and ACh.

Parasympathetic: Post-ganglionic release only ACh.

Both: Pre-ganglionic release ACh.



5. Describe each subdivision of the autonomic nervous system in terms of: Receptors

Sympathetic: Target expresses both adrenergic and muscarinic receptors.

Parasympathetic: Target expresses only muscarinic receptors.

Both: Post-ganglionic contain cholinergic receptors for ACh.



6. Describe ANS receptors and their second messenger systems.

N1, N2: Ionotropic

M1, M3, M5: G𝛼q which activates PLC leading to increased [Ca2+]i

M2, M4: G𝛼i to inhibit AC leading to decreased [Ca2+]i

𝛼1: G𝛼q which activates PLC leading to increased [Ca2+]i

𝛼2: G𝛼i to inhibit AC leading to decreased [Ca2+]i

𝛽1, 𝛽2: G𝛼s which activates AC leading to increased [Ca2+]i

7. Describe how the sympathetic and parasympathetic divisions of the ANS work
together to produce normal physiological responses

Although divisions have opposing effects, they are often working together for precise
regulation. In tissues receiving innervation from both sympathetic and parasympathetic
divisions, both are tonically active (they provide some degree of nervous input at all times).
Increasing activity of one and decreasing activity of the other produces rapid control. Each
system is dominant under certain conditions.

8. Understand the relevancy of ANS pharmacology to organ system and/or tissue

function

β1-receptor agonists: Sympathetic.

β1-receptor antagonists: Atenolol, Metoprolol. Parasympathetic.

β2-receptor agonists: Albuterol. Parasympathetic.

β2-receptor antagonists: Sympathetic.

9. Explain how co-transmission takes place at sympathetic and parasympathetic

varicosities 


Sympathetic: Three neurotransmitters. ATP, NE, Neuropeptide Y. All increase [Ca2+]i. ATP binds
to P2X purinergic receptor which is rapid contraction. NE binds to 𝛼1 receptors which is
medium speed contraction. Neuropeptide Y binds to Y1 receptor which is slowest contraction.

Parasympathetic: Three neurotransmitters. NO, ACh, VIP. All decrease [Ca2+]i. ACh and NO
produce the fastest relaxation. VIP produces delayed relaxation.

 Unit 8 - Cardiovascular System

8.1 - Cardiac Electrophysiology and Mechanics

Overview

• Purpose: Transport blood rich in oxygen and nutrients to the body

• Intimate relationship with other organ systems (GI and respiratory)
• Beats around 100,000 times/day, Highly resistant to fatigue
• The heart has three core elements: 1. Pump (myocardial infarction, congestive heart failure),
2. Liquid in vessels (loss of blood, abnormal clotting), 3. Vasculature (hemorrhage)

Structure of the Heart

• Four chamber organ, very muscular, size of closed male fist

• Important structures: Arch of aorta, vena cava, pulmonary arteries, interventricular sulcus,
pulmonary trunk, pericardial sac and fluid.
• Arteries carry blood away from heart, veins carry blood into the heart
• Asymmetric musculature compared in left and right side (left stronger because it
overcomes all of arterial pressure (significant resistance)) Thickening of left ventricle wall.
• Size change in ventricle wall is clinically significant. Wall hypertrophy evident of cardiac failure
• In-flow valves: Atrioventricular (AV) valves. Tricuspid and Bicuspid valves
Regulate flow out of atria. Dumps into ventricles
• Out-flow valves: Semi-lunar (SL) valves. Pulmonary, and Aortic valve
Regulate flow out of heart. Dumps into arteries
• Blood cycle: Blood returned to right atrium from vena cava, it passes through tricuspid to right
ventricle, then leaves through pulmonary valve into pulmonary trunk and travels through
pulmonary arteries to lungs. Returned to left atrium through pulmonary veins. Passes bicuspid
valve to left ventricle. Leaves through from aortic valve and enters descending aorta.

The Cardiac Action Potential

• Action potential in non-pacemaker, cardiac myocytes determined by changes in fast Na+, slow
Ca2+ and K+ conductances and currents.
• Length of cardiac action potential is much longer (300 ms) than skeletal (3 ms)
• Presence of gap junctions allows coupling of current flow
• Inward current: Depolarization. Faster Na+ and Slower Ca2+
• Outward current: Hyperpolarization. K+ (several different ones)
Ito is initial repolarization. IKur, IKr, IKs are rest of repolarization
• Vrest is very negative (-90 mV) due to slow potassium conductance
• Phase 0: Depolarization. Increased PNa, and decreased PK (inactivation of Ito)
• Phase 1: Peak.
• Phase 2: Plateau. Contraction. Increased PCa, and decreased PNa & PK
• Phase 3: Repolarization. Increased PK, and decreased PCa
• Phase 4: Rest. Greatest PK
Ca2+ signaling in Cardiac Muscle

• Ca2+ is key modulator of cardiac muscle

• DHPR is a calcium channel, not coupled to RyrR, instead it activates RyrR in CIRC
• Depolarization causes voltage-gated calcium channels in sarcolemma
• Catecholamines: Activates AC, leads to elevated PKA, Binds to 𝛽 receptor
PKA phosphorylates voltage-gated calcium channels, increasing PCa
PKA phosphorylates TnI which inhibits Ca2+ and TnC binding (sensitivity)
PKA phosphorylates phospholamban which increases CaATPase in SR
Keeps Ca2+ supply in SR filled
• In systole: Increased [Ca2+]i via DHPR, RyrR, CIRC, voltage-gated calcium channels in
sarcolemma. Results in calcium sparks. Ca2+ binds to TnC allowing cross bridge to proceed.
• In diastole: Decreased [Ca2+]i via CaATPase in SR, or CaATPase/Na+-Ca2+ exchanger in
sarcolemma (antiporter for 1 Ca2+ for 3 Na+, this is electrogenic) in sarcolemma
• Decreasing Na+/K+ ATPase, increases [Ca2+]i which diminishes concentration gradient. Na+/
Ca2+ doesn’t work as efficiently.
• Ouabain keeps Ca2+ inside of the cell, useful in cardiac failure (stronger contractions)

Conduction System of the Heart

• Force generating cardiac muscle is bulk of atria and ventricles (cardiac myocytes)
• Modified muscle cells (purkinje fibers) that act like neurons make up conduction system
• Conduction system ensures contraction and relaxation takes place in proper order and timing
• Sinoatrial (SA) node: Pacemaker in right atrium. Sets rhythm of heart.
• Atrioventricular (AV) node: Electrical relay between atria and ventricles. Introduces delay.
• Nodes are linked by internodal pathways
• Bundle of His: Bundle of conducting fibers.
• Purkinje fibers: Descend through septum towards apex, extend up walls and wrap around.
• Heart continues to beat removed from body if maintained within ionic environment

Conduction Velocity Through the Heart

• Normal sinus rhythm: Heart beat initiated by SA node, not initiated by ectopic pacemaker. SA
node discharging AP 60-100 times per minute. Conduction timings through system are normal
• Ectopic pacemakers: Something that shouldn't be where it is. Arises from diseased state, SA
node no longer functions as pacemaker. Other parts of the heart begin to pace it.
• Conduction velocity: SA node (0 ms) > AV node (60 ms) > Bundle of His (160 ms)
• Slowing of conduction velocity gives ventricle time to fill with blood before AP fills purkinje
fibers which causes ventricle to contract which ejects it to pulmonary trunk and aorta.

Cardiac Action Potentials in SA Node

• AP in SA node is quite different. No phase 1 or 2. Slower depolarization.

• Phase 0: Depolarization. Slope flatter. Ca2+ based instead of Na+ (Calcium channels slower)
Voltage-gated Ca2+ channels
• Phase 3: Repolarization. Opening of voltage-gated K+ channels (K+ efflux)
• Phase 4: Constant depolarizing characteristic due to slow activating Na+ current (funny)
Typically Na+ currents are very fast, but this one is slow
How does the ANS influence cardiac function?

• Inotropic: Contractility of the cardiac muscle

Positive inotropic state: increased contractility (Increase [Ca2+]i)
Negative inotropic state: decreased contractility (Decreases [Ca2+]i)
• Chronotropic: Frequency of contraction (SA node sets this)
Positive chronotropic state: increased frequency (Speeds heart)
Negative chronotropic state: decreased frequency (Slows heart)
• Dromotropic: Conduction velocity 

Positive dromotropic state: increased conduction velocity
Negative dromotropic state: decreased conduction velocity

Sinus Rhythm: Tachycardia

• Tachycardia results from increased sympathetic tone (releases epinephrine)

Positive ionotropic, chronotropic, and dromotropic event
• Sinus tachycardia: Heart rate above 100 bpm, caused by psychological (panic, anxiety) or
physical stress (anaemia, hypoxia, exercise, fever, intoxication, shock etc). SA node is still
pacemaker, and rhythm is still normal. SA node discharges faster AP.
• Circulating Epi circulates longer where NE is instantly taken up so it is shorter
• Increased NE and Epi from adrenal glands cause tachycardia

• How would you treat anxiety? β-blockers effective in slowing down the heart rate.
• Innervation of muscular of Heart is largely sympathetic (although SA node receives
parasympathetic). Parasympathetic does not play a role in force of contraction

Sinus Rhythm: Bradycardia

• Bradycardia results from increased parasympathetic tone

Negative ionotropic, chronotropic, and dromotropic event
• Sinus bradycardia: Heart rate below 60 bpm. Normal in well-trained people and the elderly
• Athletes at rest dominated by vagal tone (parasympathetic system). Heart rate low but cardiac
output is large.
• All persons react with sinus bradycardia during hypothermia, hypothyroidism, jaundice,
increased intracranial pressure, treatment β-blockers, and in sinus node disease.
β-blockers reduces sympathetic tone, which reduces heart rate
• ACh, activating muscarinic receptors, and vagal stimulation
ACh used by parasympathetics on target

Pacemaker potentials in Nodal Tissue

• ANS play role in regulating heart rhythm, but not responsible for starting it
• Key part affected by sympathetic and parasympathetic is rate of depolarization in phase 4
• Sympathetic stimulation increases rate of discharge. Increases slope of phase 4. Increases
rate of depolarization (threshold met faster, AP more frequent)
• Parasympathetics decrease rate of discharge, decrease slope of phase 4. Broader AP.
The Heart as a Pump

• Cardiac cycle: Sequence of mechanical and electrical events that repeat every heart beat.
• Electrical events: Initiation, spread, and conduction
• Mechanical events: Pumping motion.
• Duration of cardiac cycle (s/beat): 60 (s/min) / Heart rate (beats/min)
Normal around 60 bpm
• Valves opening and closing at appropriate times. Change due to pressure
• Diastole involves increased volume
• Systole involves Increased pressure

Mechanical Events

1. Late diastole: Both ventricles and atria are relaxed. Blood passively fills. (1)
2. Atria systole: Atria contracts, squeezes any remaining blood. AV valve closes. (1)
3. Isovolumic ventricular contraction: Ventricles contract. All valves are closed. No change in
blood volume in ventricle. Conduction spreads down bundle of His into purkinje fibers. (2)
4. Ventricular ejection: SL valve opens. Blood ejected rapidly then slowly. SL valves close. (3)
5. Isovolumic ventricular relaxation: All valves closed. No change in blood volume. (4)
Expansion of volume causes AV valve to re-open

Volume Changes Throughout the Cardiac Cycle

• End diastolic volume (EDV): Measured after AV closes

• End systolic volume (ESV): Measured after SL closes
• Stroke volume: Volume of blood ejected in every heart beat. EDV and ESV difference
SV = EDV - ESV
• Late stage 1: Atrial systole. Volume increases slowly. EDV measured.
• Stage 2: Isovolumic ventricular contraction. Volume = constant
• Stage 3: Volume decreases rapidly. ESV measured.
• Stage 4: Isovolumic ventricular relaxation. Volume = constant
• Dicrotic notch: As soon as AV shuts, causes slight increase in pressure
• End of 1: when AV valves close. Valve events define transition of cardiac cycle phases.

Pressure Volume Loop

• A: AV valve opens.
• A-C: Small change in pressure, large change in volume.
• C: SL valve closes EDV.
• D: SL valve opens.
• E-D: Pulse pressure. Ejection phase.
• F: AV valve closes.
• C-F: Systole, F-C: Diastole
• SV, PP, and EF calculated from this.
• Capable of readily seeing changes in stroke volume (indicator of heart health)
Cardiac Volumes, Pressures, Flows as Metrics for Cardiac Performance

• Stroke Volume: SV = EDV - ESV

Volume of blood ejected from ventricle with completion of cardiac cycle
• Cardiac Output: CO = SV * HR
Total of blood pumped per unit of time
• Ejection Fraction (EF): EF = SV / EDV
Measures healthiness of heart. Describes percentage of ejected blood
Healthy adult: Always < 0.55, anything less means SV is compromised

Stroke Volume

• EDV determined by venous return from upper and lower body

• Total Peripheral Resistance (TPR): Impedance to blood flow in arteries. Resistance of blood
leaving heart. If this is high, then SV is compromised.
• Contractility: Strength of ventricular contraction. Varies directly with EDV. Affected by
sympathetic division.
• Blood increase in fight or flight mainly goes toward skeletal muscles
• If stroke volume is reduced, heart is start to fail as a pump

Regulation of Stroke Volume: Pre-load and After-load

• EDV is workload (pre-load) on heart prior to contraction 


SV is directly proportional to preload & contractility
Filling ventricle with blood stretches the muscle (passive)

• Total peripheral resistance (TPR) is after-load which impedes ejection from ventricle 




From Contractile Filaments to Regulated Pump

• Tension increases rapidly in cardiac muscle than skeletal, less elastic components
• Passive tension is influenced by EDV

Frank-Starling Law of the Heart

• Frank-Starling Law: Strength of ventricular contraction varies directly with EDV

Intrinsic property of myocardium, not result of endocrine function but influence by it
As EDV increases, myocardium is stretched more, causing greater contraction & SV
• Textbook definition: “The mechanical energy set free in the passage from the resting to the
active state is a function of the length of the fiber."
• As EDV increases, stroke volume increases. Changing length of cardiac muscle and
optimizing tension. Changes contractility of muscle.
• Increased sympathetic tone results in larger stroke volume.
Control of Contractility

• At any given EDV, contraction depends upon level of sympathoadrenal activity

NE & Epi produce an increase in HR & contraction (positive inotropic effect)
Due to increased [Ca2+]i in sarcomeres
• High [Ca2+]o increase DFCa, more Ca2+ enters cell before systole
• Low [Ca2+]o decreases extrusion through pumps, more Ca2+ in the cell after systole

Cardiac Output (CO)

• Cardiac Output is a function of HR and SV

• HR determined by rate of depolarization in phase 4 of SA node
Slowing (parasympathetics) reduces phase 4 slope, Faster (sympathetic) increase slope
• Sympathetics and circulating Epi also affect contractility
• SV determined by force of contraction in ventricular myocardium.
Force influenced by contractility, TPR, and length-tension of muscle fibers
Length-tension varies with venous return
• Sweat glands only get sympathetics, Increases AP when stimulated
• Sympathetics adjusts TPR and redirects flow. Constricts veins which increase EDV and SV

Venous Return

• Venous return: Return of blood to heart via veins 


• Controls EDV & thus SV & CO 

• Dependent on: Blood volume & venous pressure. Vasoconstriction caused by Sympathetic.
Skeletal muscle, and respiratory pumps. Pressure drop during inhalation

Variability of the Structural Components of Arteries and Veins

• Internal radius, wall thickness, and proportions of endothelial cells, elastic fibers, collagen
fibers, and VSMC are variable in veins and arteries.
• Arteries: Aorta, medium artery, arteriole, pre-capillary sphincter
• True capillaries are in-between arteries and veins, and contain only endothelial cells
• Veins: Venules, vein, vena cava
8.2 - Structure & Organization of Vessels, and Hemodynamics


Function of the cardiovascular system

• Distribution of respiratory gases, nutrients, and chemical messengers (endocrine system)


• Dissipation of heat (thermoregulation) 

• Mediation of inflammation 

• Host defense responses against invading microorganisms

Heart Pumps in Series

• Heart is two pumps, arranged in series (not parallel). Blood returns to right side, and leaves
then enters pulmonary circulatory system, returned to left side, expelled to systemic circulation
• Output of left and right side operate independently (connected in series)
• If pumps are in series, then vasculature is in parallel.
• Matching of cardiac output between left and right is very key (regulated tightly)
If left exceeds right side in cardiac output by 2%, drains pulmonary circulation quickly
If right exceeds left side by 2%, overflow pulmonary circulation (drowning in own fluids)
• As ventricles contract, they impart energy to blood required to circulate vascular system.

Systemic Organization

• Cardiovascular system organized based on location and amount of pressure.

1. Pulmonary circulation: Carries blood from heart to lungs, and back to heart. Lower pressure,
high volume
2. Systemic circulation: Carries blood from tissues to heart, and back to heart. Higher
pressure, low volume.
1. High pressure system: Left ventricle during systole, extends through systemic circulation to
systemic capillaries.
2. Low pressure system: From systemic capillaries through right heart and through
pulmonary arteries. Blood comes back to left ventricle when in diastole
• Vasculature in parallel means no organ system is dependent on upon another for blood
supply. Ex. Lower limbs independent from upper limbs. One exception (Portal circulation, blood
absorbed from small and large intestine enter portal and brings it to the liver before returning)
Functional Structure of Arteries and Veins

• All blood vessels (besides capillaries) made up of three layers

• Tunica intimia: Inner most layer of endothelial cells that line lumen. Low friction surface which
means low drag or resistant. Inflammation disturbs flow of blood.
• Tunica media: Medium layer. Ring structure. Elastic fibers and VSMC present.
• Tunica externa (advanticia): Outer layer. Loose connective tissues (fibroblast, collagen)
• Four essential building blocks of wall: Endothelial cells, Elastic fibers, Collagen fibers, VSMC
• Endothelial cells: Single sheet. Lines all vasculature. Junctions join them together.
• Elastic fibers: Core of elastin. Stretch >100% of their length. Concentric arrangement.
Covered with microfibrils (glycoproteins)
• Collagen fibers: Much less distensible. Stretches 3-4%. Function is structural integrity,
prevents walls from expanding. Most common are type 1 and 3 (fibrillar)
• Vascular smooth muscle cells (VSMC): Arranged in circular layers. Modulate lumen
diameter. Regulate blood flow and distribution.

Functions of Various Components of the Circulatory System

• Arteries: Distribution system. Transports blood under high pressure to tissues. Pressure
reservoir. Not very distensible.
1. Elastic Arteries: Large arteries (aorta, pulmonary). Tunica media dominated by elastic
fibers, and arranged in multiple circular layers. Thick VSMC layers. Withstands enormous
pressure from systole of right and left ventricles. Allows for some stretch, but very restricted.
Prevents blowing out arteries. Empties into muscular arteries.
2. Muscular Arteries: Tunica media dominating is VSMC. More diameter regulation.
• Arterioles: Regulatory system. Control blood flow through tissues. Only single continuous
layer of VSMC, but richly innervated. Important regulators of blood pressure and flow
• Capillaries: Diffusion and filtration system. Sites of exchange of fluid, nutrients, electrolytes,
chemical messengers. Exchange between plasma and interstitial. Only consists of single layer,
no collagen, elastin, or VSMC. Drain into venules.
• Venules: Drainage system. Receives blood from capillaries
• Veins: Collection system. Low pressure return of blood to heart. Volume reservoir. Highly
distensible unlike arteries. Filled with valves in order to prevent back-flow, ensure progression.

Branching Along the Cardiovascular System

• Vessels branch along cardiovascular system. At each branch point, combined cross
sectional area of daughter vessels exceeds parent vessel area
• Expansion of cross sectional area law.
• Because of this law, steepest increase occurs in microcirculation
• Capillary only 3um, but total cross sectional area exceeds first order arteriole (30nm)
Hemodynamics

• Hemodynamics: The study of the physical laws of blood circulation. Therefore it includes
both "content" (blood) and "container" (blood vessels). Application of fluid dynamics.
• Rule #1: Fluid cannot move through a system unless energy is applied to it. In fluid dynamics
this energy is in the form of ΔP, or pressure gradient between two points in the system. P = pgh
Pressure (units) = Fluid density (units) * Gravity acceleration (units) * Height (units)
• Two points of pressure gradient: Between aorta and vena cava (inferior)
• Pressure within fluid must also be taken into account.
• Blood flow is driven by a constant pressure head across variable resistances

Effects of Gravity Pressure within Veins

• Gravity affects blood within vessels (specifically veins)

• Blood pulled down by gravity. Standing, it is taken away from head and goes towards feet.
Laying down makes this disappear. Pools in lower extremities (ankles swell, dizziness)

Factors affecting blood flow

• Blood flow is driven by a constant pressure across variable resistances.

• Blood flow: Volume of blood that flows through any tissue in a given time (Units: mL/min)
• Cardiac output: Total blood flow, i.e. volume of blood circulating through either systemic or
pulmonary blood vessels per minute.
• Resistance: Anything that impedes flow of blood
• CO = SV * HR
• CO = F = HR * SV (Cardiac Output = Flow)
• Right and left CO of the heart should be the same (symmetrical)

Hemodynamics

• Electricity: ΔV = IR
• Liquids: ΔP = FR
ΔP / R = F
• Vascular resistance: Opposition to blood flow due to friction between the blood and vessel
walls or geometrical differences.
• Flow driven by pressure gradient (mode of force applied by contraction of cardiac muscle)
• Pressure gradient along every point of the vessel
Pressure Gradient within Cardiovascular System

• Pressure gradient along every point of cardiovascular system

• Left side closer to heart than right side, Higher pressure in P1 than P2
• Resistance is the impediment of blood flow between these two points

Poiseuille’s Law

• F = ΔP (𝜋 * r4) / (8 * 𝜂 * l)
r = radius (length)
𝜂 = viscosity of blood (N*s /m2)
l = length of vessel (length)
• Flow is directly proportional to the axial (linear) pressure difference (ΔP)

• Flow is directly proportional to the fourth power of vessel radius (r4)
Radius has enormous impact on blood flow and distribution through vessel
Radius changed by VSMC (contraction constricts vessel, reduces flow)

• Flow is inversely proportional to both the length (l) of vessel and the viscosity (𝜂) of fluid
If length/viscosity goes up, blood flow goes down. Although, normally constant for us

Pressure-Flow and Pressure-Resistance Relationships

• If vessels rigid tubes, then linear relationship between pressure and flow (Poiseuille’s Law)
• For normal veins, there is non-linear relationship. At first, flow doesn’t increase that much.
Increasing pressure in stretchy object expands it before building pressure.
• Modest pressure increase causes sharp resistance drop due to the radius increasing
• As resistance drops, then flow increases similar to a linear relationship since idealized
pressure maximizes stretch on wall.
• Increasing sympathetic tone affects walls of vessels by vasoconstriction. Shrinks and
stiffens vessel. Larger pressure needed to overcome resistance of vessel

Vessel volume is a function of the vessel wall flexibility and the transmural pressure

• If pressure changes across wall of vessel, it changes volume of that vessel (Similar to balloon)
• Transmural Pressure (PT): Difference in pressure between inside and outside of vessel wall.
PT = Pint - Pext
Interior blood pushing outward (Pint)
Pressure exerting against the walls (Pext)
• Key parameters: Pressure, and characteristics of wall (stiffness/flexibility)
• Large intravascular volume has High PT in flexible vessel
• Small intravascular volume has Low PT in non-flexible vessel
Vascular Capacitance (VC)

• Vascular capacitance: Volume of blood contained in a vessel for a given PT

• VC = V / PT
Capacitance = Volume (mL) / PT (mmHg)
Capacitance proportional to volume, and inversely proportional to PT
• Linked to distensibility and compliance

Distensibility (D) and Compliance (C)

• D = ΔV / (ΔP * Vi)
• C = ΔV / ΔP or C = D * Vi
• Distensibility (D): Ability of an object to get stretched. Similar to elastance. Pressure/volume.
• Compliance (C): Buffering capacity of vessel. Opposite of elastance. Volume/pressure.
Represented by slope of Relative volume over Transmural pressure
• Arteries and veins differ greatly in distensibility and compliance
Veins more compliant (high volume), Arteries more distensible (high pressure)
Aorta has shallow slope, Vena Cava has steep slope until reaching limit
Arteries are less compliant due to thicker layer of smooth muscle in wall

Law of LaPlace - Blood vessels must overcome wall stress to be able to contract

• Tension in arterial walls and veins is an example of LaPlace’s Law

• This geometrical law applied to a tube or pipe says that for a given internal fluid pressure, the
wall tension will be proportional to the radius of the vessel
• Law of LaPlace: T = PR (Applies to only thin walls, but this doesnt work in arteries)
Tension (force*length/area) = Pressure (force/area) * Radius (length)
• Increasing diameter means it needs to overcome tension in wall
• PT exerts force on wall. Tension prevents it from ripping apart, supplied by structural integrity
(VSMC and strength of connective tissue). Opposing force

Wall Stress

• Wall Stress Equation: S = (P * r) / w

Stress (force/area) = [Pressure (force/area) * Radius (length)] / Thickness (length)
• Law of LaPlace modified for blood vessels
• Tension and stress related to vessel radius. Small radii vessels withstand higher pressure
• Because they have single layer of cells, thin wall with small radius. Reduced wall tension.
• In arteries and veins, vessels with thick walls relative to their radius are able to withstand
higher pressure than vessels with small r/w ratios 

• Wall tension and wall stress are true forces that must be overcome to contract blood vessels
Pressure within a Blood Vessel

• Pressure is same everywhere, but wall tension is different in points on the balloon
• Small radii, little wall tension. Large radii, more wall tension
• As ventricle undergoing systole, aorta distends slightly to accommodate flow. Increasing radii
increases tension. This reverses on the other side.
• Arteries have thicker walls due to being pressure reservoir, they carry higher blood pressure
• Veins have thinner walls since they don't carry large pressure

Clinical correlation: Effect of Aging on Vessel Characteristics

• Aging changes vasculature, hardens arteries. Vessels lose elastic properties which makes
them unable to distend as much
• Same change in volume exerts higher pressure on wall of vessels as age increases
ΔV = 30 each time but ΔP increases

Systemic Organization of Blood Vessels

• For each segment of cardiovascular system, variables change a lot

• Variables in cardiovascular system: Number of vessels, Radius of vessel, Aggregate cross-
sectional area (Branching), Mean linear velocity of blood flow, Relative blood volume,
Circulation time, Pressure profile, Structure of the vessel walls, Elasticity of vascular walls
• Pathway of cardiovascular system from aorta to capillaries involves branching
Velocity drops during pathway which is important because exchange is happening
Pulmonary has greater area than systemic capillaries

How Key Parameters Change Along the Cardiovascular System

• Cardiovascular System: Aorta —> Small arteries —> Arterioles —> Capillaries
And Vena Cava <— Veins <— Venules <— Capillaries
• # units (N): Increases
• Internal radius (ri): Decreases
• X-sectional area: Decreases
• Aggregate cross-sectional area: Increases
• Aggregate flow: Constant (similar to CO)
• Linear velocity: Decreases
• Single unit flow: Decreases


How Volume Changes Along the Cardiovascular System

• Total blood volume for the average human is about 5 L.

• In heart, 360 mL. The rest is divided between circulation systems.
• Vast majority in systemic circulation, but not present equally at each point
Particularly, in small and large veins (volume reservoir)

How Pressure Changes Along the Cardiovascular System

• Cardiac Output is the same for both sides

• However, systemic resistance is higher than pulmonary resistance
• Pulse pressure much higher in systemic than pulmonary circulation
This is important because large pressure gradient in pulmonary would damage lungs
• Largest pressure drop occurs in arterioles
Single VSMC layer, greatest resistance
Pressure and flow regulated at this point
• Pressure gradient drives flow from left to right side

How Aggregate Resistance Changes Between Arterioles and Capillaries

• Arterioles have greatest pressure drop because aggregate resistance is much higher
Regulation of blood flow and pressure
• Capillaries are smaller and higher resistance than arterioles, but they’re more abundant
• Rtotal = Ri/N
Individual resistance (Ri)
Number of units (N)
• Example of importance of aggregate structures in cardiovascular system
• Aggregate: Single numerical value representing every component functioning together as one
8.3 - Arterial Pressure Regulation And Cardiac Output


Physical laws governing blood flow and blood pressure

• ∆P = FR
• Pressure gradient: Aortic pressure (high) —> Central venous pressure (low)
• Resistance: Depends on Vessel radius, Vessel length, Blood viscosity (mostly constant)
• Key principle variable: Mean arterial pressure (Pa)
Patient is hypertensive or in shock if it is off. Must be controlled appropriately
• All organs see same Pa, however there are some pressure drops
• In cardiovascular system, pressure never reaches equilibrium
• ΔP of 85 mmHg in cardiovascular system

Factors regulating total peripheral resistance (TPR)

• Total peripheral resistance: Combined resistance of all vessels

• Vasodilation —> Resistance decreases
• Vasoconstriction —> Resistance increases
• Example: Radius of the vessel changes vessel resistance
Small radius has smaller rate of flow, and vice versa
Half of the radius results in half of the flow (directly proportional)
• Important in vasoconstriction and vasodilation



Pulse Pressure

• Pressure is measured when left ventricle contracts and blood is ejected into aorta
• Maximum pressure is the systolic pressure
• Minimum pressure is the diastolic pressure
• Pulse pressure (PP): (Systolic pressure) - (Diastolic pressure)
PP = Ps - Pd
Representation of force generated by heart with every contraction
Typically around 40 mmHg, Useful to predict myocardial infarction (male patient >60)
If pulse pressure is elevated (>60), then they are at risk for cardiovascular incident
If pule pressure drops (<40) indicative of poor heart function



Calculating Blood Pressure

• Pulse pressure: PP = SP - DP or PP = Ps - Pd
• Mean arterial blood pressure (MABP or Pa): = Pd +1/3(Ps -Pd)
• Example: Ps = 120, Pd = 60.
PP = 120 - 60 = 60
Pa = 60 + 1/3(120 - 60) = 80
Pa closer to Pd than Ps
• Pa is always weighted closer to diastolic pressure
Dependent on how much time heart spends in diastole or systole (more time in diastole)
Pulse Pressure Throughout the Arterial System

• Two elements of heart involved in pulse pressure. Function of left ventricle, and way aorta
behaves when receiving bolus of blood which is under pressure.
• Two factors that determine pulse pressure:
1. Stroke volume: The amount of blood injected into arteries by each heart beat.
2. Arterial Compliance: Determined by the elasticity of the arterial system. Flexible arteries
have a high compliance. Stiff arteries have a low compliance.
More distensible = Higher compliance
More stiff = Less compliance

Relationship between aortic volume and pressure

• Example: Psystolic = 130 mmHg, Pdiastolic = 85 mmHg

• Then pulse pressure = 130 - 85 = 45 mmHg
• And Pa = 85 + 1/3(130 - 85) = 100 mmHg
• As blood is injected into aorta, aortic pressure increases. Increasing stroke volume will
therefore increase aortic pressure change during injection
• Two most compliant arteries are aorta, and pulmonary artery. Reason for greater
compliance is the abundance of elastin
• When aorta receives bolus of fluid, it is able to expand. Elasticity dampens pressure surge.
• Without compliance, the pulse pressure would be higher and damage the vessel wall
Less compliance —> Higher Ps —> Higher PP
Therefore stiffing is very problematic

More Compliant Aorta Results in Smaller Pressure Change during Ventricular Ejection

• Relationship between changes in volume (ΔV) and compliance. For a given stroke volume
(ΔV), aortic pulse pressure is increased when compliance is reduced
• Aortic compliance and stroke volume are both influential in pulse pressure
• Highly compliant: Accommodates volume change without large pressure change
• Low compliant: Same change in volume creates much larger pressure change
• Age also plays a factor. With increasing age, for the same change in volume, there is larger
pressure change (PP)
• Increasing SV results in larger PP regardless of compliance
• If SV is constant, determinant of PP is compliance of vessel

Modeling Complexities of The Arterial System and Their Effect on Pulse Pressure

• PP changes from high (aortic/pulmonary) to low compliance (muscular arteries)

• As compliance decreases, Ps increases and Pd decreases
This elevates pulse pressure because it is the difference between them
• Pa should be the same despite this. PP changes but Pa doesn’t (except when diseased)
Aortic compliance and pulse pressure

• A highly compliant aorta (i.e., less stiff, normal aorta) has a smaller pulse pressure for a given
stroke volume into the aorta than a stiff, low compliant aorta. 

• A larger stroke volume produces a larger pulse pressure at any given compliance. 

• Aortic compliance decreases with age due to structural changes, thereby producing age-
dependent increases in pulse pressure. 

• For a given stroke volume, compliance determines PP and not Pa
• However, because vessels display dynamic compliance, increasing the rate of ventricular
ejection (occurs with increased ventricular ionotropy) will increase the pulse pressure compared
to the same volume ejected at a lower rate.
• Volume-pressure relationship represents compliance
• Dynamic compliance: Compliance of the vessel is dependent upon magnitude of volume
change the rate of volume change
Addition of positive ionotropic agent results in increased SV

Blood pressure values: what do they mean?

• Pulse pressure (PP): SP-DP or Ps-Pd

• Mean arterial blood pressure = MABP or Pa
Pa = Pd +1/3(Ps -Pd)
• CO = SV * HR (CO is total flow)
• ΔP = FR (hemodynamics)
• ΔP is essentially Pa
• F = CO
• R = total peripheral resistance (TPR)
• Rearranged into: Pa = CO * TPR
Easier to remember, and allows us to see how multiple variables impact Pa

SV, HR, & systemic vascular resistance interact in affecting Pa

• Mean blood pressure is controlled by changing total peripheral resistance and/or cardiac
output —> Pa (mmHg) = CO (mL/min) x TPR (mmHg * min / mL)
• TPR is usually used in this class, but sometimes it is seen as SVR, these are interchangeable

• Cardiac output (CO) is controlled by sympathetic and parasympathetic divisions
Main factors: Heart rate (sympathetics/parasympathetics), Stroke volume (sympathetics)
Increased HR means CO increases which increases Pa
• Total (systemic) peripheral resistance (TPR) controlled by nervous and chemical means to
effect constriction/dilatation of
Arterioles: Learn this
Venules: As they are constricted, blood goes to heart. Increases venous return
Increasing venous return raises EDV —> Raised SV —> Raise CO —> Raise Pa
Changing one has a cascade effect
As they are dilated, reduced venous return, reduced EDV, SV, CO, Pa
Control of blood pressure

• Mean blood pressure is controlled by changing total peripheral resistance and/or cardiac
output.
• Facet filling balloon is CO (volume of blood ejected from LV to aorta. As fluid fills balloon, this
builds pressure since it is elastic. Wall tension is generated
• Pressure generated is dependent on peripheral resistance (outflow). Not holding outflow, water
rushes out and no pressure builds. Holding outflow builds pressure and wall tension
• Tightness of TPR is determinant of Pa
• Modulation vasomotor tone (constriction/relaxation) influences Pa
• Anything that increases pressure, will increase Pa

HR, SV, & SVR effects on Arterial Pressure

• If an increase in HR is balanced by a proportional and opposite change in SV, mean arterial

pressure does not change 

Note that the decrease in in SV results in diminished pulse pressure 

As the diastolic pressure increases, the systolic pressure decreases
• An increase in stroke volume with no change in CO will not yield a change in mean arterial
pressure 

The increased SV increases pulse pressure

As systolic pressure increases, diastolic pressure decreases
• When CO increases, Pa increases. That change in Pa that is specifically due to CO. Whatever
is causing CO, the change should be independent to Pa
• Effect of change in CO on PP is greatly influenced wether it is caused by SV or HR.
• If elevated HR, but balanced by decrease in SV. Pa stays the same.
Understand variables of each equation

Example 1: Change in HR

• First two pressure waves:

Diastolic: 80 mmHg, Systolic: 129 mmHg

Pa: 93 mmHg, HR: 72 bpm
• After the 2nd beat:
Diastolic: 70 mmHg, Systolic: 130 mmHg
Pa: 93 mmHg, HR: 60 bpm


• SV increases to maintain CO

• Diastolic pressure drops because SV increases, systolic pressure rises.
• After second beat, HR decreases. Due to longer period of time, allows lower diastolic
pressure.
• This would reduce CO which makes us dizzy so body prevents this. SV increased to maintain
CO and adequate supply to organs. Because SV increases, this increases PS. Difference is the
same so Pa is constant and CO maintained
Example 2: Exercise

• CO is increased so skeletal muscles gain enough oxygen

Large mass proportionally of the body
• Pa is maintained due to vasodilation in vascular beds of working skeletal muscles. Sufficient
mass so it is a reasonable resistance drop.
• After second beat, PS and PD both increase. PP increases but Pa does not change
• Increased CO but decreased TPR so there is not a change in Pa.

Summary of the effect of dynamic exercise on mean arterial pressure

• Higher SV and HR which increase CO. Increased PP because we increase systolic but reduce
diastolic. At same time, vasodilation in vascular beds, SVR drops.
• While CO increases, TPR decreases in same amount to resist Pa change

Example 3: ↑ CO by ↑ SV with no change in HR

• HR is held constant so increased CO is from SV

• Increased PP result of higher SV, and reduced compliance of vessel wall
• After second beat, SV, HR, PP, PS, PD, and Pa all increase
• This pushes PP into compliance curve where compliance starts to decrease
• Relevant in increased BP

Effect of increased SVR on Pa and PP

• ↑ SVR —> ↓ Vessel radius —> ↓ Aorta outflow —> ↑ Aortic volume —> ↓ Aortic compliance
—> ↑ PP and Pa —> ↑ Aorta outflow
• Aortic compliance decrease due to stretching wall (filled up)
• Aortic pressure allows heart to overcome systemic resistance and flow into the next vessel
Factors Controlling Blood Pressure

• Pa = CO * TPR
• CO = SV * HR
• ↑ Peripheral resistance = ↑ mean arterial pressure
• ↑ Cardiac output = ↑ mean arterial pressure

• ↑ Stroke volume = ↑ mean arterial pressure

• ↑ Heart Rate = ↑ mean arterial pressure
• ↑ Blood Volume = ↑ mean arterial pressure
• ↑ Blood Viscosity = ↑ mean arterial pressure

Age, race, gender, diet, body weight and arterial pressure



• BP is tracked for virtually every patient. Change in BP is clinically significant.120/80 normal?
No, the actual normal values are below
• True normal human systolic pressure is 100 – 110 mmHg and the corresponding diastolic
pressure is 60 – 70 mmHg
• In Western societies, arterial pressure depends on age. BP is higher among Western African
Americans living but lower in aboriginal Negroid populations. BP is higher among men then
premenopausal women of the same age

• PS rises entire life. PD rises until the 6th decade of life then remains constant 

• Higher BP is associated with dietary fat, salt, obesity, excessive alcohol, potassium, calcium
intake, physical activity, and stress.

Regulation of blood pressure

• How pressure is measured physiologically

• Short term: Baroreceptors. Neural based. Reflex.
• Long term: Kidney via RAAS. Endocrine based, multi-system

Homeostatic Mechanisms for regulating Pa

• Feedback loop responsible for regulating Mean arterial pressure

• Elevated Pa triggers sensor (baroreceptors) which triggers a signal to brain stem nuclei.
Measured value is compared to set point, if they are different. Command by brain to effectors to
modulate Pa (change heart rate, resistance of vascular beds, release Epi)

Feedback Loops

• Short term (Seconds to minutes): Neural reflexes in Heart, Blood vessels, Adrenal medulla.
Ex. Getting up from chair, BP drops, triggers baroreceptors to increase HR.
• Long term (Hours to days): Multiple pathways in Blood vessels, Kidneys


Mean arterial pressure and its regulation

• Intrinsic control: Factors inherent in vessels themselves. Distensibility of vessel wall produces
recoil. Independent of innervation/hormonal changes.
• Extrinsic control: Chemical messages which evoke a response in the vessel (ex. NO)
Neural control (short term)

Hormonal control (long term)
Control of blood vessel radius, and blood volume
Baroreceptors (fastest)
• Changes in metabolic status of tissue linked to CO2. When there is increased CO2, then the
vessels dilate to provide more blood to it so it can be carried to the heart

Neural mechanisms for regulating arterial blood pressure: The Baroreceptors

• Mechanoreceptors in arteries. Part of feedback loop (Discovered by Corneille Heymans)

• Baroreceptor reflex is fastest tool for regulating BP. It changes HR, contractility, and TPR.
• Two locations of baroreceptors: Carotid sinus, and aortic arch. Found in highly compliant
regions of the vessel walls
• Mechanosensors sense change in wall tension of vessel where they are located
• When tension/pressure builds up, it applies stretch to baroreceptor. Results in increased
discharge of AP. If BP drops, then baroreceptor not stretched and AP firing rate decreases
• Like most sensors, it has a baseline AP firing rate. Increases or decreases based on BP
• Information sent to vasomotor portion of brainstem, goes to NTS.
• Output of nucleus of the solitary tract (NTS) is three nuclei that have common function.
1. Cardiac decelerator —> Reduced SA node firing rate, reduced HR.
2. Cardiac accelerator —> Increases SA node firing rate and contractility of ventricle walls
3. Vasoconstrictor —> Constricts arterioles and veins

Hormonal (long term) control of blood pressure

• Control of blood vessel radius: Epi, Angiotensin II, Vasopressin


• Control of blood volume: Anti-diuretic hormone (vasopressin), Aldosterone 

• Control of heart rate and stroke volume: Epi
• Changes in sympathetics affect vasomotor tone
• Angiotensin and vasopressin are both constrictors
• Sudden decrease in blood volume, then venous return decreases. Then EDV decreases, then
SV, CO, Pa decreases
• Increase in blood volume (indicative of heart failure), then venous return increases. EDV, SV,
CO, Pa increase
• Three cardiac hormone systems: RAAS, Vasopressin, Natriuretic peptides


1. Renin/angiotensin/ aldosterone system (RAAS)

• Reduced renal blood flow —> Detected by juxtaglomerular apparatus —> Renin (enzyme)
—> Angiotensinogen —> Angiotensin I —> Angiotensin II —> Vasoconstriction
• Constriction of arteries —> Increases after-load. Force working against cardiac muscle
• Constriction of veins —> Increases pre-load. Decreases volume blood in veins by increasing
venous return which leads to increased CO, SV
• Angiotensin II —> Increased aldosterone secretion —> Sodium retention —> Fluid re-
absorption —> Increased blood volume —> Increased pre-load
• Increased pre-load results in increased contraction of heart which increases PP and Pa
• Aldosterone requires hours, involves gene transcription. Vasoconstriction is immediate.
• The renin–angiotensin system (RAS), or renin–angiotensin–aldosterone system (RAAS)



2. Vasopressin

• Enhances water retention


• Causes vasoconstriction 

• Secretion increased by unloading of aortic
• Baroreceptors and Atrial sensors: Soma in hypothalamus, axons extend to posterior pituitary.
Release of vasopressin under times of dehydration (reduction in blood volume)
• Stimuli producing vasopressin: Angiotensin II, hyperosmolarity, decreased atrial receptor
firing, and sympathetics
• Vasopressin is another potent vasoconstrictor. Also called Anti-diuretic hormone
• Acts on both veins and arteries, results in increased Pa
• Increases water absorption in renal tubules, expanding the blood volume. Restores osmolarity
• Works with RAAS system

3. Natriuretic peptides

• Natriuretic peptides: Synthesized in heart and brain. Released in response to atrial/ventricular

stretch. Act on natriuretic peptide receptor which is a catalytic receptor. Linked to GC which
increase cGMP (second messenger) which activates PKG. Synergy with NO system. Arg
activates eNOS (NO synthase), NO stimulates GC.
• Atrial natriuretic peptide (ANP): Synthesized in atrial myocytes. Released due to atrial stretch
• Brain natriuretic peptide (BNP): Synthesized in ventricles and brain. Released due to
ventricular stretch.
• C-type natriuretic peptide (CNP).
• Expansion of blood volume (Failing hearts, and renal failure) causes ventricular distention, and
atrial stretch
Atrial natriuretic peptide Targets

• Involved in long term regulation of sodium, blood volume, and Pa

• Produced by: Cardiac distension, sympathetics, angiotensin II, Endothelin
• Two targets of natriuretic peptides: 1. On vasculature itself, and the kidneys
• They produce vasodilation vasculature resulting in BP reduction.
• They increase blood filtration in kidneys. This increases diuresis (water excretion) and
natriuresis (sodium excretion). Reduces blood volume and sodium because Na+ pulls water
with it. Reduces stretch in atria/ventricles, this reduces the amount of natriuretic peptides
released. Also reduces renin which decreases aldosterone which supports natriuresis
• Treatment of hypertension is low Na diet to prevent sodium build-up
• ANP and BNP —> ↑ GFR —> ↓ Renin —> ↓ Ang II —> ↓ Aldo —> Natriuresis/Diuresis —> ↓
Blood volume —> ↓ BP

Summary of long term BP control

• Cardiac output and BP depend on renal control of extra-cellular fluid volume via:
Pressure natriuresis (increased renal filtration)
Changes in: Vasopressin, Aldosterone, Atrial natriuretic peptide
Common targets and work together to alter Pa
On-top of baroreceptors but are slower
• All under the control of altered cardiovascular receptor signaling

Cardiovascular Response to Challenges

1. Standing up: Blood pulled in veins, reduced venous return and blood in thoracic cavity.
• ↓ Pa —> ↓ Baroreceptor Reflex stretch —> ↑ Sympathetics —> ↑ Pa
• Pa/PV/SV/CO ↓ —> HR/TPR ↑ —> Pa/PV/SV/CO ↑

2. Exercise: Feed-forward response. No dramatic change in Pa

• Central command —> ↑ Sympathetics and ↓ Parasympathetics. Directional
Specific arterioles and veins constricted and others aren’t
• Local response —> ↑ Vasodilation —> ↓ TPR.
• HR/CO/Arteriovenous O2 difference = ↑ ↑
• SV/PP/PV = ↑
• TPR = ↓ ↓

3. Hemorrhage: Dramatic reduction in Pa because blood volume is severely reduced.

• ↓ Pa —> ↓ Baroreceptor Reflex stretch —> ↑ Sympathetics —> ↑ Pa
• ↓ Pa —> ↑ RAAS —> ↑ Blood volume/TPR —> ↑ Pa
• ↓ Pa —> ↓ Pc —> ↑ Fluid absorption —> ↑ Blood volume —> ↑ Pa
• Some have successful compensatory mechanisms, others fail around 3 hours.
• Pale face means vasoconstriction. If producing urine, then kidneys are functioning.
• Steady BP increase due to RAAS system. Reduced renal blood flow triggers angiotensin II.
• Drop in Pa causes pressure drop at capillaries (filtration absorption system). This shifts away
from filtration (fluid leaving) and toward reabsorption (fluid entering). Restores blood volume
• Carotid sinus nerve firing rate/Unstressed volume = ↓ (increases venous return)

• Contractility/HR/CO/TPR/Renin/Angiotensin II/Aldosterone/Epi/ADH = ↑
8.4 - Microcirculation

Overview

• 5% of total blood volume resides in microcirculation.

• Carries out most of function of cardiovascular system (i.e Exchange of nutrients)
• Microcirculation: Blood vessels that extend from arterioles to venules.
• Plasma separated by capillary endothelium
• Any exchange between plasma and intracellular must be mediated by interstitial fluid

Anatomy of the Capillary Network

• Arteriole: Contains robust VSMC which regulates radius

• Pre-capillary sphincter: Rings of VSMC that is not innervated. Highly responsive to local
chemical messengers. If it constricts, it redirects blood flow away from capillary bed, and into
metarteriole. Way to regulate blood flow between capillary beds
• Metarteriole: Link arteriole to the venule, allows blood flow to bypass capillaries. Similar to
arterioles but shorter, and less VSMC.



Lymphatic System

• Lymph: Recovered fluid from the lymphatic capillaries. Thin, watery fluid. High fat content.
Resembles plasma, but much less proteins. (1) Derived from interstitial fluid and therefore
composition varies; (2) Responsible for returning fluid and proteins to plasma compartment;
(3) Contains fat (lacteals) and white blood cells.
• Lymph nodes: Filters in the lymphatic system that cleanses lymph before reaching veins.
Contains macrophage which endocytose, and T cells which produce antibodies
• Lymphatics: Lymphatic capillaries. Returns interstitial fluid to cardiovascular system. Closely
associated with capillaries. They have one way valves that allows interstitial to enter capillary,
but it cannot leave. Gap is very large, allows bacteria/immune cells. Any excess fluid in
interstitial fluid flows into terminal lymphatic capillary along with any solute that is with it.
• Drainage system.
• Lymphatic system is a subsystem of both cardiovascular and immune system
• Cardiovascular system is a closed open while lymphatic is an open-direction, one way path

Lymphatic circulation

• Driven by factors similar to venous circulation: Muscle activity, Valves, Respiration

• Low pressure system dependent upon muscle movement, including breathing, to move
lymphatic fluid around body (body needs to move to allow these to flow)
• Lymph = plasma-proteins
• Lymphatic circulation collects fluid not reabsorbed by the capillaries 

• Lymph is filtered in nodes before return to blood circulation
• Lymphatics do not have pump, no pressure drive. Lymph moves very slowly.
• Converge into subclavian vein and dumps into either right lymphatic duct, or thoracic duct
Lymphatic Function

• Protect body against infection (Immune system)


• Collect tissue fluids, solutes, hormones, and plasma proteins that are in interstitial fluid, they
are returned to systemic circulation.

• Absorb fat (chylomicrons) from lacteals which are lymphatics in microvilli of small intestine

Lymphedema


• Lymphedema: Swelling of the arm or leg due to build up of interstitial fluid.
• Due to disruption, lymphatics are unable to drain limb properly.

• Occurs when fluid normally drained by lymph vessels does not flow out of extremity

• Common problem following cancer treatment that removes lymph nodes
• Symptoms: Discomfort, achiness, tingling. Heaviness in the hand, arm, chest, or axilla
• Increased risk of skin infections, minor skin cut could be severe

Capillary Exchange of Solutes

• Capillaries have the largest cross-sectional area, and lowest blood velocity. This allows
the exchange of molecules to take place
• Capillaries permeate every tissue in our body. Roughly 25,000 miles of capillaries in body
• Important because body is reliant upon diffusion from capillary beds, needs to be close
• Width of capillary is large enough to accommodate individual blood cells, they can not clump
up, they proceed one after another (straight line)

Endothelial cell Layer making up Capillaries

• Contains associated basement membrane

• Semi-selective barrier between lumen of vasculature and interstitial fluid.
• Regulates: Vessel permeability, Movement of proteins, Filtration/reabsorption, Immune
response, and Vascular resistance
• Filtering: Anything moving out of plasma
• Absorption: From interstitial into plasma

• Angiogenesis: Formation of new blood vessels. This process involves the migration, growth,
and differentiation of endothelial cells. Endothelial involved in stimulation and growth. Controlled
by Vascular Endothelial Growth Factor (VEGF)

• Hemostatic control (Clotting). Structures in endothelial inhibit platelet aggregation

Enzymatic action on plasma clotting proteins
• Hypertension, and thrombosis caused by damage to endothelial
• Polarized: Luminal which faces lumen and Abluminal which faces basement membrane.
• Blood is under hydrostatic pressure. To counter hydrostatic pressure, blood retains high
concentration of trapped proteins in the lumen of capillaries. Generates sufficient osmotic
pressure so it can draw water back into the plasma lumen.
•Ions easily distribute across wall of vessel
• Participate in sending some signals to smooth muscle, play role in modulated arterial pressure
• Important in modifying plasma protein function. Angiotensin found in abundance in capillaries
of lungs. Enzymes are able to modify proteins
Permeability of Endothelia is Regulated By:

1. Structure of the endothelium

2. Basement membrane

3. Glycocalyx

4. Intercellular junctions

Types of capillaries: phenotypic heterogeneity and permeability characteristics

• Capillaries are classified based on phenotypic heterogeneity. Directly related to “leakiness”

1. Continuous (Non-fenestrated): Sealed solid wall. Wall is thick and dynamic. Contains
channels, vesicles, and caveolae. Most restrictive in allowing solutes and fluid to pass.
2. Continuous (Fenestrated): Fenestrations (25 nm in diameter). Large enough to accommodate
proteins. Diaphragm, and Basement membrane limits diffusion. Abundant in tissues with high
exchange rates (intestine/kidney) Open probability determined by diaphragm. some caveolae
3. Discontinuous/Sinusoidal: Most leaky. Fenestrations so large that they are gaps in wall, no
diaphragm so it is not regulated. No basement membrane. Free exchange. Principally in liver
and spleen where large molecules must cross.

Basement membrane is a negatively charged barrier on the basal surface

• Basement membrane of endothelium provides structural support. Endothelial attach to

basement membrane via integrins. Lots of proteoglycans and sugar groups which are
negatively charged. Large negative charge outside capillaries. Important role in regulating flux
• Negative charge repels proteins which helps maintain protein concentration in plasma.

Glycocalyx restricts diffusion of large, negatively charged molecules

• Brush surface that is present on apical surface of lumen.

• Thick carbohydrate layer that lines capillaries
• Made up of Glycosaminoglycans (GAGs) and proteoglycans and some soluble components
• Prevents proteins from cross permeability barrier
Removal contributes to protein loss from plasma
• When glycocalyx removed, edema (swelling) was present. Indicates proteins leaving capillary
• Changes permeability characteristics
• Negative charge

Inter-endothelial junctions and Inflammation

• Inter-endothelial junctions: Links two adjacent endothelial cell membranes

• Tight junctions: 1. Claudins & Occludens, 2. Actin (cell-cell)
• Adherens junctions: 1. Cadherins 2. Actin (cell-cell)
• Affect of inflammatory agents target cell junctions and changes permeability
Kinases phosphorylate cadherins and reduce strength on the intercellular junctions
Calcium activates MLCK which in turn phosphorylates MLC
Active myosin increases tension, generating gaps between adjacent endothelial cells
This pulls on junctions and weakens them
Mechanisms of Exchange Across The Capillary Endothelium

• Diffusion: Oxygen, Carbon Dioxide, Lipid-Soluble Substances (lipophilic)

Anything that can normally pass through lipid bilayer
• Bulk flow: Water, Electrolytes, Small Molecules (via intercellular clefts or “pores”)
If something is able to fit through gap. Refers to moving with water
• Vesicular transport: Proteins
• Active transport: Ions, Glucose, Amino Acids
• Materials that need to pass in capillary are gases, nutrients, signaling molecules, and water.



Diffusion of Solutes Across a Capillary Wall

• Continuous capillaries
• Diffusion of Solutes, NOT water
• Jx = Px ( [X]c - [X]if)
Dx = Diffusion coefficient within the wall (units: cm2/s)
[X]c = Concentration of solute in capillary
[X]if = Concentration of solute in interstitial space
Jx = Solute flux per unit area and unit time (units: moles/(cm2/s))
S = Surface area (units: cm2)
a = Thickness of capillary wall (units: cm)
• Anything that thickens wall reduces flux
• Driven by concentration gradient (passive transport)
• Paracellular route: In-between endothelial cells
• Transcellular route: Through endothelial cells
• Continuous: travels through paracellular or transcellular (aquaporin).

Fenestrated capillaries

• Endothelial permeability for hydrophilic solutes was modeled on the basis of two sets of pores.
Large pores with diameter of < 10 nm and a larger number of small pores with an equivalent
radius of 3 nm. This was wrong.

Permeability Coefficients for Lipid-insoluble Solutes: small pore effect

• Smaller radius = Higher permeability

• Relationship between radius of molecule and it’s permeability
• Larger molecules are filtered by sizes of fenestrations
Permeability to Macromolecules: Large pore effect (transcytosis)

• Large macromolecules are too large for fenestrations, especially with glycolax and negative
basement membrane
• Most of the time, endothelial are very restrictive to albumin. Carrier for hormones and lipids.
• Exchange occurs via transcytosis (large pore effect)
1. Equilibration of dissolved macromolecules in capillary lumen with fluid inside the open vesicle 

2. Pinching off of the vesicle 

3. Vesicle shuttling to the cytoplasm (possible fusion with other vesicles) 

4. Fusion of vesicle with opposite plasma membrane 

5. Equilibration with opposite extracellular fluid
• Applies to macromolecules with a radius that exceeds 1 nm
• Relatively slow
• Used in continuous non-fenestrated capillaries
• Receptor-mediated process, receptors face lumen of capillary.
• Reason why vesicles are enriched with receptors because protein called caveolin which
anchors
• As radius increases, then permeability decreases
• Not every molecule endocytosed makes it to other side, not every cargo is able to be released
in interstitial (Ferritin is held in endothelial cytoplasm so it is broken down before being released)

Transcapillary Fluid Exchange

• Path of fluid across capillary wall is combination of transcellular and paracellular path
• Transcellular pathway: cross membrane to get in and out of cell
• Passing through fenestration/gap is paracellular since it doesnt pass through membrane
• Water uses transcellular pathway through aquaporins
• Aquaporin 1 is principle transcellular pathway for water to move
• Main mechanism for solute is diffusion, while for fluid it is called convection

Net Driving Forces

• Capillary Pressure (Pc) —> Interstitial Fluid Pressure (Pif)

• Plasma Colloid Osmotic Pressure (𝛑c) <— Interstitial Colloid Osmotic Pressure (𝛑if)
• Bulk flow of water across capillary wall.
• Transcapillary hydrostatic pressure differences across capillary wall (transcapillary)
• Osmotic pressure difference across the capillary wall.
• Pc pushes water outwards.
• Pif is either 0 or negative because interstitial fluid is constantly being drained
Favors movement of fluid out of capillary
• Very few proteins in interstitial so pi if is very small
• Favors movement of fluid into capillary
Filtration - Reabsorption

• Filtration: The sum of the hydrostatic and osmotic forces favors the net movement of water
from capillary to the interstitial space.
• Reabsorption: The sum of the hydrostatic and osmotic forces favors the net movement of
water from interstitial space to the capillary

1. Hydrostatic Forces: Pressure exerted by fluid at equilibrium, due to gravity.


• Capillary hydrostatic pressure (Pc): Higher at the arteriolar end than at the venule end. Tends
to force fluid outward through the capillary membrane. Main determinant of it is Pa.
• Interstitial fluid hydrostatic pressure (Pif): Normally it is is negative. This negative pressure is
due to the pumping action of the lymphatics. This is an inward force for fluid movement.
• Forces fluid out of capillary
• Anything that drops blood pressure causes hydrostatic pressure to change (i.e. moving from
arterioles to venules)

2. Osmotic Forces: The pressure needed to stop the osmotic flow.


• Plasma colloid osmotic pressure (πp or πc): Also known as plasma oncotic pressure. Plasma
proteins are the major determinant of oncotic pressure. Albumin, the most abundant plasma
protein, generates about 70% of it. Tends to cause inward (into capillary) movement of fluid.
• Interstitial fluid osmotic pressure (πif): Also know as interstitial fluid oncotic pressure. Caused
by the small amount of plasma proteins that leak into the interstitial space. Tends to cause
outward movement of fluid.

Starling Forces

• Net Driving Force: Kf [ (Pc - Pif) - (πc - πif) ]

• If NDF > 0, then it is filtration
• If NDF < 0, then it is reabsorption
• Hydrostatic flux coefficient (Kf): Measure of capillary leakiness. Experimentally derived. Fairly
constant unless something pathological changes it. Typically considered 1 in our course.
• Kf for continuous is very low, but for sinusoidal it is very high

Example: If Pc = +35 (outward), Pif = 0 (inward). 𝛑c = +28 (inward), 𝛑if = +3 (outward)

Then, ΔP = 35, ΔPi = 25
• NDF = 10 therefore filtration

Example 2: If Pc = +15, everything else is the same

Then, ΔP = 15, ΔPi = 25
• NDF = -10 therefore absorption
Filtration-Reabsorption: Baseline Beginning and End of Capillary

Beginning:
• Pc = 30 mmHg, Pi = -3 mmHg 

• πc = 26 mmHg, πI = 6 mmHg 

• NDF = [(30-(-3))-(26-6)] = 13 mmHg

End:
• Pc = 10 mmHg, Pi = -3 mmHg 

• πc = 26 mmHg, πI = 6 mmHg 

• NDF = [(10-(-3))-(26-6)] = -7 mmHg
• Drop in hydrostatic pressure causes NDF to be negative
Hydrostatic pressure is not strong enough to overcome osmotic pressure

Filtration-Reabsorption: Baseline

• Majority of capillary bed participates on filtration

Clinical Correlates

• Dehydration: Decreased capillary hydrostatic pressure, and Increased oncotic pressure

• Example: Drinking lots of Coffee is a diuretic
• Decreasing venous return due to reduced blood volume
• Concentration of plasma proteins is increased. Osmotic pressure in capillary is elevated.
• Dropping Pa

Filtration-Reabsorption: Dehydration Beginning and End of Capillary

Beginning:
• Pc = 25 mmHg, Pi = -3 mmHg 

• πc = 31 mmHg, πI = 6 mmHg 

• NDF = [(25-(-3))-(31-6)] = 3 mmHg

End:
• Pc = 5 mmHg, Pi = -3 mmHg 

• πc = 31 mmHg, πI = 6 mmHg 

• NDF = [(5-(-3))-(31-6)] = -17 mmHg

Filtration-Reabsorption: Dehydration

• Majority of capillary bed participates on reabsorption

Reclaiming fluid from interstitial fluid in an effort to restore blood volume
• When hydrostatic pressure drops, it shifts filtration/reabsorption profile to this
Learning objectives (Unit 8):

1. Distinguish cardiac from skeletal muscle tissue.

Skeletal: Not connected. Mechanically and electrically separate, short refractory period, action
potentials sum (tetanus). Multiple nucleus towards sarcolemma.

Cardiac: Connected via gap junctions, desmosomes, and adherens junctions. Long refractory
period, action potentials do not sum (lethal). More mitochondria. Resistant to fatigue. More
myoglobin. Branched. Single, central nucleus. Thicker t tubules but less of them. Smaller SR.
DHPR is a calcium channel, not coupled to RyrR, instead it activates RyrR in CIRC.
Depolarization causes voltage-gated calcium channels in sarcolemma. Catecholamines
activate AC, and lead to elevated PKA, Binds to 𝛽 receptor. PKA phosphorylates voltage-gated
calcium channels, TnI, and phospholamban.

2. Describe the events that take place during each phase of the cardiac ventricular
myocyte action potential. Contrast this to the events that take place during the
action potential of sinoatrial node tissue.

Cardiac ventricular myocyte: Non-pacemakers.

0. Sodium, and Fast Potassium channels open. Depolarization phase.

1. Sodium, and Fast Potassium channels close. Brief repolarization.

2. Calcium channels open, and fast potassium channels close. Prolonged duration of AP.

3. Repolarization of Vm

3a. Slow potassium channels open, and calcium channels close.

3b. Fast potassium channels reopen, and calcium channels close.

4. Fast and Slow potassium channels close. Resting potential, very negative

Sinoatrial node tissue: Pacemakers. Generate regular, spontaneous action potentials.

1. Voltage-gated sodium channels open (funny current) and transient T-type calcium channels
open. Before threshold.

2. L-type calcium channels open. Depolarization phase.

3. Sodium channels close. Peak

4. Potassium channels open. Hyperpolarization phase.

3. Describe what the absolute refractory period is for a cardiac action potential.

Absolute refractory period: Cardiac muscle is much longer, almost entire duration of twitch.
Stimuli does not produce response. Long RP means it is unable to sum tension, which
prevents production of tetanus.



4. Describe the effects of sympathetic and parasympathetic activity on the heart.

Sympathetic activity on heart: Increase heart rate, contractility, cardiac output, TPR, and
decrease unstressed volume.

Parasympathetic activity on heart: Decrease heart rate, contractility, cardiac output, TPR, and
increase unstressed volume.

5. Explain in qualitative and quantitative terms: Cardiac output, and Stroke volume

Cardiac output: Total blood flow, i.e. volume of blood circulating through either systemic or
pulmonary blood vessels per minute.

Stoke volume: Anything that impedes flow of blood

6. Write an expression relating blood flow driven by a constant pressure head across
variable resistances

For liquids: ΔP = FR or F = ΔP/R.

Pressure difference (mmHg) = Flow (mL/min) * R (mmHg * min/ mL)

7. Write an expression relating cardiac output to total blood flow

CO = F = SV * HR

Cardiac output (mL/min) = Flow (mL/min) = Stroke volume (mL/beat) * Heart rate (beat/min)

8. Explain how flow is related to Axial pressure difference, Vessel radius, Length of the
vessel, Viscosity of the fluid

F = ΔP (𝜋 * r4) / (8 * 𝜂 * l)

Flow = Pressure difference * [(3.14 * Radius4)/(8 * Blood viscosity * blood vessel length)]

9. Explain how arteries and veins differ in distensibility and compliance

Arteries: High distensibility and low compliance.

Veins: High distensibility and high compliance.

10. List the types of capillaries and their physical attributes.

Continuous (Non-fenestrated): Sealed solid wall. Wall is thick and dynamic. Contains channels,
vesicles, and caveolae. Most restrictive in allowing solutes and fluid to pass.

Continuous (Fenestrated): Fenestrations/gaps (25 nm in diameter). Large enough to

accommodate proteins. Diaphragm, and Basement membrane limits diffusion. Abundant in
tissues with high exchange rates (intestine and kidney).

Discontinuous/Sinusoidal: Most leaky. Fenestrations so large that they are gaps in wall, no
diaphragm so it is not regulated. No basement membrane. Free exchange. Principally in liver
and spleen where large molecules must cross.

11. Explain the Law of Laplace.

Law of LaPlace: T = PR. Tension proportional to pressure and radius.

Wall Stress: S = (P * r) / w. Modified Law of LaPlace for blood vessels.

12. Explain each of the Starling Forces. Explain how these forces result in either filtration
or absorption.


Capillary hydrostatic pressure (Pc): Higher at the arteriolar end than at the venule end. Tends to
force fluid outward through the capillary membrane. Main determinant of it is Pa.

Interstitial fluid hydrostatic pressure (Pif): Normally it is is negative. This negative pressure is
due to the pumping action of the lymphatics. This is an inward force for fluid movement.

Plasma colloid osmotic pressure (πp or πc): Also known as plasma oncotic pressure. Plasma
proteins are the major determinant of oncotic pressure. Albumin, the most abundant plasma
protein, generates about 70% of it. Tends to cause inward (into capillary) movement of fluid.

Interstitial fluid osmotic pressure (πif): Also know as interstitial fluid oncotic pressure. Caused by
the small amount of plasma proteins that leak into the interstitial space. Tends to cause outward
movement of fluid.

13. Distinguish between pulse pressure, systolic pressure, diastolic pressure, and mean
arterial pressure

Pulse pressure (PP): (Systolic pressure) - (Diastolic pressure). Represents force generated by
heart. Typically around 40 mmHg.

Systolic pressure: Pressure in heart during systole.

Diastolic pressure: Pressure in heart during diastole.

Mean arterial pressure (Pa): Pd +1/3(Ps -Pd)

14. Identify controllable and non-controllable factors known to influence arterial pressure

Controllable factors: Diet, body weight, and physical activity. BP higher in people who eat
dietary fat, salt, excessive alcohol, potassium and calcium intake. BP higher in obesity and
during exercise.

Non-controllable factors: Age, gender, stress, and race. BP higher in western society, men, the
elderly, and stressed people. Same change in volume exerts higher pressure on wall as age
increases.

15. Relate mean arterial pressure to Cardiac output and total peripheral resistance

Pa = CO * TPR

Mean arterial pressure (mmHg) = Cardiac output (mL/min) * Total peripheral resistance (mmHg *
min / mL)





16. Identify short-term and long-term physiological mechanisms for regulating BP

Short-term: Baroreceptors (mechanoreceptor) in carotid sinus and aortic arch. Decreased

stretch results in less firing (more sympathetics and less vagal). Increased stretch results in
more firing (less sympathetics and more vagal). Baseline firing rate. Output to NTS which
functions as cardiac decelerator, cardiac accelerator, and vasoconstrictor.

Long-term: Hormones. Control of blood vessel radius (Epi, Angiotensin II, Vasopressin), control
of blood volume (Vasopressin, Aldosterone), and control of HR and SV (Epi). Three main
cardiac hormone systems: RAAS, Vasopressin, and Natriuretic peptides.

RAAS: Reduced renal blood flow —> Detected by juxtaglomerular apparatus —> Renin
(enzyme) —> Angiotensinogen —> Angiotensin I —> Angiotensin II —> Vasoconstriction

Constriction of arteries —> Increases after-load.

Constriction of veins —> Increases pre-load.

Angiotensin II —> Increased aldosterone secretion —> Sodium retention —> Fluid re-
absorption —> Increased blood volume —> Increased pre-load

Vasopressin: Enhances water retention, and causes renal fluid reabsorption and
vasoconstriction. Produced by hyperosmolarity (dehydration), angiotensin II, decreased atrial
receptor firing, and sympathetics. Increases BP.


Natriuretic peptides: Produced in response to atrial stretch. Linked to GC and NO. Produces
vasodilation and blood filtration which reduces blood volume. All lower BP.

17. Identify three mechanisms that explain acute auto-regulation 


1. Heart Rate (HR): Directly proportional to Cardiac output and therefore Pa.

2. Stroke Volume (SV): Directly proportional to Cardiac output and therefore Pa.

3. TPR or SVR: Directly proportional to Pa.

18. Describe how the body maintains Pa during Exercise, Standing, Hemorrhage

Standing: Decreased baroreceptor stretch, and increased sympathetics. Results in increased

heart rate and TPR which increases CO, SV, PV, and Pa.

Exercise: Feed-forward control. Central command increases sympathetics and decreases

sympathetics. Local response produces vasodilation which decreases TPR.

Hemorrhage: Decreased baroreceptor stretch. Increased RAAS which increases blood volume
and TPR. Decreased capillary pressure which increases fluid absorption and blood volume.

 EXAM 3 - (3/14)
Course information

• TA email: [email protected]

Questions:

Things to do before exam:

• Complete Exam 3 Tables

• Email TA’s or visit office hours for questions

Notes:

• ALWAYS CHECK UNITS!!!!!!!!! NO MATTER WHAT!!!!!! FUCK YOU.

• Take a deep breathe and think you fucking retard.