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Cardiovascular Physiology

• Sup./Inf. Vena Cava > R. atrium > R. ventricle > Pulmonary A. > Lungs > Pulmonary V. > L. atrium >
L. ventricle > Aorta
• 3 Layers: endocardium, myocardium, pericardium
• valves attached to chordae tendineae and papillary muscle

Cardiac Muscle:
• 3 Types: Atrial, Ventricular, Specialized Conduction
• striated, actin/myosin/titin filaments, t-tubules, SR, mitochondria (all similar to skeletal muscle)
• Syncytium: intercalated discs/desmosomes, gap junctions

• Sarcolemma (plasma mem.): has L-type Ca channel involved in excitation-contraction (EC) coupling
o Beta-1 receptors on membrane increase Ca movement into cell > increases force of
contraction = inotropy
• T-tubule: permits efficient ionic exchange deep within the cardiocyte between extra and intracellular
compartments; makes it easier for Ca to trigger contraction via L-type channels
• Sarcoplasmic Reticulum (SR): major site of intracellular Ca storage
o Terminal Cisternae- end pouches of SR closely assoc. w/T-tubules via “feet”
o junction between feet and SR contains Ryanodine Receptors (RyR)

• EC Coupling: Fast Na Channels are excited > depolarization of plasma mem. > T-tubules in L-type
channels open to allow Ca in > RyR activated by extracellular (trigger) Ca > release of intracellular Ca
from SR > intracellular Ca binds to troponin-C (TN-C) on actin > contraction

Myocardial Relaxation / Recovery:

• Sarcolemma: Na/Ca exchangers and Ca-ATPase pump 20% of Ca to extracellular fluid
• SR: sarcoplasmic endoplasmic reticulum Ca (SERCA-2) = Ca-ATPase pumps 80% of Ca back into SR
o Phospholamban- important regulatory/activating protein assoc. w/SERCA-2
o Beta-1 receptors also increase phosphorylation of phospholamban

Electrical Activity of the Heart

• Ventricular Myocyte AP Phases: in relation to voltage-gated channels
o 0 = depolarization: sharp/high influx of Na
o 1 = initial repolarization: K moves out of cell through transient outward K channel
o 2 = plateau: slow influx of Ca; K permeability is low
o 3 = repolarization: K permeability increases (moves K out through delayed rectifier K
channel) while Ca perm. decreases
o 4 = resting mem. potential: K continues to move out; Ca moves out via Ca-ATPase
• Nodal Cell AP Phases:
o Phase 0: Ca influx through L-type channel
o there is no phase 1 or 2, but rather a simple bell-shape from phase 0 to phase 3
o Phase 3: decrease in Ca influx; increase in K efflux
o Phase 4 (pacemaker potential): K perm. decreases; Na perm. increases (via F-type
channel); Ca perm. increases (via T-type channel)

• Absolute/Effective Refractory Period: phase 0 – phase 2

• Relative Refractory Period: phase 3

Cardiac Conduction System (72 bts/min): specialized cardiac muscle, not true nervous tissue
• 2 Components: Excitatory Impulse Generator, Impulse Conduction Pathway
• SA Node: located in upper part of R. atrium near opening of Sup. Vena Cava

o Pacemaker- has greatest automaticity = ability to generate electrical impulse with no
external input; sets the heart rate at 100 bts/min. which is reduced by other tissues
o Automaticity- increased perm. to Na and Ca; decreased perm. to K (phase 4)
• Note: all heart tissues have automaticity
o lower resting potential relative to other heart tissues
• Internodal Pathways: connect SA node with atrial muscle; gap junctions allow for innervation of all
cardiac muscle
• AV Node: located in septal wall of R. atrium posterior to the tricuspid valve
o delays impulse from SA node to ventricles (allows ventricles to fill with blood)
o delay due to: small fiber size which increases resistance and longer refractory period
• Bundle of His / Bundle Branches: conduction route from AV node to ventricles
o allows for improved conduction through nonconducting connective tissue between atria
and ventricles
• Purkinje Fibers: large/high conduction fibers that allow for fast transmission of impulse throughout
o go deep into myocardium to optimize impulse distribution
o heart apex contracts first > pumping of blood toward exit valves at base

Control of Excitation: external controls adjust contraction to normal 72 bts/min

• SA node = 100 bts/min; AV node = 50 bts/min; Purkinje Fibers = 15-40 bts/min
• primary external control = ANS (SNS and PNS)
• SNS innervates all parts of heart; PNS innervates SA and AV nodes, some atria
• Chronotropy- tone of heart rate; set by PNS (reduces SA node to 72 bts/min)
• SNS- has positive (increasing) effect on chronotropy
o norepinephrine released > stimulates Beta-1 receptors on nodes / increases Na perm.
through F-type channels > rapid rise in pacemaker potential > increase in impulse
• PNS- has negative effect on chronotropy
o ACh released > stimulates muscarinic receptors on nodes / decreases Na perm. / increases
K perm. > slower depolarization of pacemaker potential / makes pacemaker potential
more negative (farther from threshold)
• Ventricular Escape- “kicking in” of Purkinje Fiber automaticity in the case of max stimulation from
PNS which can momentarily stop the heart
• minor effects on heart rate can be generated from body temp., electrolytes, hormones (ex. epinephrine)

Electrocardiogram (ECG)
• record of electrical activity or voltage changes in heart which is recorded at the body surface
• rate, rhythm, relative heart size, anatomic orientation, effects of drugs/electrolytes, injury info.

• Components:
o P wave- atrial depolarization (0.9 sec)
o QRS complex- ventricular depolarization (0.8 sec)
o T wave- ventricular repolarization (not measured)
o PR interval- atrial depolarization + AV node delay (0.16 sec)
o ST segment- isoelectric period of depolarized ventricles (not measured)
o QT interval- length of depolarization plus repolarization (0.3 sec)

• uses reference and recording electrodes strategically placed to measure voltage due to depolar. and
repolar. of heart tissues
• normal depolar. is from base to apex / repolar. is from apex to base

• Einthoven’s Triangle (3 limb leads):

o Lead 1- between right arm and left arm

o Lead 2- between right arm and left leg
o Lead 3- between left arm and left leg
o Note: the right leg serves as the grounding source
• Augmented Voltage Limb Leads: aVR, aVL, and aVF
o unipolar positive electrode referenced against combo. of other limb electrodes
o in practive > same positive electrodes used for Leads 1,2,3
o aVR: from middle of Lead 3 to right arm
o aVL: from middle of Lead 2 to left arm
o aVF: from middle of Lead 1 to left leg
• Note: total of 6 limb leads
• 6 Chest / Precordial Leads: v1 – v6 ; give more detailed picture of heart electrical activity

• Mean Electrical Vector- sum of all electrical vectors occurring at one instant
o there is no single directional electrical wave in heart
• 5 Rules of ECG Interpretation:
1. depolar. wave traveling toward a + electrode will result in + deflection (and vice versa)
2. repolar. wave traveling toward a + electrode will result in – deflection (and vice versa)
3. depolar. or repolar. wave oriented perpendicularly to electrode axis shows no net deflection
4. instantaneous amplitude of measured potentials depends on orientation of + electrode to the mean
electrical vector
5. voltage amplitude (+ or-) is directly related to the mass of tissue undergoing depolar. or repolar.

• ECG Abnormalities:
o Tachycardia (fast) / Bradycardia (slow) = rate changes
o Rhythm Changes: atrial flutter, atrial fibrillation, ventricular fib., AV nodal blocks (1 st,
2nd, and 3rd degrees), spontaneous impulse formations (ectopic pacemakers such as
PVC’s), abnormal pathways of re-entry

The Cardiac Cycle

• Cycle (2 phases): ventricular diastole and ventricular systole; Note: ventricles = primary pumps
• V. Diastole- relaxation of ventricular myocardium and filling of ventricles with blood
• V. Systole- active contraction of ventricular muscle and ejection of blood to lungs and periphery
• Note- atria have diastole and systole also, but are opposite in order to ventricles

• Isovolumetric Relaxation- v. muscles relax, valves are closed, no blood movement ; atria are filling
with blood (actually started during v. systole)
• Ventricular Filling Phase-
o 1st Period- blood flows from atria to ventricles through AV valve via pressure gradient,
not active atrial contraction; accounts for 75% of blood going into v’s
o Diastasis- mediary period where atrio-ventricular flow is minimal
o 2nd Period- atria contract to pump remaining 25% of blood into v’s
o End-Diastolic Volume (EDV)- amount of blood in v’s at end of diastole = 125 ml
o aortic and pulmonary valves remain closed during entire diastole due their greater
pressure as compared to the v’s

• Isovolumetric Contraction- v. muscles contract > increase v. pressure; all valves still closed
• Ejection Period-
o AV valve closed using papillary muscles and chordae tendineae
o aortic and pulmonary valves open due to lower pressure as compared to filled v’s
o Stroke Volume (SV)- amount of blood pumped into aorta and pulmonary a’s = 70 ml
§ = difference between EDV and ESV

o End-Systolic Volume (ESV)- amount of blood remaining in v’s after ejection = 55 ml

• Ejection Fraction = SV / EDV = 70 / 125 = 55%; used to measure pump function

• Atrial Pressure Plot: increases in atrial pressure
o a wave- due to atrial contraction
o c wave- due to ventricular contraction
o v wave- due to atrial filling
• Murmurs- turbulent flow

• Phonocardiogram:
o 1st sound- mostly during isovolumetric contraction, but continues slightly into ejection
o 2nd sound- during isovolumetric relaxation
o 3rd sound- between rapid v. inflow and diastasis
o 4th sound- during 2nd period of v. diastole
§ Note: 3rd and 4th sounds not normally present

• ECG:
o P wave- during transition from diastasis to 2nd period of diastole (atrial systole)
o QRS complex- Q/R during atrial systole just before isovolumetric contraction; S during
isovolumetric contraction
o T wave- mostly during systole, but also continues into isovolumetric relaxation

Control of Cardiac Output

• Cardiac Output (CO) = Heart Rate (HR) x Stroke Volume (SV)
o 5 liters/min. = 70 bts/min. x 70 mL/bt
• Heart Rate- generally more important in quantitatively producing changes in cardiac output; can
regulate output in absence of ANS (primary control center)
• Stroke Volume- difference in EDV and ESV
• Venous Return (VR)- supplies blood for CO; = amount of blood flowing back to heart per min.
o VR must equal CO

• Extrinsic Stroke Volume Control:

o ANS is primary control- mostly SNS
o SNS has strong positive chronotropic effect (increases HR) and strong positive inotropic
effect (increses SV)
• Intrinsic Stroke Volume Control:
o heart can independently (from ANS) regulate CO
o Frank-Starling Law of the Heart- VR must equal CO
o for discussion: VR equals EDV
• F-S Law of Heart: based on length-tension relationship of muscle
o load or preload = stretch placed on cardiac myocytes due to blood in ventricle = EDV
§ EDV = Preload = EDP (P- pressure)
• Positive Inotropic Effect- can be due to increased SNS activity
o has decreased afterload (afterload = load against which heart must contract to eject
blood; major afterload is aortic pressure)
§ Aortic (or pulmonary) Pressure = Afterload
• Negative Inotropic Effect- can be due to loss of myocardium as a result of myocardial infarction
o has increased afterload

• Vasodilation-
o metabolites released > blood vessels dialate > increased blood flow > increased

o results in activation of F-S mechanism
• Decreased Afterload-
o increase vasodilation > decrease flow pressure / flow resistance > decreased afterload

Factors / Diseases Affecting CO:

• Decreased CO-
o Cardiac Factors- MI’s and valve disease, increased afterload (hypertension), increased
PNS or decreased SNS
o Peripheral Factors (decrease VR)- blood vol. decrease (hemorrhage), vein dilation
(decreased SNS) or obstruction, increased vascular resistance, increased R. atrial pressure
• Increased CO-
o Cardiac Factors- decreased afterload (vascular resistance), decreased PNS or increased
SNS, cardiac hypertrophy, thiamine deficiency (vasodilation), anemias, hyperthyroidism
o Peripheral Factors (increase VR)- blood vol. increase, vein constriction/tone, decreased
vascular resistance, decreased R. atrial pressure

Ventricular Pressure-Volume Loops: note graph plot in notes

• Point 1: EDV / low ventricular pressure
o 1>2 – isovolumetric contraction; increase in pressure, but no vol. change; valves closed
• Point 2: opening of aortic valve and beginning of ejection
o 2>3 – ventricular ejection; increasing pressure and decreasing vol. (stroke volume)
• Point 3: end of systole; all valves closed
o 3>4 – isovolumetric relaxation; v. pressure decreases and vol. is unchanged; ESV
• Point 4: low ventricular pressure and AV valve is open
o 4>1 – ventricular filling during diastole

-include example questions from notes in study guide

• normal blood volume = 5.6 liters = 8% of total body wt.
• % blood used (most to least): abdominal organs > kidney / skeletal muscle > brain > skin
• Viscosity- friction between molecules of flowing blood
o increased with more hematocrit (cells); plasma has little effect
o decreased in small vessels b/c cells line up
• Hematocrit- percent of blood made up of cells; Men- 42%, Women- 38%
• Laminar Flow- streamlined layers of blood flowing over each other w/highest flow rate in center;
primary type of flow
• Turbulence- seen at sharp turns, obstructions, rough surfaces, w/increased flow, in large dia. vessels,
w/sudden change in vessel dia.; murmurs result
• Flow (Q) is determine by two factors- pressure (P) and resistance (R)
o Q = ΔP / R

• CO- amount of blood pumped (L/min.) ; BP- blood pressure (mm/Hg)
• TPR- total peripheral resistance (mmHg/l/min)
o TPR = BP / CO
o determined by Viscosity (η), Vessel Length (L), Vessel Radius (r), Constant = 8/π
o TPR = (8L η)/( πr4)
• radius is most important determinant in resistance and therefore also in flow
• In Series: R is calculated as sum of ind. R’s
o Rs = R1 + R2 + R3… / ΔP = Pi – Po / Q = ΔP / Rs

• In Parallel: R is calculated as sum of reciprocals of ind. R’s
o 1/Rp = 1/R1 +1/R2 + 1/R3
o ΔP = Pi – Po
o Qtotal = Q1 + Q2 + Q3
o Qtotal = ΔP / Rp
• Note: Rtotal = 1 = 1/r1 + 1/r2 + 1/r3
• Law of LaPlace- wall tension (T) is force which would tear along length of cylinder
o T = [P(r)] / W

• Tunica Intima- innermost thin layer of endothelial cells; smooth surface with low resistance
o produces adhesion receptors and anti-coagulation factors
• Tunica Media- middle layer consisting of collagen, elastin, and smooth muscle
o smooth muscle: contraction affects vessel dia. > resistance > flow
o collagen/elastin: pressure reservoir
• Tunica Externa- outermost layer comprised of connective tissue for support and protection
• Arterial Pulse Pressure = systolic / diaostolic = 120/80 mmHg
o directly prop. to SV
o dep. on rate of filling (SV ejection rate) and rate of emptying (resistance) of arterial tree
o inversely prop. to compliance (see below)
• Windkessel Effect- dampening role of aorta and large a’s on pulse flow from heart during systole
o large dia. a’s reduce pressure and flow
• Secondary Pump- potential energy stored in arterial circulation permits flow to cap’s during diastole
o during systole: some cap flow, but most ejected blood is stored in elastic a’s (60%)
o during diastole: elastic recoil of a. walls maintains cap flow through cycle
• Compliance (C)- stretchability of vessels; C = ΔV / ΔP
o Compliant- V reaches certain value, P rises rapidly
o Non-compliant- P rises sooner at lower contained V
o with age: elastin is lost / collagen (stiffer) is gained > vessel becomes less compliant >
increased pulse
• Aortic Stenosis- slow ventricular ejection rates decreases SV rate into aorta > SV effect on pulse
pressure (PP) is reduced; also have greater time for peripheral runoff, so contained vol. in aorta is
o turbulence = systolic ejection murmur
• Aortic Insufficiency- blood leaks back into the ventricle during diastole > large stroke volume >
increased PP > added work on heart
o turbulence = during diastolic regurgitation
• Mean Atrial Pressure (MAP)- major force responsible for propelling blood through vasculature
o MAP = (1/3)PP + Diastolic Pressure
o note: PP = Systolic Pressure – Diastolic Pressure

Arterial Tree and Control of Peripheral Circulation

• 3 major circulation components: 1) heart 2) large distributing a’s and returning v’s 3) arterioles/cap’s
• Functions of Ateriolar Resistance: 1) perfusion pressure 2) metabolites 3) symp. adrenergic
(epinephrine release) constrictor system

• Resistance Vessels- small a’s and arterioles (high SM content); terminal arterioles control res. to cap’s
• Precapillary Sphincters- has SM which fine tunes flow which goes to cap beds
• Exchange Vessels- nonmuscular venules which function as terminal lymphatics; formed from fusion of

• Capacitance Vessels- muscular venules and small v’s; larger dia. and quantity than arterioles = blood
reservoir; SNS causes constriction and squeezing of blood toward heart from these vessels
• Blood Flow at Rest: muscle (20%), brain (13%), heart (4%)
• Blood Flow during Exercise: muscle (75%), brain (4%), heart (4%)
-note: > flow in muscles during exercise is controlled by metabolites (not nerves)
• Resistance = 1/r4; primary res. comes from arterioles (mainly) and precap. sphincters

Intrinsic Control: changes in extracellular fluid surrounding vascular SM of arterioles > increases r/flow
• Metabolic Factors (> r):
o Decrease- O2 (except in lung – decreases flow)
o Increase- CO2, K, osmolarity, adenosine, eicosanoids (prostaglandins), endothelial
factors, histamine < Metabolites
• Myogenic Response: increase in SM tone in response to stretch
o > flow- pressure/stretch increases, AP and/or Ca influx increases
o <flow- SM contracts
• Laplace Tension- decreased vessel wall tension
-system oscillates: pressure increase > vessel wall stretch > SM contraction > increased res. > Laplace
tension > vessel relaxation > pressure increase

Auto-Regulation of Flow: ability of tissues to maintain constant flow despite pressure changes
• Reactive Hyperemia (increased flow)- result of temporary occlusion of a
• Active Hyperemia- result of increased activity/metabolism; production of metabolites

Extrinsic Nervous Control:

• Symp. (Thoracolumbar)- adrenergic constrictor system where NE = NOR are neurotransmitters
o major control system of heart, arterioles (res), veins (capacitance)
o reticular formation (vasomotor center) > anterolateral columns of spinal cord >
preganglionic adrenergic neuron > cell bodies in paravertebral ganglia > postganglionic
o major vasomotor (dia) control is via quantity of release of impulses leaving spinal cord
o Cholinergic (ACh) Nicotinic Receptors- control transmission between preganglionic and
ganglionic neurons
o NE- controls postganglionic transmission
o decreased vasomotor activity > increased neuronal activity > vessel constriction
o increased baroreceptor activity > decreased NOR release > vessel dilation
§ note- increased NOR > vessel constriction
o vasoconstriction- increased α1 receptor
o normal tone- α1 tone
o passive dilation- decreased α1 receptor
o active dilation- increased ACh and β2 receptors

Adrenergic (NE) Receptors:

• α1 receptors- respond to NE, Epi (lower affinity than β2) ; located in SM of a’s, arterioles, and v’s
o stimulation = vasoconstriction, venoconstriction
• β receptors-
o β1- symp. innervation; located in heart
§ stimulation = increased HR/conduction velocity/contractility
o β2- respond to Epi; located in vascular beds of skeletal muscle
§ stimulation = active vasodilation
§ note: skeletal muscle beds have both α1 and β2 receptors; Epi has higher affinity
for β2 > vasodilation
• Adrenal Medulla-
o symp. pregang. neuron releases ACh > medulla (ganglion) releases Epi > vasodilation

• Parasymp. System- cranio-sacral, GI glands
o starts in dorsal motor area of vagus or nucleus ambiguous of cardiovascular center
o only minimal localized control of special organs (salivary glands, genitalia); doesn’t
control total peripheral res. (TPR)
o ACh = neurotransmitter
o Nicotinic Receptors- ganglionic receptors
o Muscarinic Receptors- blocked by Atropine
o functions: hyperpolarization of pacemaker cells (< HR), negative inotropic (muscle
contraction) effects

Non-cholinergic / Non-adrenergic Neurons: release Nitric Oxide (NO) > vasodilatation

• increase flow to GI tract and penis during erection; little effect on TPR

• Vasoconstriction:
o Neural Control- symp. nerves (release NE)
o Hormones- Epi (usually dilation), Angiotensin II, Vasopressin
o Local Control- myogenic response, endothelin-1
• Vasodilation:
o Neural Control- neurons that release NO
o Hormones- Epi, atrial natriuretic hormone
o Local Control- decreased O2, increased metabolites (CO2, K, H, Adenosine, Bradykinin)

Microcirculation - Capillary System

Blood Flow:
• wall of single endothelial cells with basement membrane; pores to allow water/electrolytes to cross
• lipid insolubles can’t pass through pores; lipid solubles (O2, CO2, alcohol, anesthetics)
• Liver- porous cap’s allow large proteins to cross / Brain- tight wall (highly selective)
• individual cross-sectional area is smallest in circulation, but total area is largest in circulation
• Flow Velocity- slowest in vascular tree
o Velocity = (Flow / Area)
• slow flow- 1cm3/yr = 1mL/yr; optimizes diffusional exchange
• total perfused (permeable) cap’s = 3 x 109; minimizes diffusion distance between cap’s and cells
o all not perfused at same time
o rest: CO = 6 L/min, cap bed area = 15 m2
o exercise: CO = 10 L/min, cap bed area = 50 m2
• increased cross-sectional area (i.e. cap’s) > decreased velocity
• decreased cross-sectional area (i.e. aorta, vena cava) > increased velocity

Capillary / Extracellular Fluid Exchange:

• Diffusion (high>low): lipids > water > electrolytes > protein (cap. usually impermeable)
• Capillary Hydrostatic Pressure (CHP = Pc)- predominant filtration pressure
o filtration = movement of water from blood to interstitial fluid (ISF)
o arteriolar end = 35 mmHg / venular end = 25 mmHg
o mean cap pressure = 25 mmHg
• Plasma Colloid Osmotic Pressure (PCOP/πp) = Plasma Oncotic Pressure = Reabsorption Pressure
o reabsorption- movement of fluid from ISF into blood
o generated by plasma proteins = 28 mmHg
o only 0.5% of total plasma (electrolytes + proteins) osmotic activity
o note: no osmotic gradient between plasma and ISF with electrolytes (i.e. Na)
• Tissue Colloid Osmotic Pressure(TCOP/πi)- generated by ISF proteins = 4 mmHg
• Tissue Pressure (TP or Pi)- positive reabsorption pressure = 1 mmHg

• Starling’s Cap. Law: Net Fluid Movement = Filtration Pressures – Reabsorption Pressures
o F = (CHP + TCOP) – (TP + PCOP)
o 0 = (25 + 4) – (1 + 28) <ideal
o if F is negative > absorption; if F is positive > filtration
o there is always imbalance which usually favors filtration
o Lymphatics- remove 2 L of ISF from ISF and return to cardiovascular system

• Filtration Decrease-
o Hemorrhage- reduces CHP as a result of reduced CO and vasoconstriction
§ decrease CHP > increase reabsorption > increase blood volume / venous return /
CO / arterial pressure
o “Endogenous Blood Transfusion Mechanism”- 12 L H2O in ISF during CHP reduction
• Filtration Increase / Edema- accumulation of fluid
o Venular Pressure Increase:
§ venous thrombosis; heart failure > R. atrial pressure increase; hepatic cirrhosis >
portal pressure increase
§ Ascites- venous hypertension due to protein loss from liver to abdomen / water
follows > abdominal edema
o Arteriolar Pressure Increase:
§ exercise- skeletal muscle edema
§ allergic rxns- histamine release > increase cap perm. > a dilation > v constriction

• PCOP Decreasing Factors-

o Hemodilution- diluted rbc’s > decreased hematocrit; normal plasma protein, but
effectiveness is reduced
o Hypoproteinemia- total plama protein decreased
• Cap. Permeability Increase-
o Burns- if skin intact > limited fluid loss due to increased TP; if skin not intact >
cardiovascular vol. decrease
o Vasoactive Agents- i.e. histamine
o Lymphatic Obstruction- uncontrolled growth as result of parasitic infection

Lymphatic System:
• Paravenous System- Lcap’s in close assoc. w/blood cap’s and veins
• low pressure/flow > 120 mL/hr; Lcap’s 5x larger than cap’s
• some SM, very permeable, one way valves
• functions: returns cap filtrate, removes large abnormal matter, immunologic function, absorbs fat in GI
• Anchoring Filaments- facilitate removal of lymph as ISF increases; attached both to connective tissue
and lymphatic channel
o increase ISF > increase tissue pressure > channel expansion > increased lymph flow
• Drainage Promoting Factors: one way valves, SM/skeletal muscle contraction, pumping of a’s and v’s
in common sheath with lymphatic vessels

• low pressure, low resistance, high capacitance, high compliance > good reservoirs (65% of total blood)
• erect- pressure increases in v’s farther below heart and decreases in v’s farther above heart
o -10 mmHg in head, 0 mmHg in ext. jugular, 80 mmHg at feet
o note: 1 cm blood = 0.77 mmHg
• supine- a pressure = 100 mmHg, v pressure = 10 mmHg, CHP in foot = 25 mmHg
o gradient = a pressure – v pressure = 90 mmHg
o note: flow pressure gradient (90 mmHg) doesn’t change
• Transmural Pressure- (inside vessel pressure) – (outside vessel pressure)
o CHP increased from 25 to 105 when erect > edema in feet

o distensible v’s will dilate > venous pooling > 30% reduced venous return
o flow decreased with initial standing, but later increased via venoconstriction if standing

Venous Return Promotion Factors:

• Neuroreflexes- cause venoconstriction (decrease capacitance/vol.) > increase return, SV, HR
• Skeletal Muscle Pump- compresses v’s; moves blood from periphery to deeper v’s with more
supporting structure; breaks up hydrostatic volumes; reduces hydrostatic pressure
• Thoraco-Abdominal Pump- reduced inspiratory pressure increase gradient for venous return;
diaphragm moves down > compresses abdominal v’s
• Arterial Pressure Increase- compresses adjacent thin walled v’s

Autonomic and Reflex Control of Blood Pressure

• Medullary Cardiovascular Center- “the integrator”
o Vasomotor Center- lateral reticular formation in rostral 2/3 of medulla
§ controls symp. outflow to heart and periphery
o Cardioinhibitory Center- dorsal nucleus of vagus and nucleus ambiguous
§ control parasymp. outflow to heart
• Baroreceptors (mechanorecptors)- in carotid sinus and aortic arch; “the receptor”
o most important under normal conditions for moment to moment arterial pressure control
o vessel stretch > pressure increase > nerve firing increase
o reciprocally regulates symp. (adrenergic) and vagal (cholinergic) outflow to heart and
§ inhibits symp. outflow > decrease HR; vasodilation
§ increase vagal outflow > decrease HR / CO
o note: HR and arterial pressure will increase without baroreceptor input
o Syncope- fainting that would result due to postural hypotension; no baroreceptor reflex
• ANS- “the effecter”; alters both flow and resistance; Pressure = Flow x Resistance
o arterial pressure reduction > symp. activity increases; vagal activity is inhibited
o Inc. Symp. Activity > increase venoconstriction / arteriolar vasoconstriction / return / SV
o Vagal Inhibition- increase HR and SV > increase CO / contractility
o note: a. pressure reduction doesn’t send any afferent info to brain

-Supine to Tilt Position: increase- HR, peripheral resistance / decrease- SV, CO

• Mean Arterial Pressure = Cardiac Output x Total Peripheral Resistance

o note: CO = SV x HR
o MAP = CO x TPR
o to correct for MAP increase > lower CO and TPR….and vice versa
• Altered Baroreceptor Reflex: weightlessness, prolonged bed rest (deconditioning), hypertension
(resetting), exercise (resetting)

Long Term Arterial Pressure Regulators:

• Kidney: increase a. pressure > increase kidney fluid output / decrease extracellular fluid > decrease
blood vol. > reduce venous return > decrease CO > decrease a. pressure
• Antidiuretic Hormone (ADH) / Vasopressin: reduce urine excretion from kidney
o ADH release receptors- cardiac stretch, osmoreceptors, Angiotensin II in brain
o secreted in extended periods of standing
o 3 Release Stimuli: decrease a. pressure, increase symp. activity, reduced Na
concentration in renal tubules
o Renin – Angiotensin System:
• liver secretes Angiotensinogen > kidney secretes Renin > conversion to
Angiotensin I > Angiotensin converting enzyme from lungs added > conversion

to Angiotensin II > adrenal cortex secretes Aldosterone > kidney retains Na and
water > less urine

• Atrial Natriuretic Peptide (ANP): opp. of ADH

o plasma increase > cardiac distension > ANP secretion > decrease Aldosterone secretion >
decrease kidney reabsorption > more urine/Na excretion
o decreases: blood vol., venous return, CO, BP

• Prolonged Standing: vascular vol. loss, decreased β receptor stretch, ADH secretion, water retention
• Supine Position: increase venous return/vol., increase cap. reabsorption, increase atrial pressure (β
receptor activation), increased urine

• Cardiogenic Shock- result of any disease or event which prevents heart muscle from pumping
• Septic Shock- usually result of bacterial infection > produce toxins which damage organs
o poor heart muscle function, > dia blood vessels, < BP, excessive clotting, organ failure
• Hypovolemic Shock- result of decrease of total blood vol.
o can be from severe bleeding, fluid loss, dehydration, excess urine, burns, GI blockage
o early shock at 25% loss (70 mmHg); serious shock at 35% loss (60 mmHg)
• Hemorrhage- leads to decreased blood vol. / CO / BP / organ function

• responses: 1) dec. baroreceptor reflex >> inc. return / CO > maintenance of BP

2) inc. ADH / Renin-Angiotensin System > dec. urine exretion > retain blood vol.

Special Circulation
Cerebral Circulation: 2% of body wt., but receives 20% of CO
• more flow in gray matter than white matter; total flow = 775 mL/min
• Circle of Willis- allows a’s to communicate at brain base
• Control- minor neurogenic effect, mainly metabolic (blood gases)
• Metabolic Effects:
o CO2- normally 40mmHg; small changes have big effect
§ Voluntary Hyperventilation- dec. CO2 > brain blood flow reduced by 35%
o O2- pressure normally 100 mmHg; no great effect until reduced to 50 mmHg
• normal flow at 60-150 mmHg; metabolic changes override local myogenic control

Coronary Circulation:
• Ventricular Supply- two main arterial trunks from aortic sinus just above semilunar valves
• uses 10% total O2; 4% of CO; 5x larger capillary network than skeletal muscle
• Myocardial Flow Factors- mainly aortic pressure; O2 demand is most important determinant
o 80% of flow occurs during v. diastole (low myocardial tension)
o heart is continuously metabolically active (req. O2) – must accommodate with inc. flow
o largest oxygen gradient in body from v’s to a’s = A-VO2 gradient
o Adenosine Hypothesis: O2 effect mediated by Adenosine in ISF > dilates arterioles

• little effect from symp. adrenergic constrictor
• dec. O2 > pulmonary a. constriction <note: opp. from other tissues

Skeletal Muscle:
• At Rest- symp. adrenergic nerves (NE) control, baroreceptor reflex system

• Preparation of Activity- symp. cholinergic nerves (ACh) control > a. dilation; inc. flow / pressure in
cap’s > anticipates activity
• During Activity- metabolic dilation controls; no adrenergic or cholinergic control

• blood flow exceeds metabolic needs
• normal: 1 L/min; increase to 3 L/min > raise core temp.
• symp. cholinergic (ACh) to skin sweat glands > Kallikren release > Globulin (tissue fluid) release >
Bradykinin release > skin arterioles dilate > increased flow
• Arteriovenous Shunts- hands, feet, lips, ears; no basal tone
o normally closed via symp.
o raise core temp. > shunts open > inc. flow

Fetal Circulation:
• Placenta- fetal exchange organ; receives over half of ventricular output; lost at birth
• Lungs- no gas exchange in utero
o Foramen ovale- R to L shunt
o Ductus arteriosus- from pulmonary a. to aorta
o at birth- foramen ovale closes and becomes fossa ovalis, ductus arteriosus closes and
becomes ligamentum arteriosum
• Liver- ductus venosus bypasses fetal liver

Blood and Homeostasis

• major cell components: erythrocytes, leukocytes, platelets
• Leukocyte: neutrophils, eosinophils, basophils, monocytes, and lymphocytes
o produced in bone marrow
• Platelets: from megakaryocytes in bone marrow; clotting function

• functions: transport oxygen and carbon dioxide, acid-base balance
• Hemoglobin- protein which binds O and some CO; req’s iron
• cell: biconcave disc with no nucleus or mitochondria; 120 day lifespan
• produced exclusively in bone marrow; destruction in spleen and liver; iron is conserved; hemoglobin
metabolized to bilirubin after destruction
• Erythropoietin- controls production
o dec. oxygen to kidney / testosterone release > kidney releases erythropoietin > stimulates
rbc maturation and differentiation in bone marrow
o folic acid and B12 necessary for cell maturation
• Anemia- dec. ability of blood to carry oxygen; due to dec. number of rbc’s or dec. in hemoglobin

• Hemostasis- mechanism to control/stop bleeding in small vessel injuries

o injury > vascular spasm > platelet plug formation > blood coagulation / clot > fibrous
tissue growth > dissolution / lysis of clot
o Vascular Spasm- vessel contracts after injury via nervous reflexes, myogenic spasm, and
humoral factors
o Platelet Plug- platelets adhere to exposed collagen in vessel wall (not to endothelium)
§ von Willebrand Factor- plasma protein necessary for plug formation
§ platelet binding > degranulation > chemical mediators > aggregation > plug
§ Nitric Oxide / Prostacyclin- prevent plug from separating; produced by
undamaged adjacent endothelial cells
• Coagulation / Clot (Thrombus) Formation- meshwork of fibrin
o includes platelets and rbc’s

o cascade of plasma enzyme activators req’s activated platelets, plasma cofactors, and Ca
o 3 Steps- 1) Formation of Prothrombin Activator
2) Activator converts Prothrombin to Thrombin
3) Thrombin converts Fibrinogen to Fibrin

• Intrinsic Pathway- clotting initiated by factors only in blood; what occurs in test tube
• Extrinsic Pathway- clotting initiated by tissue factors; what occurs in body
-both pathways converge at prothrombin activator (Xa)
• Vit. K needed for prothrombin production

• Clot Dissolution / Lysis: removed by fibrinolytic system

o Plasminogen activated to proteolytic enzyme Plasmin > digests fibrin network
o Tissue Plasminogen Activator (t-PA)- also binds to fibrin; secreted by endothelial cells;
converts plasminogen to plasmin > clot dissolution
• Anti-clotting Agents:
o Tissue Factor Pathway Inhibitor (TFPI)- prevents formation of factor Xa; secreted by
endothelial cells
o Thrombomodulin- endothelial cell receptor which binds to thrombin and inhibits clotting
o Antithrombin III- inactivates thrombin; activated by heparin on endothelial cell surfaces
• Anti-clotting Drugs:
o Asprin- inhibits cyclooxygenase enzyme (produces thromboxane)
o Coumarins- inhibit Vit. K
o Heparin- inhibits thrombin and platelet function
o Thrombolytics- t-PA and streptokinase