The black loop represents normal cardiac physiology.

Phases—left ventricle:
Isovolumetric contraction—period between mitral valve closing and aortic valve opening; period of highest O2
consumption
Systolic ejection—period between aortic valve opening and closing
Isovolumetric relaxation—period between aortic valve closing and mitral valve opening
Rapid filling—period just after mitral valve opening
Reduced filling—period just before mitral valve closing
Heart sounds:
S1—mitral and tricuspid valve closure. Loudest
at mitral area.

S2—aortic and pulmonary valve closure.

Loudest at left upper sternal border.

S3—in early diastole during rapid ventricular

filling phase. Associated with filling pressures
(eg, mitral regurgitation, HF) and more
common in dilated ventricles (but can be
normal in children, young adults, and pregnant
women).

S4—in late diastole (“atrial kick”). Best heard

at apex with patient in left lateral decubitus
position. High atrial pressure. Associated with
ventricular noncompliance (eg, hypertrophy).
Left atrium must push against stiff LV wall.
Consider abnormal, regardless of patient age.

Jugular venous pulse (JVP):

A wave—atrial contraction. Absent in atrial
fibrillation (AF).

C wave—RV contraction (closed tricuspid valve

bulging into atrium).

x descent—downward displacement of closed

tricuspid valve during rapid ventricular
ejection phase. Reduced or absent in tricuspid
regurgitation and right HF because pressure
gradients are reduced.

V wave—right atrial pressure due to filling

(“villing”) against closed tricuspid valve.

Y descent—RA emptying into RV. Prominent in

constrictive pericarditis, absent in cardiac
tamponade.
Atrioventricular block
(Heart block)
Last updated: Dec 10, 2019
QBANK SESSION
CLINICAL SCIENCES
LEARNED

Summary
Atrioventricular block (AV block) is characterized by an interrupted or delayed conduction between the atria and the
ventricles. AV blocks are divided into three different degrees depending on the extent of the delay or interruption. First-
degree blocks are identifiable on ECG by a prolonged PR interval. Most patients with first-degree block are
asymptomatic, and the condition is usually an incidental finding. Second-degree AV blocks are further divided into two
different subtypes. Mobitz type I, or Wenckebach, blocks exhibit a progressive prolongation of the PR interval that
culminates in a non-conducted P wave (“dropped beat”). Most patients with Mobitz type I blocks are asymptomatic. The
Mobitz type II block generates dropped QRS complexes at regular intervals (e.g. 2:1, 3:1, or 3:2), often leading
to bradycardia. Symptoms of patients with Mobitz type II block range from fatigue to dyspnea, chest
pain, and/or syncope. This fixed second-degree block frequently progresses to a third-degree block. A third-degree AV
block involves total interruption of the electrical impulse between the atria and ventricles. The complete absence of
conduction results in a ventricular escape mechanism, which may be dangerously slow and result in life-
threatening bradycardia or Stokes-Adams attacks. Therefore, a third-degree AV block is an absolute indication for
pacemaker placement.

NOTES
FEEDBACK

Etiology
 Physiological: ↑ vagal tone

 Pathophysiological
o Idiopathic fibrosis of the conduction system

o Ischemic heart disease

o Cardiomyopathy (e.g., due to amyloidosis or sarcoidosis)

o Infections (e.g., Lyme disease, bacterial endocarditis)

o Hyperkalemia (> 6.3 mEq/L)

 Iatrogenic
o Side effect of certain drugs (e.g.,beta blockers, calcium channel blockers, digitalis)

o Cardiac interventions (e.g., surgery, alcohol septal ablation)

References: [1][2]

NOTES
 FEEDBACK

First-degree AV block
Definition
 PR interval > 200 ms

 No interruption in atrial to ventricular conduction

 Rate of SA node = heart rate

Characteristics
 May be found in healthy individuals, e.g., in athletes with ↑ vagal tone

 Usually asymptomatic

 Often discovered incidentally on ECG

Treatment
 Clinical assessment for underlying diseases (e.g., structural heart diseases, electrolyte
imbalances)

 Usually no specific treatment necessary

 Follow-ups to evaluate progression of the disease

 Pacemaker
o If the patient also exhibits wide QRS complexes on ECG → identify the level of AV block
(within or below the bundle of His) using intracardiac electrogram → if conduction time
from the bundle of His to the ventricles is > 100 ms: pacemaker placement
o Symptomatic patients: unpleasant awareness of the heartbeat due to loss of atrioventricular
synchrony (pacemaker syndrome)

References: [3][4][5]

NOTES
FEEDBACK

Second-degree AV block
Mobitz type I/Wenckebach
Definition

 Progressive lengthening of the PR interval until a beat is dropped; regular atrial impulse does
not reach the ventricles (a normal P wave is not followed by a QRS-complex)

 Rate of SA node > heart rate; mostly regular rhythm separated by short pauses, which may lead
to bradycardia
 Symptoms/clinical findings

 Usually asymptomatic

 May present with symptoms of reduced cardiac output, resulting in hypoperfusion

(e.g., dizziness, syncope) and bradycardia

 Irregular pulse

Treatment

 Asymptomatic patients
o Clinical assessment for underlying diseases (e.g., structural heart diseases, electrolyte
imbalances)
o Usually no specific treatment necessary

o Follow-ups (ECG and cardiac monitoring) to evaluate progression of the disease

 Symptomatic patients
o Hemodynamically stable

 Monitoring with transcutaneous pacing pads

 If symptoms not reversible → placement of a permanent pacemaker

o Hemodynamically unstable

 Atropine

 Temporary cardiac pacing (if not responsive to atropine)

Mobitz type II
Definition

 Single or intermittent non-conducted P waves without QRS complexes

 The PR interval remains constant.

 The conduction of atrial impulses to the ventricles follows regular patterns:

o 2:1 block: regular AV block that inhibits conduction of every other atrial depolarization (P
wave) to the ventricles (heart rate = ½ SA node rate)
 o 3:1 block: regular AV block with 3 atrial depolarizations but only 1 atrial impulse that reach
the ventricles (heart rate = ⅓ SA node rate)
o 3:2 block: regular AV block with 3 atrial depolarizations but only 2 atrial impulses that reach
the ventricles (heart rate = ⅔ SA node rate)

Symptoms/clinical findings

 Bradycardia → ↓ cardiac output

o Fatigue

o Dyspnea

o Chest pain

o Dizziness, syncope

Treatment

 Hemodynamically stable patients:

o Monitoring with transcutaneous pacing pads

o Clinical assessment for underlying diseases (e.g., structural heart diseases, electrolyte
imbalances)
o If symptoms are not reversible → placement of a permanent pacemaker

 Hemodynamically unstable patients:

o Atropine

o Temporary cardiac pacing

The second-degree AV block Mobitz type II may progress to a third-degree block and is an unstable condition that
requires monitoring and treatment!
References: [1][4][6][7]

NOTES
FEEDBACK

Third-degree AV block
Definition
 Third-degree AV block is a complete block with no conduction between the atria and ventricles.
  AV dissociation: on ECG, P waves and QRS complexes have their own regular rhythm but
bear no relationship to each other

 A ventricular escape mechanism is generated by sites that are usually located near the AV
node or near the bundle of His.
o The more distant the site of impulse generation:

 The slower the ventricular escape mechanism

 The wider and more deformed the QRS complex

 Block proximal to bundle of His: narrow QRS complexes

 Block distal to bundle of His: wide QRS complexes

 The worse the prognosis

 Sudden onset of a third-degree AV block results in asystole, which lasts until the ventricular
escape mechanism takes over. This asystole may lead to Stokes-Adams attacks.

Symptoms/clinical findings
Symptoms depend on:

 Rate of ventricular escape mechanism

o Bradycardia (< 40 bpm) with cerebral hypoperfusion (fatigue,
irritability, apathy, dizziness, syncope, cognitive impairment), heart failure, dyspnea

 Length of asystole
o Nausea, dizziness

o Stokes-Adams attacks

o Cardiac arrest
Treatment
 Hemodynamically stable patients:
o Monitoring with transcutaneous pacing pads

o Clinical assessment for underlying diseases (e.g., structural heart diseases, electrolyte
imbalances)
o No reversible causes → placement of a permanent pacemaker

 Hemodynamically unstable patients:

o Temporary transcutaneous or transvenous cardiac pacing

 In the event of low blood pressure, administer dopamine.

  In the event of heart failure, administer dobutamine.

Cardiac physiology
Last updated: Jun 03, 2020
QBANK SESSION
LEARNED

Summary
The heart pumps blood through the circulatory system and supplies the body with blood. Cardiac activity can be assessed
with measurable parameters, including heart rate, stroke volume, and cardiac output. The cardiac cycle consists of two
phases: systole, in which blood is pumped from the heart, and diastole, in which the heart fills with blood.
The conduction system is made up of a collection of nodes and specialized conduction cells that initiate and coordinate
the contraction of the myocardium. Pacemaker cells (e.g., sinus node) of the conduction system of
the heart autonomously and spontaneously generate an action potential (AP). The conduction system transmits the AP
throughout the myocardium, and the electrical excitation of the myocardium results in its contraction. A phase of
relaxation (refractory period) prevents immediate re-excitation. The Frank-Starling mechanism maintains cardiac
output by increasing myocardial contractility and thus stroke volume, in response to an increased preload (end-diastolic
volume). The autonomic nervous system is able to regulate the heart rate as well as cardiac excitability, conductivity,
relaxation, and contractility.
NOTES
FEEDBACK

Overview
The main task of the heart is to supply the body with blood. This activity can be assessed with measurable parameters,
including heart rate, stroke volume, and cardiac output.
Definitions
 Heart rate (HR)
o The number of heart contractions per minute (bpm)

o Normal heart rate at rest: 60–100 bpm

 Stroke volume (SV): the volume of blood pumped by the left or right ventricle in a single
heartbeat
o SV = end-diastolic volume (EDV) − end-systolic volume (ESV)

 Ejection fraction (EF): the proportion of EDV ejected from the ventricle
o EF = SV / EDV = (EDV - ESV)/EDV

o Normally 50–70%

o Serves as an index of myocardial contractility: e.g., ↓ myocardial contractility → ↓ EF (seen

in systolic heart failure, where EF is < 40%)

 Venous return: the rate at which blood flows back to the heart, which typically equals cardiac
output (see preload)

 Cardiac output: the volume of blood the heart pumps through the circulatory system per
minute (∼ 5 L/min at rest)
 o Cardiac output (CO) = heart rate (HR) × stroke volume (SV)

o Measurement

 Via Fick principle: Cardiac output is proportional to the quotient of the total body oxygen
consumption and the difference in oxygen content of arterial blood and mixed venous
blood.

 Cardiac output (CO) = oxygen consumption rate/arteriovenous oxygen

difference = (O consumption)/(arterial O content − venous O content)
2 2 2

 Via mean arterial pressure (MAP): MAP = cardiac output (CO) × total peripheral
resistance (TPR)
 Mean arterial pressure (MAP) = 1⁄3 systolic blood pressure (SP) + ⅔ diastolic blood
pressure (DP) = (SP + 2 x DP)/3
o As HR increases, diastole is shortened, which decreases CO due to less filling time.

 Volumetric flow rate: the volume of blood that flows across a valve per second
o Volumetric flow rate (Q) = average flow velocity (v) x cross-sectional area occupied by the
blood (A)

 The amount of fluid entering the system must equal the amount leaving the system: Q = 1

Q so A v = A v (discharge at section 1 = discharge at section 2)

2 1 1 2 2

 Used to calculate flow across stenotic valves, vessels of different diameters, etc.

 Cardiac blood pressures

o Right atrium: < 5 mm Hg

o Right ventricle (pulmonary artery pressure): 25/5 mm Hg

o Left atrium (pulmonary capillary wedge pressure): < 12 mm Hg

o Left ventricle: 130/10 mm Hg

During exercise, a healthy young adult can increase their CO to approx. 4–5 times the resting rate of 5 L/min, to approx.
20–25 L/min. This increase in CO is achieved through a significant increase in HR and a slight increase in SV. The
increased HR shortens the filling time (diastole), which limits the increase in SV. As the HR reaches ≥ 160/bpm,
maximum CO is therefore reached and begins to decrease, as SV declines faster than HR increases.
NOTES
FEEDBACK

Cardiac cycle
The cardiac cycle can be divided into two phases: systole, in which blood is pumped from the heart, and diastole, in
which the heart fills with blood. Systole and diastole are each subdivided into two further phases, resulting in a total
of four phases of heart action. Depending on the phase, pressure and volume in the ventricles and atria change, with the
pressure in the left ventricle changing the most and the pressure in the atria the least.
Systole
1.) Isovolumetric contraction

 Main function: ventricular contraction

 Follows ventricular filling

 Occurs in early systole, directly after the atrioventricular valves (AV valves) close and before
the semilunar valves open (all valves are closed)

 Ventricle contracts (i.e., pressure increases) with no corresponding ventricular volume change
o LV pressure: 8 mm Hg → ∼ 80 mm Hg (when aortic and pulmonary valves open passively)

o LV volume: remains ∼ 150 mL

o RV pressure: 5 mm Hg → 25 mm Hg

o RV volume: ∼ 150 mL

 The period of highest O consumption

2

2.) Systolic ejection

 Main function: Blood is pumped from the ventricles into the circulation and lungs.

 Follows isovolumetric contraction

 Occurs between the opening and closing of the aortic valve and pulmonary valve

 Ventricles contract (i.e., pressure increases) to eject blood, which decreases the ventricular
volume
o Pressure: first increases from ∼ 80 mm Hg to 120 mm Hg and then decreases until aortic and
pulmonary valves close
o Volume: ejection of ∼ 90 mL SV (150 mL → 60 mL)
Diastole
3.) Isovolumetric relaxation

 Main function: ventricular relaxation

 Follows systolic ejection

 Occurs between aortic valve closing and mitral valve opening

 All valves closed (volume remains constant)

o Dicrotic notch: slight increase of aortic pressure in the early diastole that corresponds to
closure of the aortic valve

 The ventricles relax (i.e., pressure decreases) with no corresponding ventricular volume change
until ventricular pressure is lower than atrial pressure and atrioventricular valves open
o Pressure: decreases to ∼ 10 mm Hg in the left atrium and ∼ 5 mm Hg in the right atrium

o Volume: remains at ∼ 60 mL

 Coronary blood flow peaks during early diastole at the point when the pressure differential
between the aorta and the ventricle is the greatest.
o The coronary arteries fill with blood during diastole because they are compressed during
ventricular systole.
 4.) Ventricular filling
Main function: ventricles fill with blood
Rapid filling

 Follows isovolumetric relaxation

 Occurs in early diastole; immediately after mitral valve opening

 Blood flows passively from the atria to the ventricles.

 The largest volume of ventricular filling occurs during this phase.

Reduced filling

 Follows rapid filling

 Occurs in late diastole; immediately before atrioventricular valves close

o LV pressure: ∼ 8 mm Hg; RV pressure: ∼ 5 mm Hg (2–8 mm Hg)

o LV and RV volume: ventricles fill with ∼ 90 mL (60 mL → 150 mL)

During isovolumetric contraction and relaxation, all heart valves are closed. There are no periods in which all heart
valves are open!
During states of increased heart rate (e.g., during exercise), the duration of diastole decreases so that there is less time for
the coronary arteries to fill with blood and supply the heart with oxygen. Patients with narrow coronary arteries, e.g., due
to atherosclerosis, will, therefore, experience chest pain (angina pectoris) during exertion!
Left ventricular pressure-volume diagram
 Used to: measure cardiac performance

 Shape: roughly rectangular; each loop is formed in a counter-clockwise direction

 Course
o (1) End-diastolic state: closure of the atrioventricular valve and the beginning of systole (the
LV is filled with blood)
o (1 → 2) Isovolumetric contraction: With the atrioventricular and semilunar valves closed,
contraction increases the internal pressure of the left ventricle; ventricular volume is left
unchanged.
o (2) Opening of the semilunar valve when the ventricular pressure exceeds the aortic and
pulmonary arterial pressure
o (2 → 3) Ejection phase: The ventricle pumps out the stroke volume.

o (3) Closure of the semilunar valve when the ventricular pressure falls below the aortic and
pulmonary arterial pressure
 o (3 → 4) Isovolumetric relaxation: the beginning of diastole, when the ventricle relaxes and all
the valves are closed
o (4) Opening of the atrioventricular valve when the ventricular pressure falls below the atrial
pressure
o (4 → 1) Filling phase: The ventricles receive blood from the atria and a new cardiac
cycle begins.

Physiological changes in valvular disease

MAXIMIZE TABLETABLE QUIZ

Valvular Pressure-volume loop Time-pressure curves

disease

Mitral  The pressure-volume loop is rounder and flatter  Tall V-wave

regurgitation than a normal pressure-volume loop.
 ↑ LV end-diastolic volume and pressure
 ↑ Stroke volume
 No isovolumetric contraction
 No isovolumetric relaxation
 ↓ LV end-systolic volume

Mitral stenosis  The pressure-volume loop is narrower and  LA pressure > LV

flatter than the normal pressure-volume loop. pressure during diastole
 ↑ LA pressure
 ↓ LV end-diastolic volume
 ↓ Stroke volume
 ↓ LV end-systolic volume

Aortic  The pressure-volume loop is rounder and taller  ↑ Pulse pressure

regurgitation than the normal pressure-volume loop.
 ↑ LV end-diastolic volume and pressure
 ↑ Stroke volume
 No true isovolumetric relaxation

Aortic stenosis  The pressure-volume loop is narrower and  LV blood pressure > aortic pressure
taller than the normal pressure-volume loop. during systole
 ↑ LV end-systolic pressure
 No change in end-diastolic volume
 ↓ Stroke volume
 Valvular Pressure-volume loop Time-pressure curves
disease

 ↑ LV end-systolic volume
 ↑ LV end-diastolic pressure

The width of the volume-pressure loop is the SV (the difference between EDV and ESV).
NOTES
FEEDBACK

Conduction system of the heart

Definition: the collection of nodes and specialized conduction cells that initiate and coordinate contraction of
the heart muscle

MAXIMIZE TABLETABLE QUIZ

Name Anatomic localization Characteristics Frequency

Sinoatrial node  Upper wall of  Natural pacemaker center of ca. 60–

the right atrium (at the the heart with specialized pacemaker cells 80/min
junction where  Spontaneously generates electrical
the SVC enters) impulses that initiate a heartbeat
 Influenced by autonomic nervous system
 Supplied by sinus node artery (branch of
the right coronary artery)

Atrioventricular  Within the AV  Receives impulses from the SA node and ca. 40–
node septum (superior passes these impulses to the bundle of His 50/min
and medial to the  Has the slowest conduction velocity
opening of
the coronary sinus in  Delays conduction for 60–120 ms (allowing
the right atrium) the ventricles to fill with blood; without this
 Name Anatomic localization Characteristics Frequency

delay, the atria and ventricles would

contract at the same time)
 Supplied by the AV nodal artery (posterior
descending artery of right coronary
artery)

Bundle of His  Directly below  Receives impulses from the AV node ca. 30–
the cardiac skeleton, 40/min
 Splits into left and right bundle
within the branches (Tawara branches) → the right
membranous part of bundle travels to the right ventricle; the left
the interventricular bundle splits into an anterior and
septum a posterior branch to supply the left
ventricle → terminate into terminal
conducting fibers (Purkinje fibers) of the
left and right ventricle
 Prevents retrograde conduction
 Filters high-frequency action potentials so
that high atrial rates (e.g., in atrial
fibrillation) are not conducted to
the myocardium

 Terminal conducting  Conduct cardiac AP faster than any other ca. 30–
Purkinje fibers fibers in the cardiac cells 40/min
subendocardium  Ensure synchronized contraction of the
ventricles
 Purkinje fibers have a long refractory
period.
 Form functional syncytium: forward
incoming stimuli very quickly via gap
junctions to allow coordinated contraction

Normal course of electrical conduction

SA node (pacemaker) creates an action potential → signal spreads across atria and causes their contraction
→ signal reaches AV node and is slowed down → AV node conducts the signal to bundle of His down the
interventricular septum to Purkinje fibers in myocardium → they carry the signal across the ventricles → the ventricles
contract (electromechanical coupling)

The electrical activity of the heart can be recorded through electrocardiography. See ECG for an overview of ECGs and
their interpretation.
NOTES
FEEDBACK
Heart excitation
Overview
1. Pacemaker cells (e.g., sinus node) of the conduction system of the heart autonomously and
spontaneously generate an action potential (AP).

2. The conduction system transmits the AP throughout the myocardium.

3. The electrical excitation of the myocardium results in its contraction (see electromechanical
coupling and filament sliding theory in muscle tissue).

4. The phase of relaxation prevents immediate re-excitation (refractory period).

Cardiac calcium channels and calcium pumps

MAXIMIZE TABLETABLE QUIZ

Name Definition Location Direction of Activatio

flow n phase
(affected
tissue)

Calci L-type voltage-  Long-acting, high-  Cell  Influx of  Plateau

um gated calcium voltage channels membrane of car extracellul phase
chan channel that are responsible diomyocytes ar (myoca
nels (i )
Ca for electromechani Ca into
2+
rdium)
cal coupling the cytopl  Upstrok
asm
 Activation e phase
via depolarization ( (SV
- 40 mV) triggers node)
Ca influx into the
2+

cells, which in turn

stimulates the
release of Ca from
2+

the SR.

T-type voltage-  A voltage-gated  Cell  Influx of  During

gated calcium calcium membrane of extracellul the
channel channel that is cardiac ar middle
opened by low- pacemaker cells Ca into
2+
of
voltage depolarizati the cytopl phase 4
on potentials asm (SV
node)

Ryanodine  Ca channel that

2+
 Membrane of SR  Transport  Plateau
receptor opens after binding Ca from
2+
phase
of SR to (myoca
Ca (i.e., calcium-
2+
the cytopl rdium)
 induced Ca releas 2+
asm
e)

Calci SERCA (sarcopl  Ca pumps and

2+
 Membrane of SR  Efflux of  Plateau
um asmic Ca - 2+
exchangers that are Ca from
2+
phase
pum ATPase) responsible for the cytopl (myoca
ps terminating a asm into rdium)
contraction the SR

Na+/Ca2+  Cell  Efflux of

exchanger membrane of car Ca from
2+

diomyocytes the cytopl

asm into
extracellul
ar space

Other cation channels

All of these channels are located in the cell membrane.
MAXIMIZE TABLETABLE QUIZ

Name Definition Direction of Activation phase (affected

flow tissue)

Funny channels (HCN, I ) f  Nonselective cation  Extracellul  Upstroke phase (sinus node)
channels (e.g., for ar →
Na , K ) in
+ +
intracellul
pacemaker cells that ar
open as the
membrane potential
becomes more
negative
(hyperpolarized)

Fast sodium channels (I ) Na  Na channels that

+
 Depolarization (myocardium
rapidly open and )
close
following depolariza
tion

Potassiu Inward rectifier  K channels that

+
 Intracellul  Resting
m K channels
+
open during ar → potential (primarily myocard
channels the resting extracellul ium; sinus node)
potential (below −70 ar
mV) and stabilize
the resting
potential of
the cardiomyocytes

Delayed  K channels that can

+
 Repolarization (sinus node
rectifier be rapidly (I ) or Kr and myocardium)
K channels(I a
+
Kr slowly (I ) activated
Ks

nd I )Ks
 Name Definition Direction of Activation phase (affected
flow tissue)

upon depolarization

The long plateau phase of the Ca channels allows the myocardium to contract and pump blood effectively.
2+

Cardiac action potential

MAXIMIZE TABLETABLE QUIZ

Myocardial action Pacemaker action potential (SA

potential (myocardium, bundle of node and AV node)
His, Purkinje fibers)

Phase 0  Upstroke: An action potential from  Upstroke: At TMP -40 mV (threshold

(upstroke a pacemaker cell or potential of pacemaker cells), L-type
and depolarization) adjacent cardiomyocyte causes the Ca channels open → TMP increases
2+

transmembrane potential (TMP) to to +40 mV

rise above −90 mV.  No rapid depolarization phase because
 Depolarization: Fast voltage-gated fast voltage-gated Na channels are
+

Na channels open at -65 mV →

+
inactivated in pacemaker cells
rapid Na influx into the cell →
+

→ results in slower conduction velocity

TMP rises further until slightly between atria and ventricles
above 0 mV

Phase 1  Inactivation of voltage-gated  Absent

(early repolarization) Na channels
+

 Transient K channels start to open

+

(outward flow of K returns TMP +

to 0 mV)

Phase 2  K efflux through delayed rectifier

+
 Absent
(plateau phase) K channels and Ca influx through
+ 2+

voltage-gated L-type Ca channels, 2+

which triggers Ca release from

2+

the sarcoplasmic
reticulum (i.e., Ca -induced Ca rel
2+ 2+

ease)
→ contraction of the myocyte
 TMP is maintained at a plateau just
below 0 mV.

Phase 3  Inactivation of voltage-gated  Closure of voltage-

(rapid repolarization) Ca channels
2+
gated Ca channels and
2+
 Myocardial action Pacemaker action potential (SA
potential (myocardium, bundle of node and AV node)
His, Purkinje fibers)

 K efflux through delayed

+
 Opening of delayed
rectifier K channels continues:
+
rectifier K channels → K efflux (TMP
+ +

Persistent outflow of returns to -60 mV)

K exceeds Ca inflow and brings
+ 2+

TMP back to -90 mV.

 The sarcolemmal Na - +

Ca exchanger, Ca -ATPase,
2+ 2+

and Na -K -ATPase restore normal

+ +

transmembrane ionic concentration

gradients (Na and Ca ions return
+ 2+

to extracellular space, K to +

intracellular space).

Phase 4  Resting membrane potential stable  No resting phase (unstable membrane

(resting phase) at -90 mV due to a constant potential)
outward flow of K through inward+

o Gradual Na /K entry via funny

+ +

rectifier channels
channels I (funny
f

 Na and Ca channels closed

+ 2+
current or pacemaker current) →
slow
spontaneous depolarization (TMP
raises above -60 mV); no
external action potential needed
(automaticity of SA and AV nodes)
 At TMP -50 mV: T-
type Ca channels open.
2+

Pacemaker cells have no stable resting membrane potential. Their special hyperpolarization-activated cation channels
(funny channels) ensure a spontaneous new depolarization at the end of each repolarization and are responsible for
the automaticity of the heart conduction system! In sympathetic stimulation, more I channels open, increasing the heart
f

rate.
Upstroke and depolarization of a pacemaker cell are caused by the opening of voltage-activated L-type calcium channels.
In other muscle cells and neurons, upstroke and depolarization are caused by fast sodium channels!
The duration of action potentials differs in the various structures of the conduction system and increases from the sinus
node to the Purkinje fibers!
Refractory period
 Effective refractory period (ERP): a recovery period immediately after stimulation, during
which a second stimulus cannot generate a new AP in a depolarized cardiomyocyte. The
Na channels are in an inactivated state until the cell fully repolarizes (phases 1–3).
+

o See 'Refractory period' in resting potential and action potential for details.

 Phases (determined based on the number of sodium channels ready to be reactivated)

o Absolute refractory period: time interval in which no new AP can be generated because fast
Na channels are deactivated (plateau phase)
+
 o Relative refractory period: time interval in which some Na+ channels can be reactivated but
have a higher threshold potential; only a strong impulse can trigger a new, low amplitude AP

 Effect
o Ensures sufficient time for chamber emptying (during systole) and refilling (during diastole)
before the next contraction
o Prevents re-excitation of cardiomyocytes during this period to avoid circulatory excitation,
which would lead to arrhythmia and tetany of cardiac muscle

The firing frequency of the SA node is faster than that of other pacemaker sites (e.g., AV node). The SA node activates
these sites before they can activate themselves (overdrive suppression).
The plateau phase of the myocardial action potential is longer than the actual contraction. This allows the heart muscle to
relax after each contraction and prevents permanent contraction (tetany)!
Heterogeneity of the refractory period within the myocardium (in which some cells are in the absolute refractory
period, relative refractory period, or resting potential state) renders individuals more susceptible
to arrhythmias (e.g., ventricular fibrillation) when exposed to an inappropriately-timed stimulus.
During cardioversion, shock delivery must be synchronized with the R wave on ECG (indicating depolarization) and
avoided during the relative refractory period (T waves, indicating repolarization)!
NOTES
FEEDBACK

Regulation of cardiac activity

Adaptation to short-term changes is provided by the Frank-Starling mechanism. Long-term changes in cardiac activity
are regulated by the autonomic nervous system.
Frank-Starling mechanism
 Definition: a law that describes the relationship between end-diastolic volume and
cardiac stroke volume
o Cardiac contractility is directly related to the wall tension of the myocardium.

 An increase in end-diastolic volume (preload) will cause the myocardium to stretch (↑ end-
diastolic length of cardiac muscle fibers), which increases contractility (↑ force of
contraction) and results in increased stroke volume in order to maintain cardiac output.

 This relationship between end-diastolic volume and stroke volume is shown in the Frank-
Starling curve.

 Aim: maintain CO by modulating contractility and SV

o Stroke volume of both ventricles should remain the same.

Because the afterload is chronically increased in chronic hypertension, the left ventricle undergoes hypertrophy to
decrease left ventricular wall stress (↑ LV wall thickness → ↓ LV wall stress).
An increase in preload leads to an increase in stroke volume; an increase in afterload leads to a decrease in stroke
volume!
 Autonomic innervation of the heart
The autonomic nervous system is able to regulate heart rate, excitability, conductivity, relaxation, and
contractility. Sympathetic fibers innervate both the atria and ventricles. Parasympathetic fibers only innervate the atria.

 Definition: modulation of cardiac action by sympathetic and/or parasympathetic nerve fibers

 Function: long-term regulation of cardiac action

o Chronotropy: any influence on the heart rate

o Dromotropy: any influence on the conductivity of myocardium

o Inotropy: any influence on the force of myocardial contraction

o Lusitropy: any influence on the rate of relaxation of the myocardium

o Bathmotropy: any influence on the excitability of the myocardium

MAXIMIZE TABLETABLE QUIZ

Site of Nerves Effect Mechanism of action

innerva
tion

Sympathetic stimul  Atria  Fibers from  ↑ Heart  Activation of beta adrenergic

1

ation and the sympathetic rate, receptors (G protein-coupled) of

s

ventri cervical trunk conduct the heart by epinephrine and nor

cles ion, epinephrine → ↑
(superior,
contrac activity of adenylyl cyclase → ↑
middle, and
tility, intracellular cAMP concentration
inferior cardiac
and in SA node cardiomyocytes,
nerve)
relaxati which then:
on 1. Increases the conductance of
funny sodium channels
and L-type calcium
channels → ↑ influx of
cations during
spontaneous depolarization
→ faster attainment of
the threshold
potential during phase
4 of pacemaker action
potential for initiating the
rhythmic cardiac action
potential → ↑ heart
rate (positive chronotropic)
2. Activates protein kinase
A (PKA), which leads to two
effects:
 Site of Nerves Effect Mechanism of action
innerva
tion

 Phosphorylation of L-
type Ca channels in AV
2+

node → increased
Ca entry →
2+

increased Ca -induced C
2+

a release during action

2+

potential → increased
contraction and
conduction
(positive dromotropic a
nd inotropic)
 Phosphorylation of phosp
holamban
→ activation
of sarcoplasmic
reticulum Ca -ATPase
2+

(SERCA) → increased
transport of Ca back 2+

into sarcoplasmic
reticulum after a
contraction → faster
relaxation
(positive lusitropic)

Parasympathetic sti  Atria  Branches of  ↓ Heart  Exerts its action on

mulation the vagus rate an the heart through parasympatheti
nerve d atrial c muscarinic ACh
contrac receptors (subtype M2) on SA
o Cervical
tility and AV node cardiomyocytes
cardiac
branches o Activation
of M receptors on SA
o Thoracic 2

node (negative chronotropi

cardiac
c)
branches
 Reduces the conductance
of funny sodium channels
via adenylyl cyclase,
decreasing cAMP →
↓ pacemaker
current (lengthens the
rate of depolarization in
the
slow depolarization phase
)
 Increases conductance of
the slow potassium
channels
→ hyperpolarization of
 Site of Nerves Effect Mechanism of action
innerva
tion

the resting membrane

potential (harder to
overcome)
o Vagal fibers innervate
the AV
node (negative dromotropic
): slows cardiac action
potential propagation (can
result in complete AV block)

Persistent epinephrine surges and long-lasting sympathetic activity can damage blood vessel endothelium, increase blood
pressure, and increase the risk of heart attack and stroke.
Initially, a diminished ejection fraction can be compensated by
increased sympathetic tone, RAAS activation, ADH release, and the Frank-Starling mechanism. In the long term,
however, these mechanisms increase cardiac work and lead to heart failure. Antihypertensive drugs target these
mechanisms.

NOTES
FEEDBACK

Factors that affect cardiac output

 Preload: the extent to which heart muscle fibers are stretched before the onset of systole;
depends on end-diastolic ventricular volume (EDV), which changes according to:
o Venous constriction: ↑ venous tone → ↑ venous blood return to
the heart → ↑ EDV → ↑ preload
o Circulating blood volume: ↑ circulating blood volume → ↑ venous blood return to
the heart → ↑ EDV → ↑ preload

 Afterload: the force against which the ventricle contracts to eject blood during systole
o Afterload is primarily determined by the mean arterial pressure (MAP) in the aorta, which is
influenced by total peripheral resistance.
o ↑ Afterload → ↑ left ventricular pressure → ↑ left ventricular wall stress

o According to Laplace's law, ↑ left ventricular pressure → ↑ left ventricular wall stress

 Left ventricular (LV) wall stress = (LV pressure × radius)/ (2×LV wall thickness)

MAXIMIZE TABLETABLE QUIZ

 Factors that increase SV Factors that decrease SV

Preload  ↑ Venous return  ↓ Venous return

o During inspiration o During expiration
o When changing from upright to supine position o When changing
from supine to upright
o ↑ Skeletal muscle pump activity
position
o ↑ Venous tone (increased sympathetic activity)
o Nitroglycerin (venous
o ↑ Circulating blood volume (e.g., infusions) vasodilatation)
o Inferior vena
cava obstruction
during pregnancy or due
to Valsalva maneuver
o Due to ACE
inhibitors or angiotensin II
receptor blockers
o Hemorrhage
 Tricuspid and mitral valve
stenosis (↓ ventricular inflow)
 Aortic
stenosis (↑ diastolic ventricular
pressure → ↓ ventricular
filling)
 Atrial tachycardia (e.g., atrial
fibrillation ↓ ventricular
filling time)

Afterload  ↓ Systemic vascular resistance (e.g., due  ↑ Systemic and/or

to vasodilators such as hydralazine, ACE peripheral vascular
inhibitors, angiotensin II receptor blockers) resistance (e.g., due to
and/or pulmonary vascular resistance (e.g., due chronic hypertension)
to vasodilators such as phosphodiesterase inhibitors)  Aortic valve stenosis

Myocardi  ↑ Myocardial contractility (↑ inotropy)  ↓ Myocardial

al contractility (↓ inotropy)
o Sympathetic innervation (β -receptor activation)
1
contractili o Parasympathetic stimulation
ty o Catecholamines (e.g., epinephrine, norepinephrine, d
opamine) through β -receptor activation
1 o Acetylcholine
o High levels of blood and intracellular calcium o β -receptor blockers:
1

inhibition of adenylyl
o Thyroid hormones
cyclase → ↓ cAMP →
o Decreased extracellular Na (because subsequently,
+
↓ cAMP-dependent protein
the activity of the Na /Ca exchanger will decrease)
+ 2+
kinase A (PKA) activity
o Digitalis: inhibition of Na /K pump → increased
+ +
o Nondihydropyridine Ca ch 2+

intracellular Na →+
annel blockers: See effects
decreased Na /Ca exchanger activity → increased
+ 2+
in calcium channel
intracellular Ca 2+
blockers.
 Factors that increase SV Factors that decrease SV

o Systolic heart failure

o Hypoxia
o Hypercapnia
o Hyperkalemia
o Acidosis

Valsalva maneuver
 Definition: forceful exhalation against a closed airway

 Technique: four phases

o Phase 1 (start strain) & phase 2 (continued strain): increased intrathoracic pressure →
decreases venous return/ventricular preload → decreased cardiac output
o Phase 3 (release of strain) & phase 4 (recovery phase): reduced intrathoracic pressure →
reduced afterload → increased stroke volume → increased cardiac output

 Applications:
o Treatment of supraventricular tachycardia (e.g., AVNRT)

o Diagnostic tool to:

 Evaluate conditions of the heart: augments heart sounds on physical exam (e.g., earlier
click in mitral valve prolapse and louder murmur in hypertrophic obstructive
cardiomyopathy)

 Test for hernia (increased intraabdominal pressure → bulging)

o Measure to normalize middle-ear pressure (e.g., in diving)

Myocardial oxygen demand increases with an increase in HR, myocardial contractility, afterload, or diameter of the
ventricle.

Summary
The cerebrovascular system comprises the vessels that transport blood to and from the brain. The brain's arterial
supply is provided by a pair of internal carotid arteries and a pair of vertebral arteries, the latter of which unite to form
the basilar artery. The anterior cerebral artery, a branch of the internal carotid artery, perfuses the
anteromedial cerebral cortex; the middle cerebral artery, also a branch of the internal carotid artery, perfuses
the lateral cerebral cortex; and the posterior cerebral artery, a branch of the basilar artery, perfuses
the medial and lateral portions of the posterior cerebral cortex. The internal carotid arteries, the anterior cerebral
arteries, and the posterior cerebral arteries anastomose through the anterior and posterior communicating arteries to
form the circle of Willis, a vascular circuit surrounding the optic chiasm and pituitary stalk. The circle of Willis provides
an alternative channel for blood flow in case of vascular occlusion and equalizes blood flow between the cerebral
hemispheres. The cerebral hemispheres are drained by superficial cerebral veins (superior cerebral veins, middle
cerebral veins, inferior cerebral veins) and deep cerebral veins (great cerebral vein, basal vein), which empty into
the dural venous sinuses. Brain perfusion is regulated by the partial pressure of carbon dioxide (PaCO ). The
2

interruption of perfusion due to occlusion or hemorrhage of the cerebral vessels results in a stroke, which manifests
with focal neurologic deficits in the body parts controlled by the affected brain territory.
NOTES
FEEDBACK

Arterial supply
The arterial supply of the brain is provided by the internal carotid arteries and the vertebral arteries, which are
derivatives of the branches of the aortic arch.
Internal carotid arteries (ICA)
 A terminal branch of the common carotid artery

 Course:

o Neck: lies within the carotid sheath and enters the cranium through the carotid canal

o Cranium: lies on the roof of the cavernous sinus, in close proximity to CN VI

 Only has intracranial branches:

o Caroticotympanic artery (the first intracranial branch of the internal carotid artery that enters
the middle ear cavity and anastomoses with the inferior tympanic artery)

o Artery of the pterygoid canal (Vidian artery)

o Meningohypophyseal trunk (posterior trunk;

o Inferolateral trunk

o Ophthalmic artery

o Superior pituitary artery

o Posterior communicating artery: anastomosis in Circle of Willis

o Anterior choroidal artery

o Terminal branches:

 Middle cerebral artery: supplies lateral cerebrum

 Anterior cerebral artery: supplies anterior cerebrum

Vertebral arteries
 Arise from the subclavian arteries
 Course:
o Neck: The vertebral arteries pass through the foramina in the transverse processes of
the cervical vertebrae and enter the cranium through the foramen magnum.
 o Cranium: The right and left vertebral arteries unite at the midline of the anterior surface of
the pons to form the basilar artery.
 Branches:

o Anterior spinal artery and posterior spinal arteries: supply spinal cord

o Posterior inferior cerebellar arteries (PICA): terminal branches that supply inferior cerebellum

References: [1][2]

NOTES
FEEDBACK

Circle of Willis
 Definition: a vascular circuit formed by the anastomoses between branches of the internal
carotid arteries (anterior circulation) and vertebral arteries (posterior circulation) around
the optic chiasm and pituitary stalk

 Consists of paired:

o Internal carotid arteries (proximal to the origin of the middle cerebral arteries)

o Anterior cerebral arteries (terminal branches of the internal carotids)

o Posterior cerebral arteries (terminal branches of the vertebral arteries)

 Two anastomoses

o Anterior communicating artery: connects the two anterior cerebral arteries

o Posterior communicating artery (branch of internal carotid artery): connects the ICA to
the posterior cerebral artery

 Functional significance

o The circuit provides alternative channels to bypass a potential site of vascular occlusion.

o Equalizes arterial flow to both cerebral hemispheres

Most saccular cerebral aneurysms, also known as berry aneurysms, occur in the anterior circulation of the brain,
usually at the junction of the anterior cerebral artery and the anterior communicating artery in the circle of Willis. They
are the most common cause of nontraumatic subarachnoid hemorrhage.

References: [3][4]

NOTES
 FEEDBACK

Cerebral arterial territories

MAXIMIZE TABLETABLE QUIZ

Arter Arterial territory Main Features of stroke

y branches

Anterior circu Anteri  Anteromedial cortex,  Anterior  Contralateral hemiplegia (lower

lation or including: communi limbs affected more severely)
Branches of cereb cating
o Medial portion of  Minimal hemisensory loss (lower
the internal ral artery
the frontal limbs affected more severely)
carotid artery artery and parietal lobes:  Ophthal
(ACA)  Dysarthria
motor and sensory mic
supply of the artery  Aphasia
lower extremities  Abulia (lack of motivation)
 Anterior
o Anterior limb of choroidal  Limb apraxia
the internal artery (se
capsule e below)  Urinary incontinence

o Corpus callosum
o Basal ganglia
.

Middl  Lateral cortex,  Lenticulo  Contralateral hemiplegia

e including: striate  Contralateral hemisensory loss
cereb arteries
o Lateral portion of
ral  Gaze deviation towards the side
the frontal
artery of infarction
and parietal lobes:
(MCA)  Hemineglect (right MCA territory;
motor and sensory
cortex of the face nondominant hemisphere)
and upper  Contralateral homonymous
extremities hemianopia without macular
o Temporal sparing
lobe: Wernicke  Broca aphasia (inferior
area frontal gyrus of dominant
o Frontal lobe: Broca hemisphere)
area  Wernicke aphasia (superior
 Lenticulostriate temporal gyrus of dominant
arteries supply deeper hemisphere)
structures of the
brain:
o Putamen, globus
pallidus
o Parts of
the internal
capsule and cauda
te nucleus
 Arter Arterial territory Main Features of stroke
y branches

Anteri  Optic tract and lateral   Triad of:

or geniculate nuclei o Hemiparesis or hemiplegia (in
choroi  Hippocampus and late cluding dysarthria)
dal ral thalamus
artery o Hemisensory loss
 Posterior limb of o Homonymous hemianopsia
the internal capsule

Posterior circ Poste  Posteroinferior cortex  Several  Contralateral hemisensory loss

ulation rior branches
o Occipital lobes  Contralateral homonymous
Branch of cereb to the hemianopia with macular sparing
the basilar ral o Posteromedial cortical
artery artery aspect of lobes  Memory deficits
(PCA) the temporal lobes and chor  Vertigo, nausea
o Thalamus oid
plexus  Left PCA: alexia without
agraphia, anomic aphasia,
visual agnosia
 Right PCA: prosopagnosia

References: [5][6][7]

NOTES
FEEDBACK

Venous drainage
The cerebral hemispheres are drained by superficial and deep cerebral veins, which empty into the dural venous
sinuses.
Superficial cerebral veins
MAXIMIZE TABLETABLE QUIZ

Superficial veins Bridging vein Draining venous sinus

Drain the white matter

Superior Superior anastomotic vein Superiorsagittal sinus

cerebral veins

Middle cerebral veins Inferior anastomotic vein Cavernous sinus

Inferior cerebral veins Cavernous and transverse venous sinuses

Deep cerebral veins
Deep cerebral veins drain the cerebral medulla and drain into the straight sinus.
  Medullary veins: drain the gray matter

 Subependymal veins: receive blood from the medullary veins

 Basal vein (vein of Rosenthal): paired paramedian veins that receive blood from the temporal
lobe and drain into the great cerebral vein

 Great cerebral vein (vein of Galen): receives blood from the deep veins
Dural venous sinuses
 The dural venous sinuses drain blood from cerebral veins and CSF from the arachnoid
granulations into the internal jugular vein.

 They are located intracranially between the two layers of dura mater (endosteal layer
and meningeal layer).

MAXIMIZE TABLETABLE QUIZ

Venous sinus Characteristics

Superior sagittal  Located at the midline

sinus  Terminates at the confluence of sinuses
 Drains blood from cortical veins of the cerebral hemispheres
 Main location of cerebral fluid return via arachnoid granulations

Inferior sagittal  Located at the midline

sinus  Joined by the great cerebral vein of Galen before draining into the straight sinus
 Drains blood from the medial surface of the cerebral hemispheres

Straight sinus  Located at the midline

 Terminates at the confluence of sinuses

Occipital sinus  Located posteriorly

 Drains into the confluence of sinuses

Confluence of  Formed by the union of the superior sagittal sinus, straight sinus, and occipital sinus
sinuses  Located posteriorly
 Drains into left and right transverse sinus

Superior petrosal  Located laterally

sinus  Drains into the transverse sinus
(paired)
 Drains blood from the inner ear structures via the labyrinthine vein

Transverse sinus  Located laterally along the edge of the tentorium cerebelli
(paired)  Drains into the sigmoid sinus
 Venous sinus Characteristics

Inferior petrosal  Located laterally

sinus  Drains the cavernous sinus into the internal jugular vein
(paired)
 Drains blood from the medulla, pons, and inferior surface of the cerebellum

Sigmoid sinus  Located laterally

(paired)  Continuation of transverse sinus that arches downward in an S-shaped groove into
the internal jugular vein

Sphenoparietal  Located anteriorly

sinus  Drains into the cavernous sinus
(paired)

Cavernous sinus  Located anteriorly on each side of the sella turcica (pituitary fossa)
(paired)  Structures running through these sinuses include:
o Medially: internal carotid artery and abducens nerve (VI)
o Laterally: oculomotor nerve (III), trochlear nerve (IV), ophthalmic nerve (V ),
1

and maxillary nerve (V ) 2

 Receives the superior ophthalmic vein

 Drains into the petrosal sinuses

Basilar venous  Lies over the basilar part of the occipital bone (the clivus)
plexus  Connected with the cavernous and petrosal sinuses and the
(paired) internal vertebral (epidural) venous plexus.

Brain veins run in the subarachnoid space, have no valves to allow bidirectional blood flow, and have no muscular layer
in the vessel wall!
References: [8][3][9][10][11][12][13]

NOTES
FEEDBACK

Physiology
 Cerebral perfusion is modulated by the partial pressure of carbon dioxide (pCO ) 2

o Increased pCO → vasodilation → increased cerebral blood flow

2

o Decreased pCO → vasoconstriction → decreased cerebral blood flow

2

 Therapeutic hyperventilation reduces pCO → decreases cerebral blood flow →

2

lower intracranial pressure (e.g., used in acute cerebral edema)

  Cerebral perfusion pressure (CPP) = mean arterial pressure (MAP) - intracranial pressure (ICP)

o Decreased blood pressure or increased ICP → decreased cerebral perfusion

o CPP of 0 indicates no brain perfusion (brain death)
o Hypoxemia increases CPP if pO < 50 mm Hg
2

o CPP linearly increases with pCO until pCO > 90 mm Hg

2 2

References: [14][15]

NOTES
FEEDBACK

Clinical significance
 Arterial conditions:

o Stroke

o Cerebral aneurysms
o Subarachnoid hemorrhage

o Epidural hematoma

o Intraparenchymal hemorrhage

o Trigeminal neuralgia (compression of superior cerebellar artery)

o Hydrostatic cerebral edema (e.g., in severe hypertension)

 Venous conditions:

o Cerebral venous thrombosis

o Cavernous sinus syndrome

o Subdural hematoma (caused by ruptured bridging veins)

Summary
The circulatory system, which is also called the vascular system or cardiovascular system, consists of the systemic
circulation, pulmonary circulation, the heart, and the lymphatic system. Blood flow through the circulatory system is
generated by the heart. Vascular resistance is the amount of resistance in the systematic circulation that must be
overcome to create blood flow. The Poiseuille equation describes the relationship between vascular resistance, the length
and radius of the vessel, and the viscosity of blood. Blood pressure is generated by the heart, creating a pulsatile blood
flow that leads to systolic blood pressure (maximum pressure reached during a cardiac cycle) and diastolic blood
pressure (minimum pressure reached during a cardiac cycle) within the circulatory system. The pressure gradient across
the circulatory system drives the blood flow from high pressure to low pressure. Blood pressure regulation involves a
complex interaction of various sensors (baroreceptors, volume receptors, chemoreceptors) and mechanisms, including
the autonomic nervous system, the renin-angiotensin-aldosterone system (RAAS), and atrial reflex and diuresis reflex.
Perfusion is the passage of the blood through the circulatory system to the capillary bed to deliver oxygen and nutrients
to the tissue and remove waste products (e.g., removal of CO to the lungs, removal of urea to the kidneys). Perfusion
2

levels differ in organs and fluctuate depending on the activity (e.g., rest, physical activity). Autoregulatory mechanisms
(myogenic autoregulation, local metabolite production), as well as central regulatory mechanisms, modulate perfusion
levels in organs. The exchange of substances in the microcirculation occurs via diffusion, filtration, and
reabsorption. Capillary fluid exchange is described by the Starling equation, which states that the net fluid flow is
dependent on the capillary and interstitial hydrostatic pressures, oncotic pressures, and the vascular permeability to fluid
and proteins.
The heart and cardiac physiology, as well as the lymphatic system, are discussed in separate learning cards.
NOTES
FEEDBACK

Circulatory system
 Systemic circulation: Oxygenated blood flows from the left ventricle into the systemic
circulation and, after passing through the capillary bed, flows back in a deoxygenated state to
the right atrium of the heart to restart the process.
o Left atrium → mitral valve → left ventricle→ aortic valve →
aorta→ arteries → arterioles → capillary beds → veins → superior vena cava (SVC)
and inferior vena cava (IVC) → right atrium

 Pulmonary circulation: Deoxygenated blood in the right heart flows into the lungs, where it is
oxygenated and returned to the left atrium.
o Right atrium → tricuspid valve → right ventricle → pulmonary valve → pulmonary
trunk → pulmonary arteries

→ lungs

→ four pulmonary veins

→ left atrium

 Heart: connects systemic circulation and pulmonary circulation

o See heart and cardiac physiology for details.

 Lymphatic system: a network of lymphatic vessels that transport lymph toward

the heart (see lymphatic drainage for details)
NOTES
FEEDBACK

Hemodynamics
Pressure, flow, and resistance
 The relationship between pressure, flow, and resistance in the circulatory system is expressed
as ΔP = Q x R
o ΔP = pressure gradient

o Q = blood flow

o R = vascular resistance
Blood flow
 Blood flow is driven by cardiac activity pumping blood through the circulatory system.

 Volume of blood returning to the heart per minute = cardiac output (CO)
 o Rate of blood flow = blood flow / total cross-sectional area of the blood vessel

o The rate of blood flow (blood velocity cm/s) is inversely proportional to the total cross-
sectional area of the blood vessel.

Capillaries have the largest total cross-sectional area of all blood vessels (i.e., 4500–6000 cm compared to 3–5 cm in the
2 2

aorta) and, thus, the slowest blood velocity (0.03 cm/s) compared to the aorta (40 cm/s).
Laminar and turbulent blood flow
Blood flow in vessels is either laminar or turbulent depending on the smoothness of the blood vessel walls, the viscosity
of the blood, the blood velocity, and the diameter of the lumen.

 Laminar blood flow

o Definition: a layered flow pattern

o Effect: The layer with the highest velocity flows in the center of the vessel lumen.

o Low Reynolds number

o Occurrence: throughout the vascular system

 Turbulent blood flow

o Definition: a chaotic flow pattern

o Effects

 Increases vascular resistance

 Promotes thrombus formation

 Creates murmurs (e.g., bruits in a stenotic vessel)

o High Reynolds number

o Occurrence

 Vessels with a large diameter (e.g., aorta)

 High viscosity

 Low viscosity (e.g., anemia)

 Vascular bifurcations

 Vascular stenosis

Vascular resistance
 Definition: resistance offered by the circulatory system that must be overcome to create blood
flow (R = ΔP / Q)

 Vascular resistance comprises:

 o Total peripheral resistance (TPR): the amount of resistance to blood flow in the
systemic circulation = (MAP - CVP) / CO

 ↑ TPR in vasoconstriction of arterioles (e.g., in hemorrhage, ↑ vasopressor)

→ ↑ afterload and ↓ venous return → ↓ CO

 ↓ TPR in vasodilation of arterioles (e.g., in exercise, AV

shunts) → ↓ afterload and ↑ venous return → ↑ CO
o Pulmonary vascular resistance

Poiseuille equation

 This equation describes the relationship between systemic vascular resistance (R) and the length
of the vessel (L), the radius of the vessel (r), and the viscosity of blood (η).

 Resistance to flow: R = 8ηL/(πr ) 4

o Systemic vascular resistance is inversely proportional to vessel radius to the 4 power.

th

 ↓ Vessel radius (i.e., vasoconstriction) → ↑ systemic vascular resistance → ↓ blood flow

→ ↑ pressure upstream (i.e., MAP) and ↓ pressure downstream (i.e., in capillaries)

 ↑ Vessel radius (i.e., vasodilation) → ↓ systemic vascular resistance → ↑ blood flow

→ ↓ MAP and ↑ capillary pressure
o Systemic vascular resistance is proportional to blood viscosity, which is primarily determined
by hematocrit.

 ↑ Viscosity (e.g., polycythemia, hyperproteinemia) → ↑ systemic vascular resistance

 ↓ Viscosity (e.g., anemia) → ↓ resistance

o Systemic vascular resistance is proportional to blood vessel length.

Vascular stenosis (e.g., coronary artery disease) increases systemic vascular resistance significantly! When the length of
the vessel and viscosity of the blood remain constant, the relationship between systemic vascular resistance and
the radius of the vessel can be simplified to R ∼ 1/r . So, if there is a 50% reduction in radius, R = 1/(0.5 x r)^4 →
4

1/(0.0625 x r4) → 16/r4, there is a 16x increase in resistance (1600%).

Serial and parallel circuits

The total resistance in blood vessels depends on whether these vessels are arranged as serial or parallel circuits.
MAXIMIZE TABLETABLE QUIZ

Serial circuit Parallel circuit

Definition  Total resistance is the sum of individual  Total resistance is the sum of reciprocals of
resistors (R = R + R + R + R ).
x 1 2 3 ... N individual resistors (R = 1/R + 1/R + 1/R ...+
x 1 2 3

1/R )
N
 Serial circuit Parallel circuit

 Total resistance is greater than individual  Total resistance can be smaller than
resistors. individual resistors.
 Blood flow is the same in each vessel in a  Pressure is the same in each vessel in a
series circuit. parallel network.

Examples  An artery gives rise to two or more  An artery gives rise to two or more branches
branches in series (e.g., artery branches parallel to each other (e.g., capillaries in
into arterioles). a capillary bed).

Arterioles account for most of the TPR and, thus, are the blood vessels that contribute the most to blood pressure
regulation.
Pressure
 Blood pressure is generated by the pumping of the heart, which results in pulsatile blood flow
(ΔP = Q x R).
o The ΔP drives blood flow from high pressure to low pressure.

 Systolic blood pressure: maximum pressure reached during a cardiac cycle

 Diastolic blood pressure: minimum pressure reached during a cardiac cycle

 Mean arterial pressure (MAP): simplified value of systolic and diastolic blood pressure
o MAP = ⅓ systolic pressure + ⅔ diastolic pressure

o MAP = CO × TPR

 Pulse pressure: the difference between diastolic blood pressure (DP) and systolic blood
pressure (SP) of the heart cycle (SP - DP)
o Normally: 30–40 mm Hg

o Directly proportional to SV and inversely proportional to arterial compliance

 Low/narrow pulse pressure due to ↓ SV (e.g., congestive heart failure, shock, cardiac
tamponade, aortic stenosis)

 High/wide pulse pressure due to ↑ SV (e.g., exercise, hyperthyroidism, aortic

regurgitation) or stiff arteries

Wall tension

 Definition: the force within vessel walls that counteracts vessel rupture during expansion, thus
holding the vascular wall together

 Laplace's law
o Equation: σt = (P × r) / h
tm

 Units: σt = wall tension (mm Hg); P = transmural pressure (mm Hg); r =

tm

inner radius (cm); h = wall thickness (cm)

 o Increases in wall tension are proportional to increases in pressure across the vessel wall
(transmural pressure).

 Wall tension increases with decreasing wall thickness, increasing transmural pressure and/or
increasing the inner diameter.

 Given a constant transmural pressure, the smaller the vascular radius and thicker the vascular
wall, the less wall tension generated.

Vessels of the high-pressure system (arteries) have thick vessel walls and smaller internal diameters that enable them to
withstand high internal pressures, while vessels of the low-pressure system (veins) have thin vascular walls and larger
diameters.
Blood vessel elasticity
 Definition: the ability of a blood vessel to return to its original shape after expanding

Vascular compliance
 Definition: the ability of a vessel to expand in response to changes in pressure

 Equation: C = ΔV/ΔP
o Units: C = compliance (mL/mm Hg); ΔV = change in volume (mL); ΔP = change in pressure
(mm Hg)

 Greater compliance: greater increase in vascular volume during an increase in pressure

(e.g., elastic arteries)

 Less compliance: less increase in vascular volume during an increase in pressure (e.g., muscular
arteries)

Vascular elastance

 Definition: the ability of a vessel to adapt to intraluminal pressure in response to changes in

volume (i.e., the reciprocal of compliance)

 Equation: E' = ΔP/ΔV

o Units: E' = elastance (mm Hg/mL); C = compliance (mL/mm Hg); ΔP = change in pressure
(mm Hg); ΔV = change in volume (mL)

 Greater elastance: greater change in blood pressure during blood volume change

 Less elastance: less change in blood pressure during blood volume change

Compliance is mainly determined by the muscle tone of vessel walls. Arterioles, which are abundant in smooth muscle,
have low compliance and are, therefore, considered resistance vessels. Veins are less abundant in smooth muscle, have
much higher compliance, and are considered capacitance vessels.
NOTES
FEEDBACK

Blood pressure regulation

Sensors of blood flow regulation
Baroreceptors
 Definition: stretch-sensitive nerve endings that detect and regulate blood pressure in systemic
circulation via signaling to the autonomic nervous system

 Location: wall of the carotid sinus, aortic arch, atria, and venae cavae

 Mechanism of action: baroreceptor reflex

o Baroreceptors detect ↓ BP → ↓ firing frequency of baroreceptors → ↓ signaling to the brain
stem (vasomotor center) → ↓ parasympathetic stimulation and ↑ sympathetic innervation
→ vasoconstriction → ↑ HR, SV, and BP
o Baroreceptors detect ↑ BP → ↑ firing frequency of baroreceptors → triggering of baroreceptor
reflex in brain stem (vasomotor center) → ↑ parasympathetic stimulation
and ↓ sympathetic innervation → vasodilatation → ↓ HR, SV, and BP

 Only suitable for making short-term changes in blood pressure because their activity (i.e., their
firing frequency) adapts to a new blood pressure level within a few days.

 A component of Cushing reflex (hypertension, bradycardia, and respiratory depression)

Volume receptors

 Definition: specialized receptors that detect blood flow changes in the pulmonary
circulation and regulate blood flow through the autonomic nervous system, atrial natriuretic
peptide (ANP), and antidiuretic hormone (ADH)

 Location: atria, pulmonary artery, and cardiac atria (low-pressure system)

 Mechanism of action: See atrial reflex and diuresis reflex.

Chemoreceptors

 Definition: specialized receptors that detect changes in pH and respiratory gases and
regulate pH level, O , and CO concentrations through respiration
2 2

 Types
o Peripheral chemoreceptors

 Location: carotid body and aortic body

 Function: measure PaO (< 60 mm Hg), CO , and pH

2 2

o Central chemoreceptors

 Location: medulla oblongata

 Function: measure PaCO and pH

2

 Mechanisms of action
o ↑ CO , ↓ O , and ↓ pH → ↑ sympathetic innervation
2 2

o Modulate breathing via the respiratory center in the medulla

If the baroreceptors of the carotid sinus are too sensitive, even small stimuli, such as turning the head or the pressure of a
shirt collar, can lead to excessive blood pressure reduction and even fainting. This is referred to as carotid sinus
syndrome.
Carotid massage, which stimulates the baroreceptors in the carotid sinus, is an effective way of reducing the heart rate by
increasing the refractory period of the AV node.
Central blood pressure regulation
 Localization: solitary nucleus in the medulla oblongata

 Receives information (afferents) via:

o The glossopharyngeal nerve (IX): from carotid sinus baroreceptor and carotid body
chemoreceptor
o The vagus nerve (X): from aortic chemoreceptor, aortic baroreceptor, and atrial volume
receptors

 Sends information (efferents) via:

o Sympathetic cervical chain and sympathetic fibers: to blood vessels, SA node, and AV node

o Parasympathetic vagus nerve: to AV node and SA node

MAXIMIZE TABLETABLE QUIZ

Sympathetic stimulation Parasympathetic stimulation

Arterie  Arterial constriction  Arterial vasodilatation via the release of nitric

s → ↑ peripheral vascular resistance oxide (NO) only in coronary arteries and vessels of
the penis (erection)

Veins  Venous constriction  Venous dilatation → ↓ preload → ↓ stroke volume

→ ↑ preload → ↑ stroke volume

Heart  ↑ Contractility  ↓ Heart rate

 ↑ Heart rate

Atrial natriuretic peptide (ANP) and antidiuretic hormone (ADH)

regulation
Atrial reflex

 Definition: a physiologic reflex characterized by an increased heart rate in response to atrial

distention (increased venous return to the heart). It is mediated by stretch receptors in the atria.

 Mechanisms of action
o ↑ Volume → atrial stretching

1. Release of atrial natriuretic peptide (ANP) from cardiomyocytes

→ ↑ excretion of NaCl and water by

the kidneys, vasodilation of veins and arteries (↓ preload and ↓ afterload), and inhibition
of renin
 2. ↑ Parasympathetic innervation and ↓ sympathetic innervation
o ↓ Volume → less atrial stretching

1. ↓ Release of ANP → ↓ excretion of NaCl and water by the kidneys

2. ↓ Parasympathetic innervation and ↑ sympathetic innervation

Diuresis reflex (= Gauer-Henry reflex)

 Definition: a physiological reflex that adapts ADH release in the hypothalamus according to
blood pressure

 Mechanisms of action
o ↑ BP: Atrial stretch receptors inhibit ADH release via afferent vagal fibers → ↑
water excretion by the kidneys
o ↓ BP: ↑ ADH release → ↓ water excretion by the kidneys
Renal regulation
 Mechanism of action: release of renin from the juxtaglomerular cells → activation
of RAAS → direct vasoconstriction and ↑ extracellular volume (↑ sodium and water
reabsorption, ↓ K , ↑ pH)
+

 RAAS is stimulated by:

o Hyponatremia

o Decreased blood osmolality

o Decreased renal blood flow

The RAAS plays a key role in long-term blood pressure regulation and is, therefore, an ideal target for the treatment
of arterial hypertension. While beta blockers decrease renin release by the kidneys, the conversion of angiotensin
I to angiotensin II by angiotensin-converting enzyme (ACE) can be influenced by ACE
inhibitors (e.g., ramipril, enalapril). The effect of angiotensin II on target cell receptors can be inhibited by AT1
receptor antagonists (e.g., candesartan, losartan).
NOTES
FEEDBACK

Perfusion
Perfusion
Definition: the passage of the blood through the circulatory system to the capillary bed to deliver oxygen and nutrients to
the tissue and remove waste products (e.g., removal of CO to the lungs)
2

MAXIMIZE TABLETABLE QUIZ

Perfusion levels of various organs

Organs % of cardiac output at rest % of cardiac output during exercise

Viscera (hepatic-splanchnic circulation) 24 1

Skeletal muscle 20 88
 Perfusion levels of various organs

Organs % of cardiac output at rest % of cardiac output during exercise

Kidneys 19 1

Brain 13 3

Other organs 10 1

Skin 8 2

Heart muscle 3 4
Regulation of organ perfusion
Although blood pressure is the main determinant of perfusion, various other mechanisms maintain constant blood flow
within organs.
Autoregulation

 Myogenic autoregulation: Myocytes in the walls of arteries and arterioles react to changes in
blood pressure to maintain constant blood flow in the blood vessels.
o Mechanism of action: ↑ BP → ↑ transmural pressure in arteries and arterioles

→ stretch-activated ion channels opening up in myocytes → myocyte depolarization and

subsequent Ca influx → smooth muscle contraction → vasoconstriction
2+

o Sites of action: almost all organs (especially the kidneys and brain) except the lungs

 Local metabolites
o Mechanism of action: the release of vasoactive substances

 NO: produced in endothelium by NO-synthase from arginine → vasodilation

 NO production is triggered by:

 Increased BP

 Activation of endothelial receptors by binding of vasoactive substances

(e.g., serotonin, bradykinin) → increased release of NO

 Other substances: kinin, histamine, serotonin, prostaglandins, thromboxane

o Sites of action: arteries and arterioles

Central regulation

 Mechanisms
o Sympathetic innervation

o Catecholamines from adrenal medulla

 Receptors
o Alpha-1 receptors → vasoconstriction
 o Beta-2 receptors → vasodilation

 Differing effects of catecholamines

o Epinephrine: acts on both receptor types but has a greater affinity for beta-2 receptors

 Low concentrations: stronger effect on beta-2 receptors → vasodilation

 High concentrations: stronger effect on alpha-1 receptors → vasoconstriction

o Norepinephrine: mainly acts on alpha-1 receptors → vasoconstriction
Autoregulation of specific organs
 Heart
o Local metabolic autoregulation: Adenosine and NO cause vasodilation of the coronary
arteries to increase blood flow and oxygen delivery to the myocardium.
o Has the highest arteriovenous O difference of all organs (O extraction at rest ∼ 60–80%)
2 2

o During exercise, there is limited capacity to increase myocardial oxygen extraction (small
coronary flow reserve).

 Lungs
o Adjustment of vascular perfusion to ventilation

o Hypoventilation (hypoxia) causes vasoconstriction (Euler-Liljestrand mechanism).

 Kidneys
o Myogenic autoregulation

o Tubuloglomerular feedback

 Brain
o Local metabolic autoregulation (CO , pH) → vasodilation
2

o Myogenic autoregulation

 Skeletal muscle
o At rest: sympathetic innervation

o During exercise: local metabolic and chemical autoregulation, e.g., lactate, CO , adenosine, K ,
2
+

H+

o Blood flow can be increased (20–30 times) during exercise

 Skin
o Perfusion levels are determined by how much is needed for thermoregulation
(via capillaries and arteriovenous anastomoses).
o Mainly sympathetic innervation
The lungs are the only organs in which hypoxia causes vasoconstriction. This is to ensure that perfusion only occurs in
areas that are well ventilated. In all other organs, hypoxia leads to vasodilation to improve perfusion and maintain
oxygen supply.
Hypoperfusion of vital organs (e.g., hypovolemic shock, cardiogenic shock) is detected by baroreceptors and volume
receptors, leading to an increase in sympathetic tone. Autoregulatory mechanisms are then triggered and lead to
centralization of blood flow away from the extremities (skeletal muscle, skin), the GI tract, and other internal organs to
maintain perfusion of the heart and brain. In addition, vasoconstriction of precapillary resistance vessels raises systemic
vascular resistance and reduces hydrostatic pressure in capillaries, increasing the reabsorption of interstitial fluids into
vessels.
To remember the local metabolites used in autoregulation of skeletal muscle, think
“CHALK”: CO2, H+, Adenosine, Lactate, K+.
NOTES
FEEDBACK

Capillary fluid exchange

Definitions
 Hydrostatic pressure: the pressure exerted by any fluid on the wall of an enclosed space
o Intravascular hydrostatic pressure: the force exerted by the blood confined within blood
vessel walls (e.g., capillary hydrostatic pressure)

 Drives fluid out of capillaries and into the interstitium

 Osmotic pressure: the minimum pressure needed to prevent the flow of a solvent across
a semi-permeable membrane
o Determined by concentration gradients: Solvent from a lower concentration solution is drawn
across a semi-permeable membrane (via osmosis) into a higher concentration solution.
o Directly proportional to the concentration of solute in the solvent

o Opposes hydrostatic pressure

 Oncotic pressure (colloid osmotic pressure): an intravascular osmotic pressure generated

by proteins (especially albumin)
o Keeps intravascular fluid within blood vessels and opposes intravascular hydrostatic pressure
Starling forces
For information on the Starling equation for the glomerulus see measurement of renal function in physiology of the
kidney.

 Four Starling forces determine the net flow of fluid between the capillaries and interstitium.
o Capillary hydrostatic pressure (P ): drives fluid out of the capillary
c

o Interstitial hydrostatic pressure (P ): attenuates filtration or drives fluid into capillaries

i

o Plasma colloid (oncotic) pressure (π ): drives fluid into the capillary

c

o Interstitial fluid colloid osmotic pressure (π ): drives fluid out of the capillary
i

 Net fluid flow = J = K [(P - P ) - σ(π - π )]

v f c i c i
 o K = coefficient for vessel permeability to fluid
f

o σ = Staverman reflection coefficient for vessel permeability to protein

 Net filtration (capillary fluid exchange)

o Depends on the hydrostatic pressure gradient (P - P ) and the oncotic pressure gradient (π - π )
c i c i

o Filtration of fluid out of the capillary usually occurs on the arterial side of the capillary bed,
mostly because of pressure from the arterial circulation (increased P ) and high plasma fluid
c

levels (decreased π ).
c

o Filtration of fluid into the capillary usually occurs on the venous side of the capillary bed,
mostly because of capillary flow resistance (decreased P ) and higher relative plasma
c

protein levels following water filtration into the interstitium (increased π ).

c

o Outward filtration volume (arterial side) = inward filtration volume (venous side) + 10%

 10% of the filtered fluid is returned via lymphatics rather than blood vessels.

Edema is caused by the net movement of fluid into the interstitium if there is an increase in capillary hydrostatic
pressure (due to heart failure or Na retention) or a decrease in oncotic pressure (due to cirrhosis, nephrotic syndrome).
+

Burns affect vessel permeability (increased K ) and can, therefore, result in the formation of edema.
f