The Cardiovascular system (CVS)

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The cardiovascular system (CVS)

Function: Tissue blood flow

Principal functions of tissue blood flow:
1. Delivery of metabolic substrates (O2, glucose etc) to
cells
2. ‘Washout’ of tissue metabolic by-products (CO2, H,+
amines, etc)
3. Maintenance of tissue hydration (volume of cells &
interstitial space)

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 Cont----
4. Systemic heat exchange via cutaneous and
pulmonary circulation
5. Systemic fluid and electrolyte homeostasis
via the renal circulation
6. Distribute hormones and other agents that
regulate cell function

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CVS: has pump, distributive and micro-vascular network

Pump(Heart): acts as two pumps in series

RA & RV -drive the pulmonary circulation
- propel venous blood to the lungs and back to heart

LA & LV- Oxygenated blood returns to the LA where it is

pumped to the LV and then propelled through the
systemic circulation.

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 Cont-----

Distribution:
• -beyond the elastic portion of arterial tree, muscular
arteries and arterioles act to control distribution of
blood.
• -These segments control blood flow and pressure by
adjusting their luminal diameters as their walls actively
contract or relax

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Micro- vascular network: Exchange

•From arterioles, blood enters, the capillaries and post

capillary venules
•These vascular segments are under low pressure and their
walls allow O2 & CO2, nutrients & metabolic products,
hormonal signals etc. to pass back and forth between tissues
and vascular segment
•Blood return to RA carried by conductive systems

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The pericardial cavity: contains small amount of fluid
to prevent friction during heart contraction

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Heart ( Myocardium)

Basic structure: 5 subsystems

1.Working myocardium (Cardiac muscle)

2. Valves
3..Electrical conducting systems
4. Nerves which regulate the heart
5. Blood vessels(Coronary vessel) which supply the heart

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Myocardium:

Has 4 chambers,

Atria-thin -walled (2mm)

Ventricles-thick walled
LV=8-9 mm
RV=3-4 mm
RA= Deoxygenated blood from vena cava
 non valve between RA and vena cava; no valve b/n LA
and pulmonary Vein

RV= Pump blood to lungs for oxygenation

LV= Pump oxygenated blood to rest of body

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 Heart valves
Valves direct blood flow
• Has fibrous connective tissue:
-prevent enlargement of valve opening
-anchor valve flaps
 Inlet valves = Tricuspid and mitral (AV valves)
 Outlet valves = Aortic and Pulmonary valves
(semi lunar valves)
 Valve closure prevents backflow of blood during and
after contraction
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 Electrical Activity
The heart has 2 separate syncytium:
•atrial and ventricular
These are separated from each other by fibrous tissue
( electric resistant, surrounds valves).
Action potential is conducted from the atria
into the ventricle by way of the A-V bundle only

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Cardiac muscle fibers connected in series with each other
by intercalated discs

Electric resistance through the intercalated disc is only

1/100 the resistance through the outside cell membrane

Action potential spreads cell to cell, past the intercalated

disc

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 Basic properties of excitation and excitation-
contraction coupling

• Two types of myocardial fibers (based on

morphology & functional criteria)
1.Pacemaker & conducting systems:
Generate excitatory impulse and send to
working myocardial cells
2. Working myocardium of atria and ventricles
Do mechanical work of pumping

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 Origin and spread of excitation
• Intercalated discs : offer no obstacle to conduction of
excitation
• Atria and ventricle behave functionally as a syncytium
(excitation anywhere in atria or ventricles spread allover
unexcited fibers)

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 Geometry of propagation:
Sinoatrial node (SA node)
 Normal pacemaker, drive heart at a rate of 70 bpm (rest)
 Excitation spreads over working myocardium of atria
Atrioventricular node (AV node):
 Only pathway for conduction to ventricles, rest of
atrioventricular boundary consist of unexcitable connective
tissue
Propagation briefly delayed at AV node (Important for
ventricular filling
 Potential pacemaker (if SA node fails)

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 His bundle, bundle branches and
purkinje fibers

• Propagation fast for rapid successive

ventricular excitation
• Fastest propagation in the Purkinje system

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 Spread of cardiac excitation

Atrial activation
Depolzrization is complete in about 0.1 second
AV nodal delay
 The conduction in AV node is slow; rate of
conduction is 0.05 m/s.
 This allows atria to empty before ventricular
contraction begins
 Ventricular activation follows

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Excitation-contraction-coupling:
Contraction (systole):
Electrical:
Spread of excitation from cell-to cell via
gap junctions
Also spread to interior via T-tubules
During plateau phase, Ca++ permeability
increases
This Ca++ triggers release of Ca++ from SR
Ca++ level increases in cytosol
Ca++ binds to Troponin C
Ca++-Troponin complex interacts with
tropomyosin to unlock active site between
actin and myosin
Cross bridge cycling=contraction (systole)
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 Summary = excitation-contraction coupling

• AP calcium entry L-type channels (trigger

calcium)
• Sensed by “feet” of calcium release channels
(ryanodine receptors,RyR) of SR
• Calcium release into cytoplasm
• Calcium binding to Troponin-C (TN-C)
• Tropomyosine move aside uncovering actin
• Exposure of myosin binding site on actin

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• ATP hydrolysis, movement of actin relative to
myosin
• Calcium resequestered into SR by ATP-
dependent calcium pump
• Sarco-endoplasmic reticulumcalcium ATPase
(SERCA) , that is inhibited by phospholimbin
• Calcium pump remove calcium from cell

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Hormonal (catecholamines):
(Phosphorylation of Ca++ channels)
Increase Ca++ into cells by phosphorylation of Ca ++
channels by cAMP dependent protein kinase (cAMP-PK)

Relaxation (diastole): As result of Ca++ removal

Ca++ removed By:
 Uptake by SR
 Extrusion by Na+-Ca++ exchange
 Ca++ pump (to limited extent)
Hormonal: inhibition of Troponin-C-Ca++ bondage
by Troponin-I
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 Cardiac glycosides
• Inhibit Na+/K+-ATPase
• leads to increase in intracellular Ca++
• through the Na+ / Ca++ exchange pump (by
decreasing the availability of sodium to
pump calcium out
• leads to enhanced contractility

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Cardiac Innervations.

Sympathetic all parts of heart

Parasympathetic (from vagus) -
mainly:
SA node
Atria
AV node
•No Ventricular innervations.
•Strong stimulation of vagus, has no
effect on ventricles
(Vagal escape or Ventricular escape)

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Adrenergic and Muscarinic receptors in CVS

Sympathetic:
Heart:
NE(NA) binds to adrenoceptors in the heart
(affinity : β1 > > β2 and α1)
Produce positive inotropy, chronotropy, and
dromotropy
Blood vessels:
α-adrenoceptors –vasoconstriction
β2 adrenoceptors- vasodilation
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 Cont---
Parasympathetic (vagal):
Heart:
Ach binds to prejunctional muscarenic receptors
( M2 ), inhibit NE release
Ach also binds to postjunctional M2 receptor to
decrease Inotropy, chrontropy and dromotropy

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 Cont----
• in a few specific organs (eg genetalia) Ach
from parasympathetic binds to M2 vascular
receptors to produce endothelial dependent
vasodilatation

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Autonomic effects(positive or negative -tropic effects)

• Bathmotropic state: refers to the irritability of

the myocardium
• Chronotropic state: cardiac frequency
• Dromotropic state: Conduction velocity of the
myocardial conduction system
• Inotropic state: Cardiac contractility

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 Electrocardiography
The Electrocardiogram (ECG, EKG):
• Electrical impulse of heart recorded on the surface of body
Information obtained from ECG:
• -Anatomical orientation of the heart
• -Relative size of chambers
• -Rhythm and conduction disturbance
• -Extent, location and progress of ischemic damage
• -Electrolyte disturbance
• -Influence of drugs
• -HR=1/cycle length
• -Origin of excitation

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The ECG is record of overall spread of
electrical activity through the heart
 Electric current generated by heart muscle conducted
through body fluid
 A small portion reach surface of body, which can be
detected and recorded by electrodes (not record of single
AP)
 This record represents sum of electrical activity in all
muscle undergoing depolarization and repolarization
 The waves represent comparison in voltage detected by
electrodes at 2 different points on body surface, not actual
AP
Actual recording sites are arms and legs b/c they act as
extended electrodes
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 Characteristic of normal cardiac
rhythms
• Frequency of QRS complexes are ~ 1 per second
• Shape of QRS normal, and duration is less than
120msec. showing rapid normal conduction pathway
• Each QRS is followed by a P wave of normal
configuration indicating SA node rhythms
• PR interval is less than 200msec. indicating proper
conduction delay of impulse spread through the AV
node
• No extra P wave indicating no AV nodal conduction
block is present

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 Cardiac cycle
Systole - isovolumic contraction.
-Ejection

Diastole - Isovolumic relaxation

-Ventricular filling
Valves ensure flow from:
Atria - Ventricles Aorta
Pulmonary artery

Valves open/close by pressure on either side (passive)

 Closure of valves Phonocardiogram
 Mechanical phases proceeded by electrical events recorded as ECG
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•
•

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Heart sounds:
Sounds associated (usually) with valve closure
First heart sound -Closure of AV valves
Occurs at beginning of isovolumic cntraction

Second heart sound -Closure of Aortic & Pulmonic valves

(Semilunar valves)
- Occur at end of ejection (at onset of diastole)
-Sometimes splitted, since Aortic valve closes slightly
before Pulmonic valve

Third heart sound (sometimes) -due to rapid ventricular filling

Fourth heart sound (occasionally)- during atrial contraction

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 The cardiac output (CO)
CO = HR x SV
L/min beasts/min. L/beat.
SV: volume ejected during each beat , depends on
venous return, can be equal to venous return
CO (at rest) = 5-6 L/min
HR=72 beats/min , SV=0.07L/min (70ml) . All blood
pumped around circuit once each min. CO increases
when need be (eg. Exercise), Therefore, HR or SV or
both can increase

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 Factors influencing CO

 Intrinsic:
Arterial pressure (afterload)
filling pressure(preload)
 Extrinsic :
Parasymathetic and sympathetic effects

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 Changes in stroke volume(SV)
SV is determined by:
– Preload
– Afterload
– Contractility

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 Peripheral circulation

Physiology of the vascular system:

Vessels:
 Contain blood and allow pressure to be maintained
 Direct blood flow to specific organs
 Ensure adequate nutrition and removal of waste
 Regulate capillary blood pressure
 Permit direction of blood flow to be altered
 Together with the heart, permit regulation of blood
pressure
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Arterial system:
Allow Continues blood flow to the periphery
•Ejection of LV blood to aorta distention of aortic wall
(peak at systole, decline at diastolic )
•Part of the energy of ventricular contraction forward
flow during systole
•Remainder distend arterial tree (and stored potential
energy)
•This potential energy released (by recoil of arterial wall)
propel blood distally (provide diastolic “run off”)
•Alteration of systolic and diastolic propulsion provide
continues (rather than pulsatile) blood flow to peripheral
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 Microcirculatory unit
Collection of vessel originating from arteriole
• -arterioles of face, fingers, and toes often branch into
arteriovenous anastomose
• -Function as shunt vessels (non nutritional flow)
• -In certain tissues, arterioles branch into metarterioles (with
precapillary sphincter),
• then to large capillaries (preferential channels or
thoroughfare channesl)
• Shunt blood to veins (nonnutitional flow),regulation of body
temperature

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 Synthesis function of capillary
endothelial cells:
1. Endothelial derived relaxing factor (EDRF, or nitric oxide)
 formed and released in response to stimulation of endothelium by
agents
such as ACh, ATP, Serotonine, bradykinine, histamine, Substance P
-Effect=vasodilatation
2.Prostacyline
 -Produce vasodlation
 -However, major function inhibition of platelet adherence and
aggregation
 -Therefore, prevent intravascular thrombosis

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 Capillaries: structure

 No smooth muscle, no change in inner diameter

 Lumen narrow, thus RBC change shape to pass
through
 The small diameter of capillary and thin
endothelial wall minimize diffusion path
Permeability:
 Lipid soluble (O2, CO2) pass easily through
endothelial membrane
 water soluble pass through pores, some via
endothelial vesicles
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 Transcapillary exchange (Starling’s
law)
Movement across capillary influenced by:
 Nature of substance (size, shape, lipid solubility)
 Balance between hydrostatic and colloid osmotic
pressure force across membrane
 Capillary surface area available for exchange
 Physical characteristics of capillary membrane
(continuous, fenestrated, discontinuous)

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 Methods of exchange
2.General methods of exchange:

1.Diffusion:
• E.g. lipid soluble substances O2, CO2, certain anesthetic
agents diffuse with little hindrance through membrane.

• 2.Filtration-Absorption
Hydrostatic and osmotic pressure on each side of membrane
• Arterial end: hydrostatic pressure >osmotic
pressure=filtration
• Venous end: osmotic pressure>hydrostatic
pressure=reabsorption
• Intermediate: declined filtration, increased reabsorption

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 Lymphatic system
Function:
 Clear interstitial space of excess fluid, proteins, lipids and
foreign metabolites
• Secondary interstitial drainage system, thus supplement
venular drainage
Lymphatics:
 Porous, thin walled highly permeable (dying blood cells,
bacteria)
• Blind ends lying in interstitial space
All vessels empty into thoracic duct (left) and right lymphatic
ducts
 Finally drain into subclavian and internal jugular vein on their
respective sides
• Lymph flow –sluggish, 2-41/day
-Flow increased by: muscular activity, massage, increased volume
pressure, inflammation
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 Edema
Edema: accumulation of excess fluid in interstitial space.
• Develops in dependent areas (eg. Feet)
• More evident in expansion limited tissues (eg. Around the
eye) edema produced in many ways:
• eg.1.General increase in venous pressure:
• -Increase venous pressure increase venular pressure
increased pressure in arterial end of capillary
• Result=increased filtration and interstitial fluid accumulation
• Common: Pregnancy, prolonged standing associated with
increased in venous pressure, Congestive heart failure.

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 Hypoproteinemia
Eg2.Decreased plasma protein  decreased plasma oncotic
pressure, more filtration (fluid accumulation)
Causes of hypoproteinemia:
 Nephrosis (albumin lose in urine)
 Inadequate protein in diet (nutritional edema)
 Severe burns (capillary damage)
Eg. 3. Lymphatic obstruction:
 Small amount of protein “leaking” through capillaries
returned via lymph
 If not returned, accumulate in tissues
 hus prevent return of fluid into venular end of capillaries ---
edema
 Elephantiasis---massive edema in leg (Filariasis-lymph vessel
obstruction
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 Eg. 4.Local edema
-Extensive venous obstruction with elevation of venous
and capillary pressure
Eg. Wide spread venous thrombosis.
Eg.5.Left ventricular failure or mitral valve stenosis:
Pulmonary capillary hydrostatic pressure > oncotic pressure =
pulmonary edema.
 Pulmonary oedema causes interference with gas exchange in the
lungs
Eg. 6.Capillary injury:
-Toxins, severe burns etc. increase capillary permeability greatly.
-Fluid and protein leakage into interstitial space ---oedema
-Treatment of burns is replacement of lost fluid and plasma proteins

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Venous part of the systemic circulation
Function of veins:
 Constrict and enlarge -P
 Store large quantity(>60%) of blood
(making blood available when required)
 Propel blood forward by means of “venous
pump”
 Regulate CO

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 Veins
 Low resistant
 Low pressure
 Highly distensible (compliant)
 Large cross sectional area
 Pressure 10mmHg at capillary end, 0 mmHg at entrance
of vena cava to RA
Structure –
Thin walled
• Small amount of elastic tissues and smooth muscle veins of
dependent parts of body have valves
• Valves prevent backflow of venous blood

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 Varicose veins

• Dilation and valvular insufficiency of

dependent veins as a result of, familial,
occupational predisposition, or both, and
prolonged obstruction as in pregnancy
• Venous pulse:
• Pressure and volume fluctuation in veins near
heart due to retrograde transmission

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 Mechanisms that increase venous
return
Hydrostatic effect (below hydrostatic “0” level),
in upright position reduce venous return.
Venous return improved by:
 Skeletal muscle pump of lower extremities:
assist venous return during quite standing,
walking or running
Venous valves: (present only in
extremities )are important adjuncts to skeletal
muscle pump
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 Venomotor tone: sympathetic constriction aid venous
return, eg. During hemorrhage.
Conversely, skin vasodilatation aid dissipation of heat
from body core to periphery in hyperthermia
Respiratory pump: through alteration of volumes and
pressure
Suction effect of cardiac contraction and relaxation
(valve plane mechanism)

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 Skeletal muscle pump
A. Standing at rest:
 Valves are open
 Blood flow upward towards the heart
B.Contraction of the muscle :compresses the veins
so that the increased pressure in the veins drives
blood upwards and closes the valves at lower
region just below point of muscle contraction.
C. Immediately after muscle relaxation, the
pressure in the previously compressed venous
segment fall, and the reverse pressure gradient
causes the upper valve to close (to prevent back
flow).
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 Control of peripheral circulation and
blood- tissue exchange

The most important parameters controlled are:

 Cardiac output
 Distribution of blood to the different organs
and tissues
 Arterial blood pressure
 Blood volume

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 Regulation of the overall circulation
Regulation =
 regional and supraregional (higher level i.e in
vasomotor and heart center in the Medulla
oblong
 Effectors are on heart and blood vessels
Crucial mechanism:
 adjustment of TPR and CO to maintain pressure
gradient for flow through vascular system
 Adjust vessel capacity and blood volume

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 Classification
Regulatory processes classified into 2 groups
according to time of action
• 1. Short term control mechanisms
• 2. Long-term control mechanisms

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 Short-term control mechanisms:
Predominantly vasomotor adjustment and neuronal control
Include:
 Baroreceptor (Strech) reflexes:
 Chemoreceptor reflexes
 Ischemic reflexes of CNS
Common characteristics:
 Rapid onset of action (within few sec.)
 Response vigorous, but if activated continuously, within a few
days, it either dies out completely- (baroreceptors) or
attenuated -(chemoreceptors, CNS Ischemic response)
 Vasomotor responses supplemented by hormonal
mechanisms (NAD, AD), and with delayed action; vasopressin

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 Baroreceptor reflexes
Location:
 Wall of large thoracic arteries
 Wall of cervical arteries
 Aortic arch
greater functional importance
 Carotid sinus
Baroreceptors convey information about:
 mean arterial pressure (MAP)
 Amplitude of pressure fluctuation
 Steepness of pressure rise rate of pressure change
 More sensate to than pressure (P/t)
 More sensitive to sudden change
 More sensitive to decrease than increase pressure
Stimulation of baroreceptors: stretch

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 Arterial chemoreceptors
• Location:- carotid and aortic bodies (near aortic sinus and
carotid sinus
• Stimulus: decreased PO2, increased PCO2, and increased H+
• Response: hyperventilation (increased minute volume)
• Secondary effect: increased O2 delivery to tissues (heart,
brain)
-general vasoconstriction
-increased arterial pressure
• Chemoreceptor reflex protective in:
-hypoxia due to altitude (low arterial PO2)
-circulatory shock (peripheral ischemia)

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 CNS ischemic response
 Raises arterial pressure in response to diminished blood
flow in vasomotor center of the brain
 Cerebral ischemia (ie nutritional deficiency) increases PCO2
which stimulates sympathetic area of medulla of brain
 This causes increase in arterial pressure (as high as heart
can pump)
 This system is emergency arterial pressure control system
ie acts rapidly and very powerfully
 Thus prevent further decline in arterial pressure when
blood flow to brain decreases dangerously
This control system is “last ditch” mechanism for blood
pressure control

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Renin-Angiotension-Aldosterone system (long-
term control (RASS)

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Pathophysiology of blood pressure

 Hypertension
 140/90 = 18-49 yrs
• 160/95 = over 50 yrs
• -more common in male than female
• Severe hypertension 4 X more common in
black men than white
(possible reason = higher renal vascular
resistance)
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