Circulatory System

Components of Circulatory System

I. Blood: cells, water, nutrients and proteins

II. A Pump, the Heart

III. Connecting tubes, veins and arteries

Components of Circulatory System
I. Blood consists of

A. Formed elements

i. Cells
a. Erythrocytes: 99% of the blood cells
b. Leukocytes

ii. Cell fragments/Platelets

B. Plasma
• proteins, nutrients, metabolic wastes, and molecules transported
between organ systems.
Heart
Physiological Anatomy
Heart
Physiological Anatomy; Heart Valves
Heart
Cardiac Muscles

• Almost all of the bulk of the heart wall is muscle fibers.

• Broadly, three types:

i. Atrial muscle
ii. Ventricular muscle
iii. Conducting muscle fibers: 1% of all the muscle.
• No physical role in contraction.
• Responsible in dissipation of action potentials.
Heart
Cardiac Muscles; Physiological Anatomy
• Cardiac muscle fibers arranged in a
latticework, with the fibers dividing,
recombining, and then spreading
• Striated.
• Have myofibrils that contain actin and
myosin filament.
• Cardiac muscle fibers are the
syncytium of many heart cells.
• Have intercalated discs forming gap
junctions.
• Atrial and ventricular syncytia are
separated by fibrous membrane.
Heart
Innervation
Heart
Blood Supply
• The blood within the heart chambers does not exchange
nutrients and metabolic end products with the myocardial cells.

• The arteries supplying the myocardium are the coronary arteries,

and the blood flowing through them is the coronary blood flow.

• The coronary arteries exit from behind the aortic valve cusps in
the very first part of the aorta, leading to a branching network.

• Most of the cardiac veins drain into the coronary sinus which
empties into the right atrium.
Heartbeat Coordination

• Heart is a dual pump, that is, the left and right sides
pump the blood separately.

• Efficient pumping requires the atria to contract first,

followed by contraction of the ventricles.

• Contraction is triggered by depolarization.

• Depolarization starts in sinoatrial (SA) node, a group of

conducting system cells, and spreads into the rest of the
cells.
Heartbeat Coordination

• SA node
• is a small, flattened, ellipsoid strip.
• About 3mm wide, 15 mm long, and 1 mm thick.
• located in the superior posterolateral wall of the right atrium
immediately below and slightly lateral to the opening of the
superior vena cava.
• have almost no contractile muscle filament.
• Capable of self excitation, therefore, initiates contraction
and controls heart rate.

• The SA node fibers are directly connected to the wall of the atria
and the generated action potentials are spread through out the
atria.
Heartbeat Coordination
Sequence of Excitation
Heartbeat Coordination
Action Potential (Cardiac Cells)

• The resting membrane is more

permeable to K+ than to Na+ .

• Therefore, the resting membrane

potential is much closer to the K+
equilibrium potential (-90 mV).

• The Ca2+ channels are referred to

as L-type Ca2+ channels or long-
lasting Ca2+ channels because
they are open for long period of
time.
Heartbeat Coordination
Action Potential (SA node)

• The Na+ channels are funny or

F-type channels because they
open at negative values.

• Ca2+ enter through transient or T-

type Ca2+ channels.

• In case of SA node malfunction,

this sequence is initiated in other
part of the conducting cells,
referred to as ectopic
pacemaker.
Mechanical Events of Cardiac Cycle
• Cardiac events between the beginning heartbeat to the beginning
beginning of the next are called as the cardiac cycle.
• Spontaneous generation of an action potential in the SA node.
• The action potential spreads rapidly through both atria and then
through the AV bundle into the ventricles.
• Due to the special arrangement of the conducting system,
ventricles contract 0.1s after the atria.
• Therefore, atria are primer pumps for ventricles and ventricles
provide the force for general circulation in the body.
• Two major phases:
i. Ventricular contraction and blood ejection, the systole.
ii. Ventricular relaxation and blood filling, the diastole.
• For a heart rate of 72 beats/min, each cardiac cycle lasts
approximately 0.8 sec, with 0.3 sec in systole/0.5 sec in diastole.
Mechanical Events of Cardiac Cycle
• Systole is further divided into two discrete events:
i. Isovolumetric ventricular contraction:
• ventricles contract but the blood is not ejected due to closed
valves, no effect on ventricular volume.
• lasts for 0.02-0.03s.
ii. Ventricular ejection: ejection of the blood when the
ventricular pressure is higher then aorta/pulmonary trunk,
i.e., 80/8 mm of Hg in left/right ventricles, respectively.

• Diastole can be divided into:

i. Isovolumetric ventricular relaxation: ventricles relax but the
blood does not fill in due to closed valves, no effect on
ventricular volume (0.03-0.06s).
ii. Ventricular filling: valves open and blood floods from the
Mechanical Events of Cardiac Cycle
End-diastolic Volume (EDV): The final volume of ventricles reached at
the end of diastole that is about 110 to 120 mL (milliliters).

Stroke Volume (SV): The volume ejected during each

stroke/contraction which is about 70 mL.

Ejection fraction: The fraction of EDV ejected which is about 60%.

End-systolic Volume (ESV): The remaining volume in each ventricle,

about 40 to 50 ml, after the stroke when the ventricles are
contracted.

SV = EDV – ESV
SV= (filled-ejected)
Mechanical Events of Cardiac Cycle
Heart Sounds – The lub-dub

• The heart makes two sounds under normal conditions

i. Lub
• The first softer sound
• Arises from the closing of AV valves.
• Marks the onset of systole

ii. Dub
• The second louder sound
• Comes from the closing of pulmonary/aortic valves
• Marks the onset of diastole
Mechanical Events of Cardiac Cycle
Heart Sounds – The murmurs
• Normally the blood flows in
concentric layers (laminar flow).

• Irregular or turbulent flow results in

abnormal murmur sounds.

• Turbulent flow results from

i. Stenosis-narrow valve
ii. Insufficiency-leaky valve
iii. Septal defect
The Cardiac Output (CO)
• The volume of blood a ventricle pumps per unit time.
• Usually expressed in liters per minute (L/min).
• In the steady state, the cardiac output flowing through the
systemic and the pulmonary circuits is the same.
• Mathematically, CO is product of heart rate (HR)-number of beats
per minute- and SV.
CO = HR (heart rate) × SV (Stroke Volume: volume ejected)
• For average adult having 5.5 L of blood, at rest, almost all the blood
is pumped throughout the body.
• For athletes the CO can reach up to 35 L/min, whereas, 20-25
L/min for untrained individuals.
• HR and SV are the determinants of CO.
• HR and SV can have opposing effects on CO, for example, e.g.,
during blood loss HR increases whereas SV decreases.
The Cardiac Output (CO)
Control of HR
• Inherent discharge rate of SA node could produce 100
beats/min, that is (i-e,) in absence of any influence.
• SA node is under constant influence of nerves and hormones,
therefore, the HR can be faster or slower than 100 beats/mins.
• Normally due to parasympathetic firing, the HR is to 72 beats/min.

• Sympathetic NS increases the HR by

i. Increasing the permeability of F-type channels to Na+
ii. Increasing the conduction velocity in the conducting system.

• Parasympathetic NS decreases the HR by

i. Increasing the permeability K+ channels.
ii. Decreasing the conduction velocity in the conducting system.
The Cardiac Output (CO)
Control of HR
The Cardiac Output (CO)
Control of SV
• Ventricles do not completely empty during contraction.
• More forceful contraction can produce an increase in SV.

• There are dominant factors that can change SV

i. Changes in the EDV (volume filled) or preload

ii. Changes in the magnitude of sympathetic NS input
iii. Changes in the arterial pressures against which the ventricles
pump or the afterload.
The Cardiac Output (CO)
Control of SV
i. Relationship between SV (ejected volume) and EDV/preload
(volume filled).
• The ventricle walls do not usually stretch to their optimal length.
• The ventricle contracts more forcefully during systole when it has
been filled to a greater degree during diastole.
• In other words, all other factors being equal, the stroke volume
increases as the end-diastolic volume increases.
• This relationship between SV and EDV is known as the Frank–
Starling mechanism or Starling’s law of the heart.
• Another significance of Frank-Starling mechanism is that increase
in SV results in increase in venous return.
• Increase in venous return assures the equality in the left and right
cardiac outputs.
The Cardiac Output (CO)
Control of SV
ii. Sympathetic regulation
• Sympathetic nerves are distributed to the entire myocardium.
• Epinephrine/norepinephrine acts on b-adrenergic receptors.
• As a result, ventricular contractility increases, defined as the
strength of contraction at any given EDV.
• Plasma epinephrine acting on
these receptors also increases
myocardial contractility which
is independent of EDV.
The Cardiac Output (CO)
Control of SV
iii. Afterload

• The resistance provided by the arterial pressure to blood ejection.

• An increased arterial pressure reduces SV.

• The arterial pressure constitutes a “load” that contracting

ventricular muscle must work against when it is ejecting blood.
The Vascular System
• The muscular heart provides the driving force for blood
movement.

• The vascular system regulates blood pressure and distributing

blood flow to the various tissues.

• Elaborate branching and regional specializations of blood vessels

enable matching of blood flow to metabolic demand of tissues.

• All vessels posses a common, single-layered, specialized

endothelial cells which are in direct contact with the flowing blood.

• The structural characteristics of the endothelial vary by region.

Arteries
• Have thick walls containing large
quantities of elastic tissue/smooth
muscles.

• Most conveniently viewed as elastic

tubes.

• Do for pressure reservoir during

diastole.

• Large radii of arteries to assure low-

resistance to incoming blood.
Arterial Blood Pressure
• During systole, about one-third of the stroke volume
leaves the arteries.
• The rest of the stroke volume remains in the arteries during
systole, distending them and increasing the arterial pressure.
• When ventricular contraction ends, the stretched arterial walls
recoil passively and blood continues to be drain into the arterioles
during diastole.
• Therefore, the arterial pressure does not decrease to zero.
• As blood leaves the arteries, the arterial volume and pressure
slowly decrease.
• Compliance is the term used to denote the stretch in a
structure/vessel.
Compliance = ΔVolume/Δpressure
• The greater the compliance, easier to stretch.
Arterial Blood Pressure
• Maximum arterial pressure
reached during peak systole is
called systolic pressure (SP).

• Minimum arterial pressure

occurs during diastole called
diastolic pressure (DP).

• Arterial pressure is generally

recorded as systolic/diastolic

• Both SP and DP average about

10 mmHg lower in females than
in males.
Arterial Blood Pressure
• Difference between SP/DP is called the pulse pressure.
• Can be felt as a pulsation or throb in the arteries of the
wrist or neck with each heartbeat.
• During systole, blood is pushed out of the artery wall resulting in
expansion of the vessel that produces the detectable pulse.
• The magnitude of the pulse pressure is determined by:
i. Stroke volume
ii. Speed of ejection of the stroke volume, and
iii. Arterial compliance (arterial stretch).
• This last phenomenon occurs in arteriosclerosis, stiffening of the
arteries, that progresses with age and accounts for the increasing
pulse pressure that often occurs in older people.
Arterial Blood Pressure
Mean arterial Pressure (MAP)
The pressure in artries during one cardiac cycle is mean arterial
pressure. It helps in determining how well the vital organs are
perfused in body.
Formula :
MAP= 2(DBP) + SBP/3
Normal value: 70-100 mm Hg
• Arterial pressure is continuously changing throughout
the cardiac cycle.
• The average pressure during the cycle is referred to as the mean
arterial pressure (MAP).
• The MAP is the average of the arterial pressures
measured over a period of time.
• As diastole lasts twice as long as the systole, MAP is not
merely the value halfway between SP/DP.

• Normally, determined about 60 percent by the DP and

40 percent by the SP.
• However, at very high heart rates diastole comprises a
smaller fraction of the cardiac cycle.
Arterial Blood Pressure
Mean arterial Pressure (MAP)

• MAP is the pressure driving blood into the tissues averaged over
the entire cardiac cycle.
• Although arterial compliance is an important determinant of pulse
pressure, it does not have a major influence on the MAP.
• Person with a low arterial compliance (due to arteriosclerosis) but
a normal CVS will have a large pulse pressure due to elevated SP
and lowered DP but closer to normal.
• Pulse pressure is, therefore, a better diagnostic indicator of
arteriosclerosis than mean arterial pressure.
Arterioles
• Arteries after entering an organ divide progressively 6-8
times to give arterioles.
• Generally, internal diameters of only 10-15 micrometers (μm).
• Major sites of resistance in the vascular tree.
• Large decrease in MAP, i-e., from about 90 mmHg to 35 mmHg.
• Pulse pressure also decreases.
• Highly muscular and their diameters can change many fold.
• Arteriolar smooth muscle possesses a large degree of spontaneous
contraction which is called as intrinsic tone/basal tone.
• Arterioles can relax to increase vessel radius (vasodilation), or
contract and decrease the vessel radius (vasoconstriction).
• Therefore, determine the relative blood flow to organs.
• Arteriolar muscular activity controlled either locally or extrinsically.
Local Controls
i. Local chemical factors
• Hyperemia is an increase in blood flow to an organ.
• Active hyperemia is the increase in blood flow to an organ due to
increase in metabolic activity.
• Local chemical changes in the extracellular fluid surroundings
resulting in local vasodilation.
• Examples of chemical changes include:
a. Respiratory products such as CO2, H+, adenosine.
b. K+ accumulation from repeated membrane repolarization.
c. Bradykinin, derived from kininogen by enzyme kallikrein.
d. Breakdown products of membrane phospholipids
(eicosanoids)
e. Nitric oxide (NO) released from endothelial cells.
Local Controls
ii. Flow autoregulation
• If arterial pressure to an organ is reduced because of
blockade in the artery supplying the organ, blood flow is reduced.
• In response, local controls cause arteriolar vasodilation to increase
blood flow back toward normal levels.
• Increase in blood flow in response to arterial pressure changes is
referred to as flow autoregulation.
• Responsible local changes are ↑CO2, ↑H+, ↓O2 etc.
• On the other hand, increase in flow due to the increase in
pressure removes the local vasodilator chemical factors.
• This results in vasoconstriction, thereby maintaining a relatively
constant local flow despite the increased pressure.
• Also, myogenic responses which are contractions of arterioles in
response to stretch in their walls due to high pressure.
Local Controls
iii. Reactive hyperemia
• If blood supply to a tissue is occluded for long, the the
local chemical vasodilators accumulate in excess.
• When the blood supply is restored, the excessive vasodilation
results in instant increase in blood flow to the tissue.
• An extreme case of flow autoregulation and is referred to as
reactive hyperemia.

iv. Response to Injury

• Inflammation is the response of the body to injury.
• Certain chemical factors, such as, interleukins, are secreted which
lead to local vasodilation.
Extrinsic Controls
i. Sympathetic Regulation
• Most arterioles are richly innervated by sympathetic
postganglionic neurons.
• release norepinephrine, which binds to α-adrenergic receptors on
the vascular smooth muscle to cause vasoconstriction.
• Normally, sympathetic NS keeps the basal tone of the arteriolar
muscles by its frequent discharge.
• Therefore, vasodilation can be induced by diminishing the release
of norepinephrine.
• For example; during cold or blood loss, there is vasoconstriction in
the skin arterioles but in cases of elevated body temperature, there
is vasodilation to increase blood to the skin to dissipate the heat.
• In contrast to the local factors, the sympathetic NS has generalized
effect on the body.
Extrinsic Controls
ii. Noncholinergic, Nonadrenergic, Autonomic Neurons
• Most arterioles are richly innervated by sympathetic NS.
• a population of autonomic postganglionic neurons that are referred
to as noncholinergic, nonadrenergic neurons because they do not
release acetylcholine or norepinephrine.
• Instead they release NO as vasodilator.
• These neurons are particularly prominent in
• Enteric nervous system
• Penile vessels
• Vessels in clitoris
Extrinsic Controls
iii. Hormones
• Epinephrine released from the sympathetic neurons
and act on α- as well as β2-adrenergic neurons to induce
vasoconstriction and vasodilation, respectively.
• However, due to higher number of α-adrenergic neurons on the
vascular muscles, it has vasoconstriction activity, except in skeletal
smooth muscle because of presence of β2-adrenergic neurons.
• Angiotensin II is also a vasoconstrictor.
• Vasopressin, secreted from posterior pituitary gland, is also a
vasoconstrictor which release in response to low blood pressure.
• Atrial natriuretic peptide, released from atria of the heart leads to
vasoconstriction in response to low venous return.
Microcirculation
• Formed by of arterioles, capillaries and venules.
• The arterioles formed two to five times, reaching
diameters of 5 to 9 μm and are referred to as metarterioles.
• The metarterioles do not have a continuous muscular coat, but
smooth muscle fibers encircle the vessel at intermittent points.
• Precapillary sphincter surround the origin of true capillary.
Microcirculation
• The venules are larger than the arterioles.
• have a much weaker muscular coat.
• The pressure in the venules is much less than that in the arterioles,
so the venules can still contract considerably despite the weak
muscle
Capillaries
• Contains approx. 5% of the total circulating blood.
• This 5% that is performing the ultimate purpose of
cardiovascular system which is the exchange of nutrients, metabolic
end products, and cell secretions.
• permeate every tissue of the body except the cornea
• from a capillary, diffusion distances are very small and exchange is
highly efficient.
• Although individual capillary is only 1 mm long, an adult has an
estimated 40,000 km of capillaries.
• Have internal diameter of about 4-9 μM, hardly enough for
erythrocytes to get through.
• Angiogenesis is the formation of new capillaries which is initiated
by angiogenic factors such as vascular endothelial growth factor
(VEGF) and is blocked by angiostatin, e.g., in cases of cancer.
Anatomy of Capillaries Wall
• Thin-walled (0.5 μM) tube of
endothelial cells, one layer thick
resting on a basement
membrane, without any elastic
tissue.
• Endothelial cells in capillaries are
separated by narrow, water-filled
spaces intercellular clefts which
are usual 6-7 nm apart.
• Endocytotic/exocytotic vesicles
often fuse to form continuous
fused-vesicle channels because
exchange is very quick
• Precapillary sphincter to control
blood flow.
Anatomy of Capillaries Wall
• There are many minute plasmalemmal vesicles,
also called caveolae (small caves).
• Formed from oligomers of proteins called caveolins that are
associated with molecules of cholesterol and sphingolipids.
• Some caveolae may contain small packets of plasma or extracellular
fluid that contain plasma proteins.
• Although the precise functions of caveolae are still unclear, but are
supposed to play role in cellular transport.
Transport Across the Capillary Wall
• The extremely slow movement of blood allows enough
time for the exchange of substances across the wall.
• Three basic mechanisms:

i. Diffusion:
• Lipid-soluble substances (CO2/O2) easily diffuse through the
plasma membranes of the capillary endothelial cells.
• Polar molecules are poorly soluble in lipid and must pass through
intercellular cleft.

i. Vesicle transport:
• Only a small amount of protein diffuse through the walls.
• Specific proteins (like hormones) exploit endo/exocytosis.
Transport Across the Capillary Wall
iii. Carrier-mediated transport:
• Brain capillaries have a second set of cells that
surround the basement membrane affecting free diffusion.
• Therefore, even for water-soluble substances, carrier mediated
transport is needed.
Transport Across the Capillary Wall
iv. Bulk flow:
• Along with the diffusion of substances, there is flow of
protein-free plasma, bulk flow, into the interstitial spaces.
• For distribution of the extracellular fluid (ECF) volume.
• Normally, there is 3 L of plasma and 11 L of interstitial fluid.
• The interstitial fluid serves as reservoir for plasma volume.
• Only exchange of fluid, not protein, hence called ultrafiltration.
• extent of bulk flow is determined by the difference of the capillary
blood pressure and the hydrostatic pressure in the interstitial fluid.
• Usually, capillary blood/hydrostatic pressure is higher, leading to
filtration of plasma, leaving proteins in the capillaries.
• Consequently, the osmotic pressure increase due to these proteins
(colloids), resulting in flow in the reverse direction (absorption).
Transport Across the Capillary Wall
iv. Bulk flow:
• Water concentration of the plasma is lower by 0.5%
than that of interstitial fluid, creating an osmotic force.
• Although, there is movement of fluid between plasma and
interstitial fluid, the concentration of Na+, K+, Cl- (crystalloids)
remain the same in both due to their unhindered diffusion.
• Four factors set the net filtration pressure (NFP) and are termed as
the Starling forces:
i. Capillary hydrostatic pressure (PC)
ii. Interstitial hydrostatic pressure (PIF)
iii. osmotic force in capillaries (πc), and
iv. and the osmotic force of the interstitial fluid protein (πIF).
NFP = Pc + πIF – PIF – πc
Veins
• Capillaries drain into venules which drain into veins.
• Exchange of material is often the same as capillaries.
• Last set of tubes through which blood flows to heart.
• Pressure in the peripheral veins (veins outside the chest cavity) is
10-15 mm Hg and that of the right atrium is close to 0 mm Hg.
• This pressure difference is the driving force for the venous return.
• As veins have large diameter, offering low resistance to the blood
flow, therefore, this small pressure difference is adequate for
venous return.
• However, if blood volume increases, venous pressure increases
and thus the venous return increases.
• As the venous return is a prominent determinant of EDV and SV,
therefore EDV and SV increases with increase in venous return.
Veins Anatomy
Determinants of Venous Pressure
• Veins have low resistance and high compliance,
therefore can accommodate large amount of blood.
• Veins bear 60% of the systemic blood.
• Secretion of norepinephrine leads to the contraction of the veins
resulting in increased venous pressure and venous return.
• Venous smooth muscles also respond to hormonal and paracrine
vasodilators/vasoconstrictor.
• Other mechanisms determining venous pressure are:
i. Skeletal muscles pump:
• When muscles contract, the press the veins within.
• This reduces the diameter and pressure increases.
• Therefore, blood flows to the heart.
• Reverse flow is prevented by two-flapped valves in the veins.
Determinants of Venous Pressure
ii. Respiratory pump:
• During inspiration of air, the diaphragm descends,
pressing the abdominal contents.
• This increases abdominal pressure which is transmitted passively
to the intra-abdominal veins.
• Simultaneously, the pressure in the thorax decreases, decreasing
the pressure in the intrathoracic veins and right atrium.
• The net effect is the increase pressure in the peripheral veins and
decrease in the pressure changes thorax and right atrium.
• During expiration the process can reverse but the valves prevent
the back flow of blood.
The Lymphatic System
• An accessory route through which fluid can flow from
the interstitial spaces into the blood.
• The lymphatics can carry proteins and large particulate matter away
from the tissue spaces.
• This return of proteins to the blood is an essential function without
which we would die within about 24 hours.
• In the lymphatic vessel fluid derived from the interstitial fluid,
known as lymph, flows.
The Lymphatic System
• The lymphatic system is a network of lymph nodes,
lymphatic vessels/lymphatics.
• Like blood vessel capillaries, lymphatic capillaries penetrate
almost every tissue of the body.
• Exceptions are superficial skin, CNS, bones and endomysium of
muscles.
• There are water-filled gapes in the lymphatic vessels which are
large enough for even proteins to pass.
• Lymph is continuously collected from the interstitial fluid, passed
on to larger lymph vessels, and flows through lymph nodes.
• Lymph nodes are particular present in the neck, armpits, groin,
and around the intestines
• The entire network ends in two large lymphatic ducts that drain
into the veins near the junction of the jugular and subclavian veins
in the upper chest.
The Lymphatic System
• Valves at these junctions permit only
one-way flow.
• The lymphatic vessels carry interstitial
fluid to the CVS.
• This circulation is important because it
replenish the fluids in the plasma.
• Occlusion of the lymph vessels results
in edema of the effected area, a
condition known as elephantiasis.
• Also, lymphatic system helps in
distribution of fats absorbed from GIT.
• Exploited by cancers cells to spread in
the body.
Mechanism of Lymph Flow
• Smooth muscles in the wall of the lymphatic exert a
pumplike action by inherent rhythmic contractions.
• Due to the valves similar to those in veins, these contractions
produce a one-way flow.
• The lymphatic vessel smooth muscle is responsive to stretch.
• In addition, there is sympathetic connections to smooth muscle
of the lymphatic vessels.
• Also, skeletal muscle pump and respiratory pump also contribute
to the lymphatic flow.
Arterial Baroreceptors
• At the division of the carotid artery, the wall
of the artery is thinner and possesses sensory
neuronal processes. This portion of the artery
is called the carotid sinus
• The sensory neurons are highly sensitive to
stretch or distortion which is directly related
to the pressure within the artery.
• Therefore, the carotid sinuses serve as
pressure receptors, or carotid baroreceptors.
• An area functionally similar to the carotid
sinuses is found in the arch of the aorta and is
termed the aortic arch baroreceptor.
• The two carotid sinuses and the aortic arch
baroreceptor constitute the arterial
baroreceptors.
Arterial Baroreceptors
• Action potentials recorded in
single afferent neuron from (a)

the carotid sinus demonstrate

the pattern of baroreceptor
response.
• At a particular steady
pressure, e.g, 100 mmHg,
there is a certain rate of
discharge by the neuron.
• The pressure in the carotid
sinus is controlled so that the
pressure is steady.
• Action potential rising in
carotid sinus having pulsatile
pressure.
The Medullary Cardiovascular Center
• The reflexes arising from the arterial baroreceptors
in response to changes in pressure are known as
baroreceptor reflex.
• Highly interconnected neurons located in medulla oblongata
called the medullary cardiovascular center.
• The neurons in this center receive input from the baroreceptors.
• This input determines the action potential frequency from the
cardiovascular center along neural pathways that terminate
upon the cell bodies and dendrites of the vagus neurons to the
heart and the sympathetic neurons to
the heart, arterioles, and veins.
• Increase their rate of discharge,
the result is a decrease in
sympathetic neuron activity
Operation of the Baroreceptor Reflex
• The baroreceptor reflex functions primarily as a
short-term regulator of arterial blood pressure.

• It is activated instantly by any blood pressure change and

functions to restore blood pressure rapidly toward normal.

• However, if arterial pressure remains increased from its normal

set point for more than a few days, the arterial baroreceptors
adapt to this new pressure and decrease their frequency of
action potential firing at any given pressure.

• Thus, in patients who have chronically elevated blood pressure,

the arterial baroreceptors continue to oppose minute-to-minute
changes in blood pressure, but at a higher set point.
Other Baroreceptors
• The large systemic veins, the pulmonary vessels, and
the walls of the heart also contain baroreceptors

• Most of which function in a manner analogous to the arterial

baroreceptors.
• These other baroreceptors provide a further degree of regulatory
sensitivity.

• Contribute a feed forward component of arterial pressure control.

• For example, a slight decrease in ventricular pressure reflexively

increases the activity of the sympathetic nervous system even
before the change decreases cardiac output and arterial pressure
enough to be detected by the arterial baroreceptors.
Long-Term Regulation of BP
• Arterial baroreceptors adapt to prolonged changes
• Therefore, not suitable for long-term regulation of BP.
• Blood volume is the major determinant of arterial pressure
Other Cardiovascular Reflexes
• Decreased arterial oxygen concentration
• Increased arterial carbon dioxide concentration
• Decreased blood flow to the brain, and
• pain originating in the skin.
• In contrast, pain originating in the viscera or joints may cause
decreases in arterial pressure.
• Many physiological states such as eating and sexual activity are also
associated with changes in blood pressure.
• Attending a stressful business meeting may increase mean blood
pressure by as much as 20 mmHg.
• Mood also has a significant effect on blood pressure, which tends to
be lower when people report that they are happy.
• Input from receptors or higher brain centers to the medullary
cardiovascular center
Other Cardiovascular Reflexes
• Cushing’s phenomenon is a situation in which increased
intracranial pressure causes a dramatic increase in MAP.
• A number of different circumstances can cause increased pressure
in the brain, including the presence of a rapidly growing cancerous
tumor or a traumatic head injury that triggers internal hemorrhage
or edema.
Hypotension/Causes of Hypotension
• Hypotension means a low blood pressure, regardless
of the cause.

• Cause of hypotension include:

i. Hemorrhage
• Factors changed as a directly are SV, CO, MAP-are restored by the
baroreceptor reflex toward but not to normal.
• Factors not altered directly but only by the reflex response are HR
and TPR—increase above their prehemorrhage values.
• Results from increases in sympathetic outflow to the arterioles in
many vascular beds (but not those of the heart and brain).
• Blood flow considerably decreases to skin (resulting in pale color of
the subject), kidneys, intestines.
Hypotension/Causes of Hypotension
i. Hemorrhage
• Another compensatory mechanism of restoration of
blood volume is the movement of plasma from IF to blood vessels,
referred to as autotransfusion.
• Occurs because of decrease in BP and the increase in arteriolar
constriction decrease capillary hydrostatic pressure, thereby
favoring the absorption.
• Can virtually restores blood volume to normal levels within 12 to
24 hours after a moderate hemorrhage.
• What’s its effect on hemotocrit?
• Slower-acting compensations include an increase in thirst and a
reduction in the excretion of salt and water in the urine mediated
by hormones, including renin, angiotensin, and aldosterone.
Hypotension/Causes of Hypotension
ii. Volume depletion other than Hemorrhage
• Can occur through skin as in sweating or burns.
• Through GIT in diarrhea or vomiting.
• By kidneys in excessive urination.
• Body can be depleted of water and ions such as Na+, Cl-, K+, H+,
and HCO3-, leading to loss of blood volume, resulting in similar
cardiovascular changes as in hemorrhage.

iii. Emotional state

• Higher brain centers involved with emotions inhibit sympathetic
activity to the CVS and enhance parasympathetic activity to the
heart, resulting in a markedly decreased arterial pressure and
brain blood flow, a process, known as vasovagal syncope.
The upright Posture
• There is decrease in effective circulation when
the plane of the body changes from horizontal
to vertical.
• Because in addition to the cardiac pressure,
there is weight of the column of the blood.
• In an average adult, the weight of a column of
blood extending from the heart to the feet
would amount to 80 mmHg.
• One of the outcome is venous pooling due to
distention in vein in the standing still position.
• Leads to increase in ultrafiltration due to
increased hydrostatic pressure manifested as
swelling in the legs during prolonged standing.
• Causes effects similar to mild hemorrhage.
The upright Posture
• When suddenly stand up, due to venous pooling,
there is decrease in venous return leading decreased
EDV and SV, therefore, decreasing general circulation
and resulting in black out or fainting of the subject.
• Compensatory mechanisms for upright posture effects includes
baroreceptor reflex and using of the muscle pump and even
fainting.
Exercise
• The CO increase from 5 to 35 L/min.
• Most of the CO goes to the muscles.
• Increased blood flow to coronary flow to
compensate for the workload.
• Increased blood flow to the skin to
dissipate the generated heat.
• Increased in blood flow is due to decrease
in TPR due to vasodilation.
• Vasodilation is caused in the muscles by
metabolic factors and in the skin by
decreased sympathetic firing.
• There is decreased blood flow to kidneys
and GIT because of increased sympathetic
activity.
Exercise
• MAP is not affected much because the decrease in TPR
compensates for the increase in CO (MAP = CO x TPR).
• Pulse pressure increased significantly because there of higher SV
and speed of ejection of blood.
• The increase in CO is supported by a large increase in HR and a
small increase in SV.
• The increase in HR is caused by a combination of decreased
parasympathetic activity to the SA node and increased
sympathetic activity.
• The increased SV is due mainly to an increased ventricular
contractility mediated by the sympathetic activity.
• These factors are not sufficient by themselves to increase the CO,
venous return needs to be increased as well.
Exercise
• Factors promoting venous return during exercise are
i. increased activity of the skeletal muscle pump,
ii. the respiratory pump,
iii. sympathetically mediated increase in venous tone, and
iv. Decrease in TPR
• The driving force for these changes is imperfect matching between
blood flow and metabolic demands.
• Local chemical changes in the muscle can develop, particularly
during intense exercise.
• These changes activate chemoreceptors in the muscle.
• Afferent input from these receptors goes to the medullary CVS
center and facilitates the output reaching the autonomic neurons
from higher brain center.
 Maximal Oxygen Consumption and
Training
• With increase with the exercise, there is increase in O2 consumption
in exact proportion until a point.
• Afterwards it fails to increase despite of increase in work load.
• This is known as maximal oxygen consumption (VO2 max ).
• After VO2 max has been reached, work can be there is only a brief
support of anaerobic respiration in the muscles.
• Theoretically, VO2 max could be limited by
i. The CO,
ii. The respiratory system’s ability to deliver O2 to the blood, or
iii. The exercising muscles’ ability to use O2.

• Typically, CO is the factor that determines VO2 max.

 Maximal Oxygen Consumption and
Training
• HR increases until it reaches a maximum
• SV increases much less and tends to level off
at 75% of VO2 max.
• The major factors responsible for limiting the
increase in SV are
i. The very rapid heart rate, which
decreases diastolic filling time; and
ii. Inability of the peripheral factors
favoring venous return to increase
ventricular filling further during the
very short time available.
• VO2 max is not fixed and can be altered by
habitual level of physical activity.
 Maximal Oxygen Consumption and
Training
• For a trained individual, even at rest there is SV is
higher with decreased HR, therefore, no change in CO.
• At VO2 max, there is increase in CO because of SV, HR is unchanged
• SV is increased due to a combination of
• Remodeling of the ventricular walls produces moderate
hypertrophy and an increase in chamber size; and
• Peripheral effects, including increased in the number of blood
vessels in skeletal muscle, which permit increased muscle blood
flow and venous return.
Hypertension (HTN)
• Defined as a chronically increased systemic arterial
pressure.
• Systolic pressures of 130 to 139 mm Hg and diastolic pressures of
85 to 89 mm Hg.
• One of the organs most affected is the heart itself.
• Chronically pump against an increased afterload, it develops an
adaptive increase in muscle mass called left ventricular hypertrophy
• In the start, hypertrophy helps the heart to increase pumping.
• With time changes in the organization and properties of myocardial
cells occur, and these result in diminished contractile function and
heart failure.
• The presence of hypertension also enhances the possible
development of atherosclerosis and heart attacks, kidney damage,
and stroke (rupture of the cerebral arteries).
Hypertension (HTN)
• For every 20 mmHg increase in systolic pressure and
every 10 mmHg increase in diastolic pressure, the risk
of heart disease and stroke doubles.
• HTN is classified on basis of nature of its causes:
i. Primary HTN
• Also known as essential HTN.
• Uncertain causes.
• Although a number of genetic and environmental factors are
suspected to be involved.
• In cases of inherited condition, a number of genes including some
coding for enzymes in the renin-angiotensin-aldosterone pathway
are thought to be involved.
• In other cases, some involved in the regulation of endothelial cell
function and arteriolar smooth muscle contraction.
Hypertension (HTN)
i. Primary HTN
• Also known as essential HTN.
• Uncertain causes.
• Although a number of genetic and environmental factors are
suspected to be involved.
• In cases of inherited condition, a number of genes including some
coding for enzymes in the renin-angiotensin-aldosterone pathway
are thought to be involved.
• In other cases, some involved in the regulation of endothelial cell
function and arteriolar smooth muscle contraction.
• HTN could be a result of either increased CO or increased TPR,
mostly the reason for primary HTN is the increased TPR.
• Obesity is also a major risk factor.
Hypertension (HTN)
i. Primary HTN
• Chronic high intake of salt leading to elevations in plasma
Na+ levels results in chronic overstimulation of the sympathetic NS,
consequently, constriction of arterioles, and narrowing of the
lumen of arteries.
• Significant reduction in blood pressure occurred in experimental
subjects who ate a low-salt diet in a large, well-designed study
known as Dietary Approaches to Stop Hypertension or DASH.
• Environmental factors as well as life style choices smoking; excess
alcohol consumption; diets low in fruits, vegetables, and whole
grains; diets low in vitamin D and calcium; lack of exercise; chronic
stress; excess caffeine consumption; maternal smoking; low birth
weight; and not being breast-fed as an infant.
• Primary HTN accounts for 90% of all the cases.
Hypertension (HTN)
ii. Secondary HTN
• HTN with well established causes.
• For example, renal HTN;
• Damage to kidneys or their blood flow.
• in which increased renin release
• leads to excessive concentrations of the potent vasoconstrictor
angiotensin II
• decreased urine production by the kidneys,
• resulting in excessive ECF
• HTN
• Some individuals are genetically predisposed to excess renal Na 1
reabsorption.
• Such patients respond well to diuretics.
Hypertension (HTN)
• List of antihypertensive drugs
The Blood Cells
• There are undifferentiated cells,
pluripotent hematopoietic stem cells
(PHSC), capable of giving rise to
precursors (progenitors) of any of the
different blood cells.
• The two formed daughter cells either
remain PHSC or become committed
to a particular pathway.
• The first branching yields either
lymphoid stem cells, which give rise to
the lymphocytes, or myeloid stem
cells.
• At some point, the proliferating
offspring of the myeloid stem cells
become committed to differentiating
Erythrocytes
• Erythrocytes contain of the protein hemoglobin.
• Carry O2 and, to a lesser extent, CO2 reversibly.
• The average concentration of hemoglobin is 14.5 g/100 ml blood in
women and 15.5 g/100 ml in men.
• Each gram of pure hemoglobin is can combine with 1.34 ml of O2.
• The major breakdown product of hemoglobin is bilirubin which
returns to circulation and gives plasma its characteristic yellowish
color.
• Biconcave discs having a mean diameter of about 7.8 μm and
thickness of 2.5 μm at the thickest point and 1 μm in the center.
• Shapes of red blood cells can change remarkably as the cells
squeeze through capillaries
• Produced in red bone marrow.
Erythrocytes
• With differentiation the erythrocyte precursors produce
hemoglobin, but then they ultimately lose their nuclei
and organelles—their machinery for protein synthesis.
• Fresh erythrocytes posses ribosomes until a day after they are
released into the blood which produce weblike (reticule)
appearance, therefore, known as reticulocytes.
• Reticulocytes constitute only about 1% of circulating erythrocytes.
• Ave. life span of an erythrocyte is approx. 120 days, which means
that almost 1% of the erythrocytes are destroyed and must be
replaced every day.
Erythrocytes
Iron
• The element in hemoglobin to which O2 binds.
• amounts of iron are lost from the body via the urine, feces, sweat,
menstrual and cells sloughed from the skin.
• The amount of iron lost from the body must be replaced by
ingestion of iron-containing foods, such as meat, liver, shellfish, egg
yolk, beans, nuts, and cereals.
• A significant disruption of iron balance can result in iron deficiency.
• An excess of iron in the body, hemochromatosis, which results in
abnormal iron deposits and damage in various organs, including the
liver, heart, pituitary gland, pancreas, and joints.
• The homeostatic control of iron balance resides primarily in the
intestinal epithelium, which actively absorbs iron from ingested
foods. Normally, only a small fraction of ingested iron is absorbed.
Erythrocytes
Iron
• The absorption can be increased or decreased
depending upon the need of the body.
• The body has a considerable store of iron, mainly in the liver, bound
up in a protein called ferritin.
• About 50% of the total body iron is in hemoglobin, 25% is in other
heme-containing proteins (mainly the cytochromes) in the cells of
the body, and 25% is in liver ferritin.
• As old erythrocytes are destroyed in the spleen (and liver), their
iron is released into the plasma and bound to an iron- transport
plasma protein called transferrin.
• Transferrin delivers almost all of this iron to the bone marrow to be
incorporated into new erythrocytes.
Erythrocytes
Folic Acid
• Essential for the formation of DNA and thus for normal
cell division.
• Deficiency of this vitamin impairs the rapidly dividing cells including
erythrocyte precursors, and as a result fewer erythrocytes are
produced when folic acid is deficient.

Cobalamin/Vitamin B12
• Found only in animal products.
• Absorption of vitamin B12 from the gastrointestinal tract requires a
protein called intrinsic factor, which is secreted by the stomach.
• Required for the action of folic acid.
Erythrocytes
Regulation of Erythrocyte Production
• Erythropoiesis is the formation of new erythrocytes.
• Primarily controlled by a hormone called erythropoietin, a 34 kDa
glycoprotein, secreted into the blood by the kidneys.
• About 90 percent of all erythropoietin is formed in the kidneys, rest
is formed mainly in the liver.
• The exact location of erythropoietin production is not known.
• Acts on the bone marrow to stimulate the proliferation of
erythrocyte progenitor cells and their differentiation.
• Normally secreted in small amounts to replace the usual loss.
• Increased markedly in case of decreased O2 delivery to the kidneys,
e.g., insufficient pumping of blood by the heart, lung disease,
anemia, prolonged exercise, and exposure to high altitude.
• Erythropoietin begins to form within minutes to hours in hypoxia.
Erythrocytes
Regulation of Erythrocyte Production
Erythrocytes
Erythrocyte Production sites
• In the embryonic life, primitive, nucleated RBCs
are produced in the yolk sac.
• During the middle trimester of gestation, the liver is the main organ
for production of red blood cells but reasonable numbers are also
produced in the spleen and lymph nodes.
• During the last month of gestation and after birth, RBCs are
produced exclusively in the bone marrow.
• All bones produce RBCs until a person is 5 years old, except for the
proximal portions of the humeri and tibiae which become fatty.
• Afterwards, RBCs are produced in the marrow of the membranous
bones, such as the vertebrae, sternum, ribs, and ilia.
• The marrow becomes less productive as age increases.
Erythrocytes
Erythrocyte Genesis
Erythrocytes
Erythrocyte Genesis
Erythrocytes
Formation of hemoglobin
• Synthesis of hemoglobin begins in the proerythroblasts.
• Continues even into the reticulocyte stage of the RBCs.
• When reticulocytes pass into the blood stream, they continue to
form minute quantities of hemoglobin for another day or so until
they become mature erythrocytes.
Anemia
• Defined as deficiency of hemoglobin in the blood.
• Which can be due to:
i. Decrease in the total number of normal erythrocytes
ii. Diminished concentration of hemoglobin per
erythrocyte
iii. A combination of both.
Anemia
Types of Anemia
A. Blood Loss Anemia
• After rapid hemorrhage, the fluid
portion of the plasma usually
restores in 1-3 days and RBCs
returns to normal in 3-6 weeks.
• In chronic blood loss, enough iron
is not absorbed from to
hemoglobin as rapidly as it is lost.
• As a result RBCs are smaller
(microcytic anemia) and have less
hemoglobin (hypochromic
anemia).
Anemia
Types of Anemia
B. Aplastic Anemia
• Bone marrow aplasia means lack of functioning bone marrow.
• For instance:
i. High-dose radiation or chemotherapy for cancer treatment
can damage stem cells of the bone marrow
ii. High doses of certain toxic chemicals, such as insecticides or
benzene in gasoline.
iii. In autoimmune disorders, such as lupus erythematosus, the
immune system begins attacking healthy cells such as bone
marrow stem cells
• In about half of aplastic anemia cases the cause is unknown, a
condition called idiopathic aplastic anemia
Anemia
Types of Anemia
C. Megaloblastic anemia/Pernicious
anemia
• Loss of intrinsic factor, vitamin B12 and
folic acid can lead to slow reproduction
of erythroblasts in the bone marrow.
• This can occur in atrophy or surgical
removal of stomach which production
site of intrinsic factor.
• Also, in atrophy or surgical removal of
stomach ilium which is the absorption
site of vitamin B12.
Anemia
Types of Anemia
C. Megaloblastic anemia/Pernicious anemia
• The erythroblasts cannot proliferate rapidly enough to
form normal numbers of erythrocytes.
• As a result, the red cells grow too large, with odd shapes,
and are called megaloblasts.
• Because of their oversize, these cells rupture easily and
decrease the hematocrit and decrease in O2 supply.
Anemia
Types of Anemia
D. Hemolytic anemia
• Hereditarily acquired abnormalities of the RBCs make the cells
fragile, so they rupture easily while passing through capillaries.
• Therefore, RBCs are destroyed faster than they can be formed and
serious anemia results.
Examples;
i. Sickle cell anemia
• The cells have an abnormal type of hemoglobin called hemoglobin
S, containing faulty beta chains in the hemoglobin molecule.
• When exposed to low concentrations of oxygen, it precipitates into
long crystals inside the RBCs, elongating them into sickle-like
appearance rather than a biconcave disc.
Anemia
Types of Anemia
D. Hemolytic anemia
Examples;
i. Sickle cell anemia
• The precipitated hemoglobin also
damages the cell membrane, so the
cells become highly fragile, leading to
serious anemia.
• A circle of events called a sickle cell
disease crisis, in which low O2 tension
in the tissues causes sickling, which
leads to ruptured red cells, which
causes a further decrease in oxygen
tension and still more sickling and red
cell destruction.
Anemia
Types of Anemia
D. Hemolytic anemia
Examples;
ii. Hereditary Spherocytosis
• RBCs are very small and spherical rather than being
biconcave discs.
• Such cells are fragile cannot withstand compression forces.
Anemia
Types of Anemia
D. Hemolytic anemia
Examples;
iii. Erythroblastosis Fetalis
• Rh-positive red blood cells in the
fetus are attacked by antibodies
from an Rh-negative mother.
• These antibodies make the Rh-
positive cells fragile, leading to rapid
rupture and causing the child to be
born with serious anemia.
Polycythemia
• More erythrocytes than normal.
• When the tissues become hypoxic because of:
• too little oxygen in the air such as at high altitudes, or
• failure of oxygen delivery to the tissues, as in cardiac failure.
• Automatically produce large quantities of extra RBCs.
• This condition is called secondary polycythemia.
• The red cell count commonly rises to 6-7 million/μL, about 30
percent above normal.
• A common type of this condition is physiologic polycythemia.
• Occurs in natives living at altitudes of 14,000-17,000 feet, where
the atmospheric oxygen is very low.
• The blood count is generally 6 to 7 million/ μL which allows these
people to perform well in a rarefied atmosphere.
Polycythemia
Polycythemia Vera/Erythema
• A pathological condition.
• RBC count may be 7-8 million/μL.
• Hematocrit may be 60-70 % instead of the normal 40-45 %.
• Caused by a genetic aberration in the hemocytoblastic cells that
which keep on producing RBCs well beyond the needs.
• Usually causes excess production of white blood cells and platelets
as well.
• The total blood volume also increases, sometimes up to double.
• Moreover, the viscousity of blood, that is normally 3 times that of
water, increases to 10 times that of water.
Polycythemia
Effects on the CVS
• Because of the increased viscosity, blood flow is sluggish,
decreases the rate of venous return to the heart.
• Conversely, the increased blood volume tends to increase venous
return.
• Therefore, the cardiac output in moderate polycythemia is almost
normal because these two factors tend to neutralize each other.
• The arterial pressure is also normal because of the baroreceptors.
• Beyond certain limits, however, these regulations fail and
hypertension develops.
• As the disease progresses, the skin adopts blue coloration
(cyanosis) due larger quantity of deoxidized hemoglobin.
Leukocytes
• Also called white blood cells or WBCs
• Are the mobile units of the body's protective system.
• Some are formed in the bone marrow (granulocytes and monocytes
and a few lymphocytes) and some in the lymph tissue (lymphocytes
and plasma cells).
• After formation, they are transported in the blood to different parts
of the body where they are needed.
• The adult human being has about 7000 white blood cells per μL of
blood (in comparison with 5 million red blood cells).
• Six types of WBCs are neutrophils, eosinophils, basophils,
monocytes, lymphocytes, and, occasionally, plasma cells.
• Neutrophils, eosinophils and basophils have granular appearance
because of presence of secretory granules and are therefore called
as granulocytes.
Types of Leukocytes
i. Neutrophils
• are phagocytes and the most abundant leukocytes.
• Generally, they are found in blood but leave capillaries and enter
tissues during inflammation.
• After neutrophils engulf microbes by phagocytosis, are destroyed
within endocytotic vacuoles by proteases.
• The production and release of neutrophils from bone marrow are
greatly stimulated during the course of an infection.

ii. Eosinophils
• are found in the blood and in the mucosal surfaces lining of
gastrointestinal, respiratory, and urinary tracts.
• In some cases, eosinophils act by releasing toxic chemicals that kill
parasites, and in other cases by phagocytosis.
Types of Leukocytes
iii. Basophils
• Secrete anticlotting factor called heparin at the site of
an infection, which helps the circulation flush out the infected site.
• Also secrete histamine, which attracts infection-fighting cells

• Generally, the normal life span of granulocytes is 4-8 hours in the

blood and another 4-5 days in tissue.
• In infections their life shortens because they are destroyed while
performing their functions.

iv. Monocytes
• are phagocytes that circulate in the blood for 10-20 hours, after
which they migrate into tissues and organs and develop into
macrophages.
Types of Leukocytes
v. Macrophages
• are large phagocytes capable of engulfing
viruses/bacteria.
• are strategically located in the epithelia in contact with the external
environment, such as skin and the linings of respiratory and
digestive tracts.

vi. Lymphocytes
• comprised of several different types of cells that play key roles in
protecting against specific pathogens, including viruses, bacteria,
toxins, and cancer cells.
• Some lymphocytes directly kill pathogens, and others secrete
antibodies into the circulation that bind to foreign molecules and
begin the process of their destruction.
Platelets
• Are colorless, non-nucleated cell fragments
• Contain numerous granules.
• Are much smaller than erythrocytes.
• Produced when cytoplasmic portions of large bone marrow cells,
called megakaryocytes, pinch off and enter the circulation
• Functions in blood clotting.
• Each μL of blood normally contains about 300,000.
Hemostasis
• Means prevention of blood loss.
• The immediate response to vessel rupture is vasoconstriction
which is sufficient to stop flow from small vessels.
• Constriction presses the opposed endothelial surfaces of the vessel
together and induces a stickiness capable to hold them together.
• Venous bleeding leads to less rapid blood loss because veins have
low blood pressure.
• Also, decreasing hydrostatic pressure by raising the bleeding part
above the level of the heart level may stop hemorrhage from a vein.
• In addition, if the venous bleeding is internal, the accumulation of
blood in the tissues (hematoma) eliminate the pressure gradient
required for continued blood loss.
• Usually bleeding from a medium/large artery cannot be controlled.
Hemostasis
• Stoppage of bleeding depends upon two other
interdependent processes, occurring in rapid succession:
i. Formation of a platelet plug, and
ii. blood coagulation (clotting).

i. Formation of Platelet Plug

• Injury to a vessel disrupts the endothelium and exposes the
underlying connective-tissue collagen fibers.
• Platelets adhere to collagen, largely via an intermediary called von
Willebrand factor (vWF), a plasma protein secreted by endothelial
cells and platelets.
• This protein binds to exposed collagen molecules, changes its
conformation, and becomes able to bind platelets.
Hemostasis
i. Formation of Platelet Plug

• This binding leads to the release of adenosine diphosphate (ADP)

and serotonin from the platelets secretory vesicles.
• Act locally to induce changes in the metabolism, shape, and surface
proteins of the platelets, a process called platelet activation.
• New platelets to adhere to the old ones, a positive feedback
phenomenon termed platelet aggregation.
Hemostasis
i. Formation of Platelet Plug
• The resultant platelet mass is called as
platelet plug.
• Adhesion of the platelets rapidly
induces them to synthesize
thromboxane A2, a member of the
eicosanoid family, from arachidonic
acid in the platelet plasma membrane.
• Released into the ECF and acts locally
to further stimulate platelet
aggregation and release of their
secretory vesicle contents.
• Fibrinogen also facilitates plate
aggregation.
Hemostasis
i. Formation of Platelet Plug
• Once the platelet plug is formed, it contracts to
completely seal off the ruptured vessel because of the presence of
actin/myosin filaments in the plug.
• The local factors also induce vasoconstriction of the damaged vessel
so as to decrease the blood flow to the ruptured site.
• Cells adjacent to the damaged site release chemical mediators
known as prostacyclin or prostaglandin I2, which are inhibitors of
plate aggregation and prevents the plug formation elsewhere.
• In addition, NO produced by the endothelial cell is also an inhibitor
of plate aggregation.
Hemostasis
ii. Blood coagulation/Clot formation
• Refers to the transformation of blood into a gel called
as clot or thrombus.
• Consists mainly of meshwork of a protein polymer known as fibrin.
• Occurs locally around the original platelet plug to reinforce it.
• Injury to a vessel initiates a locally occurring cascade of chemical
conversion of an inactive plasma protein or factor is converted into
an activated proteolytic enzyme/cofactor.
• Shortly, prothrombin is activated into thrombin when then acts as
an enzyme to convert fibrinogen into fibrin.
• Prothrombin (66.7 kDa) is a plasma protein (α2-globulin) and
present in plasma in a concentration of about 15 mg/100 mL.
• In addition to other factors, vitamin K is required by the liver for
normal activation of prothrombin.
Hemostasis
ii. Blood coagulation/Clot formation
• Thrombin (33.7 KDa) is a proteolytic enzymes, reduces
four low molecular weight chains form fibrinogen to give fibrin.
• Fibrinogen is produced in the liver and present in plasma in
quantities of 100-700 mg/mL.
• Prothrombin is activated by intrinsic and extrinsic pathways.
• Intrinsic pathway has all the elements present in the blood whereas
the extrinsic pathway needs a tissue factor/tissue thromboplastin.
• Tissue factor or is composed of membrane phospholipids and a
lipoprotein complex that functions mainly as a proteolytic enzyme.
• Extrinsic pathway begins with trauma to the vascular wall and
intrinsic pathway that begins in the blood itself.
• The two pathways interact constantly with each other.
Hemostasis
ii. Blood coagulation/Clot formation
Hemostasis
ii. Blood coagulation/Clot formation
Heart Failure
• Also congestive heart failure (CHF) is a collection of signs
and symptoms that occur when the heart fails to pump
an adequate CO.
• Either due to pumping against a chronically increased arterial
pressure, as in HTN, or structural damage to the myocardium due
to decreased coronary blood flow.

• Two categories:
i. problems with ventricular filling (diastolic dysfunction) , and
ii. problems with ventricular ejection (systolic dysfunction).

• However, some patients may exhibit elements of both categories.

Heart Failure; Diastolic Dysfunction
• The ventricular walls has reduced compliance.
• The stiffness results in a reduced ability to fill ventricles.
• Consequently, the EDV reduces and therefore, reduced SV, although
the ventricular pressure is very high.
• In pure diastolic dysfunction, ventricular compliance is decreased
but ventricular contractility is normal.
• The most common is the existence of systemic hypertension which
results in ventricular hypertrophy.
• The structural and biochemical changes associated with this
hypertrophy make the ventricle stiff and less able to expand.
Heart Failure; Systolic Dysfunction
• Results from myocardial damage.
• Result from coronary diseases.
• Characterized by a decrease in cardiac contractility, a lower SV at
any given EDV.
• The affected ventricle does not hypertrophy.
Heart Failure
• The reduced CO in CHF, regardless of the diastolic or
systolic dysfunction, triggers the arterial baroreceptor.
• The baroreceptors discharge less rapidly than normal which is
interpreted by the brain as larger-than-usual decrease in the BP.
• As a result the sympathetic outflow increases and parasympathetic
outflow decreases which culminates in:
i. Increased HR, and
ii. Increased TPR.
• Maintained chronically, the kidneys reduce their excretion of
sodium and water.
• Therefore, there is fluid retention in the body which leads to
expansion of ECF.
• In moderate cases, fluid retention can be a compensatory process
to restore CO by increasing venous return, EDV and SV.
Heart Failure
• However, in severe cases of systolic dysfunction, the
increased venous return cannot increase CO because of
loss of contractile strength.
• Therefore in severe cases of CHF, edema is observed.
• CHF (diastolic or systolic dysfunction) leads to pulmonary edema
which impairs pulmonary gas exchange.
• Because when the left ventricle fails to pump blood to the same
extent as the right ventricle, the volume of blood in all the
pulmonary vessels increases.
Hypertrophic Cardiomyopathy
• Is a condition in which a
portion of the heart becomes
thickened without an obvious
cause.
• Results in the heart being less
able to pump blood
effectively.
• Left ventricle is mostly
affected
• Most common inherited
cardiac diseases, occurring in
about one out of 500 people.
• The thickness of the walls
interferes with the blood
ejection.
Hypertrophic Cardiomyopathy
• In addition, the orderly array of myocytes and
conducting cells within the walls.
• The disruption of conduction pathway can lead to dangerous,
sometimes fatal arrhythmias.
• The heart itself is commonly the victim.
• One symptom that can be an early warning sign is the associated
chest pain (angina pectoris/angina).
• However, in most cases this disease is asymptomatic and the
disease undergo unnoticed until progressed to an advance stage.
• Although the exact cause of this disease in not known but genetic
mutations have been found to be the reason.
Coronary Artery Disease
• Changes in one or more of the coronary arteries cause
insufficient blood flow (ischemia) to the heart.
• May result in damage in the affected region, or even death of that
portion of the heart known as myocardial infarction/heart attack.
• The symptoms of myocardial infarction include prolonged chest
pain, often radiating to the left arm; nausea; vomiting; sweating;
weakness; and shortness of breath.
• The major cause of coronary artery disease is the presence of
atherosclerosis in these vessels.
• Atherosclerosis can result from
i. large numbers of cells (smooth muscle cells, macrophages)
ii. deposits of cholesterol and other fatty substances, and
iii. dense layers of connective tissue matrix.
Coronary Artery Disease
• Also, dysfunctional endothelial cells in the
atherosclerotic area release excess endothelin-1,
a vasoconstrictor) and amounts of vasodilators (NO/prostacyclin).
• Total occlusion is usually caused, however, by the formation of a
blood clot (coronary thrombosis).
 Test Result
Name Marks/38 Name Marks/38
Abdur Rahman 20 M Abbas 16
Aiman 10 M Abu Bakar 24
Aisha 24 M Osama Waheed 34
Azan Ullah 18 M Uzair 14
Bakhti Alam 14 M Yasir 18
Farman Ullah 18 Naseer Ahmad 26
Fawad Ahmad 20 S Ahsan Raza 22
Hamza Zeb 28 Sadaf Gulalai 22
Haris Ali 34 Saif Ali 30
Hayat Muhammad 30 Sayed Hamza 22
Ibrar Ali 18 Shah Fahad 20
Iqra Noor 22 Suqaina 24
Iqrar Hussain 10 Syed Aitzaz Ali Shah 16
Irfan Ullah 22 Tayyeb Khan 24
Ishtiaq Hussain 30 Umair Ahmad 22
Izza Farooq 28 Uzma Gul 22
Jamal Shah 26 Wajeeha Mazhar 18
Kanwal Jabeen 8 Waqas Ameen 18