Circulation:

The function of the circulation is to serve the needs of the body tissues to transport nutrients to
the body tissues, to transport waste products away, to transport hormones from one part of the
body to another, and in general, to maintain an appropriate environment in all the tissue fluids of
the body for optimal survival and function of the cells.

BLOOD
It is composed of liquid, plasma, suspended with the cells erythrocytes (red blood
cells), leukocytes (white blood cells) and platelets (cell fragments). Blood is bright
red when its hemoglobin is oxygenated and dark red when it is deoxygenated. In
terms of anatomy and histology, blood is considered a specialized form of
connective tissue. Blood accounts for 7% of the human body weight, with an
average density around 1060 kg/m3, very close to pure water's density of 1000
kg/m3. The average adult has a blood volume of roughly 5 liters.
Functions
 Nutritive function: transport food to required sites.
 Respiratory function: carry O2 from lungs & CO2 from tissues.
 Excretory function: carry metabolic end products to excretory organs.
 Buffering function: neutralize acid-base disturbances.
 Transport medium: for enzymes, vitamins, minerals, salts etc.
 Defensive function: defensive cells – fight against harmful substances.
 Maintenance function: maintain constant environment like temp, blood
pressure, blood volume etc.
 Haemostatic function: clotting factors – prevent hemorrhage.
Composition of Blood
Plasma
Plasma consists of a number of inorganic and organic substances - nutrients,
metabolic wastes, hormones dissolved in water. Also contains bilirubin, - a

1
product of hemoglobin breakdown, the proteins, albumin- synthesized by liver
and the most abundant ones, globulins and fibrinogen - functioning in clotting.
Type %age Normal Functions
plasma level
Albumin 55% 3-5 gm/100ml Controls osmotic pressure.
Helps in transport of ions, cations,
dyes, drugs, hormones, fatty acids,
metals, amino-acids, enzyme &
bilirubin.
Globulin 38% 2-3 gm/100ml α-globulin: helps in iron absorption
from GIT, lipid metabolism.
β-globulin: coagulation factor.
Gamma-globulin: defensive action.
Fibrinogen 7% 0.3 gm/100ml Helps in blood clotting.
Prothrombin 40 mg/100ml Helps in blood clotting.
Functions of plasma
 Transport of substances
 Maintains osmotic pressure
 Blood clotting – due to fibrinogen & prothrombin
 Maintains acid-base balance
 Stores proteins for supply in need
 Fight against diseases – due to gamma-globulins
 Maintains BP & blood viscosity
Serum
Serum is part of blood which expresses out after clotting from clot. It is plasma
minus fibrinogen & clotting factors.
Blood Cells
Erythrocytes

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Have circular, biconcave, non-nucleated discs. Biconcave shape can change
remarkably as cells squeeze through capillaries. RBCs can be deformed into
almost any shape, thus prevent lysis. Carry oxygen and carbon dioxide by
binding them with iron in hemoglobin. Have a high surface-to-volume ratio.
Plasma membrane has surface proteins and polysaccharides that confer blood
group. Reticulocytes, produced in the soft interior of bones, called bone marrow,
lose their cell organelles and enter the circulation as erythrocytes. Degraded at
end of their lives in liver and spleen. Iron, folic acid and vitamin B12 are important
constituents. Life span is 120 days
Iron - Homeostatic control of iron balance resides in intestinal epithelium. Iron is
stored in liver as ferritin. Iron released from degraded erythrocytes is carried to
bone marrow by plasma protein transferrin, and incorporated into new
erythrocytes.
Count: At birth: 6-7 million/mm3. Adults – male: 5-6 million/mm3, female: 4.5-5.5
million/mm3. Clinically 5 million/mm3 is taken as 100% RBC count
Regulation of Erythrocyte Production - Erythrocyte production is stimulated by
a hormone called erythropoietin, secreted mainly by kidneys.
Anemia- A decrease in the ability of blood to carry oxygen due to (1) a decrease
in total number of erythrocytes or (2) a lower concentration of hemoglobin per
erythrocyte or (3) a combination of both.
Sickle cell anemia results in abnormal shape of hemoglobin due to a genetic
mutation. Results in a blockage of capillaries.
Polycythemia is an excess of erythrocytes that results in a lower flow of blood in
capillaries.
Leukocytes
Consists of 3 types of polymorphonuclear granulocytes (have multilobed nuclei
and granules) - (a) eosinophils, (b) basophils and (c) neutrophils (most
abundant), monocytes and lymphocytes. All leukocytes are produced in bone
marrow. Participate in body defense.

3
WBC count: Range: 4000-11000 cells/ml of blood. Average: 7000 cells/ml of
blood.
Types of White Blood Cells
Granulocytes: Presence of granules in cytoplasm and multiple nuclei. Divided
into Neutrophil, Basophil, Eosinphil
Agranulocytes: Do not contain granules. Divided into Lymphocytes, Monocytes,
Plasma cells (ocassionally)
Platelets
Platelets are colorless cell fragments that enter circulation when cytoplasmic
portions of bone marrow cells called megakaryocytes are pinched off. Their
Destruction occurs mainly in spleen
Count: Normal count – 1.5-4 lacs/mm3. 60-75% in circulation. Remaining in
spleen (reservoir).
Variations: Thrombocytosis is the increase in platelet count and
Thrombocytopenia is the decrease in platelet count.
Regulation of Blood Cell Production
In children, marrow of most bones produces blood cells while in adults only
bones of upper body produce blood cells. All blood cells are descended from
single population of bone marrow cells called pluripotent hematopoietic stem
cells. These cells can divide into either (1) pluripotent stem cells or (2) lymphoid
stem cells that gives rise to lymphocytes or (3) myeloid stem cells that gives rise
to all other types of blood cells. Division and differentiation of these cells are
regulated by protein hormones and paracrine agents, collectively called
hematopoietic growth factors (HGFs).

BLOOD FLOW AND RESISTANCE

Blood flow refers to the movement of blood through a vessel, tissue, or organ,
and is usually expressed in terms of volume of blood per unit of time. It is initiated
by the contraction of the ventricles of the heart. Ventricular contraction ejects

4
blood into the major arteries, resulting in flow from regions of higher pressure to
regions of lower pressure, as blood encounters smaller arteries and arterioles,
then capillaries, then the venules and veins of the venous system.
Five variables influence blood flow and blood pressure: Cardiac output,
Compliance, Volume of the blood, Viscosity of the blood, Blood vessel length and
diameter. Jean Louis Marie Poiseuille was a French physician and physiologist
who devised a mathematical equation describing blood flow and its relationship
to known parameters.

Blood flow= πΔPr4 / 8ηλ

Where P is pressure difference, r radius of vessel, η is viscosity of blood and λ is

length of blood vessel.

Rate of blood flow (F) is given:

F = ΔP / R
Where ΔP is the difference in pressure between two points and R is resistance to
flow. R, in turn, is determined by viscosity of blood and length & radius of blood
vessels. Under most physiological conditions, changing the radius of blood
vessels controls flow of blood. (I.e. vasoconstriction, vasodilatation)
HEART ANATOMY
The heart is a muscle enclosed in a sac called pericardium. Walls of the heart
are composed of cardiac muscle cells, called myocardium. A thin layer of cells
called endothelial cells lines the inner surface. Located between the atrium and
ventricle on each side are the atrioventricular (AV) valves, right AV valve is called
the tricuspid valve, and the left AV valve is called the mitral valve. The valve at
the opening of right ventricle into pulmonary artery is called pulmonary valve, the
valve where left ventricle enters aorta is called aortic valve and these two valves
are also called semilunar valves. These valves will only allow blood to flow in one
direction and their opening and closing is a passive process resulting from
pressure differences across the valves.

5
Cardiac Muscle
Cardiac muscle cells are striated and desmosomes and gap junctions at
structures called intercalated disks join adjacent cells. Some cells do not function
in contraction but they do form the conducting system, which initiates the
heartbeat and spreads it throughout the heart.
These muscle cells are obviously vital and they are innervated with a rich supply
of sympathetic fibers that release norepinephrine and parasympathetic fibers that
release acetylcholine.
Blood supply to cardiac muscle cells is supplied and drained by coronary
arteries, and coronary veins, respectively. Blood being pumped through the
chambers does not exchange substances with the cells of the heart muscle.
HEARTBEAT COORDINATION
Sequence of Excitation
A group of cells, called the sinoatrial (SA) node in right atrium depolarizes first.
The discharge rate of the SA node determines heart rate. Depolarization quickly
spreads to left atrium and the two atria contract simultaneously. The action
potential then spreads to ventricles, after a small delay, through the
atrioventricular (AV) node, located at base of the right atrium. The delay in the
action potential allows atrial contraction to be completed before the ventricle
contracts. The potential then spreads to the ventricles via the bundle of His
(atrioventricular bundle) and the Purkinje fibers and both ventricles contract
simultaneously. Capacity of the SA node for spontaneous, rhythmical self-
excitation is a result of gradual depolarization, called the pacemaker potential, of
the cells as a result of Na+ channels opening once again during the repolarization
phase of the previous potential.
Control of Heart Rate
SA node is innervated by the autonomic nervous system. Activity in
parasympathetic nerves releases Ach, which close Na+ channels and decreases
the slope of pacemaker potential, causing heart rate to decrease. Activity in

6
sympathetic nerves releases norepinephrine, which then opens Na+ channels
and increases the slope of pacemaker potential, causing heart rate to increase.

Mechanical Events of the Cardiac Cycle

The cardiac cycle is divided into two phases:
(1) Systole is the phase of ventricular contraction and blood ejection. During the
first part of the systole phase, the ventricles contract while all valves are still
closed and therefore no blood is ejected. This period is called isovolumetric
ventricular contraction. The volume of blood ejected from each ventricle is called
stroke volume (SV). The amount of blood remaining after ejection is called end-
systolic volume (ESV).
(2) Diastole is the phase when the ventricles relax and blood fills into the
chambers. During the first part of diastole, the ventricles relax while all valves are
still closed and this period is called isovolumetric ventricular relaxation. The
amount of blood in ventricle at the end of diastole is called end-diastolic volume
(EDV).
SV = EDV - ESV
EDV & SV: Frank Starling Mechanism
The greater the EDV results in a greater stretching of ventricular muscles, thus
producing a more forceful contraction. Cardiac muscle is normally not at its
optimal length (lo), so additional stretching increases force of contraction. In sum,
as the end systolic volume decreases, the overall stroke volume increases.
Cardiac Output
Quantity of blood pumped into aorta each minute by heart. Normal value for men
is 5.6 lit/min and for women is 10-20% less than men. Avg. 5 lit/min.
Cardiac index is the Cardiac output per square meter of body surface area. Avg.
cardiac index for adults is 3 lit/min per m2 of body surface area.

7
Cardiac output equals heart rate (HR) multiplied by stroke volume (SV).
CO = HR x SV
Cardiac output decreases with increase in age i.e. 2.4 lit/min at 80 years. It is
directly related to body surface area, weight, metabolism, exercise, blood
volume, venous return, force of cardiac contraction and blood pressure. CO is
indirectly related to peripheral resistance.
High cardiac output is due to chronically reduced total peripheral resistance.
Causes include Beriberi, Anemia etc. Low cardiac output is due to those
abnormalities that cause pumping effectiveness of heart to fall too low. Causes
include cardiac diseases such as Myocardial infarction, valvular heart disease.
Peripheral causes include decreased blood volume and acute venous dilation.
Measurement of Cardiac Function
There are a variety of methods available to assess cardiac function. Some of
these are noninvasive (e.g., auscultation of the chest to evaluate valve function,
electrocardiography to evaluate electrical characteristics, and various imaging
techniques to assess mechanical pumping action) and others require some
invasive instrumentation.
Auscultation of the chest
Auscultation of chest is performed with a stethoscope to listen to the sounds of
heart inside the body e.g., to detect an irregular heartbeat. Sounds are produced
due to closure of valves, so vibration starts in valves, walls of heart & in adjacent
blood. This vibration is heard in form of sounds from chest wall.
Electrocardiography
Electrical events in the heart can be indirectly recorded at the surface of the skin
from the currents generated in the extracellular fluids. With the help of ECG we
can detect heart rate, heart rhythm, site of pacemaker, site & type of heart
disease and effects of electrolytes & drugs.
An EKG (ECG) recording should consist of 3 deflections: (1) P wave - the atrial
depolarization, (2) QRS complex - the ventricular depolarization and (3) T wave -

8
the ventricular repolarization. P wave represents the passage of impulse from SA
node over atria. Impulse reaches AV node about middle of P wave. Normal P
wave indicates that SA node is acting as pacemaker, impulses travel in a normal
direction and there is no ectopic focus. QRS complex represents spread of
impulse through ventricles. It indicates ventricular muscle mass, strength of
contraction and duration of contraction. T wave helps in assessing ventricular
repolarization defects.
P-Q interval represents interval b/w beginning of contraction of atrium &
beginning of contraction of ventricle. Its duration is approx. 0.35 sec. QT interval
is duration from beginning of QRS complex to end of T wave. Total duration of
one ECG is approx. 0.83 sec.
The long refractory period of heart muscle cells limits re-excitation of cardiac
nerve cells, thus inhibiting tetanus.
Echocardiography
It is the most widely used of the cardiac imaging techniques currently available.
This noninvasive technique is based on the fact that sound waves reflect back
toward the source when encountering abrupt changes in the density of the
medium through which they travel. A transducer, placed at specified locations on
the chest, generates pulses of ultrasonic waves and detects reflected waves that
bounce off the cardiac tissue interfaces. The longer the time between the
transmission of the wave and the arrival of the reflection, the deeper the structure
is in the thorax. Such information can be reconstructed by computer in various
ways to produce a continuous image of the heart and its chambers throughout
the cardiac cycle. Doppler echocardiography can provide additional information
about blood flow velocity and direction across the cardiac valves. It is particularly
useful in detecting valve stenosis or insufficiency.

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Baroreceptor Reflex
Arterial Baroreceptors are the short-term regulators of MAP. Pressure receptors
are present in the carotid sinus at the neck, the aortic arch, pulmonary vessels,
wall of the heart and large systemic veins. Afferent neurons, the firing rate of
which is positively correlated to MAP, from these receptors travel to the
brainstem.
Medullary Cardiovascular Center is the primary integrating center for
baroreceptor reflexes in the brainstem medulla oblongata. When arterial
baroreceptors decrease their discharge as a result of less MAP, sympathetic
outflow increases, increasing heart rate, ventricular contractility, and
vasoconstriction. Also elicits an increased secretion of Angiotensin II and
vasopressin, which constrict arterioles.
Chemoreceptor reflex
Chemoreceptors are specialized nerve endings in aortic bodies and carotid
bodies. They are stimulated by decreased O2, increased CO2 & increased H+
conc. due to decrease in BP. Whenever blood flow to chemoreceptor falls too
low, impulses are transmitted through glassopharyngeal & vagus nerve to
vasoconstrictor area. As a result vasonconstriction occurs which elevates arterial
pressure back to normal.
CNS ischemic response
When blood flow to vasomotor center decreases, it results in cerebral ischemia.
Neurons in vasomotor center are strongly excited due to ischemia, causing
systemic BP to rise to normal.
Hormones

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Adrenaline, noradrenaline and renin angiotensin cause vasoconstriction and
increase BP. ADH is released by hypothalamus and is responsible for water
retention, vasoconstriction & elevating BP back to normal value.
Long term regulation
Long term regulation of MAP is dependent upon blood volume. An increase in
MAP decreases blood volume by increasing excretion of salt and water by
kidneys, consequently bringing down MAP.

HYPOTENSION
Hypotension is low blood pressure due to low blood volume. SV, CO, MAP
decrease as a direct result of hemorrhage and arterial baroreceptor reflexes work
to restore them to normal. HR and TPR increase as reflex responses due to
increases in sympathetic outflow. Interstitial fluid is moved into the vascular
system due to reduced capillary pressure. In the long term, fluid ingestion and
kidney excretion are altered, erythropoiesis is stimulated to replace blood
volume. Loss of large quantities of cell-free extracellular fluid through sweating,
vomiting, diarrhea etc. also invoke similar symptoms and responses.
Hypotension can cause fainting. Hypotension can be an indicator of
insufficiencies of the autonomic nervous system.
Shock
Tissue or organ damage due to reduced blood flow is called shock.
(1) Hypovolemic shock is caused by a decrease in blood volume due to
hemorrhage or loss of fluid.
(2) Low-resistance shock is due to a decrease in TPR due to excessive release
of vasodilators, greatly increased capillary permeability, greatly reduced venous
return as in allergy and infection. E.g., Penicillin sensitivity, mismatching blood
transfusion.
(3) Cardiogenic shock due to a decrease in CO (cardiac output), as in a heart
attack.

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(4) Neurogenic shock results from sudden loss of vasomotor tone throughout
body causing massive dilatation of veins. As a result normal volume of blood
becomes incapable of adequately filling circulatory system. Caused by Deep
general anesthesia, Spinal anesthesia, Brain damage.
Upright Posture
Upright posture refers to the position of the human body when standing or sitting
straight, with the head, shoulders, hips, knees, and ankles aligned in a straight
line. There is a decrease in the effective circulating blood volume during
transition from a horizontal to a vertical position. In a horizontal position, all blood
vessels are at the same level and almost all pressure is due to cardiac output. In
a vertical position, there is an additional pressure at every point, equal to weight
of the blood column from the heart to that point. This results in distension of
blood vessels due to pooling of blood and increased capillary filtration in lower
parts of the body. Effect of gravity can be offset by contraction of skeletal
muscles in the legs.
Exercise
As CO increases, there is an increased blood flow to muscles and skin (to
dissipate heat). CO is increased by a large increase in HR - caused by increased
activity in the SA node, and a small increase in SV - caused by an increased
ventricular contractility mediated by sympathetic activity. There is also an
increase in EDV (refers to the volume of blood in the ventricles at the end of the
diastole (relaxation phase) of the cardiac cycle) and the Frank Starling
mechanism comes into play. Venous return is promoted by:
(1) Increased activity in skeletal muscle pump.
(2) increased activity in respiratory pump inspiration (due to increased depth
and frequency of inspiration).
Control mechanisms for these cardiovascular changes involve feed forward
regulation, active hyperemia, resetting of arterial baroreceptors.
Maximal Oxygen Consumption and Training

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Oxygen consumption increases in proportion to magnitude of exercise until a
point maximal oxygen consumption (V02max). After V02max is reached, any
further increase in work can be only briefly sustained by anaerobic metabolism.
V02max is limited by:
(1) CO,
(2) ability of respiratory system's to deliver oxygen to blood
(3) ability of muscles to use oxygen.
Normally, V02max is determined by cardiac output.
HYPERTENSION
When arterial pressure is greater than upper range of accepted normal limit.
Hypertension limits are;
Mean BP – greater than 110 mmHg
Systolic BP – greater than 135-140 mmHg
Diastolic BP – greater than 90 mmHg
Increased arterial pressure, generally due to an increased TPR resulting from
reduced arteriolar radius. Renal hypertension results from increased secretion of
renin, which generates angiotensin II - a vasoconstrictor. Volume loading
hypertension results from increased accumulation of salt & water in body, due to
increased aldosterone secretion by kidney. Hypertension results in an increase in
muscle mass of the left ventricle (left ventricular hypertrophy) since it has to
pump against an increased arterial pressure. This could decrease contractility
leading to heart failure. High BP may rupture major blood vessel in brain. Very
high BP causes multiple hemorrhages in kidneys.

HEART DISEASES
Heart Failure
In heart failure, the heart fails to pump an adequate CO. In diastolic dysfunction,
the wall of the ventricle has reduced compliance and has a reduced ability to fill
adequately resulting in reduced EDV and therefore a reduced SV. Systolic

13
dysfunction results from myocardial damage and results in a decrease in cardiac
contractility and a lower SV. Adaptive reflexes to counter the reduced CO results
in (1) fluid retention and can cause edema - one in the lung can impair gas
exchange, and (2) increased TPR makes it harder for the heart to pump.
Heart failure can be caused by CAD, heart attacks, hypertension, faulty heart
valves, cardiomyopathy, myocarditis, congenital heart problems, arrhythmias,
diabetes and other severe infections.
Coronary Artery Disease and Heart Attacks
In coronary artery disease, changes in the coronary arteries cause insufficient
blood flow (ischemia) to heart, resulting in damage to myocardium (myocardial
infarction or heart attack). Chest pains associated with this are called angina
pectoris. Ventricular fibrillation triggers abnormal impulse conduction by
damaged myocardial cells resulting in uncoordinated ventricular contractions.
Major cause of coronary artery disease is atherosclerosis - a thickening of the
arterial wall due to:
(1) Abnormal smooth muscle
(2) Cholesterol deposits
(3) Dense layers of connective tissue. The thickened wall reduces blood flow
and also releases vasoconstrictors. Atherosclerosis of a cerebral artery can lead
to localized brain damage - a stroke or reversible neurologic deficits called
transient ischemic attacks (TIAs). Coronary thrombosis is total occlusion of a
blood vessel by a blood clot.

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HEMOSTASIS - PREVENTION OF BLOOD LOSS
Hemostasis is the stoppage of bleeding from small vessels. Venous bleeding
leads to a less rapid blood loss because veins have lower blood pressure.
Accumulation of blood in a tissue as a result of bleeding is called hematoma.
When a blood vessel is cut, it constricts and the opposite endothelial surfaces of
the vessel sticks together to slow the outflow. It is followed by other processes
including clotting.
Formation of a Platelet Plug
Injury to a vessel exposes the underlying connective tissue collagen, and
platelets bind to the collagen via an intermediary called von Willebrand factor
(vWF) - a plasma protein secreted by endothelial cells and platelets. Binding of
platelets to collagen triggers the release of secretions from platelets that change
the shape and surface proteins of platelets (platelet activation), causing them to
stick together (platelet aggregation) and creating a platelet plug. The platelet plug
acts as a primary sealer. The plug does not expand away from the damaged
endothelium because intact endothelium synthesize and release prostacyclin
(prostaglandin 12, PGI2) that inhibits platelet aggregation.
Blood Coagulation: Clot Formation
Process of formation of blood clot at site of injured vessel, preventing blood loss.
Over 50 important substances affect blood coagulation. Procoagulants promote
coagulation while anticoagulants inhibit coagulation. Balance b/w these two
decide whether coagulation will occur or not. Normally anticoagulants
predominate. During trauma procoagulants predominate.
Blood is transformed into a solid gel, called a clot or thrombus that consists
mainly of the protein fibrin. It supports and reinforces the platelet plug. Plasma
protein prothrombin (alpha2 globulin, formed by liver continually) is converted to
the enzyme thrombin by Prothrombin activator, which then catalyzes the
formation of fibrin from fibrinogen. Fibrin threads forms reticulum of clot. Fibrin

15
stabilizing factor causes covalent bonds & multiple cross linkages b/w fibrin
threads. Clot is meshwork of fibrin threads running in all directions & entrapping
blood cells, platelets and plasma. Clot contracts after few minutes of formation
and expels most of fluid (serum) in 20-60 minutes. Finally actin & myosin filament
of platelets retracts. Platelets are essential to clot formation since they provide
the surface on which many of the reactions occur. Vitamin K is required as a
precursor to produce prothrombin and other clotting factors. Plasma calcium is
also required for this process.
Anticlotting Systems
Anticlotting mechanisms are important in restricting clot formation to the site of
injury. The two major systems are the anticoagulant and fibrinolytic systems. The
anticoagulant system comprises four enzyme pathways whose function is to
reduce thrombin production, limit its activity, or both. The fibrinolytic
(thrombolytic) system removes the clot after the vessel is repaired. Plasminogen
activators activate a plasma proenzyme, plasminogen to the enzyme plasmin
that digests fibrin to dissolve the clot.
Common Anticlotting Drugs
Anticlotting drugs are also called as blood thinners. There are two main types of
blood thinners.
Anticoagulants, such as heparin or warfarin (also called Coumadin), work on
chemical reactions in your body to lengthen the time it takes to form a blood clot.
Heparin is present in blood in small amount released by mast cells. It produces
its major anticoagulant effect by inactivating thrombin and activated factor X
through an antithrombin (AT). Heparin binds to AT through a high-affinity
pentasaccharide, which is present on about a third of heparin molecules.
Antiplatelet drugs, such as aspirin, prevent blood cells called platelets from
clumping together to form a clot. Aspirin suppresses the production of
prostaglandins and thromboxanes, due to its irreversible inactivation of the

16
cyclooxygenase (COX) enzyme. Cyclooxygenase is required for prostaglandin
and thromboxane synthesis. Thromboxane is essential for platelet aggregation.

VASCULAR SYSTEM

Arteries
Arteries are large, elastic tubes lined at the interior by endothelial cells. Arterial
walls have connective tissue and smooth muscles. During systole, contraction of
ventricles ejects blood into arteries, distending the arterial walls. During diastole,
the walls recoil passively and more blood is driven out. There is always some
blood in the arteries to keep them semi-inflated. Maximum arterial pressure
reached during systole is called systolic pressure (SP), and minimum arterial
pressure reached during diastole is called diastolic pressure (DPI) and difference
between SP and DP is called pulse pressure (PP). Average pressure driving
blood into tissues is called mean arterial pressure (MAP).
Arterioles
Contain smooth muscles, which can relax to increase vessel radius
(vasodilatation) or contract to decrease vessel radius (vasoconstriction), and
control blood flow through an organ. Blood flow through an organ can be
calculated with:
Forgan = MAP / Resistance organ
Local Controls
Local controls are mechanisms independent of hormones and nerves.
Hyperemia occurs by arteriolar dilation in response to an increase in metabolic
activity that causes local changes such as decrease in O 2, increase in CO2 and
H+.
Extrinsic Controls
Sympathetic nerves provide a rich supply of impulses to arterioles. Release
norepinephrine and cause vasoconstriction.

17
Hormones such as vasopressin (from posterior pituitary) and angiotension II
(from liver) constrict arterioles.
Capillaries
Capillaries permeate every tissue in the body to provide front line access to cells
in order to exchange nutrients and metabolic end products.
Anatomy of the Capillary Network
A capillary is a thin walled tube of endothelial cells one layer thick resting on a
basement membrane without any surrounding muscle or elastic tissue. The
endothelial cells are separated from each other by narrow, water-filled spaces
called intercellular clefts.
Velocity of Capillary Blood Flow
Blood velocity decreases as blood passes through the huge cross sectional area
of a capillary.
Diffusion and Exchange across Capillary Wall
There are three basic mechanisms by which substances move across capillary
walls to enter or leave the interstitial fluid:
(1) Diffusion is the only important means by which net movement of nutrients,
oxygen and metabolic end products can occur. Intercellular clefts allow the
passage of polar molecules. Brain capillaries, however, are tight with no
intercellular clefts. Liver capillaries are leaky with large clefts for movement of
substances. The transcapillary diffusion gradient is setup by utilization or
production of a substance.
(2) Vesicle transport allows for the passage of molecules via endo- and
exocytosis.
(3) Bulk flow enables protein-free plasma to move from capillaries to the
interstitial fluid due to hydrostatic pressure. This is opposed by an osmotic force,
resulting from differences in protein concentration that tends to move interstitial
fluid into the capillaries.
The net filtration pressure (NFP) can be calculated by:

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NFP = Pc – PIF – πP + πIF
Where:
Pc = capillary hydrostatic pressure (favoring fluid movement out of capillary)
PIF = interstitial fluid hydrostatic pressure (favoring fluid movement into capillary)
πP = the osmotic force due to plasma protein concentration (favoring fluid
movement into capillary)
πIF = the osmotic force due to interstitial fluid protein concentration (favoring fluid
movement out of capillary)
These four factors are called Starling forces.
Veins
Veins are thin walled, low resistance vessels that carry blood from the tissues to
the heart.
Determinants of Venous Pressure
Total blood volume is the important determinant of venous pressure. At any given
time, most of the blood is in veins. Walls of veins are more elastic and thus can
accommodate large volumes of blood with relatively small increase in pressure.
The walls contain smooth muscle innervated by sympathetic neurons which
release norepinephrine and constricts vessels which increases pressure and
drives more blood.
During skeletal muscle contraction, veins in the muscle are compressed, which
reduces their diameter and increases pressure. This is called skeletal muscle
pump. When the diaphragm descends during inspiration, there is an increased
pressure in intraabdominal veins and a decreased pressure in intrathoracic veins,
increasing venous pressure. This is called the respiratory pump. Venous valves
prevent backflow of blood in veins.
LYMPHATIC SYSTEM
The lymphatic system is a network of vessels, tissues, small organs (lymph nodes) and tubes
(lymphatic vessels) through which flows lymph, that play a crucial role in our body's immune
system and overall health. Its main functions include:

19
1. Fluid balance: Draining excess fluids and proteins from tissues and returning them to the
bloodstream.
2. Immune response: Helping to defend the body against infection and disease through the
production of white blood cells (lymphocytes).
3. Waste removal: Aiding in the removal of waste products, toxins, and cellular debris from the
body.
4. Fat absorption: Assisting in the absorption of fats and fat-soluble vitamins from the digestive
system.
Key components of the lymphatic system include:
1. Lymph vessels (lymphatics): A network of vessels that transport lymph fluid throughout the
body.
2. Lymph nodes: Small, bean-shaped organs that filter lymph fluid and trap pathogens.
3. Spleen: An organ that filters the blood, removing old red blood cells and other waste products.
4. Thymus: A gland that produces and matures lymphocytes (white blood cells).
5. Tonsils: Masses of lymphoid tissue in the throat that help filter out pathogens.
6. Lymphoid organs (e.g., adenoids, Peyer's patches): Tissues that contain immune cells and help
activate the immune response.
Lymph Fluids
Lymph fluid, also known as lymph, is a clear or pale yellow fluid that circulates through the
lymphatic system. It is a vital component of the immune system and plays a crucial role in
maintaining the body's overall health.
Composition:
Lymph fluid is a mixture of:
1. Water
2. Proteins (e.g., albumin, globulins)
3. Electrolytes (e.g., sodium, potassium, calcium)
4. Nutrients (e.g., glucose, amino acids)
5. Waste products (e.g., urea, creatinine)
6. Immune cells (e.g., lymphocytes, macrophages)
7. Fatty acids and cholesterol
Functions:

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The lymphatic system provides a pathway by which fat absorbed in gastrointestinal tract reaches
the blood. Some substance like histamine & lipase reach circulation by lymphatics mainly after
their secretion from cells into interstitial fluid. Infections causing blockage of lymphatic system
leads to accumulation of interstitial fluid, called edema. The continual movement of lymphocytes
exposes antigen to large number of lymphocytes which specifically react with it and disperses
memory lymphocytes for second encounter with antigen.
Lymph fluid performs several essential functions:
1. Transports immune cells to areas of the body where they are needed.
2. Carries nutrients and oxygen to cells.
3. Removes waste products and toxins from tissues.
4. Helps maintain fluid balance and blood pressure.
5. Supports the immune system by transporting antibodies and activating immune responses.
Abnormalities in lymph fluid or its circulation can lead to various health issues, such as
lymphedema, inflammation, and immune disorder

The term "interstitial" refers to something that is located between things, often in a small or
narrow space. It can be used in various contexts, such as:

- Biology: Interstitial cells, tissues, or fluids are those that exist between other cells, tissues, or
structures.

- Medicine: Interstitial lung disease refers to a group of conditions that affect the tissue between the air
sacs of the lungs.

Mechanism of Lymph Flow

Lymph is propelled by the rhythmical contractions of smooth muscle lining the
walls of lymphatic vessels. The contractions are triggered by stretching of the
walls when lymph enters the system. Lymphatic vessels have valves to produce
a one-way flow. The vessels are innervated by sympathetic neurons and are also
influenced by the skeletal muscle pump and the respiratory pump.
REGULATION OF SYSTEMIC ARTERIAL PRESSURE

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Perpendicular pressure exerted by blood on walls of blood vessels as it passes
through it. Systolic pressure is the pressure during systolic phase i.e. 120 mmHg.
Diastolic pressure is the pressure during diastolic phase i.e. 80 mmHg.
Mean arterial pressure is Average pressure tending to push blood through
systemic circulation. Nearer to diastolic pressure i.e., usually 96 mmHg, but often
taken as 100 mmHg.
Mean arterial pressure = cardiac output x total peripheral resistance
Arteriolar resistance is the main determinant of TPR. Any deviation in MAP elicits
homeostatic reflexes so that CO or TPR is changed to minimize the deviation.
Short-term regulation

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