Physiological Mechanisms -...
Transcript of Physiological Mechanisms -...
Physiological Mechanisms
Circulation
By
Dr Smita Bhatia BP-5, II floor,
Shalimar Bagh (West) Delhi 110088
Contact: 27483738 Email: [email protected]
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Circulation Learning objectives Blood
Functions of bloodConstituents of blood
Blood groupsHeart: Structure and function
The cardiac muscleChambers of the heartHeart and circulationCardiac cycleCoronary circulationElectrocardiogram (ECG)Heart sounds
Blood vessels: structure and functionsCapillary exchange
Blood pressure Measurement of blood pressure Factors affecting blood pressure
Control of blood pressureNeural regulationHormonal regulation Autoregulation
HemostasisLymph
Blood
A unicellular organism can derive nutrients and oxygen directly from the environment, and
eliminate wastes into it. But, in a multicellular organism, all the constituent cells are not
directly in contact with the environment. So to perform these functions a special fluid
circulates the nutrients and oxygen (O2) to each cell and takes away carbon dioxide (CO2) and
wastes. This fluid is known as blood. Also assisting in this function is the interstitial fluid, i.e.
the fluid present in-between cells (plasma—the fluid component of blood is a part of interstitial
fluid as they are interchangeable to a certain extent. See filtration and reabsorption in the
capillaries at the tissue level).
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Functions of blood
• Transport: It is responsible for carrying O2 from the lungs to the body cells and CO2 from
the cells to the lungs. It also transports hormones from the endocrine glands to the target
cells, nutrients from the gastrointestinal tract to various cells and wastes to be eliminated
from the body.
• Homeostasis: It is responsible for the maintenance of the internal body environment. Blood
helps maintain temperature by carrying heat away from the cells and by losing heat through
the skin (from the capillaries). It maintains the pH by buffers present in the blood.
• Osmotic balance: Osmotic balance in the cells is maintained by the blood. It maintains
blood volume in the body as it can prevent its own loss by clotting and by other
mechanisms (hemostasis — vasoconstriction/platelet plug formation/blood coagulation).
• Defense: The white blood cells in the blood protect the body from various diseases by
destroying microorganisms using a variety of mechanisms.
Constituents of blood Blood consists of a fluid portion called plasma (55% of total volume) and cells (45% of the
total volume). Fig 1: Blood constituents
Plasma (55%) Cells (45%)
Water Solutes Red blood cell (RBC) White blood cell (WBC) Platelets or erythrocyte or leucocyte (1,50,000 (91.5%) (8.5%) (4.8 – 5.4 x 106/mm3) (5000–10,000/mm3) –4,00,000/mm3)
Proteins (7%) Other solutes (1.5%)
• Albumins (54%) • Globulin (38%) • Fibrinogen (7%) • Others (1%)
• Electrocytes • Nutrients • Regulatory substances • Gases • Wastes
Plasma
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Water
It is the solvent for the various solutes and medium for suspension of various constituents of
blood.
Solutes
Proteins:
Albumins
• Smallest plasma proteins
• Produced in the liver
• Exert osmotic pressure which helps maintain the osmotic balance between blood and
tissues and maintains the blood volume
• Function as transport proteins for fatty acids, certain fat-soluble hormones (steroids) and
certain drugs.
Globulins
• Most of them are produced by the hepatocytes.
• There are three types:
o α-globulins include high density lipoproteins which transport lipids (extra cholesterol
from the body cells to the liver to be eliminated). Thyroxine-binding globulin
(transports thyroxine), cortisol-binding globulin (transports cortisol) and vitamin B12-
binding globulin (transports vitamin B12).
o β-globulins include transferrin (transports iron), low density lipoproteins and very low
density lipoproteins (transport cholesterol from the liver to the body cells).
o γ-globulins are antibodies which are produced by plasma cells derived from B-
lymphocyte.
Fibrinogen
• Protein needed for blood clotting
• Produced by hepatocytes.
Other solutes:
Electrolytes
• Inorganic salts; Cations, such as Na+, K+, Ca2+ and anions like Cl-, HCO3-, HPO42-, SO4
2.
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• Maintain the osmotic pressure of blood.
• Maintain the excitability of cell membranes, participate in blood clotting (Ca2+) and act as
buffers.
Nutrients
• Products of digestion like amino acids, glucose, fatty acids, glycerol and vitamins.
Regulatory substances
• Enzymes produced by cells responsible for catalyzing various chemical reactions. <link to
enzymes in chapter on Digestion>
• Hormones produced by the endocrine glands are carried to the target organs where they
produce the desired effect. <link to chapter on Hormonal control>
• Growth factors
• Vitamins <link to vitamins in chapter on Digestion>
Gases
• Oxygen (O2): mostly associated with haemoglobin in RBC. Carried from lungs to the body
cells to be utilized for various cellular activities.
• Carbon dioxide (CO2): mostly presents as HCO3- ions in the plasma, carried to the lungs
where it is exhaled.
• Nitrogen (N2): In plasma; no known function.
Wastes
• These include urea, uric acid, creatinine (from creatine), ammonia, bilirubin, urobilin.
Cells: Fig 2: Types of cells in blood
< External link http://cache.eb.com/eb/image?id=91871&rendTypeId=34>
Erythrocytes
Leucocytes
Platelets
Eosinophil BasophilNeutrophil
LymphocyteMonocyte
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Erythrocytes: Also known as red blood cells (RBCs) because of the red colour due to the presence of iron-
containing red pigment — haemoglobin.
• There are 5–5.5 million RBCs/mm3 of blood in a male and 4.5–5 million /mm3 of blood in
a female.
• RBCs are biconcave discs without nucleus. This shape and lack of nucleus increases the
space available for transporting oxygen. The cell membranes are strong and flexible. The
biconcave shape (larger surface area for their volume) of RBCs facilitates their distortion
without damage while squeezing through narrow capillaries.
• RBCs lack mitochondria, endoplasmic reticulum and other organelles.
• They cannot reproduce or synthesize proteins.
• They generate energy glycolytically (anaerobically) so they do not use up any oxygen that
they carry.
• Since they cannot synthesize any new proteins for cell repair, their life is very short (120
days).
• Every day many RBCs are destroyed and replaced by new ones (haematopoiesis; see
external link: http://en.wikipedia.org/wiki/Hematopoiesis).
• The products of their destruction are removed or recycled. Worn out RBCs break down
while passing through the narrow capillaries of the spleen. These damaged RBCs are
removed from circulation and phagocytosed by the macrophages in the spleen, liver or red
bone marrow.
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Haemoglobin (Hb) <link to respiration>
Structure The haemoglobin of the RBCs is made up of into heme and globin portions. It consists of four heme groups each containing an iron atom and four polypeptide chains that constitute the globin part. In the adult, haemoglobin (HbA) these polypeptide chains are of α and β type (2α and 2β chains) so the adult haemoglobin molecule is written as Hbα2β2, with the α chain containing 141 amino acids and the β chain containing 146 amino acids. Fetal haemoglobin (HbF) contains 2 α and 2 γ chains forming its globin part. The γ chain differs from the β chain in 37 amino acids. Fetal Hb has a greater affinity for O2 than adult Hb. Haemoglobin from the destroyed RBCs has the following fate:
Haemoglobin
Globin Heme
Breaks down into Amino acids
Iron non-iron part Reused for synthesizing Combines with Converted into a green new proteins transferrin in the blood pigment biliverdin Transported to
spleen / liver / muscle Stored in these organs as Converted into an ferritin and hemosiderin orange pigment, bilirubin Transported by transferrin to bone marrow when needed Used by precursor RBCs for the Transported to the liver by synthesis of haemoglobin blood
Secreted with bile juice Bile juice in small intestine Some of it is absorbed Some part is not absorbed Reaches the large intestine Converted to urobilinogen by bacteria
Iron transport and storage Iron absorbed in the small intestine is transported by the
blood by a β globulin, apotransferrin, which combines with iron to form transferrin. Iron is then released to be deposited in the hepatocytes, muscle cells or the macrophages of spleen and liver. In the cell cytoplasm this iron combines with a protein, apoferritin, to form ferritin. Most of the iron is stored in this form. When all the apoferritin is converted to ferritin the extra iron is stored as hemosiderin. Whenever iron is needed in the body it is released from this storage pool and delivered to the cells where it is needed, e.g. erythroblasts in the red bone marrow, by transferrin.
Enterohepatic circulation
Some of it is absorbed into the blood, converted Some part is not absorbed into a yellow pigment (urobilin) and carried to the kidneys Excreted by the kidneys as a yellow Converted to stercobilin by Pigment in the urine bacteria in the large intestine
Excreted with feces (the characteristic colour and odor of the fecal matter is due to stercobilin)
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Production of RBCs (Erythropoiesis)
• RBCs, like all other blood cells are formed in the red bone marrow of an adult. RBCs are derived from the pleuripotent stem cells along specific lines:
Pleuripotent stem cell Myeloid stem cell Colony forming unit: Erythrocytes (CFU-E), progenitor cells, not capable of dividing, committed to differentiating into RBCs Basophilic erythroblast (Prorubricyte) Polychromatophillic erythroblast (Rubricyte, haemoglobin synthesis starts here) Acidophilic erythroblast (Normoblast, haemoglobin synthesis is maximum here)
loss of nucleus, most endoplasmic reticulum and mitochondria Reticulocyte (34% haemoglobin, with some endoplasmic reticulum and mitochondria) Reticulocytes released into blood stream
mature in 1-2 days
Erythrocytes
• At any given point of time 0.5 to 1.5% of blood cells are reticulocytes. This is known as the reticular count.
Hematocrit • 45% of the total blood volume is represented by RBCs (hematocrit). • Males have an average hematocrit of 47% and females have an average of 42%. • Males have a higher hematocrit because testosterone stimulates the secretion of
erythropoietin which in turn stimulates RBC synthesis. • A reduction in hemtocrit indicates anaemia.
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White blood cells or leucocytes: These are cells with nuclei and other cells organelles. They are of two types, granulocytes and agranulocytes
Leucocytes (White blood cells)
Granulocytes Agranulocyte (Have chemical-filled vesicles in their (Have very fine vesicles that are not visible cytoplasm that look like granules when stained) under a light microscope when stained) Neutrophils Eosinophils Basophils Lymphocytes Monocytes(60-70%) (2-4%) (0.5-1%) (20-25%) (3-8%) Of total WBCs Of total WBCs Of total WBCs Of ALL WBCs Of total WBCs
Lymphocyte
Monocyte
Basophil
Eosinophil
Neutrophil
Neutrophils: Granules stain with both basic and acidic dyes. Nucleus is multi-lobed with
lobes connected with thin strands of chromatin. Responsible for destruction of microorganisms
by phagocytosis, by using lysozymes, defensins and oxidants.
Eosinophils: granules stain with acidic dyes like eosin. Nucleus bilobed or kidney shaped.
Destroy certain parasitic worms, phagocytose antigen-antibody complexes.
Basophils: granules stain with basic dyes. Nucleus is irregular or kidney shaped and obscured
by the thick granules. Responsible for the inflammatory response in allergic reactions.
Lymphocytes: Circular nucleus with very little cytoplasm around it. These are the only blood
cells that can divide even after they leave the bone marrow. They leave the bone marrow and
differentiate into T lymphocytes, B lymphocytes and natural killer cells. T lymphocytes are
responsible for destroying viruses, cancer cells and transplanted tissue cells. B lymphocytes
form plasma cells which produce antibodies to destroy foreign antigens. Killer cells destroy
infectious microbes and certain tumour cells.
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Monocytes: Kidney shaped or horse-shoe shaped nucleus. Monocytes differentiate into
macrophages which can be of two types:
1. Fixed macrophages which reside in a particular tissue and phagocytose foreign matter e.g.
the macrophages in the spleen, alveolar macrophages in the lung alveolar epithelium,
reticuloendothelial (Kupffer) cells in the liver.
2. Wandering macrophages which do not reside in a particular tissue but keep moving
throughout the body and aggregate at the site of infection or inflammation.
Production of WBCs
• White blood cells are also produced in the red bone marrow.
Pleuripotent stem cell
Myeloid stem cell Lymphoid stem cell Eosinophilic Neutrophillic Basophilic Monoblast T lymphocyte B lymphocyte myeloblast myeloblast myeloblast myeloblast Eosinophil Neutrophil Basophil Monocyte T lymphocyte B lymphocyte Plasma
Begin their development in the red bone marrow
Since WBCs are involved in protecting the body from diseases, many WBCs leave the blood
stream to aggregate at the site of infection or inflammation. These WBCs leave the blood
stream by squeezing through spaces between endothelial cells in a blood vessel. This process is
known as emigration (earlier known as diapidesis)
Lymphocytes keep circulating between the blood stream and interstitial fluid and lymph. But
granulocytes and monocytes do not return to the blood stream after once leaving it.
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WBCs, like other nucleated cells of the body, have certain specific protein antigens protruding
from their surface. These are called major histocompatibility (MHC) antigens (RBCs lack
them).
Platelets (Thrombocytes): They are also formed in the red bone marrow from the haemopoeitic (pluripotent) stem cells
that give rise to the myeloid stem cell.
Production of Platelets
Pleuripotent stem cell
Myeloid stem cell
Megakaryoblast
Megakaryocyte
Fragmentation (takes place in the bone marrow)
Platelets (Thrombocytes)
Platelets have no nuclei but have special vesicles. They cannot reproduce and have a short life
of 5-9 days. Worn out platelets are removed by macrophages in the spleen and liver. Platelets
have certain special characteristics that facilitate their functioning in hemostasis, such as
• Residual endoplasmic reticulum and Golgi bodies that synthesize various enzymes and
store large quantities of Ca2+ ions.
• Mitochondria and enzymes that synthesize ADP and ATP.
• Certain enzymes that are responsible for the synthesis of prostaglandins like Thromboxane
A2.
• A protein called fibrin-stabilizing factor (Factor XIII, see blood coagulation) that helps
strengthen a blood clot.
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• Actin, myosin and another contractile protein, thrombosthenin (in their cytoplasm) that
cause the platelets to contract.
• A growth factor (Platelet Derived Growth Factor—PDGF) that can cause proliferation of
vascular endothelial cells, vascular smooth muscle fibres and fibroblasts to help repair the
damaged blood vessel.
• Serotonin which is a vasoconstrictor
• Large amounts of a phospholipid (in their membranes), the platelet factor, which
participate in blood clotting,
The red bone marrow in adults is located
in the microscopic spaces between the
trabeculae of the spongy part of the
bones, e.g. the epiphyses of femur and
humerus bones, of the pelvic and pectoral
girdles, the vertebrae and the ribs. During
embryonic life RBCs are formed in the
yolk sac, liver, spleen and red bone
marrow of bones. In an adult, as the age
increases the production of RBC
decreases as the red bone marrow gets
converted into yellow marrow which
only stores fat.
Many factors, such as the haemopoeitic
growth factors regulate the formation of
blood cells through haematopoiesis.
Formation of RBCs is stimulated by such a
factor called erythropoietin produced by the
kidneys. Under conditions of hypoxia a
larger amount of erythropoietin is produced
that increases the number of RBCs produced
to counter the hypoxia. Thrombopoetin
produced by the liver cells stimulates the
formation of platelets (thrombocytes).
Cytokines produced by the bone marrow
cells, macrophages, fibroblasts, endothelial
cells and leucocytes stimulate the formation
of leucocytes. Two such cytokines are the
colony stimulating factors and interleukins.
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Blood groups RBCs have some antigens (glycolipid and glycoprotein molecules) called agglutinogens on the
surface that are important in identifying the blood groups. There are at least 100 different types
of antigens and 24 different types of blood groups. Within a particular blood group there may
be two or three different blood types. Out of the 24 different blood groups, there are two major
blood groups: ABO and Rh.
ABO blood group
This is based on the type of agglutinogen (a glycolipid) present on the surface of RBCs which
could be either A type (Group A), B (Group B), both A and B (Group AB) and none (Group
O). There are readymade antibodies circulating in the body against the antigen NOT present on
the surface of RBCs, e.g. a person with agglutinogen A will have circulating antibodies against
agglutinogen B.
Agglutinogen Circulating antibodies Blood group on RBC surface A Anti-B A B Anti-A B AB None AB None Anti-A, Anti-B O
The antibodies of the recipient attack the RBCs of the donor
that carry agglutinogens. For example, if a person (a
recipient) with blood group A (and antibodies of the anti-B
type) is given blood from a person (donor) with blood group
B, the anti-B antibodies of the recipient attack the RBCs of
the donor as they have agglutinogen B on their surface which
results in clumping (or agglutination) of the donors RBCs and their destruction. It is the
destruction products of these RBCs which accumulate in the body of the donor and are harmful
(even fatal).
The antibodies of the donor do not cause agglutination of the recipients’ RBCs (e.g. in case of a donor with blood group O and a recipient with blood group A or B or AB, because the donor’s antibodies get diluted by the recipient’s blood.
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Theoretically, a person with blood group AB can receive blood from any donor (any blood
group) as there are no circulating antibodies in the recipient’s body to attack the donor RBCs.
Thus a person with AB blood group is known as a universal recipient.
Also a person with blood group O can give blood to any person (with any blood group) as there
are no antigens present on the surface of the RBCs that can be attacked by the antibodies of the
recipient. Thus, a person with blood group O is called a universal donor.
In practice, however, this is more complicated because in addition to the A and B antigens,
many other antigens are present on the surface of RBCs that may cause agglutination. Thus it is
essential that a sample of blood from the donor be tested by mixing with a sample of blood
from the recipient to see if there is any agglutination of the RBCs. This is known as cross-
matching.
Rh Factor
Another antigen important for blood grouping is the Rh factor (so named because it was first
discovered in the Rhesus monkey). This factor is coded by three genes C, D and E and a person
having any one of these alleles in its dominant form will have this factor. Such a person is said
to have a Rh positive (Rh+ve) blood group and if all these alleles are in their recessive form
this factor is absent and the blood group is said to be Rh negative (Rh-ve). The Rh type of
blood grouping when combined with the A, B, O type of grouping the blood groups are
designated as A+ve, B+ve or A–ve and B–ve, etc.
Antibodies against the Rh antigen are not circulating in the plasma but are synthesized only
after exposure to the antigen.
External links
Blood groups types and transfusions
<http://nobelprize.org/educational_games/medicine/landsteiner/readmore.html>
Blood typing game
<http://nobelprize.org/educational_games/medicine/landsteiner/index.html>
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Haemolytic Disease of the Newborn or Erythroblastosis foetalis
This is a disease caused by the presence of an Rh+ve foetus in the uterus of an Rh-ve mother (where the gene for Rh factor comes from an Rh+ve father). When the mother’s body is exposed to the Rh antigen (especially during the birth of the first child) the mother’s body starts producing antibodies against the Rh antigen. Though the first child is not affected, if the second child is also Rh+ve then the already formed antibodies cross the placenta to attack the RBCs of the fetus causing hemolysis. Also, because of destruction of a large number of RBCs the fetal system responds by producing large number of RBCs at a fast pace so much so that instead of reticulocytes, erythroblasts are released into circulation (thus erythroblastosis foetalis). Such a situation does not arise for the A,B,O type of blood groups because the antibodies for these antigens cannot cross the placenta.
Heart: Structure and function Heart is a vital organ present in the thoracic cavity resting on the diaphragm. It is protected by
the rib cage, the sternum and the vertebral column.
Fig 3: Structure of the heart
Aorta
Left coronary artery
Right coronary artery
Pulmonary trunk
Left ventricle
Right atrium
Right auricle
Left auricle
Superior vena cava
Inferior vena cava
Left pulmonary veins
Right ventricle
The human heart is made up of four chambers – two atria which receive blood from different
parts of the body and two ventricles that are responsible for pumping the blood to different
parts of the body.
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The outer surface of the heart is covered by a protective covering called the pericardium.
Pericardium consists of two components:
1. Fibrous pericardium which is a thick outermost covering that protects and anchors the heart
and prevents its overstretching. It is made up of dense connective tissue.
2. Serous pericardium consists of a double membrane covering the heart. The outer membrane
called the parietal layer is associated with the fibrous pericardium and the inner membrane
called the visceral layer is associated with the surface of the heart forming the epicardium.
The small space between these two membranes, the pericardial cavity is filled with a fluid
(pericardial fluid) secreted by the cells of the membranes. The pericardial fluid provides
lubrication to the heart when it contracts and relaxes. Fig 4: Outer surface of the heart
The heart wall is made up of three layers
1. innermost endocardium
2. middle myocardium
3. outermost epicardium
The myocardium is the thickest layer of t
The endocardium is made up of the endo
provides a smooth lining to the inner surf
the endothelium of the blood vessels asso
to the heart valves. The epicardium is the
mesothelium and connective tissue.
Pericardium
Myocardium:
he heart wall made
thelium and a layer
ace of the heart. Th
ciated with the hea
serous layer of the
Fibrous pericardium
Serous pericardium:
Endocardium parietal layerPericardial cavity
Serous pericardium: visceral layer
up of mainly cardiac mu
of connective tissue ben
e endothelium is contin
rt and it also provides a
pericardium consisting
Epicardium
scle cells.
eath it. It
uous with
covering
of
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The cardiac muscle The cardiac muscle is a specialized type of muscle designed to carry out the specific functions
of the heart. It has certain distinctive characteristics to suit these functions. Cardiac muscle
fibres (each fibre is a cell):
• are striated
• are shorter and thicker than skeletal muscle fibres
• are mostly uninucleated, at times binucleated
• are branched
• also have A and I bands and Z-discs as in a skeletal muscle fibre. [<link to skeletal muscle
in muscular system>)
• have transverse tubules that are less numerous than in skeletal muscle fibres though they
are wider. Only one t- tubule is
present at the Z-disc in a
sarcomere.
Fig 5: Cardiac muscle fibres
Intercalated disc
• have scanty sarcoplasmic
reticulum (so a small amount of
Ca2+ is stored within the muscle
cell, most of it comes from the
extra cellular fluid during
contraction)
• have adjacent muscle fibres connected to each other by transverse thickenings of the
sarcolemma called the intercalated discs that serve to convey the force of contraction from
one cell to another and also serve to keep them together.
• intercalated discs also contain desmosomes that keep the fibres together,
• have gap junctions present between the cells that serve to convey the action potential from
one cell to another without any delay so that all the muscle cells in a network contract
together (muscle fibres of atria form one network and those of the ventricles form another).
• have numerous mitochondria in the sarcoplasm that help to generate ATP for contraction
aerobically (energy is not generated in the heart muscle anaerobically)
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Gap junction
They are tunnel like openings between adjacent cells. These are known as connexions and are
made up of tubular proteins. Molecules from one cell can pass to another through these. Fig 6: Gap junction
Cell 1 Cell 2
Connexons A gap junction
Chambers of the heart
The Atria: The left and right atria are the receiving chambers of the heart and are separated
from one another by a thin interatrial septum. The right atrium receives deoxygenated blood
from the major veins of the body, the superior and inferior venae cavae and the coronary sinus
that brings blood back from the heart tissue. <See coronary circulation>.
The left atrium receives oxygenated blood from the lungs via the four pulmonary veins. The
anterior inner walls of the atria are not smooth but have muscular ridges called pectinate
muscles. The atria empty the blood they receive into the ventricles of their side. The atria are
separated from ventricles by valves (the atrioventicular (AV) valves) that open into the
ventricles and prevent back flow of blood into atria when the ventricles contract. The left
atrium is separated from the left ventricle by the bicuspid (made up of two cusps) valve or the
mitral valve and the right atrium is separated from the right ventricle by the tricuspid (made up
of three cusps) valve.
Atria have extensions called auricles (shaped like dog’s ears) that increase their capacity to
hold blood.
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The Ventricles: These are the chambers that pump blood into the body. The left and right
ventricles are separated from one another by an interventricular septum. The left ventricle
pumps oxygenated blood to the body tissues through the aortic arch and the right ventricle
pumps deoxygenated blood into the lungs through the pulmonary aorta (which then divides
into the pulmonary arteries carrying blood to each lung; these are the only arteries that carry
deoxygenated blood). The opening of these major arteries is guarded by semilunar (SL) valves,
which prevent the back flow of blood into the ventricles when the ventricles relax. (Major
veins entering the atria do not have any valves because their openings constrict when the atria
contract.)
Heart and circulation
Fig 7: Circulatory pathways of the heart
Deoxygenated
blood
Aorta
Pulmonary artery Superior vena cava
To lungs
From lungs From lungs
m
Pulmonary valve
Atrioventricular valves
Inferior vena cava
D
Rightatrium
Right ventricle
eoxygenated blood
O
Left atriu
Pulmonary veins Left ventricle
Aortic valve
Aorta
xygenated blood
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The blood takes the following route with the heart receiving deoxygenated blood from the
body and pumping it into the lungs for oxygenation (called pulmonary circulation), receiving
oxygenated blood from the lungs and pumping it into the body (called systemic circulation).
Lungs
Pulmonary veins (oxygenated blood) Left atrium Aorta Bicuspid valve Left ventricle Aortic valve
Pulmonary circulation
Route of blood in the heart
Superior and inferior venae cavae and the coronary sinus
Right atrium
Tricuspid valve
Right ventricle
Body tissue Pulmonary valve
Pulmonary arteries (deoxygenated blood)
Systemic circulation
The left ventricle is more muscular than the right ventricle as it pumps blood with a greater
force to the tissues. The walls of the ventricles are not smooth but bear ridges called the
trabeculae carneae—cone shaped modifications of these, called the papillary muscles, have
cord-like extensions, the chordae tendinae, attached to the atrioventricular valves (the tricuspid
and the bicuspid valves) which prevent the valves from being pushed back into the atria when
the ventricles contract.
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Fig 8: Inner structure of the heart
Bicuspid valve
Tricuspid valve
Chordae tendinae
Papillary muscles
Trabeculae carneae
The atria and the ventricles form separate units which are electrically insulated from one
another by the dense connective tissue forming a fibrous skeleton which also anchors the heart
valves and cardiac muscle bundles.
The conducting and non-conducting cells of the heart
All the cells of the heart do not function as contractile cells. About 1% of the cells of the heart,
during its embryonic development, differentiate into specialized cells that are responsible for
generating and conducting an action potential. These cells are the conducting system cells.
They have certain special characteristics:
• They have automaticity, i.e. they automatically generate pacemaker potentials that
gives rise to an action potential.
• They have autorhythmicity, i.e. an inherent automatic rhythm of pacemaker potential
generation.
Since the heart beat originates in the heart muscle itself, such a heart is known as a myogenic
heart.
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C
S
t
1
f
t
t
bF
A
A
t
s
t
t
t
A pacemaker potential is generated by the opening of slow Ca2+ ion channels that gradually cause a slow depolarization resulting in the generation of action potential when the threshold is reached, the same effect can be achieved by a reduction in the permeability of the membrane to K+ ions so less K+ ions can move out.
omponents of the conducting system
inuatrial node or SA node: It is a group of conducting system cells located near the entry of
he superior vena cava in the right atrium. It has an inherent rate of potential generation of 90–
00 depolarizations/min. This acts as the pacemaker of the heart because it has the highest
requency of depolarization. The atria contract in response to the action potentials generated by
he SA node. In a normal individual its rate of depolarization is under inhibitory influence of
he parasympathetic nervous system (Vagus nerve) so the heart beat is set at about 72–75
eats/min. ig 9: Components of the conducting system (diagrammatic)
SA node
Left bundle branch
Bundle of His
AV node
rrows
triove
he inte
pread
his co
he atri
he ven
Right bundle branch
Purkinje fibres
show the spreading of the action potential from the SA node.
ntricular node or the AV node: This group of conducting system cells are present in
ratrial septum. The action potential is picked up by the AV node from the SA node as it
s through the atria. At the AV node the action potential slows down because the fibres of
mponent are much smaller. This ensures a delay of 0.1 sec between the contraction of
a and the ventricles—the nodal delay—so that all the blood in the atria is emptied into
tricles before the ventricles start contracting.
22
Atrio-ventricular bundle or Bundle of His: This is located in the interventricular septum and
is the only electrical connection between the atria and ventricles. The ventricles cannot directly
pick up the action potential from the atria as the two are separated by an insulating fibrous
skeleton.
Right and left bundle branches: From the Bundle of His arise the left and right bundle
branches that carry the action potential down the interventricular septum towards the apex from
where the branches separate with the left branch moving along the left ventricle wall and the
right branch moving along the right ventricle wall.
Purkinje fibres: The left and right bundle branches give off fibres called the Purkinje fibres in
the wall of the ventricles that make contact with the non- conducting system (muscle) cells of
the ventricle. These fibres convey the action potential to the muscle cells of the ventricle
making them contract as a unit (through the gap junctions by which the muscle cells are
joined).
Each of these components have an inherent rate of depolarization with the SA node being the
fastest. So, normally, the SA node acts as the pace maker; but if the SA node stops working
other components can act as pacemakers but with a lower rate of depolarization e.g. the AV
node has a frequency of 40–50 depolarizations per minute and all the other components (the
Bundle of His, the bundle branches and the Purkinje fibres) have a frequency of 20–40
depolarizations per minute.
The non-conducting system: the cardiac muscle cells
These cells respond to an action potential (AP) by undergoing contraction. The AP in these
cells is generated by the following sequence of events resulting in contraction.
23
AP reaches the sarcolemma of a cardiac muscle fibre (from a conducting system cell)
Voltage-gated fast Na+ ion channels open (1) Na+ rushes in Fast depolarization As these Na+ ion channels start to close Slow Ca2+ ion channels open and some K+ ion channels close (2) Ca2+ ions move in and less K+ ions are allowed to go out Depolarized state is maintained for some time longer (250 msec) than in a skeletal muscle fibre (1 msec)) Membrane regains its polarized state due to closure of Ca2+ ion channels and opening of K+ ion channels (3)
Why does the cardiac muscle not show tetany? The cardiac muscle has a long refractory period (almost as long as the contraction period) so another contraction cannot be generated before the first one is over. That is why heart muscle does not show summation or tetany. This has a physiological significance that each contraction has to be followed by relaxation so that heart can receive blood. If it contracts again before it relaxes it would not be able to perform its function as a pump.
Fig 10: Action potential in relation to contraction in a non-conducting system cell
Depolarization Repolarization
(2)
(3)
Membrane potential
+ 20 mV
(1)
– 90 mV c
Refra
Co
Tim
0.3 se
ctory period
ntraction
e (seconds)
24
Fig 11: Pacemaker potential in a conducting system cell
Pacemaker potential
Action potential
Membrane potential
+ 10 mV
– 60 mV
Threshold
Time (seconds)
Cardiac cycle At an average normal heart rate of 72 beats/min, each heart beat lasts for 0.8 seconds. Each
heart beat consists of a period of contraction (systole) and a period of relaxation (diastole)
which comprises one cardiac cycle. The ventricular systole lasts for 0.3 sec. and ventricular
diastole lasts for 0.5 sec. (with the cardiac cycle lasting for a total of 0.8 sec). The atrial systole
and diastole overlap the ventricular diastole or systole, e.g. when the ventricles are in diastole,
for some part of it the atria are in systole and when the ventricles are in systole the atria are in
diastole.
The different parts of the cardiac cycle with the state of different chambers and valves are as
follows (considering the beginning of the cardiac cycle as time 0). Time 0 – 0.1 s 0.1 – 0.4 s 0.4 – 0.8 s Atria/ventricles Atrial systole
Ventricular diastole Atrial diastole Ventricular systole
Atrial diastole Ventricular systole
AV valves Open Closed Open Aortic and pulmonary valves
Closed Open Closed
Blood flow
Atria Ventricles Superior and inferior vena cavae to right atrium, pulmonary veins to left atrium, left ventricle to aortic arch, right ventricle to pulmonary arteries
Superior and inferior vena cavae to right atrium, pulmonary veins to left atrium, left atrium to left ventricle, right atrium to right ventricle
25
Phases of the cardiac cycle
Atrial systole and ventricular diastole (0–0.1 s). When the atria contract the ventricles relax so
that all the blood in the atria is pumped into the ventricles. During this time the atrioventricular
(bicuspid and tricuspid valves) remain open.
Ventricular systole and atrial diastole. As the ventricles start contracting and the atria relax,
due to the increase in pressure inside the ventricles, the atrioventricular valves close. The aortic
valves are already closed (they have not yet opened) so during this brief period in the
beginning of ventricular systole the ventricles are neither receiving blood from the atria nor are
they pumping any blood out into the major arteries. This period is called the period of
isovolumetric ventricular contraction.
As the contraction progresses further the pressure inside the ventricles increases further to push
the aortic (semilunar) valves open and blood is pumped into the major arteries. This is called
ventricular ejection.
Ventricular diastole and atrial diastole (Joint diastole). In the beginning of ventricular
diastole (when the atria are already in diastole), as the pressure in the ventricles starts to
decrease, the semilunar valves close (because the pressure in the aortic arch and pulmonary
aorta is greater than that in the ventricles). The atrioventricular valves are already closed (as
the pressure in the ventricles has not reduced so much as to cause their opening); at this stage
no blood is entering or leaving the ventricles. This is known as isovolumetric ventricular
relaxation.
As ventricles relax further and the pressure inside drops, the atrioventricular valves open and
blood starts pouring in from the atria. This is known as ventricular filling.
The atria keep receiving blood from the superior and inferior venae cavae and the pulmonary
veins. This blood keeps flowing into the relaxing ventricles. Whatever blood is left in the atria
is conveyed to the ventricles when the atria contract (atrial systole).
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External link for cardiac cycle animation: <link> http://bcs.whfreeman.com/thelifewire/content/chp49/49020.html
http://anatimation.com/cardiac-cycle/cardiac-cycle-animation-and-diagram.html
Coronary circulation The heart does not derive oxygen from the oxygenated blood present in the left ventricle but is
supplied by special blood vessels called the coronary arteries arising from the aorta.
Fig 12a: Anterior view of heart Fig 12b: Posterior view of heart
Aorta
Pulmonary trunk Right atrium
Right coronary artery
Left coronary artery Coronary
sinus
Great cardiac vein
Left ventricle
There are two major branches, the right and the left coronary artery which further divide into
smaller arteries. These arteries form capillaries in the myocardium to supply oxygen and
nutrients to the heart tissue and to collect carbon dioxide and wastes. Blood is returned to the
heart by the coronary sinus that opens into the right atrium. There are many connections
between the different branches of the coronary arteries so that if one route is blocked the heart
muscle still receives oxygen and nutrients via another.
Electrocardiogram (ECG)
It is a recording of the electrical currents generated on the surface of the body because of the
action potentials in the different regions of the heart. It is NOT a recording of the action
potential in a heart muscle cell.
27
ECG is recorded by using an instrument called the electrocardiograph. The instrument uses 12
leads (electrical wires) placed on different regions of the body: 6 on the limbs and 6 on the
chest). With the recordings it is possible to find out if
• there is any conduction system disorder Fig 13: Components of a typical normal ECG
• there is any damage in any region of
the heart
• any of the heart chambers is enlarged
A typical normal ECG has the following
components:
• P wave: This is an upward dome-
shaped deflection corresponding to
the atrial depolarization.
• QRS complex: It is a complex made
up of a downward deflection (Q wave) followed by a spike shaped upward deflection (R
wave) and again a small downward deflection (S wave). This entire complex represents the
ventricular depolarization.
Since atrial repolarization occurs at the same time when ventricles are depolarizing, atrial
repolarization is not recorded.
• T wave: This is a small dome-shaped, upward deflection representing the ventricular
repolarization.
Since an EGG is recorded on a graph paper the intervals of each wave and the intervals in
between can be calculated, on the basis of which several conclusions can be drawn, e.g.
• Enlarged P wave indicates enlarged atria (may be due to a defective atrioventricular valve).
• Enlarged Q wave indicates a myocardial infarction.
• Enlarged R wave indicates enlarged ventricles.
• Flat T wave indicates insufficient oxygen supply to the heart muscle as in a coronary artery
disease.
• Enlarged or elevated T wave indicates high levels of K+ ions in blood (hyperkalemia).
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• Elevated ST segment (above the base line) indicates an acute myocardial infarction.
• Depressed ST segment (below the baseline) indicates that the heart muscle is receiving
insufficient oxygen.
• Increased QT interval indicates damaged myocardium or myocardial ischemia (insufficient
oxygen supply) or conduction system disorders.
Heart sounds
Two prominent heart sounds can be heard through a stethoscope placed on the chest of a
person (auscultation). The first heart sound called lubb is a longer and louder sound made by
the turbulence of blood caused when the AV valves close in the beginning of ventricular
systole. The second sound dupp, is a dull, shorter sound produced by the turbulence of blood
caused by the closure of the semilunar valves at the beginning of the ventricular diastole.
Any abnormal heart sounds heard in addition to the two normal sounds are called heart
murmurs. The time of the heart murmur indicates the possible defect in the heart, e.g. a
murmur heard during systole indicates a stenotic (narrowed) semilunar valve or an insufficient
(leaky) AV valve. A murmur heard during diastole indicates an insufficient semilunar valve or
a stenotic AV valve.
29
Cardiac output. It is the volume of blood pumped by the ventricle (right or left) per minute. It is given
by: Stroke volume x heart rate = 70 ml x 75 beats/min = 5.25 L.
Stroke volume. The volume of blood pumped out at each systole by the ventricle (left or right). It is given
by: End diastolic volume – End systolic volume = 130 ml – 60 ml = 70 ml.
Cardiac reserve. The difference between the maximum cardiac output possible and the cardiac output at
rest. In a normal person during strenuous exercise the heart can pump four times the normal volume of
blood, i.e. the cardiac reserve is 400%. In trained athletes the cardiac reserve could be as high as 600%.
Frank-Starling’s Law of Heart. It states that the force of contraction of the heart is directly proportional
to the initial length of the cardiac muscle fibres. This means that, within a limit, if the cardiac muscle
fibres are stretched more during diastole (because of filling of the chambers with a larger amount of blood)
the heart will contract with a greater force during systole (to pump out this greater volume of blood). This
property of the cardiac muscle ensures that if the heart receives more blood from the body (venous return)
it pumps out a greater volume of blood.
Blood vessels: structure and functions
Blood vessels carrying blood from the heart to the body tissues are known as arteries. All the
arteries, except the pulmonary arteries, contain oxygenated blood. Large arteries form medium-
sized arteries which then branch into arterioles further branching into metarterioles that finally
form capillaries. Branches of arteries may join each other to form anastomoses that provide an
alternative route for blood flow if one branch gets blocked. Capillaries are the site of exchange
of gases, nutrients and waste material between the blood and the body tissues. Capillaries join
to form venules which in turn give rise to veins which carry blood back to the heart from the
body tissues. With the exception of pulmonary veins, which bring back oxygenated blood from
the lungs, all veins contain deoxygenated blood.
Fig 14: Comparative structure of blood vessels
Artery
Vein
Tunica interna
Lumen
Endothelium
Basement membrane
Arteries
The walls of arteries are made up of the following three layers:
1. Tunica externa consisting of elastic and collagen fibres.
Tunica externa
External elastic lamina
Tunica media Valve
Internal elastic lamina
Smooth muscle
30
2. Tunica media consisting of:
• Elastic fibres and circularly arranged smooth muscle fibres.
• External elastic lamina made up of elastic fibres that provide elasticity to the walls of
the arteries.
3. Tunica interna is the innermost layer of endothelial cells which are in contact with blood in
the lumen, and consists of
• A basement membrane
• Internal elastic lamina made up of elastic fibres
It is the smooth muscle fibres of the tunica media that contract or relax in response to various
stimuli (e.g. sympathetic stimulation causes them to contract and reduction in sympathetic
stimulation causes them to relax that results in vasoconstriction or vasodilation, respectively).
Large arteries: These are the major arteries, such as the aortic arch, the pulmonary artery, the
common carotid, which serve to carry blood to the various parts of the body. Their tunica
media have a lot of elastic fibres making these highly distensible. Due to this characteristic,
when blood is pumped from the heart
into these arteries they distend and
when the heart relaxes, their elastic tissue
causes them to return to their original
position pushing the blood forward into
the medium-sized arteries. So these
arteries are also known as elastic arteries
or conducting arteries.
Fig 15: Smooth muscle fibres in arteriole and metarteriole
Smooth muscle cell Arteriole
Metarterioles
Medium-sized arteries: These are also known as the muscular arteries because their tunica
media contains many muscle fibres and a few elastic fibres. Since they help to distribute blood
to the various body parts they are also known as the distributing arteries. An example of this
type of artery is the femoral artery in the thigh region.
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Arterioles: These are branches of the medium-sized arteries which give rise to metarterioles.
The walls of arterioles have the same structure as that of the medium-sized arteries though in
very fine arterioles there may be only an endothelial lining surrounded by some smooth muscle
fibres. Since arterioles can dilate or constrict they can regulate the flow of blood to the
capillary bed. They are also known as resistance vessels because they can alter the resistance to
blood flow.
Metarterioles: Metarterioles arise from arterioles and give rise to capillaries. Rings of smooth
muscle, called the precapillary sphincters, are present at the junction of metarterioles and
capillaries. These precapillary sphincters keep contracting and relaxing intermittently to
increase and decrease the blood flow through the capillaries. This contraction and relaxation of
the sphincters is called vasomotion. (No such sphincters are present at the other end of the
metarterioles where they join a venule).
Fig 16: Arteriole, metarteriole, veins, venules and capillary network showing direction of blood flow
Venule
Direction of blood flow
Direction of blood flow
Precapillary sphincter
Arteriole
Artery
Vein
Capillaries
Metarteriole
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Capillaries: These are the finest blood vessels that are the site for exchange of material
between the blood and body tissues, so they are also known as exchange vessels. The walls of
capillaries are made up of a layer of endothelial cells resting on a basement membrane.
Types of capillaries
There are three types of capillaries found in the body:
1. Continuous capillaries, e.g. in skeletal and smooth muscle, lungs and connective tissue. In
these the endothelial cells form a continuous sheet of cells and there are only intercellular
clefts between them.
2. Fenestrated capillaries,e.g. in kidneys, villi of small intestine, some endocrine glands.
These capillaries have fenestrations (pores) in the cell membrane of the endothelial cells.
3. Sinusoids, e.g. in liver, spleen, red bone marrow and some endocrine glands. These are
wide capillaries with an incomplete basement membrane. The endothelial cells have large
pores and large intercellular clefts.
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Fig 17: Capillary wall types
Fenestrated capillary
Continuous capillary
Sinusoid
Basement membrane
Endothelial cell
Lumen
Nucleus of endothelial cell
Intercellular cleft
Basement membrane
Endothelial cell
Nucleus of endothelial cell
Intercellular cleft (fenestration)
Lumen
Basement membrane (incomplete)
Endothelial cell
Nucleus of endothelial cell
Intercellular cleft (fenestration) Lumen
Venules: Capillaries join to form venules. Venules have a tunica interna made up of
endothelial cells and a tunica media consisting of a few smooth muscle fibres. Endothelium of
venules is very porous and allows exchange of material. White blood cells also reach a site of
infection by emigrating through venules.
Veins: Have the same three layers in their walls as the arteries, but veins have a larger lumen
compared to an artery of the same diameter. They are different from arteries in the following
features.
1. Tunica interna is thinner with very thin layers of smooth muscle and elastic fibres.
2. Tunica media is thinner. The internal and elastic laminae are absent.
3. Tunica externa forms flap-like valves in most veins to prevent the backflow of blood.
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Capillary exchange
The exchange of material between the blood in the capillaries
and the cells of the body takes place in the capillary bed by
three mechanisms.
1. Diffusion: Where the substances move from a region of
higher concentration to a region of lower concentration.
Substances such as CO2, O2, wastes, nutrients, hormones, are exchanged by this
mechanism. The degree of diffusion of material is different in different types of capillaries.
Many materials, inclduing CO2, O2, lipid soluble substance, hormones, wastes, can cross
the capillaries through the intercellular clefts or fenestrations in fenestrated capillaries but
proteins and cells cannot. In the sinusoids as in the liver cells or bone marrow, proteins
(those synthesized by the hepatocytes) and cells (found in the bone marrow) can also pass
through.
In the brain, capillaries are continuous type, and only selected molecules can pass through
the capillary walls because here the endothelial cells are joined to each other by tight
junctions to form the blood–brain barrier. This barrier is absent in certain regions of the
brain, e.g. pineal gland, pituitary gland, and the hypothalamus.
A venous sinus, e.g. the coronary sinus of the heart has a thin endothelial wall, no smooth muscle and dense connective tissue in place of tunica media and tunica externa.
2. Transcytosis: This is a mechanism for the transport of those substances across the capillary
wall which cannot diffuse through it, e.g. insulin. Here the molecule is picked up by the
endothelial cell from the blood on the luminal side by pinocytosis. This vesicle then moves
across the endothelial cell to be exocytosed on the other side (interstitial fluid) of the
endothelial cell.
35
Fig 18: Transcytosis
Pinocytotic vesicle Molecule taken in by pinocytosis
Lumen of capillary
Interstitial fluid
Molecule released into the interstitial fluid by exocytosis endothelial cell
3. Bulk flow. It is the movement of substances together in one direction, i.e. from a region of
high pressure to a region of low pressure. Fluid containing many molecules, ions etc.,
moves out of the capillaries into the interstitial fluid at the arterial end. This process is
called filtration. Most of this fluid is reabsorbed at the venular end of the capillaries
because the pressure differences here are reversed. This process is called resorption. Four
factors affecting these two processes (known as Starling’s forces) are:
i. Hydrostatic pressure in the capillaries (HPC) due to the presence of blood in the
capillaries. It causes the fluid to move out of capillaries.
ii. Osmotic pressure in the capillaries (OPC) due to ions and proteins in the blood causes
fluid to move into the capillaries.
iii. Hydrostatic pressure in the interstitial fluid (HPIF) causes the fluid to move out of the
interstitial spaces into the capillaries.
iv. Oncotic pressure in the interstitial fluid (OPIF) causes the fluid to move into the
interstitial spaces (out of capillaries).
36
Fig 19: Direction of movement of fluid due to different factors
Interstitial fluid
HPIF OPc HPc OPIF
Capillary
At the arterial end of capillaries HPC = 35 mmHg HPIF = 0 mmHg (because the fluid is in open space)
Net filtration pressure of 35 mmHg (35–0) causes the movement of fluid out of the capillaries (into the Interstitial spaces).
OPc = 28 mmHg
Net difference of 25 mmHg (28–3) causes the movement of fluid into the capillaries.
OPIF = 3 mmHg (because a very small amount of ions and proteins are present in the fluid in the interstitial spaces)
Due to a pressure difference of 35 mmHg fluid moves out of capillaries and due to a pressure
difference of 25mm Hg fluid moves into the capillaries so there is a net movement of fluid out
of the capillaries because of a pressure difference of 10 mmHg (35 mmHg – 25 mmHg). i.e.
there is a net filtration because of which the cells get oxygen and nutrients while the wastes and
CO2 are released into the interstitial fluid from the cells.
At the venular end of capillaries
Movement of fluid out of the capillaries (into the interstitial spaces) because of a pressure difference of 15 mmHg—[a]
HPC = 15 mmHg HPIF = 0 mmHg Movement of fluid into the
capillaries because of a pressure difference of 25 mmHg (28 mmHg–3 mmHg)—[b]
OPC = 28 mmHg OPIF = 3 mmHg
37
Since [b] is greater than [a] there is a net movement of fluid into the capillaries because of a
pressure difference of 10 mmHg (25 mmHg–I5 mmHg), i.e., there is a net absorption of fluid
into the capillaries at the venular end. The pressure difference causing filtration at the arterial
end is same as that causing absorption at the venular end (10 mmHg) so most, but not all, of
the fluid that filters out is reabsorbed. Whatever extra fluid is left in the interstitial spaces is
returned to the heart via the lymphatic ducts. This near equilibrium of the filtered and absorbed
fluid is known as Starling’s law of capillaries.
Blood pressure
Any fluid when enclosed in a tube exerts pressure on its walls. Similarly, blood exerts pressure
on the walls of blood vessels. Clinically, blood pressure is the pressure exerted by the blood on
walls of the arteries. As the blood keeps flowing from the major arteries to the capillary bed
the blood pressure keeps decreasing because of the resistance offered to blood flow. The
pressure in an artery during a cardiac cycle can be shown as:
Fig 20: Pressure in an artery during a cardiac cycle
Systolic pressure
Diastolic pressure
Pressure increase caused by aortic valve closure
120
Pressure (mm Hg)
80
Time
As the ventricles start contracting more blood is added to the arteries (which are never empty).
This causes a rise in the blood pressure till the end of systole to a value of 120 mmHg. When
the ventricles start relaxing the pressure starts reducing as the pumping force of the heart is
withdrawn and the blood flows ahead. A slight increase in pressure (the hump in the curve) is
seen due to the closure of the aortic valves after which the pressure steadily drops to the
diastolic value of 80 mmHg. The difference between the systolic (120 mmHg) and diastolic
38
pressure (80 mmHg) is known as the pulse pressure as it is this difference that causes the pulse
to be felt (in the superficial arteries). The mean arterial pressure is not an average of the
systolic and diastolic pressure values because the heart remains in diastole for a longer time
(0.5 s in a cardiac cycle) than it remains in systole (0.3 s in a cardiac cycle).
The mean arterial pressure can be calculated by the following formula:
Mean arterial pressure = diastolic pressure + 1/3 (systolic pressure – diastolic pressure) = 80 + 1/3 (120 – 80)
= 93.33 mmHg Measurement of blood pressure
Blood pressure can be measured using an instrument known as the sphygmomanometer
(sphygmo = pulse, manometer = pressure measuring
instrument). It consists of a cuff made of cloth that is
wrapped around the upper arm to measure the blood
pressure in the brachial artery. The cuff is attached to a
rubber bulb through a tubing which is used for inflating the
cuff. It is also attached to a mercury column, which is used
for reading the pressure in the cuff. A screw attached to the
rubber bulb is used for releasing the air from the cuff to
reduce the pressure. A stethoscope is used for hearing
sounds in the brachial artery.
Stethoscope
Fig 21: Sphygmomanometer
Principle of working of the sphygmomanometer
When the cuff is wrapped around the arm and inflated, it compresses the brachial artery to stop
the flow of blood through it. When the pressure in the cuff is above the systolic pressure, blood
does not flow at all through the compressed artery— Curve A.
When the pressure in the cuff is reduced slightly below the systolic pressure the artery opens
slightly and blood flows through this narrow opening intermittently (only for that period in the
39
cardiac cycle when the systolic pressure is higher than the cuff pressure). A soft intermittent
sound is heard at this cuff pressure. This pressure is an indication of the systolic pressure,
though it is slightly lower than the actual systolic pressure — Curve B.
On further reducing the cuff pressure, as the artery opens up further, blood flows through it
with a greater turbulence so the sounds are louder and intermittent— Curve C.
On further reduction in the cuff pressure when the diameter of the artery is near normal and the
turbulence is minimum, the sounds become very dull— Curve D.
Fig 22:
Curve A Curve B Curve C Curve D Curve E
Dotted line shows cuff pressure
When the pressure is reduced below the diastolic pressure no sound is heard as the artery is
completely open. When no sound is heard the reading in the mercury column corresponds to
the diastolic pressure (though it is slightly lower than the actual diastolic pressure) — Curve E.
All sounds heard during measurement of blood pressure are called Korotkoff sounds.
40
Factors affecting blood pressure Cardiac output
An increased cardiac output increases blood pressure and vice versa. Cardiac output is
determined by the stroke volume and heart rate. Any factor causing a change in the stroke
volume or heart rate would affect the blood pressure, e.g. during exercise the heart rate and
stroke volume both increase resulting in increased blood pressure.
Blood volume
A normal person has about 5 litres of blood in the body. An increase in the volume of blood
causes an increase in blood pressure and vice versa. Blood volume may increase under certain
circumstances such as increased Na+ and water retention due to increased Na+ intake. Blood
volume may decrease under certain other conditions, e.g. dehydration or loss of blood due to
haemorrhage.
Elasticity of arterial walls
When blood is pumped into the already filled arteries, during ventricular systole the arteries
distend due to the elasticity of their walls. When the ventricles relax this extra pressure from
the ventricles is removed and the arteries return to their original position due to elastic recoil.
This serves to push the blood ahead. If this elasticity decreases, the arterial walls do not distend
adequately and blood pressure increases. The elasticity of arterial walls reduces with age.
Viscosity of blood
Blood pressure increases with increase in blood viscosity (as during dehydration) because
resistance to blood flow increases. A reduced blood viscosity as in anaemia or reduced plasma
protein concentration reduces blood pressure.
Peripheral resistance or systemic vascular resistance
It is the resistance offered by all blood vessels to blood flow. Since the major arteries and all
veins have a large lumen they do not offer much resistance to blood flow but considerable
resistance is offered by narrower blood vessels like the arterioles, metarterioles, capillaries and
41
venules. Greater the resistance, greater the blood pressure. Peripheral resistance itself varies
with:
1. Size of the lumen of the vessel. If the vessel is narrower resistance is more.
R α 1/r4, where R is resistance to blood flow and r is the radius of the blood vessel.
2. Length of blood vessel. Longer the blood vessel greater the resistance offered. (Obese
people have a higher blood pressure because they have an increased blood vessel length
due to the extra blood vessels in the adipose tissue, in addition to other factors).
Control of blood pressure Blood pressure is regulated both by the nervous system and the endocrine system. Neural regulation
There is a specialized group of neurons in the medulla forming the cardiovascular (CV) centre.
It has three types of neurons: 1. Neurons that stimulate the heart (cardiostimulatory neurons).
2. Neurons that inhibit the heart (cardioinhibitory neurons).
3. Neurons that control the blood vessel diameter (vasomotor centre). These can cause
vasodilation or vasoconstriction by decreasing or increasing the sympathetic impulses.
The cardiovascular centre receives inputs from:
1. Upper brain regions, such as the cerebral cortex, the limbic system and the hypothalamus.
2. Baroreceptors, which perceive blood pressure in the blood vessels and atria.
3. Chemoreceptors, which perceive the levels of H+ ions, CO2, and O2 in the blood.
The cardiovascular centre sends outputs to the heart through the
• Parasympathetic fibres to the heart (Vagus nerve; cardioinhibitory nerve) which results in
an inhibition of heart (reduced heart rate and contractility).
• Sympathetic fibres to the heart (cardioaccelerator nerves) which stimulate the heart
(increase the heart rate and contractility).
• Sympathetic fibres to blood vessels. When impulses in these fibres increase
vasoconstriction occurs in most blood vessels, in the blood vessels of the heart and skeletal
42
muscle sympathetic stimulation causes vasodilation. Reduced impulses in the sympathetic
fibres cause vasodilation, in most blood vessels.
Under normal resting conditions the sympathetic fibres sending signals to the smooth muscle
fibres of the blood vessels are under some degree of stimulation so the blood vessels are
always slightly constricted (and not totally dilated to their normal diameters). This state of
tonic constriction is known as the vasomotor tone.
Under conditions of strenuous exercise, sympathetic stimulation of blood vessels increases to
cause vasoconstriction in areas such as abdominal viscera, and vasodilation in skeletal muscle
and heart (so that more blood is made available to these organs).
Inputs to the CV centre from higher brain regions (link to earlier heading)
• Inputs from the limbic system cause the stimulation of heart (increased heart rate and
contractility) e.g., when one is preparing for a race.
• During exercise, when the body temperature rises, inputs from the hypothalamus
(thermoregulatory centre) cause the CV centre to facilitate vasodilation in the capillaries of
the skin to lose heat.
Inputs to the CV centre from baroreceptors
Baroreceptors or pressoreceptors are present in the walls of the carotid sinus and the aortic arch
(See diagram of chemoreceptors in chapter on respiration <link>).
Those in the carotid sinus are supplied by the sensory fibres of the Glossopharyngeal (IX)
nerve. These monitor the pressure of blood going into the brain region. Baroreceptors in the
aortic arch are supplied by the sensory fibres of the Vagus (X) nerve and are concerned with
monitoring the pressure of blood going to the body tissues. These baroreceptors perceive
changes in blood pressure and send signals to the CV centre to regulate blood pressure.
43
Increase in blood pressure Perceived by the baroreceptors Signals sent to the CV centre in the medulla Increased parasympathetic impulses from the cardioinhibitory neurons Reduction in sympathetic impulses from vasomotor neurons Reduced heart rate and contractility Vasodilation Reduced (restored to normal) blood pressure Decreased blood pressure Perceived by baroreceptors Impulses sent to the CV centre Increased sympathetic impulses Increased sympathetic impulses From the cardioaccelerator neurons from the vasomotor neurons Increased heart rate and contractility Vasoconstriction Increased (resorted to normal) blood pressure This relationship between blood pressure and heart rate is known as Marey's Law of Heart. Baroreceptors are also present in the right atrium and
the venae cavae. They are also innervated by the
sensory fibres of the Vagus (X) nerve.
Sympathetic stimulation of
veins causes vasoconstriction
(as in the arteries) so that
venous return increases and
heart rate and contractility
increase (Starling’s Law of
Heart) to restore (increase) the
blood pressure.
When pressure in the right atrium or venae cavae increases (due to increased venous return) Perceived by baroreceptors in the right atrium and the venae cavae Signals sent to the CV centre Increased sympathetic impulses from the cardioaccelerator neurons
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Increased heart rate and contractility which shows that greater volume of blood is pumped out
when the venous return is more. This is known as Bainbridge reflex (related to Starling’s Law
of Heart).
Inputs to the CV centre from chemoreceptors
Close to the baroreceptors in the carotid sinus and the aortic arch are present chemoreceptors
that are sensitive to the levels of H+ ions, CO2 and O2 in the blood. They perceive these
changes and send impulses to the CV centre to adjust the heart rate and contractility and the
vasomotor tone to meet the demands of the body tissue.
Increase in levels of H+ ions or CO2 Perceived by chemoreceptors Signals sent to the CV centre Increased sympathetic signals to the heart and blood vessels Increased heart rate and contractility Vasoconstriction Increased blood pressure Increased delivery of blood to tissues Increased delivery of O2 to tissues Reduced (restored to normal) levels of H+ ions and CO2
These chemoreceptors also send signals to the respiratory centre (link to respiration chapter:
control of respiration) to adjust the rate of breathing according to the heart rate.
Hormonal regulation
Many hormones regulate the blood pressure by changing the heart rate or blood vessel
diameter or by changing the factors that affect blood pressure.
Epinephrine and nor epinephrine. These hormones are produced from the adrenal medulla
and axon terminals of sympathetic nerve fibres. They increase the heart rate and contractility
and cause vasoconstriction in the blood vessels of abdominal viscera and skin and vasodilation
of cardiac and skeletal muscle blood vessels.
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Antidiuretic hormone (ADH) or vasopressin. This hormone is produced by the
hypothalamus and stored and released by the posterior lobe of pituitary. It causes increased
water reabsorption in kidney tubules and vasoconstriction resulting in increased blood
pressure. (Alcohol intake causes reduced secretion of ADH resulting in vasodilation and
reduced blood pressure.)
Renin-angiotensin- aldosterone system. A reduced blood volume (and reduced blood
pressure) reduces the blood flow to kidneys which stimulates the cells of the juxtaglomerular
apparatus to secrete an enzyme renin which acts in the following manner.
Reduced blood supply to kidney tubule
Stimulation of Angiotensinogen in
juxtaglomerular cells blood (from liver)
Secertion of renin
Angiotensin I
Angiotensin converting enzyme in lungs
Angiotensin II
Stimulation of adrenal cortex Vasoconstriction Secretion of aldosterone Increased Na+ reabsorption in kidney tubules Increased water retention
Increased blood volume
Increased/restored blood flow
Increased blood pressure
to kidney tubules
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Atrial natiuretic peptide or factor (ANP or ANF). This is a hormone secreted by the right
atrial cells in response to an increased blood volume in the right atrium.
Increased blood volume (or venous return)
Stimulation of cells in the right atrium
Secretion of ANP or ANF
Increased Na+ loss from kidney tubules Vasodilation
Reduced blood volume Reduced venous return Histamines and kinins. Histamine is produced by mast cells and kinins are present in plasma.
Both cause vasodilation (reduced blood pressure) and play an important role in inflammatory
responses.
Parathyroid hormone. This is secreted by the parathyroid gland and causes vasodilation
(reduces blood pressure).
Calcitriol. This is the active form of vitamin D. It causes vasoconstriction (increased blood
pressure). Autoregulation
Some substances produced by the blood vessel walls and blood cells regulate blood pressure by
regulating the diameter of the blood vessels. These substances are called vasoactive
substances. Such changes are especially important in different regions of the brain where blood
supply is increased to a particular area which is active during a particular activity, e.g. blood
supply to the speech area increases while talking. Vasoactive substances can be
vasoconstrictors or vasodilators:
Vasodilators
• K+ ions, H+ ions, lactic acid,
adenosine(All these are produced when
O2 levels are low so vasodilation should
occur locally to supply more blood and
oxygen)
• Nitric oxide (endothelium derived
relaxation Factor: EDRF)
Vasoconstrictors
• Eicosanoids (Thromboxane A2, PGF2α )
• Angiotensins
• Endothelins
• Serotonin from platelets
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Hemostasis
It is the prevention of blood loss from the body in case of any injury and is achieved by three
mechanisms:
1. Vascular constriction. This is an immediate response following injury to or rupturing of a
blood vessel. It reduces the flow of blood from the ruptured vessel. It is caused by:
• Nervous reflexes initiated by pain or other impulses originating from the traumatized
blood vessel or tissues.
• Myogenic (originating in the smooth muscle layer of the blood vessel) contraction of
blood vessel caused by direct damage to the blood vessel wall, especially in larger
blood vessels.
• In small blood vessels vasoconstriction is brought about by Thromboxane A2, a
vasoconstrictor produced by platelets.
This local vascular spasm reduces the loss of blood in the beginning following which
platelet plug formation and blood clotting prevent further loss of blood.
2. Platelet plug formation. Whenever there is a small hole in a blood vessel it is sealed by a
platelet plug formed by aggregation of
platelets at the site of damage. The following
steps are involved in platelet plug formation:
T
• Platelets contact and stick to the damaged
blood vessel’s exposed collagen fibres
beneath the endothelium. This is known
as platelet adhesion. A protein produced
by the endothelial cells and platelets
called the von Willebrand Factor (VWF)
is necessary for the adhesion of platelets
at the site of injury.
• As a result of adhesion the platelets
become activated and their characteristics
Fig 23: Platelet plug formation
hromboxane A2
ADP
Platelet aggregation
Platelet release reaction
Platelet adhesion
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change and they become irregular by developing projections which help the platelets to
contact each other. Then they begin to release the contents of their granules. This is
known as platelet release reaction.
• The released ADP and Thomboxane A2 activates the neighbouring platelets also, which
then becomes sticky and adhere to already activated platelets. This is known as platelet
aggregation which results in a platelet plug formation. This platelet plug is reinforced
by fibrin threads when a clot is formed.
3. Blood clotting. Whenever there is an injury to a vessel or tissue the blood forms a clot
consisting of threads of fibrin that entrap the cells of blood. The final part of the process
of formation of these fibrin threads is given below:
Prothrombin Thrombin
Prothrombinase or Prothrombin activator
Certain substances in the blood, called clotting factors, are res
clot. The factors involved in the process of blood clotting are
the blood. They are synthesized in the liver. They are number
XIII (except number VI which has not been assigned). Clotting factors Factor Name I Fibrinogen II Prothrombin III Tissue factor or thromboplastin IV Calcium V Proaccelerin (Labile factor) VII Proconvertin (Stable factor) VIII Antihemophilic factor A, Antihemophilic globulin IX Antihemophilic factor B, Plasma thromboplastin comp
X Stuart-Prower factor XI Plasma thromboplastin antecedent, Anti-hemophilic f
XII Hageman factor, Glass factor XIII Fibrin stabilizing factor, Laki-Lorand factor HMW-Kininogen
High molecular weight kininogen
Kallikrein
Fibrinogen Fibrin (clot)
ponsible for the formation of a
present in their inactive form in
ed in Roman numerals from I to
onent, Christmas factor
actor C
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One factor gets activated under certain conditions and it activates another factor, which in turn
activates another one, forming a cascade. There are two pathways by which fibrin threads (a
clot) are formed — intrinsic and extrinsic — but the final part of the process (formation of
fibrin from prothrombin) is common to both. The intrinsic pathway is so named because all the
factors necessary for the formation of a clot are present in blood (intrinsic to it). In the extrinsic
pathway, one factor, the tissue thromboplastin or tissue factor is derived from injured tissue
and is extrinsic to blood. These two pathways can occur independently or together to form a
clot.
The formation of prothrombinase or prothrombin activator occurs by the combination of
activated factor X (X a) and factor V in the presence of Ca2+ ions.
Intrinsic pathway XII XII a
Thrombin
PF =
HMW-Kininogen, Kallikrein
XI XI a
IX IX a
Exposed collagen in a damaged blood vessel (or any such electronegatively charged surface e.g., glass)
VIII VIII a X X a, V
Ca2+, PFThrombin
V a Prothrombin Thrombin platelet factor
Fibrinogen Fibrin
Loose clot
Ca2+, PF
XIII a XIII
PF, Ca2+
Stabilized clot
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Extrinsic pathway Damaged tissue Tissue thromboplastin or tissue factor (Factor III) VII VII a
Blood plasma devoid of clotting factors is known as serum
IX IX a VIII VIII a X X a, V
Thrombin
PF, Ca2+ V a
Prothrombin Thrombin Fibrinogen Fibrin XIII
PF, Ca2+
XIII a
Loose clot
Positive feedback effects of thrombin
PF = platelet factor
Stabilized ClotExternal link <For details on coagulation factors visit :
http://en.wikipedia.org/wiki/Coagulation#Coagulation_factors>
The cascade of blood clotting is further
stimulated by thrombin by a positive feedback
where once thrombin is formed in small amounts
it causes its own formation by:
• activating factor V to V a, which
enhances the formation of
prothrombinase (initially inactive factor
V combines with X a to form prothrombinase).
Role of vitamin K in clotting Vitamin K is needed for the synthesis of prothrombin and factors VII, IX and X in the liver. Liver itself helps in the absorption of this vitamin which is lipid soluble and requires bile for its absorption. Through this vitamin can also be synthesized by bacteria in the large intestine.
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• activating factor XI and VIII (in the beginning inactive factor VIII catalyses the
activation of factor X to X a in the presence of factor IX a).
• activating platelets which then stimulate blood clotting by releasing the platelet factor.
Once formed the clot retracts because of the contraction of platelets. On retraction, some serum
oozes out and the broken ends of the blood vessel are brought together to reduce further loss of
blood. Then the blood vessel can be repaired by formation of new fibroblasts and endothelial
cells.
After the vessel is repaired the clot is dissolved. Dissolution of clot is known as fibrinolysis. It
is brought about by an enzyme called plasmin (fibrinolysin) which is formed from its inactive
precursor plasminogen. This activation is catalyzed by thrombin and a tissue plasminogen
activator.
Why blood does not clot in uninjured vessels
There are three mechanisms that prevent
clotting in an uninjured vessel:
1. Plasma protein tissue factor pathway
inhibitor secreted by the endothelial cell binds to the tissue factor and VII a complex, so
that they cannot activate factor X (that is why only a small amount of thrombin is formed
by extrinsic pathway if it operates alone).
Platelet aggregation in uninjured areas of blood vessels is prevented by the presence of prostacyclin, another eicosanoid.
2. Thrombin binds to an endothelial cell receptor called thrombomodulin.
Bound thrombin binds to another plasma protein, Protein C
Protein C is activated
Activated Protein C in combination with another plasma protein, inactivates factor VIII
a and factor V a and inactivates the inhibitor of tissue plasminogen activator, increasing
the formation of plasmin (so that if a small amount of fibrin is formed it is broken down
by plasmin).
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3. An anticoagulant antithrombin II or III combines with another anticoagulant produced by
endothelial cells, and heparin to inactivate various clotting factors.
Lymph
Lymph is a clear pale yellow fluid formed from the interstitial fluid. It flows in lymphatic
vessels where it finds its way through the lymphatic capillaries. They act as one-way carriers
for lymph because lymph can enter these capillaries from the interstitial fluid but cannot leave
the capillaries to return into the interstitial spaces. These lymphatic capillaries are also made up
of endothelial cells which overlap one another and have intercellular spaces. These spaces open
up when the pressure of fluid in the interstitial spaces is more than in the capillaries. When
there is more fluid in these capillaries, the intercellular spaces close so that no more fluid can
enter or leave the capillaries. The endothelial cells are anchored to the surrounding tissues by
anchoring filaments.
Fig 24: Lymph draining into lymphatic capillary from interstitial fluid
Intercellular space opening into lymphatic capillary
Lymphatic capillary
Anchoring filament
Tissue cells
Interstitial fluid
Endothelial cells in the lymph capillary
Lymph entering lymph capillary
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These capillaries form larger lymphatic ducts to eventually return the lymph to the blood.
Lymph takes the following route:
Lymph capillaries Lymphatic vessels Lymph nodes Lymphatic trunks Lymphatic ducts Join the blood vessels (at the junction of the internal jugular and subclavian vein) Lymphatic vessels also contain valves (as in the veins) to prevent backflow.
Functions of lymph
• Returns the fluid to blood
• Carries lost proteins (those that manage to escape the capillaries) and large particulate
matter away from the tissue spaces which cannot be removed by absorption into the blood
capillaries.
• Carries products of digestion especially fats in lacteals of the small intestine.
• Pathogens such as bacteria are removed by the lymph from tissue and when lymphatics
enter the lymph nodes these bacteria are destroyed.
Disorders of the cardiovascular system Anemia
It is a condition of reduced haemoglobin content either because of a reduction in the number of
RBCs or reduced content of haemoglobin per RBC. Different factors cause different types of
anemia.
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• Iron deficiency anemia: It is caused by insufficient intake or absorption or excessive loss of
iron. Women are more prone to this type of anemia because of loss of blood during
menstruation and increased demands of iron during pregnancy.
• Pernicious anemia: This is caused by insufficient intake or absorption of folic acid
(Vitamin B12) which is necessary for RBC production. Absorption of folic acid is affected
if the gastric glands do not produce enough intrinsic factor.
• Haemorrhagic anemia: This is caused by excessive loss of blood.
• Aplastic anemia: This occurs when the bone marrow fails to produce red blood cells due to
certain toxins, gamma irradiation or drugs.
• Thalassemia: It is a genetic disorder where the RBCs are fragile or the haemoglobin
synthesis is not adequate affecting the oxygen carrying capacity. The RBCs are microcytic
and hypochromic.
• Hemolytic anemia: In this condition the RBCs are fragile and undergo hemolysis with their
breakdown products accumulating in the body adversely affecting the kidneys. This is
caused by parasites or toxins or due to some genetic defect.
• Haemophilia: It is a disorder where the blood does not clot easily. It is a genetic disorder
where the clotting factors are not produced in adequate amounts. Haemophilia A or the
classic haemophilia is caused by the absence of clotting factor VIII; haemophilia B is
caused by the absence of clotting factor IX; and haemophilia C is caused by the absence of
clotting factor XI. Haemophilia A and B primarily occur in males because they are sex-
linked recessive disorders.
• Sickle-cell anemia: This is a genetic disorder where there is a defective gene for
haemoglobin synthesis. Instead of the normal haemoglobin, Hb-S is synthesized which
forms crystals when it gives up oxygen to the tissues causing the RBCs to become sickle-
shaped. These RBCs are then destroyed. This gene is found in populations inhabiting those
regions of the world where malaria is prevalent because the sickle-shaped RBCs are
resistant to malarial parasite. A person with one sickle cell gene and one normal gene (a
carrier) is more resistant to malaria.
Leukemia
It is a malignant disease where WBCs are produced in uncontrolled numbers.
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Polycythemia
It is an abnormal increase in the number of RBCs. It may be caused by hypoxia as at high
altitudes or unchecked production of RBCs (a type of tumour).
Leucocytopenia
It is a reduction in the number of WBCs caused by damage to the bone marrow by irradiation
or certain drugs.
Myocardial ischemia
It is the weakening (not death) of cardiac cells due to insufficient oxygen supply caused by a
blocked coronary artery.
Myocardial infarction or heart attack
It is the death of heart tissue because of lack of oxygen caused by blockade in the coronary
artery. The infarcted tissue becomes non contractile and may interfere with the conduction of
the impulse. The extent of damage and the consequences depend upon the location and size of
the infarcted area.
Arteriosclerosis
It is a group of disorders where there is a thickening of the arterial wall and loss of elasticity.
One of such disorders is atherosclerosis where there is a formation of an atherosclerotic
plaque. Its formation is initiated by factors such as high levels of low-density lipoproteins,
cytomegalovirus, prolonged high blood pressure, diabetes mellitus and cigarette smoke. It
starts with an injured endothelium where there is an aggregation of platelets and phagocytes. In
the inner layer of the arterial wall cholesterol and triglycerides get deposited. Macrophages
also get collected here. Smooth muscle cells, collagen fibres etc. start proliferating abnormally.
The plaque thus formed narrows the lumen of the artery obstructing blood flow. It also
provides a rough surface for the platelets to aggregate and stimulate blood clotting
(thrombosis). A thrombus thus formed may move away from its formation site (such a
thrombus is called an embolus) and may obstruct small blood vessels, which could be fatal.
Angina pectoris
It is the chest pain associated with tightness caused by ischemia of heart muscle. Common
cause is constriction of coronary arteries due to stress or due to strenuous exercise particularly
after a heavy meal when the blood flow is diverted towards the digestive tract.
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Coronary artery disease (CAD)
It is a disorder that affects the coronary artery due to atherosclerosis which results in a reduced
blood flow to the myocardium. Many risk factors make a person prone to CAD. These include
genetic factors, smoking, obesity, diabetes mellitus, high cholesterol levels and a sedentary
lifestyle.
Arrhythmias
It is a disorder of the conduction system of the heart where the heart may beat too slowly
(bradycardia), too fast (tachycardia) or irregularly. Arrhythmias may be caused by substances
that stimulate the heart (e.g. caffeine, alcohol, cocaine) or due to a congenital defect.
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