Physiological Mechanisms
Circulation
By
Dr Smita Bhatia
BP-5, II floor, Shalimar Bagh (West)
Delhi 110088 Contact: 27483738
Email: [email protected]
Circulation
Learning objectives Blood
Functions of blood Constituents of blood Blood groups
Heart: Structure and function The cardiac muscle Chambers of the heart Heart and circulation Cardiac cycle
Coronary circulation Electrocardiogram (ECG) Heart sounds
Blood vessels: structure and functions Capillary exchange
Blood pressure
Measurement of blood pressure Factors affecting blood pressure Control of blood pressure
Neural regulation Hormonal regulation Autoregulation Hemostasis
Lymph
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).
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
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-, SO42.
• 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 Basophil Neutrophil
Lymphocyte Monocyte
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.
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)
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.
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.
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.
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.
• 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.
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.
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>
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.
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
Pericardium Myocardium
Fibrous pericardium
Endocardium Serous pericardium:
parietal layer Pericardial cavity Serous pericardium:
visceral layer Epicardium
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 the heart wall made up of mainly cardiac muscle cells.
The endocardium is made up of the endothelium and a layer of connective tissue beneath it. It provides a smooth lining to the inner surface of the heart. The endothelium is continuous with the endothelium of the blood vessels associated with the heart and it also provides a covering to the heart valves. The epicardium is the serous layer of the pericardium consisting of mesothelium and connective tissue.
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)
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.
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
Left atrium Right
atrium
Pulmonary valve
Pulmonary veins Left
ventricle Right
ventricle Atrioventricular valves
Aortic valve Inferior vena cava
Aorta Deoxygenated
blood
Oxygenated blood
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.
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.
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.
Components of the conducting system
Sinuatrial node or SA node: It is a group of conducting system cells located near the entry of the superior vena cava in the right atrium. It has an inherent rate of potential generation of 90–
100 depolarizations/min. This acts as the pacemaker of the heart because it has the highest frequency of depolarization. The atria contract in response to the action potentials generated by the SA node. In a normal individual its rate of depolarization is under inhibitory influence of the parasympathetic nervous system (Vagus nerve) so the heart beat is set at about 72–75 beats/min.
Fig 9: Components of the conducting system (diagrammatic)
SA node
Left bundle branch
Bundle of His Right bundle branch
AV node
Purkinje fibres
Arrows show the spreading of the action potential from the SA node.
Atrioventricular node or the AV node: This group of conducting system cells are present in the interatrial septum. The action potential is picked up by the AV node from the SA node as it spreads through the atria. At the AV node the action potential slows down because the fibres of this component are much smaller. This ensures a delay of 0.1 sec between the contraction of the atria and the ventricles—the nodal delay—so that all the blood in the atria is emptied into the ventricles before the ventricles start contracting.
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.
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 0.3 sec
Refractory period Contraction Time (seconds)
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
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).
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.
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).
• 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.
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
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.
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
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.
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.
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.
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).
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
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
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
