Blood Physiology 2023 PDF

Blood Physiology Lecturer: Abdullah Hassan  Blood and Immunity Syllabus 1.Composition and function of blood. 2.Red blood cells: Production of RBC – Types and formation of hemoglobin – Iron metabolism – Destruction of RBC – Anemia and Jaundice – Polycythemia. 3.White blood cells : Gene...

Blood Physiology Lecturer: Abdullah Hassan  Blood and Immunity Syllabus 1.Composition and function of blood. 2.Red blood cells: Production of RBC – Types and formation of hemoglobin – Iron metabolism – Destruction of RBC – Anemia and Jaundice – Polycythemia. 3.White blood cells : Genesis and properties different types and their functions – reticule-endothelial system – Leukocytosis – Leukopenia – Leukemia. 4.Plasma Proteins : Types – Origin and Functions. 5.Blood groups – Rh immune response – Erythroblastosis foetalis. 6.Hemostasis and blood coagulation: Events of hemostasis and mechanism of blood coagulation – Coagulation Test –Hemophilia. 7.Immunity and allergy: Types of Acquired Immunity – Role of Lymphoid tissues – Vaccination – Passive Immunity – Allergy.  Blood Definition Blood is an extracellular matrix tissue in which various blood cells are suspended in the plasma matrix. Blood is a specialized bodily red fluid that circulates in the arteries and veins of humans and other vertebrate animals. Blood is fluid connective tissue that circulates throughout the body. It is composed of living cells suspended in plasma, the liquid that makes up around 55% of the blood. Plasma transports blood cells, proteins, electrolytes, hormones, and nutrients throughout the body. It also brings waste products from the body tissues to the urinary system, where the kidneys filter them out of the blood. Blood is considered as a connective tissue, because: (1) Embryological, it has the same origin (mesoderm) as do the other connective tissue types. (2) Blood connects the body systems together. There are three broad categories of blood cells that have important functions. Red blood cells, or erythrocytes, carry oxygen from the lungs out to the rest of the body. White blood cells, or leukocytes, help protect the body from pathogens. There are five different types of leukocytes that combat infection in different ways. Platelets, or thrombocytes, clump together and form clots to repair torn blood vessels.  What are the functions of the Blood Blood has three main functions: transportation, regulation and protection. It supplies oxygen to cells and tissues. It supplies essential nutrients to cells, such as amino acids, fatty acids, and glucose. It removes carbon dioxide, urea and lactic acid (waste products) Its white blood cells have antibodies which defend us from infection and foreign bodies. It has specialized cells, such as platelets, which help the blood to clot (coagulate) when we are bleeding. It transports hormones - chemicals released by a cell in one part of the body that sends out messages that affect cells elsewhere in the body. It regulates our acidity (pH) levels. It regulates our body temperature. When the weather is very warm or during strenuous exercise there will be increased blood flow to the surface, resulting in warmer skin and faster heat loss. When environmental temperatures drop, blood flow focuses more on the important organs deep inside the body.  Physical Properties of Plasma The Average adult has a blood volume of Plasma contains 50-70 mg of protein per ml. approximately 5 litres, which composes Approx. 70% Albumin (35-50 mg/ml). about 8% of the body's weight. Approx. 10% Immunoglobulin G antibody Blood constitution: (IgG) (5-7 mg/ml). 1.Red blood cells about 45% of whole. Plasma Composition: 2.Plasma about 54.3%. 90% Water 3.White cells about 0.7%. 8% Protein 4.Platelets make up less than 1%. 0.9% Inorganic Salts Haemoglobin is the principal determinant Sodium 135-146 mM of the colour of blood. Potassium 3.5-5.2 mM It is estimated that plasma may contain Calcium 2.1-2.7 mM as many as 40,000 different proteins from Carbonate 23-31 mM about 500 gene products. Approximately Phosphate 0.7-1.4 mM 1,000 proteins have been detected. 1.1% organic substances  Where are blood cells produced? Blood cells are produced in the bone marrow What is bone marrow? White cells, red cells and platelets are made in the bone marrow Bone marrow is a jellylike substance that fills the cavities of bones. Bone marrow consists of fat, blood, and special cells (stem cells) that turn into the various kinds of blood cells. The main areas of bone marrow in the body involved in the formation of blood cells are in the vertebrae, ribs, sternum, skull and hips. There are two types of marrow, red marrow and yellow marrow. Most of our red and white blood cells, as well as platelets are made in the red marrow. Haematopoiesis or haemopoiesis is the formation of blood cellular components. All cellular blood components are derived from haematopoietic stem cells. Haematopoiesis  Red Blood Cell (RBC) Erythrocytes, or red blood cells, are anucleated, which means they don't have a nucleus. This extra room allows for more haemoglobin to be stored in red blood cells. Haemoglobin is a respiratory pigment, which binds to either oxygen or carbon dioxide. This allows oxygen to be transported around the body to the tissues and organs (and carbon dioxide to be taken away). Haemoglobin is largely comprised of iron, which when combined with oxygen, gives blood its red colour. In humans erythropoiesis usually occurs within the red bone marrow. In the early fetus, erythropoiesis takes place in the mesodermal cells of the yolk sac. By the third or fourth month, erythropoiesis moves to the liver. After seven months, erythropoiesis occurs in the bone marrow. Red Blood Cell (RBC)  Erythropoietin and Red Blood Cell Formation Erythropoietin also known as EPO or hematopoietin. It is a glycoprotein hormone that controls erythropoiesis, or red blood cell production. It is a cytokine (protein signalling molecule) for erythrocyte (red blood cell) precursors in the bone marrow. Human EPO has a molecular weight of 34 kilodalton. Erythropoietin is produced by interstitial fibroblasts in the kidney in close association with peritubular capillary and proximal convoluted tubule. It is also produced in perisinusoidal cells in the liver. While liver production predominates in the foetal and perinatal period. Renal production is predominant during adulthood. Erythropoietin hormone stimulates proliferation and differentiation of red blood cell precursors. Precursors activates increased erythropoiesis in the hemopoietic tissues, ultimately producing red blood cells.  Blood group or blood type Blood group or blood type is a classification of blood based on the presence or absence of inherited antigenic substances on the surface of red blood cells (RBCs). These antigens may be proteins, carbohydrates, glycoproteins, or glycolipids, depending on the blood group system. Plasma usually contains antibodies (agglutinins) against the missed antigen. ABO blood group system. In this system, there are two types of antigens: antigen A and antigen B, they are inherited by a dominant genes. In this system, people are classified in to four groups, A, B, AB and O. Blood Group A B AB O % of population 40% 10% 5% 45% Antigen (agglutinogen) on RBCs A B AB - Antibody (agglutinin) in plasma Anti B Anti A - Anti A, Anti B Genotype AA,AO BB,BO AB OO  Rh Blood group system The Rh blood group system is the most polymorphic of the human blood groups, consisting of at least 45 independent antigens and, next to ABO, is the most clinically significant in transfusion medicine. There are 5 main Rh antigens on red cells, C, c, D, E, e. The most important of these is the Rh D. Having the D antigen on the red cell gives the positive (+) and lacking it gives the negative (-) after the letter A, B, AB or O. In this system, people are classified in to two groups, Rh+ or Rh-.’ Blood groups Rh + Ve Rh – Ve % of population 85% 15% Antigen on RBCs D – Antibodies in plasma – Normally not present genotype DD, Dd dd  Importance of blood group determination Blood group related disorder. The susceptibility to various diseases, such as cancer, cardiovascular diseases, infections and hematologic disorders, cognitive disorders, circulatory diseases, metabolic diseases, and malaria, and more diseases, have been linked with blood groups. Medicalegal importance. Blood group test might be used for Disputed paternity and Paternity confirmation, however, DNA test is more accurate and mor used nowadays. Evidence in crimes. Blood group test might help in crimes investigations. Blood transfusion. (will be explained).  Blood transfusion Reaction between Donor’s RBCs (antigen) and recipient’s plasma (antibodies) may occur during blood transfusion. Blood group O-Ve contain no antigen, (universal donor). Blood group AB+Ve contain no antibody, (universal recipient). Universal should be restricted. Precautions before blood transfusion Tests for compatibility: Blood grouping, ABO system and Rh system. Cross matching test, by: Mixing donor RBCs with recipient plasma (major test). Mixing recipient RBCs with donor plasma. Tests for blood born diseases, Hepatitis and AIDS. Blood should have normal (haemoglobin) HB and fresh –stored at 4°C for not more than three weeks.  Blood group matching Type O– blood is a universal donor. Type AB+ blood is a universal recipient.  White blood cell White blood cell: (Leukocytes) One of the tiny colourless cells of the blood the body makes to help fight infections. WBCs are an important part of the immune system. An average normal range for white blood cells is between 4,000 and 11,000/ml. There are five different types of white blood cells, or leukocytes. and we can break them up into two main categories. These are granulocytes and agranulocytes. These terms simply refer to how these cells look when stained. Granulocytes have visible granules in their cell bodies, and agranulocytes do not. There are three types of granulocytes, neutrophils, eosinophils and basophils. There are two types of agranulocytes, monocytes and lymphocytes. Blood cell development  Types of White blood cell Granulocytes: neutrophils, eosinophils & basophils. Agranulocytes: monocytes & lymphocytes. Neutrophils (Microphages) are formed in the Bone marrow. They are 60% of WBC. They attack and destroy the invaded bacteria and foreign substances. (accumulate , stick squeeze and pass to the capillary wall – amoeboid movement attracted, engulf and digest 5 – 20 bacteria) Eosinophils are formed in the Bone marrow. They are 3% of WBC. They defence against the parasites. (amoeboid movement and chemical reactions to kill the parasites) Basophils are formed in the Bone marrow. They are 1% of WBC. They have important role in allergic reactions  Types of White blood cell Monocytes (Macrophages) are formed in the Bone marrow. They are 6% of WBC. Phagocytosis inside the tissue, engulf as many as 100 bacteria). They release chemical substances which increase the inflammatory reactions and immune response against invading microorganisms. Lymphocytes are formed in the lymphatic tissue (lymphatic notes, spleen, liver, etc). They are 30% of WBC. There are two types of lymphocytes: T lymphocytes cell. B lymphocytes cell. They have an important role in the immunity. WBC increase physiologically (Exercise, emotions or pregnancy) or pathologically (infection, allergic, leukemia or tissue damage).  The Immunity The immunity is the ability of the body to resist organisms or toxins that tend to damage the tissues or organs. The immune system is the body’s tool for preventing or limiting infection. Its complex network of cells, tissues and organs, to defend the body from bacteria, viruses, parasites, and more. Types of immunity Innate immunity: is the type of immunity that people are born with which will attack invaders from day one. Adaptive (acquired) immunity is the type of immunity that people develop from attacked pathogens as they go through life. Passive immunity is a temporary type of immunity that derives from another person. Such as, a new-born baby receives antibodies from the mother through the placenta before birth and in breast milk following delivery. Types of immunity - Non specific immunity (Innate) Non specific immunity (Innate) (inherent). The innate immune system is the type of immunity that is present naturally in the child at the time of birth. These natural protectors are already present in human body. Non specific immunity includes: Skin, Acidity of stomach, phagocytosis, natural killer cell (lymphocytes cells attach viruses and tumour cells), substances in the blood such as: interferon (viruses and tumour cells), properdin system (bacteria and viruses), complement system - stimulation (bacteria & antigen antibody reaction).  Types of immunity - Specific (acquired) immunity Specific (acquired) immunity: Acquired Immunity develop specifically against antigen (bacteria, viruses etc.). It is the immunity that our body gains over time. Acquired immunity can be active (produced in the body) or passive (from placenta or immunisation). Lymphocytes are responsible for acquired immunity. T & B lymphocytes are originated in the boon marrow during foetal life and shortly after birth. B lymphocytes are differentiated in the liver and migrate to the lymphoid tissue. They are responsible for humoral acquired immunity. T lymphocytes are differentiated in the thymus gland and migrate to the lymphoid tissue. They are responsible for cellular acquired immunity.  Humoral immunity Humoral immunity is mediated by circulating antibodies. Antibodies (immunoglobulins) are gamma globulins secreted by plasma cell in the lymphoid tissue. Each antibody is specific to certain antigen. B lymphocytes is responsible for Humoral immunity. Types of antibodies – immunoglobulins: 1.Immunoglobulin G (IgG), it has the smallest MW, it can cross the placenta. 2.Immunoglobulin M (IgM), it has the highest MW, can not cross the placenta, ABO blood group antibodies are of this type. 3.Immunoglobulin A (IgA), secreted by mucous lung and intestine to act as a local immune system. 4.Immunoglobulin D (IgD), little known about it. 5.Immunoglobulin E (IgE), attached to the surface of basophils and mast cells stimulating the release of histamine during allergic reaction. Mechanism of Humoral immunity: 1.Activation of B lymphocytes. 2.Formation of plasma cells and antibodies. 3.Formation of the memory cells. 4.Production of antibodies by plasma cells is inhibited by the suppressor T cells.  Antibodies - Immunoglobulins IgG, IgA, IgD, IgE are Y shaped. IgM composed of 5 unites of Y shape  Mechanism of antibody action Direct action: direct attack the agent and inactivate it through: 1) Agglutination, clumping of antigens. 2) Precipitation, antigen-antibody reaction. 3) Neutralization, antitoxins the antigen. 4) Lysis, attack the membrane of cellular agents. Indirect action: trough activation of complement, which then inactivate the invader through: 1) Agglutination. 2) Opsonization (identifying the invading particle to the phagocyte). 3) Neutralization. 4) Lysis. All antibodies can fix and activate compliment except IgA.  Cellular immunity Cell mediated immunity is an immune response that does not involve antibodies. It is mediated by T lymphocytes. Mechanism of cellular immunity: Activation of T lymphocytes Formation of effector (activated) T cells. Types of effector T cells: Cytotoxic (killer) T cells, they attack antigens directly. Helper T cells, they stimulate immune response through lymphokines Suppressor T cells, inhibit unnecessary function of B lymphocytes and other types of T lymphocytes. Types of immune response: Primary immune response, it is the antibody response when the antigen enters the body for the first time. It is slow, week and short duration. Secondary immune response, it is the antibody response on subsequent exposure of the body to the same antigen. It is rapid, more potent and longer than the primary response.  Immunization and Immunity Abnormalities Immunization is the potentiation of the immunity of the person. Types of immunization: 1.Passive immunization, by injecting the body with already prepared antibodies. 2.Active immunization, by stimulation of acquired immunity through injection of dead or week organisms. Immunity abnormalities: 1.Immune deficiency: A.Congenital immune deficiency (failure of development of the immune system). B.Acquired immune deficiency syndrome (AIDS). 2.Hypersensitivity, very sensitive to one or more antigens, e.g. asthma and urticaria. 3.Auto immune diseases, failure of self recognition.  Platelets and Blood coagulation Platelets are the cells that circulate within the blood and bind together when they recognize damaged blood vessels. Platelets bind to the site of the damaged vessel, thereby causing a blood clot. There’s an evolutionary reason why they’re there, it’s to stop bleeding. Blood coagulation: The ability of the body to control the flow of blood following vascular injury. Haemeostasis: The process of blood clotting and then the subsequent dissolution of the clot, following repair of the injured tissue.  Four Major Events of Haemostasis 1.The initial phase of the process is vascular constriction. This limits the flow of blood to the area of injury. 2.Platelets become activated by thrombin and aggregate at the site of injury, forming a temporary, loose platelet plug. The protein fibrinogen is primarily responsible for stimulating platelet clumping. Platelets clump by binding to collagen that becomes exposed following rupture of the endothelial lining of vessels. 3.To insure stability of the initially loose platelet plug, a fibrin mesh (also called the clot) forms and entraps the plug. If the plug contains only platelets it is termed a white thrombus; if red blood cells are present it is called a red thrombus 4.Finally, the clot must be dissolved in order for normal blood flow to resume following tissue repair. The dissolution of the clot occurs through the action of plasmin.  Mechanism of Blood Coagulation - Platelet Activation Signalling Pathways: Regulation of platelet activation occurs via the interaction of numerous effector molecules with receptors present in the plasma membranes of platelets. Mechanism of Blood Coagulation Factors involving in the blood coagulation Mechanism of Blood Coagulation – The Clotting Cascades  Anticoagulants Anticoagulants is a chemical that blocks or inhibits the coagulation process. Physiological anticoagulants are normally produced in the body. Therapeutic anticoagulants are manufactured, and can be administered to block coagulation. There are many types of therapeutic anticoagulant medications: such as: Vitamin K antagonists. Direct Oral Anticoagulants (DOACs). Low molecular weight heparins (LMWH). Each type works in a different way to prevent unneeded blood clots.  Common Blood Disorders - Blood Diseases Anaemia is a decreased RBCs count or Hb Intra-corpuscular causes (hereditary content or both below the normal range for haemolytic anaemia), 1 - cell membrane age and sex. defect, 2 - Hb defect or 3 - enzymatic Three types of anaemia: defect. I. Normocytic normochromic anaemia. Extra-corpuscular causes (acquired II.Microcytic hypochromic anaemia. haemolytic anaemia), 1 - chemical III.Macrocytic hyperchromic anaemia. poisons, 2 - drugs, 3 - snake venoms, 4 – I. Normocytic normochromic anaemia: bacteria toxins – antibodies against RBCs. In which: ❑Acute Blood Loss (Haemorrhagic anaemia) RBCs size -mean corpuscular volume (MCV) ❑Bone marrow depression (Aplastic are normal (normocytic). anaemia) due to: Amount of Hb in each RBC -mean Excessive exposure to x-ray. corpuscular haemoglobin- (MCH) is normal Some viral infection. (normochromic). Chemical toxins. It may due to: Invasion of bone marrow by malignant ❑Haemolysis of RBCs (haemolytic anaemia), cells. which may due to:  II. Microcytic hypochromic anaemia Iron deficiency anaemia In which: RBCs size -mean corpuscular volume (MCV) are less than normal (Microcytic). Amount of Hb in each RBC -mean corpuscular haemoglobin- (MCH) is less than normal (hypochromic). Iron deficiency may be due to, 1.Diminished intake: starvation. 2.Decreased absorption of Iron. 3.Chronic blood loss: as in Gastrointestinal bleeding (ulcer), haematuria, excessive menstruation. 4.Decrease storage as in liver disease. 5.Increased requirement: Pregnancy, lactation.  III. Macrocytic hyper-chromic anaemia Maturation failure anaemia In which: RBCs size -mean corpuscular volume (MCV) is more than normal (Macrocytic). Amount of Hb in each RBC -mean corpuscular haemoglobin- (MCH) is more than normal (hypochromic). It is due to deficiency of Vitamin B12 or folic acid Causes of Vitamin B12 deficiency: 1. Deficient intake: (rare – unlikely liver storage). 2. Decreased absorption of Vitamin B12. 3. Decrease storage as in liver disease. 4. Increased requirement: (rare – unlikely liver storage). Causes of folic acid deficiency: 1. Decreased intake: Starvation 2. Decreased absorption of folic acid. 3. Decrease storage as in liver disease. 4. Increased requirement, Pregnancy.  Effects of anaemia Polycythaemia Physiological effects: Definition: polycythaemia is the abnormal increase in RBCs count. Decrease O2 supply to tissues. Types: On Cardio Vascular System (blood viscosity). Primary Polycythaemia. And more… Secondary Polycythaemia. Clinical effects: Causes: Headache. Tumour like condition. Blurring of vision. Heart failure. And more… Chronic lung diseases. Anaemia is diagnosed by calculation of Polycythaemia effects cardio vascular RBCs count and haemoglobin content. system (blood viscosity).  Disorders of haemostasis I. Hypercoagulable disorders (interavascular clotting). Definition: formation of blood clots inside blood vessels. II. Hypocoagulable disorder: Types: 1. Purpura: Definition: bleeding from small vessels under the skin, due to decreased platelet count or abnormal function of platelet. 2. Haemophilia: Definition: severe bleeding, inherited as a sex linked disease, female carry and do not suffer from it. Types: Haemophilia A (85%) due to deficiency of factor VIII. Haemophilia B (10%) due to deficiency of factor IX. Haemophilia C (5%) due to deficiency of factor XI.  Haemophilia Inflammation Haemophilia is a disease Inflammation is a localized physical condition in which part of the body referring to the inability to clot becomes reddened, swollen, hot, blood. It is an X-linked disorder and often painful, especially as a resulting from a deficiency in reaction to injury or infection. These changes are caused by chemicals factor VIII in the plasma, a key released from the effected tissues component of the coagulation such as, Histamine, Serotonin, cascade. Bradykinin etc.