Hematopoietic System Lecture Notes PDF

HEMATOPOIETIC SYSTEM  The hematopoietic system consists of the bone marrow and the cells it produces, including leukocytes, erythrocytes, and thrombocytes. The blood is connective tissue fluid formed by cells that are suspended in the plasma. Blood Functions...

HEMATOPOIETIC SYSTEM  The hematopoietic system consists of the bone marrow and the cells it produces, including leukocytes, erythrocytes, and thrombocytes. The blood is connective tissue fluid formed by cells that are suspended in the plasma. Blood Functions Transport O2 from lungs to tissues 1-Respiratory Transport CO2 from tissues to lungs Transport “food” from gut to tissues 2. Nutrition Transport waste from tissues to kidney 3. Excretory (urea, uric acid)  White blood cells , antibodies, antitoxins. Injury to blood vessels is followed by blood 4. clotting which stops further loss of this Protective vital fluid. regulate body temperature 5. regulate pH through buffers Regulatory water balance. Physical characters of the blood: Volume: The normal total circulating blood volume is 5-6 L in a 70-kg man. About 55% of this volume is plasma. 5-6 Liter  Blood components White blood cells, Red blood cells, Platelets. Physical characters of the blood: pH: The normal blood pH is: oArterial blood 7.40 + 0.02 oVenous blood 7.38 + 0.02 Arterial blood is bright red due to presence of oxyhemoglobin. Venous blood is dark red (bluish) due to presence of reduced hemoglobin.  Viscosity ▪ Blood is 5 times more viscous than water. ▪ This high viscosity is due to presence of cells (mainly RBCs) and plasma proteins. ▪ Blood viscosity decreases in cases of anemia and hypoproteinamia and increases in cases of polycythemia and dehydration. ▪ Blood viscosity is essential for maintaining normal arterial blood pressure (ABP) by preventing rapid flow of blood from arteries to veins. PLASMAIs the yellow clear fluid portion of the blood in which the cellular elements of the blood are suspended. 1. Water (90%) 2. Inorganic constituents (1%) e.g. sodium, chloride, calcium, potassium 3. Organic constituents (9%). a- Plasma proteins (7%) b- Nutrients & waste products (2%) PLASMA PROTEINS Their concentration ranges from 7-9 g/dL. Plasma proteins include: 1. Albumin, fibrinogen, prothrombin and most of alpha and beta globulins are formed in liver. 2. Gamma globulins are formed by plasma cells(B lymphocytes) that differentiated in bone marrow. Types of plasma proteins Gamma glob. Lymphoid tissue Liver  Functions of plasma proteins Protein metabolism : constantly used by tissues for their protein metabolism Blood coagulation: (prothrombin and fibrinogen). Immunity: Antibodies (gamma globulins) protect body against pathogenic organisms and their toxins. Transport of important substances Regulation of blood volume : exert a colloid osmotic pressure of about 25 mmHg. Buffering action Regulation of arterial blood pressure : Blood viscosity is due to red blood cells and plasma proteins  RED BLOOD CELLS (Erythrocytes) RBCs deliver oxygen (O2) to the body tissues—via blood flow through the circulatory system. Erythrocytes take up oxygen in the lungs and deliver it into tissues while squeezing through the body's capillaries. Shape and size: -non- nucleated-to accommodate maximum space for hemoglobin-, biconcave disks, -The shapes of red blood cells can change remarkably as the cells squeeze through. Life span: 120 days Number: *in men: 5.2 ( ±300,000) million/cubic milliliter. *in women: 4.7 ( ±300,000) million/cubic milliliter. Percentage volume of red cells in relation to whole blood is the "haematocrit value".  RED BLOOD CELLS Functions (Erythrocytes) Respiratory function : RBCs contain large amounts of the protein hemoglobin. Which is an iron-containing biomolecule that can bind oxygen and is responsible for the red color of the cells and the blood. o The average concentration of hemoglobin is: *14 g/100 ml blood in women *16 g/100 ml in men. Blood viscosity Keep PH of the blood.  Life cycle Human red blood cells are produced through a process named erythropoiesis, developing from committed stem cells to mature red blood cells in about 7 days. When matured, in a healthy individual these cells live in blood circulation for about 100 to 120 days. At the end of their lifespan, they are removed from circulation by macrophages and subsequent phagocytosis in spleen, liver and lymph nodes. In many chronic diseases, the lifespan of the red blood cells is reduced. Fate of RBCs (after 120 days) Haemoglobin Hb concentration: 16+ 2 g/dI in adult men 14 + 2 g/dI in adult women * 4 Heme fractions = * 4 Oxygen Molecules  Erythropoiesis Process of development, differentiation and maturation of RBCs from primitive stem cells Features of the maturation process of RBC 1. Reduction in size 2. Disappearance of the nucleus 3. Acquisition of haemoglobin  Factors affecting formation of red blood cells (erythropoiesis) 1.Tissue oxygenation: role of erythropoietin 2. Nutritional factors 3. Hormones 4. Liver 5. Bone marrow 1. Tissue oxygenation: role of erythropoietin Erythropoiesis is stimulated by erythropoietin hormone produced by the kidney in response to hypoxia (low oxygen in the blood) Hypoxia caused by: Low RBC count (Anaemia) Hemorrhage High altitude Prolong heart failure Lung disease 22 Erythropoietin ▪ Glycoprotein hormone ▪ Lack of O2 (hypoxia) stimulates formation of erythropoietin. ▪ 90% of erythropoietin is formed in the kidney; the rest is formed mainly in the liver. ▪ Erythropoietin stimulates production of proerythoblasts from haemopoietic stem cells in bone marrow. ▪ When O2 transport to tissues rises above normal, the rate of erythropoietin formation decreases (negative feedback mechanism). 2. Nutritional factors a) Proteins Animal proteins: liver, kidney and muscles production of haemoglobin (globin fraction) Animal proteins contain essential amino acids b) lron ▪ 60% in hemoglobin (heme fraction) ▪ 3% in myoglobin ▪ The rest is mostly in ferritin (enterocytes, hepatocytes and many other cells). c) Vitamins VitaminB12 and folic acid are required for formation of thymidine triphosphate (essential building block of DNA) Important for nuclear maturation and cell division of red cell precursors. Therefore,lack of either vitamin B12 or folic acid causes abnormal and diminished DNA and, consequently, failure of nuclear maturation and cell division. Vitamin B12 absorption 3. Hormones They promote tissues metabolism in general They are not specific except erythropoietin. Thyroxine hormones are most powerful stimulant of body metabolism -Their deficiency for long time can cause anemia. Male hormones (androgens) Growth hormones  4. Liver A healthy liver is essential for normal red blood cell formation. The liver manufactures globin. Stores iron, copper, vitamin B12 and folic acid, and a small fraction of erythropoietin. 5- Bone marrow It is factory in which red cells and most other blood cells are formed. Destruction of bone marrow by: irradiation, chemicals, drugs or bacterial toxins deficiency of all blood cells "aplastic anaemia"  Anemias Definition: a decrease in the ability of the blood to carry oxygen due to (1) a decrease in the total number of RBCs, each having a normal quantity of hemoglobin, or (2) a decreased concentration of hemoglobin per RBC, or (3) a combination of both. It is expressed in terms of reduction in the concentration of Hb (or RBC or Hct%) compared to values obtained from a reference population. Anemias Blood loss  Pathogenic classification (Causes of anemia) 1- Blood loss – Anemia due to acute bleeding – Chronic blood loss : piles, fibroids. 2-Decreased RBC production Anemia due to nutritional defects Aplastic anaemia : bone marrow destruction. Megaloblastic anaemia. 3-Anemias caused by increased RBC destruction (hemolytic anemias) Hereditary hemolytic diseases Infections : malaria Mismatchedblood transfusion Autoimmunity Specific features Specific signs are associated with particular types of anemia : ❖ Spoon nail with iron deficiency, ❖ Leg ulcers with sickle cell anemia ❖ Jaundice with hemolytic anemia ❖ Bone deformities in thalassemia major Iron deficiency is a common form of malnutrition that affects more than 2 billion people globally. Causes Increased iron requirements 1. Blood loss 2. Gastrointestinal disorders (esophageal varices, hemorrhoids) 3. Extensive and prolonged menstruation 4. Rapid growth in body size between 2 and 36 months of age 5. Pregnancy and lactation Inadequate iron supply 1. Poor nutritional intake 2. Malabsorption  Symptoms of IDA a b c Beside symptoms and signs of anaemia +/- bleeding patients present with: (a): Koilonychia (spoon-shaped nails) (b): Angular stomatitis and/or glossitis (c): Dysphagia due to pharyngeal web (Plummer-Vinson syndrome) 37  Vitamin B12 Deficiency Anemia Vitamin B12 and folate are needed for DNA synthesis in RBCs Causes 1. Conditions that give rise to malabsorption of vitamin B12 particularly autoimmune gastritis , surgical removal of the stomach, chronic inflammation of the pancreas, certain medications such as long-term use of proton pump inhibitors. 2. Inadequate dietary intake such as with the diets of vegetarians, and in the malnourished.  Pernicious anemia is the most common cause of vitamin B12 deficiency anemia in adults, which results from malabsorption of vitamin B12 due to a lack or loss of intrinsic factor. IF is a glycoprotein produced by the parietal cells of the stomach. It is necessary for the absorption of vitamin B12 later on in the distal ileum of the small intestine. Clinical features Hematologic Classically, vitamin B12 deficiency has been associated with megaloblastic macrocytic anemia. The blood counts show a high mean corpuscular volume Neurologic peripheral neuropathy demyelination of the corticospinal tract and dorsal columns Leukocytes – White Blood Cells (WBCs) Protect the body from infectious microorganisms 6000 – 11,000/cubic millimeter ▪ Function outside the bloodstream in loose connective tissue ▪ WBCs have a nucleus and are larger than RBCs ▪ Most produced in bone marrow ▪ Lifespan of 12 hours to several years THANK YOU