ErythrocytesLeukocytesPlatelets

Where blood is made?  Haemopoietic cells first appear in the yolk sac of the 2-week embryo.  By 8 weeks, blood making has become established in the liver of the embryo  By weeks the liver has become the major site of blood cell formation.  The spleen is also active during this period.  The highly cellular bone marrow becomes an active blood making site from about 20 weeks Hematopoietic stem cell

About two-thirds of its mass functions in leucopoiesis, and one-third in red cell production erythropoiesis. In old age, red marrow sites are slowly replaced with yellow, inactive marrow. They develop in the shafts of the long bones and continues until, by years, red marrow is present only in the upper ends of the femur and humerus and in the flat bones of the sternum, ribs, cranium, pelvis and vertebrae The red marrow is then very gradually replaced by inactive, fatty, yellow, lymphoid marrow. At birth, active blood making red marrow occupies the entire capacity of the bones and continues to do so for the first 2-3 years after birth.

The gradual appearance of hemoglobin and disappearance of ribonucleic acid (RNA) in the cell The progressive degeneration of the cell's nucleus which is eventually extruded from the cell The gradual loss of cytoplasmic organelles, for example mitochondria A gradual reduction in cell size

 The developmental pathway consists of three phases 1 – ribosome synthesis in early erythroblasts 2 – Hb accumulation in late erythroblasts and norm oblasts 3 – ejection of the nucleus from normoblasts and formation of reticulocytes  Reticulocytes then become mature erythrocytes 1- 2% of RBC in health people  The developmental pathway consists of three phases 1 – ribosome synthesis in early erythroblasts 2 – Hb accumulation in late erythroblasts and norm oblasts 3 – ejection of the nucleus from normoblasts and formation of reticulocytes  Reticulocytes then become mature erythrocytes 1- 2% of RBC in health people Dr Gihan Gawish

 Erythropoietin (EPO) release by the kidneys is triggered by:  Hypoxia due to decreased RBCs or hemoglobin content  Decreased oxygen availability  Increased tissue demand for oxygen  Enhanced erythropoiesis increases the: RBC count in circulating blood  Oxygen carrying ability of the blood  Erythropoietin (EPO) release by the kidneys is triggered by:  Hypoxia due to decreased RBCs or hemoglobin content  Decreased oxygen availability  Increased tissue demand for oxygen  Enhanced erythropoiesis increases the: RBC count in circulating blood  Oxygen carrying ability of the blood Dr Gihan Gawish

Kidney (and liver to a smaller extent) releases erythropoietin Enhanced Erythropoiesis increases RBC count Homeostasis: Normal blood oxygen levels Reduces O2 levels in blood Increases O2-carrying ability of blood Erythropoietin stimulates red bone marrow

In thyroid deficiency and anterior pituitary deficiency, anaemia may occur due to reduced erythropoiesis. polycythaemia Androgens stimulate and oestrogens depress the erythropoietic response Erythropoietin is also produced by a variety of tumours of both renal and other tissues very high doses of steroid hormones seem to inhibit erythropoiesis. Thyroid hormones, thyroid-stimulating hormone, adrenal cortical steroids, adrenocorticotrophic hormone, and human growth hormone (HGH) all promote erythropoietin formation (erythropoiesis)

 Heme is degraded to a green pigment biliverdin  Biliverdin is converted to a yellow pigment called bilirubin  The bilirubin is picked up by the liver and secreted into the intestines as bile  Heme is degraded to a green pigment biliverdin  Biliverdin is converted to a yellow pigment called bilirubin  The bilirubin is picked up by the liver and secreted into the intestines as bile Dr Gihan Gawish

 The intestines metabolize it into urobilinogen and stercobilinogen  These degraded pigments leave the body in feces and urine, in a pigment called stercobilin and urobilin  The intestines metabolize it into urobilinogen and stercobilinogen  These degraded pigments leave the body in feces and urine, in a pigment called stercobilin and urobilin Dr Gihan Gawish

 Globin is metabolized into amino acids and is released into the circulation  Hb released into the blood is captured by haptoglobin and phagocytized Dr Gihan Gawish

DEGRADATION OF HEME TO BILIRUBIN P 450 cytochrome  75% is derived from RBCs  In normal adults this results in a daily load of mg of bilirubin  Normal plasma concentrations are less then 1 mg/dL  Hydrophobic – transported by albumin to the liver for further metabolism prior to its excretion “unconjugated” bilirubin

Heme (250 to 400 mg/day) Heme oxygenase Biliverdin reductase Hemoglobin (70 to 80%) Erythroid cellsHeme proteins myoglobin, cytochromes (20 to 25%) Biliverdin Bilirubin NADPH + H + NADP + 3 [O] Fe 3+ + CO apoferritinferritin indirect unconjugated pre-hepatic albumin Dr Gihan Gawish

albumin-Bilirubin ligandin Bilirubin diglucuronide ER hepatocyte UDP-Glucuronyl transferase albumin ligandin-Bilirubin bile (gall bladder) direct conjugated post-hepatic 2 UDP-glucuronate 2 UDP

Dr Gihan Gawish Bilirubin diglucuronide Intrahepatic urobilinogen cycle Stercobilinogen Bacterial enzymes Bilirubin Bacterial enzyme2 glucuronate Bacterial enzyme Urobilinogen 8H liver Urobilin kidneys urine Stercobilinfeces kidneys intestines

Dietary element Role in red blood cell production ProteinRequired to make red blood cell proteins and also for the globin part of haemoglobin Vitamin B 6 Not clear what the role is but deficieny has occasionally been associated with anemia Vitamin B 12 and folic acidNeeded for DNA synthesis and are essential in the process of red blood cell formation Vitamin CRequired for folate metabolism and also facilitates the absorption of iron. Extremely low levels of Vitamin C are needed before any problems occur. Anemia caused by lack of Vitamin C (scurvy) is now extremely rare IronRequired for the haem part of haemoglobin Copper and CobaltThere is some evidence that these two trace minerals are essential for the production of red blood cells in other animals but not in humans

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Monocytes are actively phagocytic (engulf other cells) and, on migration into the tissues, they mature into larger cells called macrophages These cells form the mononuclear phagocytic cells of the mononuclear phagocytic system (reticuloendothelial system) in bone marrow, liver, spleen and lymph nodes.

 Lymphocytes are produced in bone marrow from primitive precursors  The lymphoblasts and prolymphocytes.  Immature cells migrate to the thymus and other lymphoid tissues, including that found in bone marrow, and undergo further division, processing and maturation.

 Granulocytes is the collective name given to three types of white blood cell. Namely these are neutrophils, eosinophils and basophils, respectively as figures.  They all derive from myeloblasts.  After birth and into adulthood granulopoiesis occurs in the red marrow.  The process of producing granulocytes is characterized by the progressive condensation and lobulation of the nucleus, loss of RNA and other cytoplasmic organelles, for example mitochondria, and the development of cytoplasmic granules in the cells involved.

 Mature cells pass actively through the endothelial lining of the marrow sinusoid into the circulation.  In the circulation, about half the granulocytes adhere closely to the internal surface of the blood vessels (marginating cells);not normally included in white cell count.  The other half circulate in the blood and exchange with the marginating population.

 Within 7 hours, half the granulocytes will have left the circulation in response to specific requirements for these cells in the tissues.  Once a granulocyte has left the blood it does not return. It may survive in the tissues for 4 or 5 days, or less, depending on the conditions it meets.  The turnover of granulocytes is, therefore, very high. Dead cells are eliminated from the body in faeces and respiratory secretions and are also destroyed by tissue macrophages (monocytes).

 The stem cell for platelets is the hemocytoblast  The sequential developmental pathway is as shown Dr Gihan Gawish Stem cell Developmental pathway Hemocytoblast Megakaryoblast Promegakaryocyte Megakaryocyte Platelets

 platelet budding.  Megakaryocytes mature in about 10 days, from the megakaryoblast.  At any one time, about two-thirds of the body's platelets are circulating in the blood and one-third are pooled in the spleen.  The life span of platelets is between 8 and 12 days.  They are destroyed by macrophages, mainly in the spleen and also in the liver.