Blood Physiology Red Blood Cells

BLOOD

Topic: Red Blood Cells (RBCs) Morphological Features of RBCs. Production of RBCs Regulation of production of RBCs Nutritional substances need for RBC production Haemoglobin (Iron metabolism)

Sites of blood formation Adults………….. Bone Marrow (Flat bones) Children …………. Bone Marrow (Flat & long bones) Before Birth: …. Bone Marrow Liver & spleen,lymph nodes Fetus 1st 4 months …Yalk Sac

Production of RBC-cont.

Monophyletic theory of cell formation Red blood cells

Genesis of RBC

Hematopoiesis (17.9)

Erythropoiesis, (Formation/genesis of RBC) Growth factors (inducers): Control growth and maturation of stem cells: Interleukin-3 Erythropoeitin Granulocyte stimulating factor (GSF)

Production of Erythrocytes: Erythropoiesis Figure 17.5

Maturation Sequence

Erythropoiesis, (Formation/genesis of RBC) Stages of RBC development Pluripotential haemopoietic STEM CELL Committed Stem cell Proerthroblast early, intermediate and late normoblast Reticulocytes Erythrocytes

Erythropoiesis Starts in red bone marrow with proerythroblast Cell near the end of development ejects nucleus and becomes a reticulocyte Develop into mature RBC within 1-2 days Negative feedback balances production with destruction Controlled condition is amount of oxygen delivery to tissues Hypoxia stimulates release of erythropoietin

Stages of differentiation of RBC

Features of the maturation process of RBC Reduction in size Disappearance of the nucleus Acquisition of haemoglobin

Control of Erythropoiesis Erythropoiesis is stimulated by erythropoietin hormone Stimulated by: Hypoxia (low oxygen) Anaemia Hemorrhage High altitude Lung disease Heart failure

Erythropoietin(EPO) A glycoprotein - a hematopoietic growth factor of red blood cells (erythrocytes) in mammals A cytokine for erythrocyte precursors (hematopoietin or hemopoietin) - produced in the kidney and liver

Erythropoietin Erythropoietin use should be targeted to patients aged under 70 years who are scheduled for major blood losing surgery and who have a presenting haemoglobin <130 g/l. Erythropoietin can be used to prepare patients with objections to allogeneic transfusion for surgery that involves major blood loss.

Functional EPO Haematocrit 紅血球容積 Erythrocyte precursor cells reside in the bone marrow, and are part of erythropoesis, the formation of circulating erythrocytes (i.e., red blood cells). The erythroid progenitor cells develop in two phases: erythroid burst-forming units ( BFU-E) followed by erythroid colony-forming units ( CFU-E); BFU-E differentiate into CFU-E on stimulation by erythropoietin, and then further differentiate into erythroblasts when stimulated by other factors. Also : playing a significant role in the brain's response to neuronal injury involvement in the process of wound healing

The effect of erythropoietin The effect of erythropoietin in minimising allogeneic blood exposure compared to placebo has been studied in patients undergoing orthopaedic , cardiac or colon cancer surgery. With the exception of one study, all showed a significant reduction in allogeneic transfusion

Hemoglobin Globin – 4 polypeptide chains Heme in each of 4 chains Iron ion can combine reversibly with one oxygen molecule Also transports 23% of total carbon dioxide Combines with amino acids of globin Nitric oxide (NO) binds to hemoglobin Releases NO causing vasodilation to improve blood flow and oxygen delivery

Shapes of RBC and Hemoglobin Copyright 2009, John Wiley & Sons, Inc.

Tissue oxygenation and RBC formation

Control of erythropoiesis Cont. Erythropoietin glycoprotein 90% from kidneys 10% liver Stimulates the growth of: early RBC-committed stem cells Can be measured in plasma & urine High level of erythropoietin anemia High altitude Heart failure

Maturation Times

Control of erythropoiesis cont. Other hormones Androgens, Thyroid, cortisol & growth hormones are essential for red cell formation Deficiencies of any one of these hormones results in anaemia

Control of erythropoiesis

Erythropoitein- Mechanism of production of Hypoxia, (blood loss)  Blood O2 levels Tissue (kidney) hypoxia  Production of erythropoietin  plasma erythropoietin Stimulation of erythrocytes production  Erythrocyte production

Topic: Red Blood Cells (RBCs) Morphological Features of RBCs. Production of RBCs Regulation of production of RBCs Nutritional substances need for RBC production Haemoglobin (Iron metabolism)

Nutritional deficiency anaemia clinical application Angular Cheilosis Glossitis Koilonychia Marrow iron stores Plummer-Vinson syndrome

Nutritional requirements for RBC formation Amino acid HemoGlobin Iron Deficiency  small cells (microcytic anaemia )

Nutritional requirements for RBC formation cont. 3. Vitamins Vit B12 and Folic acid Synthesis of nucleoprotein DNA Deficiency  macrocytes megaloblastic (large) anemia Vit C Iron absorption

Production of Erythrocytes: Erythropoiesis Figure 17.5

Hemoglobin Globin – 4 polypeptide chains Heme in each of 4 chains Iron ion can combine reversibly with one oxygen molecule Also transports 23% of total carbon dioxide Combines with amino acids of globin Nitric oxide (NO) binds to hemoglobin Releases NO causing vasodilation to improve blood flow and oxygen delivery .

Vitamin B12 & Folic acid Macrocytic (megaloblastic) anaemia Important for cell division and maturation Deficiency of Vit. B12 > Red cells are abnormally large (macrocytes) Deficiency leads: Macrocytic (megaloblastic) anaemia Dietary source: meat, milk, liver, fat, green vegetables

Vitamin B12 Pernicious anaemia Absorption of VB12 needs intrinsic factor secreted by parietal cells of stomach VB12 + intrinsic factor is absorbed in the terminal ileum Deficiency arise from Inadequate intake Deficient intrinsic factors Pernicious anaemia

Nutritional requirements for RBC formation cont. Essential elements Copper, Cobalt, zinc, manganese, nickel Cobalt  Erythropoietin

ANAEMIAS Definiation Decrease number of RBC Decrease Hb Symptoms: Tired, Fatigue, short of breath, (pallor, tachycardia)

40

Causes of anaemia 1. Blood Loss 2. Decrease RBC production acute accident Chronic  ulcer, worm 2. Decrease RBC production Nutritional causes Iron  microcytic anaemia VB12 & Folic acid  megaloblastic anaemia Bone marrow destruction by cancer, radiation, drugs  Aplastic anaemia. 3. Haemolytic  excessive destruction Abnormal Hb (sickle cells) Incompatible blood transfusion

The most common cause for a hypochromic microcytic anemia is iron deficiency. The most common nutritional deficiency is lack of dietary iron. Thus, iron deficiency anemia is common. Persons most at risk are children and women in reproductive years (from menstrual blood loss and from pregnancy).

The most common cause for a hypochromic microcytic anemia is iron deficiency. The most common nutritional deficiency is lack of dietary iron. Thus, iron deficiency anemia is common. Persons most at risk are children and women in reproductive years (from menstrual blood loss and from pregnancy)

Macrocytic anemia The RBC are almost as large as the lymphocyte. Note the hypersegmented neurotrophil. There are fewer RBCs.

The RBC's here are smaller than normal and have an increased zone of central pallor. This is indicative of a hypochromic (less hemoglobin in each RBC) microcytic (smaller size of each RBC) anemia. There is also increased anisocytosis (variation in size) and poikilocytosis (variation in shape).

Macrocytic anemia Note the hypersegmented neurotrophil and also that the RBC are almost as large as the lymphocyte. Finally, note that there are fewer RBCs.

Polycythemia Increased number of RBC Relative Types: True or absolute Primary (polycythemia rubra vera): uncontrolled RBC production Secondary to hypoxia: high altitude, chronic respiratory or cardiac disease Relative Haemoconcentration: loss of body fluid in vomiting, diarrhea, sweating