Adaptive Changes in Anemia Dr Oscar Mbembela Outline • • • • Define anaemia Classification of anaemia Clinical presentation of anaemia Adaptive changes in anaemia Introduction • Anaemia is a condition in which the number of red blood cells or their oxygen-carrying capacity is insufficient to meet physiologic needs, which vary by age, sex, altitude, smoking, and pregnancy status or • Anaemia is the deficiency of hemoglobin in blood which can be caused by either too few RBC or too little Hb in the cell.or • Anaemia (An-without ,Emia-blood) is a decrease in the RBC count, haemoglobin and/or haematocrit value resulting in low ability for blood to carry oxygen to the body tissues Normal range of Hb Factor affecting Haemoglobin • Haemoglobin interpretation is affected by plasma – In dehydrated patient haemoglobin level may be high due to depletion of plasma which cause the rise in Hb concentration • In pregnant woman Hb is low due to increase in plasma caused by increase in fluid retention by estrogen • In haemorrhagic anaemia soon after bleeding Hb is high because haemodilution has not yet taken place where by after dilution the Hb drops Classification of anaemia Classification of anaemia • Anaemia can be classified in main three categories – According to the causes • Increased blood loss • Impaired /reduced RBCs Production • Increased RBCs destruction – According to the morphology • Size of RBCs – Microcytic – Macrocytic – normocytic Classification of anaemia • Hb concentration (Mean cell haemoglobin concentration) – Normochromic – Hypochromic • Finally in combination – Normocytic hypochromic – Normocytic normochromic – Microcytic hypochromic – Macrocytic normochromic Classification of anaemia • Other classification due to severity – Mild anaemia – Moderate anaemia – Severe anaemia – Very severe anaemia Classification based on causes of anaemia • Blood loss anaemia – Overt blood loss • Surgery • Accident • Epistaxis – Occult blood loss • GI bleeding • Genital urinary bleeding Decreased RBC production • Inadequate supply of nutrients for erythropoiesis – Iron ,Vit B 12 deficiency – Folic acid deficiency – Protein calories malnutrition • Depression of erythropoietin activity • Chronic diseases – Malignancies – infections Decreased RBC production • Aplastic anemia – Lack of bone marrow functioning which may be due to – Exposure to high dose of radiation or chemotherapy – Autoimmune disorder : lupus erythrematosis – 50% of case are idiopathic(unknown) • Replacement of bone marrow by – Leukemia, lymphoma, myeloma etc • Inheritance eg thalassaemia Excessive RBC destruction (haemolytic anaemia) • Intrinsic defects in RBCs – Congenital • Membrane defect – Hereditary spherocytosis , elliptocytosis , xerocytosis • Haemoglobin defect – Sickle cell anaemia – Thalasaemia » β –thalasaemia and ∞- thalasaemia • Enzyme defect – G6PD-Glucose 6 phosphate dehydrogenase deficiency Count.. • Acquired – Paroxysmal nocturnal haemoglobinuria • Extrinsic defect – Immune mechanism – Haemolytic disease of new born – Chemical induced haemolysis – Mismatch haemoglobin • Infection and toxic material • Malaria • Poisons &toxins eg. Lead poisoning Morphological classification • Microcytic hypochromic – Iron deficiency(causes-menstruation , bleeding peptic ulcers , hookworm infestation) – Anaemia of Chronic disease – Lead poisoning – Thalassemia – Vitamin B6 (pyridoxine) Morphological classification • Macrocytic normochromic – Vit B 12 and Folic acid deficiency – Intrinsic factor deficiency • Condition (pernicious anaemia and intestinal sprue) affect the absorption of vit B 12 and Folic acid • Thus lead to the slow production of erythroblast in bone marrow as a result RBC grow too large with odd shapes(megaloblastic) – Alcoholism – Liver diseases Morphological classification • Normocytic normochromic – Anaemia of chronic disease – Renal failure – Iron deficiency-early – Aplastic anaemia – Invasion of bone marrow with cancer cell from blood stream – Chemotherapy and radiation therapy Clinical presentation • Clinical presentation of anaemia is due to the body response to decrease in oxygenation of tissues and physiological adaptation of organs especially the heart • Signs and symptom of anaemia depend on the – cause and Hb level – Acuteness and severity of anaemia Clinical presentation for chronic anemia in children and young adult symptoms are mild until Hb fall below 7-8 g/dl For acute anemia significant symptoms develop at high Hb level Symptoms weakness or fatique, shortness of breath, palpitation, jaundice,dizziness,headache,chastpain, tiredness Signs of anaemia • General: pallor of mucus membranes • Signs of hyperdynamic circulation (tachycardia, bounding pulse, cardiomegaly, and systolic flow murmur), heart failure, orthostatic hypotension • Koilonychia (ridging and spoon shape nails in iron deficiency anemia) • Jaundice (hemolytic anemia) Signs of anaemia • • • • Leg ulcers (sickle cell disease) Splenomegaly, petechaie/purpura (bleeding disorder) Glossitis (iron, folate, vitamin B12 deficiencies) Neurologic abnormalities (vitamin B12 deficiency) Adaptive changes in anaemia • The function of the RBCs is to deliver oxygen from the lungs to the tissue and carbon dioxide from tissues to the lungs(accomplished by using haemoglobin) • Decrease in number of RBCs decrease oxygen delivery to the tissue hence tissue hypoxia • Adaptive and coordinated physiological process is initiated to maintain oxygen delivery and limit oxygen consumption. • Physiological response to anaemia varies according to acute and type of the insult • Allow onset of compensatory mechanisms to take place • Mechanisms for adaptive changes in anaemia – Stimulation of erythropoiesis – Increase cardiac output – Changes in regional blood flow – Decrease haemoglobin oxygen affinity Stimulation of erythropoiesis Stimulation of erythropoiesis • Tissue deoxygenation stimulate erythropoiesis(RBCs production) • Condition that decrease quantity of oxygen transported to tissue increase the rate of RBCs production – Example • • • • Anaemia Lung diseases Cardiac failure Very high altitudes Stimulation of erythropoiesis • Anaemia cause hypoxia to different tissue, hypoxia in the kidney cause synthesis of erythropoietin which stimulate erythropoiesis(RBC production) • Mechanism of erythropoietin production – Renal hypoxia increase tissue level of hypoxia inducible factor 1(HIF 1) (act as transcription factor) – HIF-1 bind to hypoxia response element in the erythropoietin gene and induce transcription of mRNA – Hence increase erythropoietin synthesis Stimulation of erythropoiesis • Erythropoietin secreted from the kidney but the exactly part is unknown suggested to be from – Fibroblastic like interstitial cells surrounding the tubules in the cortex and outer medulla – Renal epithelial cells • Non renal – Other tissue hypoxia sensors send signal to the kidney to produce erythropoietin, the role played by – Epinephrine, norepinephrine and prostaglandins Stimulation of erythropoiesis • When on organism is placed in hypoxic state – Erythropoietin begin to be formed in minutes to hours and attain maximum in 24 hours – After 5 day RBCs appear in blood • Role of erythropoietin – Stimulate production of proerythroblast from hematopoietic stem cell – Fasten the different erythroblast stages than normal Increase in cardiac output • In mild and moderate anaemia cardiac output is not affected • In severe anaemia whether acute or chronic adaptive mechanism in increasing cardiac output is set in motion • Response in anaemia – Rapid velocity blood flow and tachycardia with increase in volume of cardiac output Increase in cardiac output • less concentration of RBCs low viscosity more fluid entry increase in venous return increase in cardiac output • Hypoxia peripheral (venous) vasodilatation more fluid entry increase in venous return increase in cardiac output Increase in cardiac output • In acute blood loss physiological response • Blood loss decrease in blood volume reduction in oxygen carrying capacity hypoxia and hypovolemia hypotension • Detected by stretch receptors in the carotid bulb, aortic arch, heart and lung • Impulse send to medulla oblongata, cerebral cortex and pituitary gland through vagus and glossopharyngeal Increase in cardiac output • In medulla sympathetic is activated and renin angiotensin aldosterone mechanism is stimulated lead to increase in water reabsorption(in response to decrease renal perfusion) • Hence increase in blood volume and blood flow and oxygen delivery is enhanced Increase in cardiac output • Sympathetic N.S– increase systemic vascular resistance – Increase in venous tone increase pre load ,end diastolic volume stroke volume(cardiac output) Sympathetic discharge dominate the vasodilator effect of hypoxia Change in regional blood flow The brain and the heart are the two most organs demanding oxygen in the body To enable enough blood flow to the vital organs, the small blood vessels in the skin contract, causing resistance to flow of blood to the skin Pallor Since blood pumped out of the heart follows the path of least resistance, it will go through vital organs faster. Change in regional blood flow • As a result of diversion or redistribution of the blood the patient becomes pale as observed in the skin and mucous membranes. Decrease haemoglobin oxygen affinity • Hypoxia caused by poor tissue blood flow increase formation of 2,3 biphosphoglycerate in RBCs hence increase concentration in blood. • Increase in 2,3 BPG and acid and other metabolites decrease Hb oxygen affinity and increase oxygen extraction by the tissues • shifting the O2-hemoglobin dissociation curve to the right. • Therefore, under some conditions, the BPG mechanism can be important for adaptation to hypoxia, Shift of the oxygen-hemoglobin dissociation curve to the right caused by an increase in hydrogen ion concentration (decrease in pH). BPG, 2,3-biphosphoglycerate THANKS references • Guyton and hall: textbook of medicalphysiology 13th edition • www.emedicine.mediscape.com • Pubmed –pathophysiology of anaemia: focus on the heart and blood vessels
