Anemia

Dr. Tanbira Alam MBBS, M.Phil.

Learning outcome

What is the normal concentration of hemoglobin in blood in adult males, adult females, newborns, and infants? How is anemia defined? What are the striking symptoms experienced by an individual with a blood [Hb] of about 6 g/dl? Explain the physiologic basis of exercise intolerance and breathlessness in an individual with anemia. Define the following RBC indices mean corpuscular volume, mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration, and red cell distribution width Mention the normal ranges for each and the significance of deviations from normal. Describe how anemia's are classified on the basis of RBC indices. Briefly describe the peripheral blood picture observed in each one of the following anemia's: iron deficiency anemia; vitamin B12 deficiency anemia; and folate deficiency anemia. What is the basic defect in thalassemia? What is the basic defect in sickle cell anemia? What is the basic defect in hereditary spherocytosis? Define polycythemia. How is polycythemia classified? Give an example of each. Briefly describe the mechanism of each type of polycythemia.

Hemoglobin Definition: Hemoglobin is a conjugate protein or metaloporphyrin. It is the red pigment inside the red blood cell. It is a chromo protein consisting of two parts: i. Globin: 96% ii. Heam: 4% Normal count In male : 14-18 gm./100 ml of blood In female : 12-15.5gm/100ml of blood At birth : 23gm/100ml of blood At first year : 10gm/100ml of blood Functions of hemoglobin 1. Transport of respiratory gases (Oxygen from the lungs to the tissues and carbon dioxide, from the tissues to the lungs.) 2. Regulation of blood pH 3. Various pigment of bile, stool, urine etc. are derived from it. 4. It reserves iron and protein.

Anemia: Definition: Anemia may be defined as a reduction of hemoglobin concentration per unit volume of peripheral blood below normal for the age and sex individual of the patient which is not invariably associated with the reduction of RBC.

Causes of anemia: Excessive blood loss due to acute or chronic hemorrhage. Reduced production of RBC due to lack of some factor which are necessary for the production of RBC. Excessive blood cell destruction in comparison to destruction of blood cells. Destruction of bone marrow. Site of observation of anemia: Lower palpebral conjunctiva Dorsal surface of the tongue Oral mucous membrane Skin of the palm Skin of the sole of the feet

Symptoms common to many types of anemia include the following:

Easy fatigue and loss of energy Unusually rapid heart beat, particularly with exercise Shortness of breath and headache, particularly with exercise Difficulty concentrating Dizziness Pale skin Leg cramps Insomnia

Physiological basis of exercise intolerance and breathlessnessIn severe anemia- Blood viscosity fall to as low 1.5 times than normal the resistance to blood flow in the peripheral blood vessel So far greater than normal quantities of blood flow through the tissue & return to the heart There by greatly increase cardiac out put

[ Hypoxia resulting from transport of O2 by the blood that causes the peripheral tissue blood vessel to dilate allowing a further increase in the return of blood to the heart & increase cardiac output.]

Major effect:

1. cardiac output

2. pumping workload on the heart When a person with anemia begins exerciseThe heart is not capable of pumping much greater quantities of blood, consequently exercise induced tissue demands for O2 Results extreme hypoxia Severe breathlessness followed byAcute cardiac failure.

Absolute corpuscular volume and indices From the estimated Hb concentration, RBC count and PCV, it is possible to drive other values, which indicate the red cell volume, Hb content and concentration in red cells. These values are commonly referred to as the red cell indices or absolute values and used to classify the morphological type of anemia. These are : Mean corpuscular volume (MCV) Mean corpuscular hemoglobin (MCH) Mean corpuscular hemoglobin concentration (MCHC)

Mean corpuscular volume (MCV) : It is the average volume of RBC. It is determined by MCV =PCV/RBC count

= 45 ml per 100ml of blood/ 5106 per cu mm of blood = 450 ml per liter of blood / 5106106 per liter of blood = 4501012cubic micron / 51012 (1 ml = 1012cubic micron) = 90 cubic micron Normal range : 78-94 cubic microns Average both male & female: 87 fl

Mean corpuscular hemoglobin (MCH) Amount of hemoglobin by weight in each cell MCH = Hb concentration RBC count

15 mg per 100ml of blood / 5106 per cu mm of blood = 150 mg per liter of blood / 5106106 per liter of blood (1 liter = 106cubic mm) = 1501012picogram / 51012 (1 gm. = 1012 picogram) = 30 picogram Normal range : 26.5-35.5 picogram Average both male & female : 29 picogram

Mean corpuscular hemoglobin concentration (MCHC) The amount of hemoglobin as a percentage of the volume of RBC MCHC = Hb in gm. per 100 ml of blood /PCV in ml per 100 ml of blood X 100 =15 mg / 45 100 = 33.30 gm. Average : 34 gm./ dl

Classification of anemia: A. Pathological & Aetiological : (according to the cause of anemia) 1. Anemia due to blood lossa. Acute post haemorrhagic- due to trauma, accident. b. Chronic post haemorrhagic- ex.- chronic blood loss due to hookworm infestation 2. Anemia due to impaired red cell formation: a. Anemia due to disturbance of bone-marrow function due to deficiency of erythropoietic factor:
i. Iron deficiency anemia ii. Megaloblastic anemia iii. Anemia associated with scurvy iv. Anemia due to malnutrition (rare)

b. Anemia due to disturbance of bone-marrow function due to deficiency of substances essential for erythropoiesis: i. anemia associated with infection, renal failure, liver disease, collagen diseasesetc. ii. Aplastic anemia iii. Sideroblastic anemia iv. Anemia associated with myxoedema & hypopituitarism v. Congenital diserythropoietic anemia.

3. Anemia due to increase red cell destruction: a. Haemolytic anemia due to corpuscular defect b. Haemolytic anemia due to abnormal haemolytic mechanism B. Morphological anemia: (based on the characteristics of red cell as determined by blood examination mainly MCV & MCHC) 1. Normocytic normochromic anemia ex. Aplastic anemia, Acute post haemorrhagic anemia 2. Microcytic hypo chromic anemia ex. Iron deficiency anemia, Thalassemia 3. Macrocytic anemia ex. Megaloblastic anemia

Iron deficiency anemia

Fig: Peripheral blood showing centrally pallor, red blood cells characteristic of iron deficiency anemia

Peripheral blood picture of megaloblastic anemia:

Fig: Peripheral blood smear showing hyper segmented neutrophils and macro blast, characteristic of megaloblastic anemia.

Iron deficiency anemia: Etiology & pathogenesis Major etiological factor: 1. In females in reproductive lifea. Menstruation b. Pregnancy c. Pathological blood loss d. Defective diet 2. In adults & post menopausal womena. Pathological blood loss 3. In infants & childrena. Defective diet b. Diminished iron store at birth Pathogenesis- When supply of iron to the bone-marrow is insufficient for the requirements of Hb synthesis, iron deficiency anemia takes place. Two stages- for developing IDA1. Progressive depletion of the available tissue iron stores 2. Ultimate exhaustion of the available tissue iron stores followed by the developing anemia

There for factors in the pathogenesis of IDA1.An increase in physiological demand for iron 2.Loss of blood 3.Inadequate iron intake 4.Impaired absorption of iron

Aplastic anemia DefinitionAplastic anemia may be defined as a disorder characterized by the occurrence of anemia, leucopenia and thrombocytopenia resulting from aplasia of the bone marrow.
Megaloblastic anemia: The anemia which are characterized by distinctive and functional abnormalities in peripheral blood and bone marrow cell due to impaired DNA synthesis as a result of vitamin B12 or folic acid deficiency or both are known as megaloblastic anemia. Hemolytic anemia: A hemolytic anemia may be defined as an anemia resulting from an increase in the rate of red cell destruction.

Pernicious anemia: Pathogenesis: The fundamental defect in pernicious anemia is a failure of secretion of intrinsic factor of castle by the stomach due to permanent atrophy of the gastric mucosa. Gastric atrophy is the end result of complex interaction between genetic and auto immune factor. Gastric atrophy Reduced intrinsic factor secretion Failure of absorption of dietary Vit B12 Deficiency of Vit B12 Pernicious anemia

Thalassemia: Def: Thalassemia are a heterogeneous disorders in which there is a genetically determined reduction in the rate of synthesis of one or more types of normal haemoglobin polypeptide chains resulting in a decrease production of haemoglobin having defective chain. Classification: A. Haematological: 1. thalassemia- affecting the synthesis of chain. 2. thalassemia- affecting the chain a. + thalassemia- incomplete suppression of chain synthesis. b. 0 thalassemia- complete absence of chain synthesis B. Clinical: 1. Thalassaemia major or Cooley's anemia: Total suppression of beta chain synthesis and it is the homozygous from the disease. 2. Thalassaemia minor: Heterozygous from the disease. Clinical features: 1. Pallor, Diarrhoea & recurrent fever 2. Hepatomegaly & spleenomegaly 3. Slow growth in the childhood 4. Mongoloid face 5. Severe anemia 6. Epistaxis, skin pigmentation

Difference between Iron deficiency anemia & thalassemia

Thalassaemia 1. Congenital 2. Break down of RBC prominent 3. Nucleated RBC plenty 4. Serum iron increased 5. Serum TIBC increased

Iron deficiency anemia 1. Acquired 2. Not present 3. A few nucleated RBC in severe case 4. Serum iron decreased 5. Serum TIBC increased

Sickle cell anemia Def: it is a hereditary disorder where there is anemia due to presence of Hb-S in red cells. Types: 1. Sickle cell anemia (homozygous state ) 2. Sickle cell trait (heterozygous state) Pathogenesis: In sickle cell anemia red cell containing Hb -S differs from Hb- A in substitution of valine for glutamic acid in the 6th position from N- terminal end of the beta chain. In the deoxygenated state, the conformational changes in Hb-S are tactoid formation. As a result the red cells containing Hb-S become rigid and deformed to assume a sickle or crescent shape. Red cell begin to sickle at an O2 tension experienced by the cells in parts of microcirculation and thus sickling occurs in vivo. Major pathological effect: 1. The distorted cells cause a great increase in blood viscosity and block some blood vessels, impairing flow and causing ischemia and infarction of the tissue. 2. Repeated sickle- unsickle cycle leads to loss of fragments of red blood cell membrane and the cells become spherocyte and fragile.

They are removed by the R.E. system and to lesser extent destroyed in the circulation resulting in both extra vascular and intravascular haemolysis leading to anemia. Hereditary spherocytosis: In this condition, the RBC are small in size, spherical in shape rather than biconcave. They can not compressed because they do not have the loose bag like structure. There fore, on passing through the small capillaries they easily ruptures and causes anemia. Polycythaemia: Polycythaemia is defined as an increase in the concentration of red blood cells, above the normal for the age and sex of the patient. Types: 1. Polycythaemia vera/ physiological polycythaemia 2. secondary Polycythaemia Secondary polycythaemia: Whenever the tissues become hypoxic because of too little O2 in the atmosphere, such as at high altitudes, or because of failure of delivery of O2 to the tissues, as occurs in cardiac failure, the blood forming organ automatically produced large quantities of extra red blood cells. This condition is called secondary polycythaemia. RBC count-6-7 million/cu mm about 30% above normal.

Polycythaemia Vera (Erythraemia): in this condition red blood cell count may be 7-8 million/mm3 and the haematocrit 60-70% Causes of polycythaemia vere: Caused by genetic aberration that occurs in the hemocytoblast cell lines that produces the blood cells. The blast cells no longer stop producing red cells when too many cells are already present. It usually causes excess production of white blood cell and platelets as well. Effect of polycythaemia: 1. Blood viscosity increased 2. Blood volume increased 3. Cardiac output more or less normal 4. The arterial pressure usually normal 5. Cyanosis present.