Anaemia by Pandian M.

This PPT for all Medicos and Non medical Students for better understanding of Anemia in clinical practice

1. ANAEMIA Pandian M Dept. of Physiology

2. Anemia is defined as a decrease in the O 2 carrying capacity of the blood either due to A decrease in the total number of erythrocytes (RBC count), each having a normal quantity of hemoglobin or A diminished concentration of hemoglobin per erythrocyte (decrease in Hb content of blood) or A combination of both below the normality for that particular age and sex.

3. Classification: We classify the anemia according to aetiology & morphology. Aetiological (Whitby’s) classification Morphological (Wintrobe’s) classification.

4. Aetiological classification: I. Anaemia due to blood loss (Haemorrhagic anaemia):

5. Acute blood loss : Trauma or accident. After rapid hemorrhage, the body replaces the fluid portion of the plasma in 1 to 3 days, but this leaves a low concentration of red blood cells. If a second hemorrhage does not occur, the red blood cell concentration usually returns to normal within 3to 6 weeks.

6. Chronic blood loss : Worm infestation Peptic ulcer Bleeding piles Menstrual disorders. In chronic blood loss, a person frequently cannot absorb enough iron from the intestines to form hemoglobin as rapidly as it is lost. Red cells are then produced that are much smaller than normal and have too little hemoglobin inside them ,

7. II. Anemia due to decreased R.B.C. production 1) Deficiency Of Nutrients – i)Deficiency of vitamins: Vit.B 12 ,Folic Acid, Vit.C help in the synthesis of nucleic acid. Vit.C also help in absorption of iron from gut. ii) Deficiency Of Minerals : Iron, Copper, Cobalt, Zinc, Nickel & Manganese (help in haem formation). iii)Deficiency of Proteins: Help in globin formation.

8. 2)Endocrine disorders: Hypothyroidism, Hypopituitarism, Addison’s disease, Hypogonadism (hormones increase erythropoietin production). 3)Chronic Diseases: Tuberculosis, Liver Cirrhosis,renal disorders & lung disorders (activate tissue macrophages so RBCs are removed from blood faster than can be formed in bone marrow.

9. 4). Anemia due to bone marrow depression or hypo functioning of bone marrow (aplastic anemia) i) Idiopathic: (Spontaneous or unknown cause) (Autoimmune) ii) Irradiation: (excessive exposure to X rays) or gamma ray irradiation. For instance, a person exposed to gamma ray radiation from a nuclear bomb blast can sustain complete destruction of bone marrow, followed in a few weeks by lethal anemia.

10. iii)Exposure to Chemotherapy (anti cancer drugs), Sulphonamides, Chloramphenicol & anti malarial drugs (produce G6PD deficiency in normal individuals). iv)Drug Idiosyncrasy (abnormal reaction to a drug no relationship to dose or duration of therapy).

11. III)Due to increased destruction of RBCs (Haemolytic anaemia) 1)Intracorpuscular defects 2)Extracorpuscular defects

12. Intra-corpuscular Defect (Hereditary)- i)Membrane Defect: Spherocytosis (contractile protein – spectrin is defective due to genetic glycolysis defect). ii)Enzyme Defects: G6 Phosphate Dehydrogenase deficiency. (required for formation of NADP which maintains glutathione in reduce state. Reduced glutathione protects Hb & RBC membrane from oxidative stress.

13. iii) Haemoglobinopathies : Abnormal formation of Hb due to disorders of globin synthesis. Two types: 1) Formation of abnormal polypeptide chains due to substitution of an abnormal amino acid chain in HbA. e.g: Sickel Cell haemoglobin (HbS) & Anaemia.

14. Substitution of Valine for glutamic acid at position 6 in beta chain of HbA. When HbS is reduced in low oxygen tension it becomes insoluble & precipitates into crystals within RBCs. Crystals elongate to change shape of RBCs to sickle shape. These cells are fragile so undergo haemolysis.

15. 2) Thalassemias : Suppression in the synthesis of polypeptide chains of HbA. β Thalassaemia is common. Further subdivided as Thalassaemia 1) major & 2) minor (more common). In Thalessaemia minor Partial synthesis of β chain. Survival upto adult life. In Thalessaemia major there is complete absence of any one chain. Short life span dies young.

16. Extra-corpuscular Defects (Acquired)- i )Parasitic infections like Malaria.(Plasmodium falciparum infect & reproduce within the RBCs. During their release into the blood stream the RBCs cell membrane is ruptured. ) ii) Mismatched blood transfusion reactions: ABO & Rh incompatibility.

17. iii)Exposure to chemicals like Antimalarial Drugs (Act as oxidising agents, reduces G6PD enzyme & enhances damage of RBCs) & anti cancer drugs (bone marrow depression). iv)Exposure to biological agents like Snake Venom (contains lecithinase which destroys lecithin in RBC cell membrane) & Endotoxins (direct toxic effects).

18. v) Autoimmune hemolytic disorder vi) Chemical injury – lead poisoning vii)Exposure to irradiation like X rays & gamma rays. viii)Exposure to mechanical factors like shaking, alternate freezing & thawing.

19. B. Morphological (Wintrobe’s) classification of Anaemia: Based on cell size & Haemoglobin concentration: Blood Indices: Significance: Give idea about morphology of RBCs i.e size & colour of RBCs. i )Mean Corpuscular Volume (MCV): Average volume of the RBC. Normal Range:78 - 94 μ 3

20. ii)Mean Corpuscular Haemoglobin (MCH): Average weight of Haemoglobin in one RBC. Normal Range: 27 - 32 μ gms iii)Mean Corpuscular Haemoglobin Concentration ( MCHC): Amount of Haemoglobin per 100 ml of RBCs Normal Range: 32 - 38%

21. B. Morphological (Wintrobe’s) classification of Anaemia: I) Normocytic normochromic II) Microcytic hypochromic III) Macrocytic normochromic

22. 1. Normocytic Normochromic - e.g: Acute Blood Loss, Haemolytic & Aplastic anaemias. After rapid hemorrhage, the body replaces the fluid portion of the plasma in 1 to 3 days, but this leaves a low concentration of red blood cells but of normal size & Hb content per cell is also normal. If a second hemorrhage does not occur, the red blood cell concentration usually returns to normal within 3to 6 weeks.

23. 2. Microcytic Hypochromic: eg: Iron Deficiency anaemia, Chronic blood loss & Thalessaemia. In chronic blood loss, a person frequently cannot absorb enough iron from the intestines to form hemoglobin as rapidly as it is lost. Red cells are then produced that are much smaller than normal and have too little hemoglobin inside them, giving rise to microcytic, hypochromic anemia.

24. 3. Macrocytic Normochromic: Megaloblastic anaemia. eg: Vit-B 12 & Folic Acid Deficiency Cause: Defective DNA synthesis. Failure of maturation of nucleus & cell. Cell remains large & fragile.

25. Pathophysiology of Anaemia: Basic pathology is tissue hypoxia. Several cardio respiratory compensatory responses occur. Hypoxia → vasodilatation → increases the venous return & cardiac output. Decrease in RBCs → viscocity of blood (lack of slipperiness) decreases. Both the factors lead to hyperdynamic circulation.

26. Clinical features: Generalized muscular weakness, Easy fatigability, Loss of appetite. Palpitations, Exertional dyspnoea,

27. Pallor, Platynychia, Koilonychia, Glossitis, Angular stomatitis & Ulcers in mouth.

28. Deficiency anaemias: 1.Iron deficiency anaemia 2.Megaloblastic anaemia : a)Pernicious anaemia) due to deficiency of Vit B 12 b)Due to deficiency of Folic acid

29. Iron deficiency anaemia In India Iron deficiency is the commonest cause of anaemia. More common in Women between age group of 20 - 45. At periods of active growth of infancy, childhood & adolescence. The total body iron in a 70-kg man is about 4 - 5 gm. This is maintained by a balance between absorption and body losses.

30. Iron Metabolism: Total Iron content in the body is 4 - 5 gm. Present in following forms: Haemoglobin contains 70% of total body iron(2.5gm) Storage iron is 20 - 23%. 2/3 rd of iron stored as Ferritin & 1/3 rd as haemosiderin . Myoglobin present in red muscles : 5%. Intracellular enzymes : 2 - 3 % includes cytochrome oxidase, catalase, peroxidase.

31. Although the body absorbs only 10% of dietary intake (1 mg of iron daily ) to maintain equilibrium, the internal requirement for iron is greater (20-25 mg). An erythrocyte has a lifespan of 120 days so that 0.8% of red blood cells are destroyed and replaced each day .

32. A man with 5 L of blood volume has 2.5 g of iron incorporated into the hemoglobin, with a daily turnover of 20 mg for hemoglobin synthesis and degradation and another 5 mg for other requirements. Daily Loss of Iron A man excretes about 0.6 mg of iron each day, mainly into the feces. Additional quantities of iron are lost when bleeding occurs. For a woman, additional menstrual loss of blood brings long term iron loss to an average of about 1.3 mg/day.

33. daily requirement- 10 mg in adult males 20 mg in females 40 mg in pregnancy & lactation 10 % of diet intake is absorbed dietary sources- meat eggs & leafy vegetables, BEET, FRUITS - APPLE, POMOGRANATE,ANJEER ETC. whole wheat, jaggery , dates etc

34. ABSORPTION OF IRON: Iron is absorbed from the small intestine, mainly in doudenum & upper part of jejunum. Dietary iron : 2 types of iron in the diet. Haem iron and Non-haem iron. Haem iron is present in Hb containing animal food like meat, liver & spleen. Non- haem iron is obtained from cereals, vegetables & beans. Milk is a poor source of iron, hence breast-fed babies need iron supplements.

35. Absorption of Haem iron is not affected by ingestion of other food items. It has constant absorption rate of 20-30% which is little affected by the iron balance of the subject. The haem molecule is absorbed intact and the iron (ferrous form) is released in the mucosal cells ( enterocytes ).

36. The absorption of non- haem iron varies greatly from 2% to 100% because it is strongly influenced by The iron status of the body, The solubility of iron salts, Integrity of gut mucosa Presence of absorption inhibitors or facilitators.

37. Promoters of Iron Absorption: Foods containing ascorbic acid like citrus fruits, broccoli & other dark green vegetables. Because ascorbic acid reduces iron from ferric to ferrous form, which increases its absorption. Foods containing muscle protein enhance iron absorption due to the effect of cysteine containing peptides released from partially digested meat, which reduces ferric to ferrous salts and form soluble iron complexes.

38. Gastric HCL tends to break insoluble iron complex apart thus facilitates iron absorption. Food fermentation aids iron absorption by reducing the phytate content of diet. Iron stores in the body affects iron absorption: Decrease in iron stores (iron defi anaemia or when erythropoisis is increased due to hypoxia) enhances iron absorption. Vice a Varsa .

39. Inhibitors of iron absorption : Food with polyphenol compounds i.e cereals like sorghum & oats. Vegetables such as spinach and spices. Beverages like tea, coffee, cocoa and wine. A single cup of tea taken with meal reduces iron absorption by up to 11%.

40. other inhibitors: Food containing phytic acid i.e. Bran, cereals like wheat, rice, maize & barely. Legumes like soya beans, black beans & peas. Cow’s milk due to its high calcium & casein contents. Some fruits inhibit the absorption of iron although they are rich in ascorbic acid because of their high phenol content e.g strawberry, banana and melon.

41. INHIBITION-HOW? The dietary phenols & phytic acids compounds bind with iron decreasing free iron in the gut & forming complexes that are not absorbed. Cereal milling to remove bran reduces its phytic acid content by 50% .

42. Mechanism of Iron absorption: I)Transport of iron across the brush border of enterocyte . II)Fate of iron in the enterocyte . III)Transport of iron in the blood.

43. I)Absorption of haem iron: Haem iron → In GIT acted by Proteolytic enzymes → From lumen of GIT →Enters the enterocyte across the brush border by haem transport protein → Inside the cell ferrous iron is released from the haem by enzyme haemoxygenase .

44. II)Absorption of non - haem iron: Present in ferric form & forms insoluble complexes like dietary phytates, phosphates & dietary fibers. They are soluble at low pH. HCL breaks these insoluble complexes & facilitates iron absorption. Also Vit C reduces ferric iron to ferrous iron. Ferrous iron is transported across brush border by iron transport protein.

45. Fate of iron in the enterocyte: i)Depending on body’s requirement, it is actively transported across basolateral membranes of the enterocyte → interstitum →blood. ii)Rest of the ferrous iron is oxidized to Ferric form & bound to apoferritin to form ferritin (storage form) in enterocyte. This iron is difficult to release & it is lost when the cell is sloughed off at the tip of villus after 2 -3 days.

46. Transport of iron in the blood: In the blood iron binds loosely with beta globulin Apo transferrin to form Transferrin. Via plasma it reaches tissue cells. In the tissue cells the released iron combines with apoferritin to form ferritin & stored. Maximum amount of iron is stored in the hepatocytes of liver & reticuloendothelial system (tissue macrophages lining the hepatic & splenic sinusoids).

47. If dietary intake is more some amount of iron is stored as compound Hemosiderin in reticuloendothelial system as stable form so not available for exchange. Excess iron overload results in accumulation of hemosiderin in tissues called as hemosiderosis. It damages the tissues & produces the condition of haemochromatosis. Damage to Pancreas →Bronze diabetes, Liver cirrhosis, Carcinoma of liver & atrophy of gonads.

48. Regulation of body iron (Iron balance) is achieved by control of absorption rather than excretion. Iron cycle Diet Hepatic & splenic macrophages (2mg/day) (iron from dead RBCs (30mg/day) ↑ Plasma Transferrin → RBCs ↓ ↓ Other tissues Alveolar macrophages

49. Iron deficiency anaemia: Causes: 1)Inadequate dietary intake of iron: Milk fed infants, Diet low in animal protein (pure vegetarians), Poor economic status, In high economic status due to junk food or improper diet. Anorexia in pregnancy, Elderly individuals due to atrophy of GIT mucosa & poor dentition.

50. 2)Impaired iron absorption Iron chelators in diet, e.g. tannins, Histamine H2 blockers Disrupted GI mucosa Peptic ulcer, Loss of functional bowel- Surgical resection, Total or partial gastrectomy . Achlorhydria .

51. 3)Increased loss of iron: i ) GIT bleeding: In worm infestation, Peptic ulcers, piles, ulcerative colitis. ii)In females -Uterine bleeding :Excessive menstruation, repeated abortions, post menopausal bleeding. iii) Genito Urinary tract bleeding, Stag horn renal calculi - Hematuria, iv)Repeated epistaxis, v) Hemoptysis. vi) Blood loss GI tract bleeding Aspirin ingestion.

52. 4)Increased demand of iron: Infancy, childhood, pregnancy & menstruation. Clinical features – Symptoms- Muscle weakness, fatiguability, loss of appetite, palpitation, exertional dyspnoea. Signs: Pallor, platynychia, glossitis, angular stomatitis & odema . CVS.-increased pulse rate, bounding pulse RS- Respiratory rate is increased.

53. Laboratory findings: Blood picture & Red cell indices: Haemoglobin concentration is decreased. Severity: < 12 gm% - Mild < 8 gm% - Moderate < 6 gm% - severe RBC count < 4 million/cmm of blood. Peripheral smear: RBCs - hypochromic & microcytic. They show anisocytosis & poikilocytosis.

54. Packed cell volume or Haematocrit value (PCV) : Normal :42 -45% ↓ in iron deficiency anaemia. Red cell indices: MCV,MCH & MCHC ↓.

55. Biochemical findings : Serum iron levels : Amount of iron in blood serum carried by a protein transferrin in plasma(normal : 60 - 160 μ g%. Decreases < 50 μ g% in Iron deficiency anaemia Serum bilirubin : < .4 mg% (normal : .8 to 1 mg%

56. Total Iron Binding Capacity (TIBC) : Amount of iron that blood would carry if transferrin levels were fully saturated. Normal levels: 300 - 450 micrograms/dl Increased in Iron deficiency anaemia.

57. Transferrin test : Direct measurements of transferrin or siderophilin in blood. Normal: 200 - 300 mg/dl Transferrin saturation levels :Serum iron levels TIBC Normal levels:30 - 40% Decreased in Iron deficiency levels < 12 %

58. Ferritin test: Measures levels of a protein in blood that stores iron for later use by the body Normal :20 – 200 ng /ml. Ferritin decreased in chronic iron deficiency.

59. Treatment: Depending on severity & cause: Treat the cause Dietary advice :Rich sources of dietary iron, Deworming, Cooking in iron pot. Supplement therapy: Mild to moderate :Oral supplements of ferrous salts 150 - 180 mg daily. Take after food but not with milk.

60. In severe iron deficiency :Blood transfusion or PCV to prevent overload to cardio vascular system. Parenteral therapy: GIT Intolerance to iron or severe anaemia in the form of Iron dextran or Iron sucrose(risk of anaphylactic reactions).

61. Thank You

62. Megaloblastic Anemia Deficiency of vitamin B12, folic acid, and intrinsic factor from the stomach mucosa, that loss of any one of these can lead to slow reproduction of erythroblasts in the bone marrow. As a result, the red cells grow too large, with odd shapes, and are called megaloblasts . Thus, atrophy of the stomach mucosa, as occurs in pernicious anemia, or loss of the entire stomach after surgical total gastrectomy can lead to megaloblastic anemi a

63. Aplastic Anemia. Bone marrow aplasia means lack of functioning bone marrow. Likewise, excessive x-ray treatment, certain industrial chemicals, and even drugs to which the person might be sensitive can cause the same effect.

64. Also, patients who have intestinal sprue, in which folic acid, vitamin B12, and other vitamin B compounds are poorly absorbed, often develop megaloblastic anemia. Because the erythroblasts cannot proliferate rapidly enough to form normal numbers of red blood cells, those red cells that are formed are mostly oversized, have bizarre shapes, and have fragile membranes. These cells rupture easily, leaving the person in dire need of an adequate number of red cells.

65. Iron is absorbed from all parts of the small intestine, When the quantity of iron in the plasma falls low , In people who do not have adequate quantities of transferrin in their blood, failure to transport iron to the erythroblasts in this manner can cause severe hypochromic anemia —that is, red cells that contain much less hemoglobin than normal.

66. progressively less active, and the cells become more and more fragile, & wear out. Once the red cell membrane becomes fragile, the cell ruptures during passage through some tight spot of the circulation. Many of the red cells self-destruct in the spleen, where they squeeze through the red pulp of the spleen.

67. There, the spaces between the structural trabeculae of the red pulp, through which most of the cells must pass, are only 3 micrometers wide, in comparison with the 8-micrometer diameter of the red cell. When the spleen is removed, the number of old abnormal red cells circulating in the blood increases

68. When red blood cells burst and release their hemoglobin, the hemoglobin is phagocytized almost immediately by macrophages in many parts of the body, but especially by the Kupffer cells of the liver and macrophages of the spleen and bone marrow. During the next few hours to days, the macrophages release iron from the hemoglobin and pass it back into the blood, to be carried by transferrin either to the bone marrow for the production of new red blood cells or to the liver and other tissues for storage in the form of ferritin.

69. References Harsh Mohan  Textbook  of  Pathology Rapid Review  Pathology  by Edward F Robbins and Cotran Review of  Pathology  by Klatt and Kumar · Robbins Basic  Pathology  by Kumar, Abbas & Aster.