ANAEMIA.Physiology by Dr. Naushi Mujeeb pptx

Anemia- definition, classification and management

1. ANAEMIA By Dr. Naushi Mujeeb Professor Dept of Physiology

2. DEFINITION- Anaemia is a clinical condition in which Hb concentration of blood is below the normal range for the age and sex of the subject. This could be due to either too few RBCs or too little Hb in the cells. Therefore anaemia is labelled when the Hb concentration is less than: 13 g/dL in adult males, 12 g/dL in adult females, 15 g/dL in newborn, and

3. Grading of anaemia - depending upon the level of Hb - Mild anaemia – Hb 8–11 g/dL, Moderate anaemia – Hb 6–8 g/dL and Severe anaemia – Hb below 6 g/dL.

4. CLASSIFICATION- Aetiological (Whitby’s) classification- Types of anaemia depending upon the causative mechanism are: A. Deficiency anaemias - Iron deficiency anaemia Megaloblastic anaemia (pernicious anaemia ) due to deficiency of vitamin B12 Megaloblastic anaemia due to deficiency of folic acid Protein and vitamin C deficiency can also cause anaemia .

5. B. Blood loss anaemias or haemorrhagic anaemias - are commonly known and can be: Acute -as in accidents and Chronic- slow loss of blood e.g. piles, peptic ulcer, menstruation. C. Haemolytic anaemias - These are relative uncommon and occur in conditions associated with increased destruction of RBCs. These can be

6. 1. Hereditary haemolytic anaemias , e.g. as seen in: Thalassaemia , Sickle cell anaemia , Hereditary spherocytosis and Glucose 6-phosphate dehydrogenase (G6PD) deficiency. 2. Acquired haemolytic anaemias such as Immunohaemolytic anaemia (due to antibodies against RBCs), Haemolytic anaemia due to direct toxic effects (e.g. in malaria, snake venom, toxic effects of drugs and chemicals, etc.), Haemolytic anaemia in splenomegaly.

7. D. Aplastic anaemia - It occurs due to the failure of bone marrow to produce RBC e.g. X-ray irradiation, hypersensitivity of bone marrow to cytotoxic drugs, chemicals. E. Anaemia due to chronic diseases- It is seen in tuberculosis, chronic infections, malignancies, chronic lung diseases, etc. Morphological ( Wintrobe’s ) classification- Based on the mean cell volume (MCV), i.e. cell size and the mean corpuscular haemoglobin concentration (MCHC),

8. Diagnosis of the type of anemia may be assisted by relating the measurements of red blood cell count, hematocrit and hemoglobin to derive the  mean corpuscular volume (MCV)  and  the mean corpuscular hemoglobin concentration (MCHC) .

9. Formulas for RBC Indices-

10. i.e. haemoglobin saturation of RBCs, the anaemias can be classified as: 1. Normocytic normochromic anaemias - These are characterized by normal MCV (78–94 μ m3 or 78–94 μ L) and normal MCHC (30–38%). Such a morphological picture is seen in: Acute post- haemorrhagic anaemia , Haemolytic anaemias except thalassemia and Aplastic anaemias .

11. 2. Microcytic hypochromic anaemias - These are characterized by reduced MCV (< 78 μ m3 ) and reduced MCHC (< 30%). Examples of such anaemias are: Iron deficiency anaemia and Thalassaemia . 3. Macrocytic normochromic anaemia - It is characterized by increased MCV (> 94 μ m3 ) and normal MCHC (30–38%). Examples are: Megaloblastic anaemia due to deficiency of Vit B12, folic or intrinsic factor.

12. GENERAL CLINICAL FEATURES OF ANAEMIA- Anaemic hypoxia results due to decreased O2 carrying capacity of blood in anaemia owing to reduced Hb concentration. The hypoxia brings about several cardiorespiratory compensatory responses. So, general clinical features (symptoms and signs) in patients with anaemia are due to those caused by: Resulting tissue hypoxia and Resulting compensatory mechanisms .

13. General clinical manifestations of anaemia - which occur either due to tissue hypoxia or due to compensatory mechanisms are: Generalized muscular weakness, tiredness and easy fatiguability occur due to muscle hypoxia. Pallor of skin and mucous membranes (buccal and pharyngeal mucous membrane, conjunctiva, lips, ear lobes, palm and nail bed) occurs due to the deficiency of red coloured Hb in the blood. Respiratory symptoms such as breathlessness with increased rate and force of respiration occur due to compensatory stimulation of respiratory centre . Cardiovascular manifestations, such as palpitation, tachycardia and cardiac murmurs occur as a result of compensatory mechanisms increasing the cardiac output. In very severe cases of anaemia , features of cardiac failure, angina pectoris may also occur

14. Central nervous system manifestations due to cerebral hypoxia include lethargy, headache, faintness, especially on exertion, tinnitus, restlessness, confusion and drowsiness. Gastrointestinal system symptoms include anorexia, flatulence, nausea, constipation. In pernicious anaemia , there occurs atrophy of papillae on tongue. Reproductive system involvement occurs in females in the form of the menstrual disturbances such as amenorrhoea and menorrhagia and loss of libido. Basal metabolic rate is increased in severe anaemia .

15. IRON DEFICIENCY ANAEMIA- Iron deficiency anaemia is the commonest nutritional deficiency disorder present throughout the world, but its prevalence is higher in the developing countries. In India, iron deficiency is the commonest cause of anaemia . Iron deficiency anaemia is much more common: In women between 20–45 years than in men, At periods of active growth in infancy, childhood and adolescence. Daily requirement and dietary sources of iron- Daily requirement- Only 10% of the dietary intake of iron is absorbed. Therefore, daily requirement in the adult males is 5–10 mg/day and in females is 20 mg/day (to compensate the menstrual loss). Pregnant and lactating women require about 40 mg of iron per day.

16. Dietary sources- Foodstuffs vary both in their iron content and availability of iron for absorption into the body. The dietary sources of iron are meat, liver, egg, leafy vegetables, whole wheat and jaggery. The iron in foods of animal origin is better absorbed than iron in foods of vegetable origin.

17. CAUSES OF IRON DEFICIENCY ANAEMIA- Causes of iron deficiency vary with age, sex and country of residence of patient. In general, the causes of iron deficiency anaemia can be grouped as: 1. Inadequate dietary intake of iron as in: Milk fed infants, Poor economic status individuals, Anorexia, e.g. in pregnancy and Elderly individuals due to atrophy and poor dentition. 2. Increased loss of iron (as blood loss) from the body, - e.g. Uterine bleeding in females in the form of excessive menstruation, repeated miscarriages, postmenopausal bleeding,

18. 3. Increased demand of iron as in: Infancy, childhood and adolescence, Menstruating females and Pregnant females. 4. Decreased absorption of iron, as seen in: Partial or total gastrectomy, Achlorhydria and Intestinal malabsorption diseases.

19. CLINICAL FEATURES, LABORATORY FINDINGS AND TREATMENT- Clinical features of anaemia - 1. General features of anaemia . 2. Characteristic features of iron deficiency anaemia are in the form of following epithelial tissue changes: Nails become dry, soft and spoon-shaped (koilonychia). Tongue becomes angry red (atrophic glossitis). Mouth may show angular stomatitis. Oesophagus may develop their membranous webs at the postcricoid area leading to dysphagia (Plummer– Vinson syndrome).

20. Clinical features of anaemia - Nails become dry, soft and spoon-shaped (koilonychia). Tongue becomes angry red (atrophic glossitis). Mouth may show angular stomatitis. Oesophagus may develop their membranous webs at the postcricoid area leading to dysphagia (Plummer– Vinson syndrome).

21. Laboratory findings – 1. Blood picture and red cell indices- Hb concentration is decreased. RBCs are hypochromic (deficient in Hb) and microcytic (smaller in size). They show anisocytosis and poikilocytosis. Red cell indices like MCV, MCH and MCHC are decreased.

22. 2. Bone marrow findings - Marrow cellularity: Erythroid hyperplasia, Marrow iron: Deficient. 3. Biochemical findings – Serum iron decreases, often under 50 mg% (normal 60–160 mg%). Serum ferritin is very low indicating poor tissue iron stores. Total iron binding capacity is increased( normal:150-350microgm/dl). Treatment - Treatment of iron deficiency anaemia consists of: Oral administration of Fe2+ salts and Correction of causative factor if possible.

23. MEGALOBLASTIC ANAEMIA- Megaloblastic anaemias are characterized by the abnormally large cells of erythrocyte series. These are caused by defective DNA synthesis due to deficiency of vitamin B12 and/or folic acid (folate).

24. AETIOLOGICAL TYPES- I. Megaloblastic anaemia due to vitamin B12 deficiency- Causes of vitamin B12 deficiency are: 1. Inadequate dietary intake may occur in: Strict vegetarians and Breast-fed infants. 2. Malabsorption of vitamin B12 is more often the cause of deficiency and may be due to: Gastric causes leading to the deficiency of intrinsic factors such as an autoimmune cause of failure of secretion of intrinsic factor (Addisonian pernicious anaemia ), gastrectomy and congenital lack of intrinsic factor. Intestinal causes which are associated with decreased vitamin B12 absorption are tropical sprue, ileal resection, Crohn’s disease.

25. Pernicious anaemia - Aetiology - Addisonian pernicious anaemia is the term which is used specifically for the megaloblastic anaemia due to vitamin B12 deficiency occurring as a result of failure of secretion of intrinsic factor by the stomach owing to an autoimmune atrophy of gastric mucosa. Thus, pernicious anaemia is an autoimmune disease and in about 50% of patients, antibodies to intrinsic factor can be demonstrated. The disease is rare before the age of 30 years, occurs mainly between 45 and 65 years, and affects females more frequently than males. Features of pernicious anaemia include: Features of megaloblastic anaemia and Specific features of pernicious anaemia are: – Anti-intrinsic factor antibodies in serum (present in 50% cases) – Abnormal vitamin B12 absorption test corrected by the addition of intrinsic factor. Treatment of pernicious anaemia consists of regular administration of vitamin B12 by intramuscular route

26. II. Megaloblastic anaemia due to folate deficiency- Salient features of folic acid and its role in erythropoiesis. Causes of folate deficiency are: 1. Inadequate dietary intake due to poor intake of vegetables as seen in poor people, infants and alcoholics. 2. Malabsorption, e.g. in coeliac disease, tropical sprue and Crohn’s disease.

27. 3. Increased demand as occurs in: Physiological conditions, such as pregnancy, lactation and infancy and Pathological conditions of cell proliferation, such as increased haematopoiesis (as in haemolysis ) and malignancies. 4. Effect of drugs, such as certain anticonvulsants (e.g. phenytoin), contraceptive pills and certain cytotoxic drugs (e.g. methotrexate). 5. Excess urinary folate loss, e.g. in active liver disease. Features of folate deficiency anaemia include: Features of megaloblastic anaemia and Specific features of folate deficiency are: – Low serum folate levels.

28. CLINICAL FEATURES OF MEGALOBLASTIC ANAEMIA- A. General features of anaemia . Features specific to Megaloblastic anemia- Soreness & inflammation of tongue. Diarrhoea . Neurological manifestations e.g.tingling , numbness (functions of dorsal column pathway are affected).

29. CLINICAL FEATURES OF MEGALOBLASTIC ANAEMIA- B. Characteristic features of megaloblastic anaemia - 1. Blood picture and red cell indices Hb level is low. RBCs are larger in size (macrocytosis) but contain a normal concentration of Hb ( normochromia ).

30. MCV increases to 95–160 μm3 (normal 78–94 μm3 ). MCH increases to 50 pg (normal 28–32 pg ). MCHC usually normal (35 ± 3%) because both MCV and MCH increase. In late stages, MCHC may decrease

31. Peripheral smear shows nucleated RBCs with marked anisocytosis and poikilocytosis. Reticulocyte count increases to more than 5% (normal less than 1%). Life span of RBCs is decreased. WBCs and platelets decrease because of encroachment of megaloblastic tissue. 2. Bone marrow picture Bone marrow shows megaloblastic hyperplasia characterized by presence of: – 70% proerythroblasts and early normoblasts (normal 30%) and – 30% intermediate and late normoblasts (normal 70%).

32. 3. Biochemical finding- Serum bilirubin increases more than 1 mg/dL (normal 0.2–0.8 mg/dL) due to excessive destruction of RBCs in spleen, liver and bone marrow. Urine urobilinogen excretion may increase due to increased serum bilirubin. Serum iron and ferritin is usually increased because iron is not utilized by the immature RBCs. Serum vitamin B12 levels are decreased (normal 200– 900 pg /mL) in patients with megaloblastic anaemia due to vitamin B12 deficiency. Serum folate levels are decreased in the patients with megaloblastic anaemia due to folic acid deficiency. Red cell folate levels are more reliable indicator of tissue stores of folate than serum. In folic acid deficiency, red cell folate levels are decreased.

33. Changes in Nervous system- In advanced cases demyelination of white fibers of the spinal cord occurs, affecting the dorsal column called subacute combined degeneration of Spinal cord . This is associated with tingling and numbness in the hands and feet, motor and psychological disturbances. Administration of either Vit B or Folic acid will improve the blood picture of pernicious anemia, but while Vit B12 also protects against neuropathy, folic acid has no such effect.

34. Case 1: Elderly 68 years old male, Presented with loss of balance and paresthesia in the hand and feet for 8 months. Patient is type 2 diabetic and alcoholic. Physical examination showed a short-termed memory loss and an absence of vibration sensation and proprioception in the toes and ankles, he was positive for Romberg test when he closes his eyes. Hemoglobin is 9.7 g/dL, MCV 105 fl /cell, white and platelet counts are normal he is “Macrocytic”. Blood film has a hypersegmented neutrophil. What is your Diagnosis? Write the management.

35. Case 2: 62 years old male patient, Presented with fatigue, pallor, progressive shortness of breath and generalized weakness “symptoms of anemia”. Hemoglobin is 9.7 g/dL “anemic” MCV 69 fl /cell.(normal 80-96”). RDW is 18% . What other investigations will you do to confirm your diagnosis.

36. in a case like this the elderly people are not suppose to be iron deficient so when we see a patient with these symptoms we have to rule out malignancy first, this patient could be bleeding from gastric cancer, or bleeding from colonic cancer So to complete your work up, any patient above the age of 50 with iron deficiency anemia should have an upper and lower Endoscopy to detect any tumor there.

37. we have high MCV and patient is anemic and hypersegmented neutrophil the patient then is diagnosed with B12 deficiency. Red blood cell distribution width (RDW) is the variation of the size/volume of your  red blood cells .  A  normal range  for red cell distribution width is 12.2 to 16.1 percent in adult females and 11.8 to 14.5 percent in adult males. *When there is low hemoglobin and low MCV. then the patient have Iron deficiency anemia or Thalassemia trait (thalassemia minor), if the RDW is normal then it is Thalassemia trait if it’s high then it’s Iron deficiency anemia. Blood film shows pallor in the red blood cells. which indicates for hypochromic iron deficiency anemia. Also in iron deficiency anemia we have to do iron studies like serum iron levels, serum ferritin levels and total iron binding capacity.

38. END