1. Anaemias
Polycythaemia

2. PATHOPHYSIOLOGY OF ANAEMIAS
Anaemia is defined as a condition in which the hemoglobin concentration is below the normal range, for the age and sex of the individual.
In adults, the lower extreme of the normal range is taken as 13 g /dl in males and 12 g / dl in females
or haematocrit below 40 % in males and 35 % in females). .

3. Subnormal levels of hemoglobin decrease the oxygen carrying capacity of the blood leading to hypoxia.
The function of tissues with high oxygen demand such as heart, brain and exercising muscles are most affected.

4. Normal Tongue

5. Anaemia

6. Symptoms of anemia tiredness, palpitation, easy fatigability,
generalized muscle weakness,
lethargy, and headache.
In older patients,
angina pectoris, (effect on heart)
mental confusion, visual disturbances (effect on brain)
intermittent claudications (pain in the skeletal muscles during exercise which disappears on rest) may be the presenting symptoms.
The severity of these symptoms varies with the severity of anaemia

7. Anaemia may be classified as mild, moderate and severe in the basis of haemoglobin concentration of the blood as follows:
Anaemia Hb Conc. (g /dl)
Mild
Moderate
Severe Less than 7

8. When a patient is diagnosed as suffering from anaemia, the treatment would depend on its etiology (cause).
However, before trying to find the cause, it is helpful to first classify anemia according to the red cell indices discussed below (laboratory classification of anaemia).
Once these indices are known, one can proceed to find out the cause:

9. Haematocrit (PCV) tube

10. RED CELL INDICES If the RBC count, haemoglobin concentration
and haematocrit (PCV) value
are known, certain indices (or absolute values) of the red cells of the person can be calculated.
These absolute values ( red cell indices) are helpful in the laboratory diagnosis of anaemia.

11. normal range Calculation

12. normal range Calculation

13. normal range Calculation

14. In an anaemic patient, the red cells may be:
On the basis of MCV, red cells can be
macrocytes, : MCV greater than 100 µ 3
normocytes : MCV µ 3
microcytes. : MCV less than 80 µ 3
On the basis of MCHC, red cells can be
Hypochromic : MCHC less than 32 %
Normochromic: MCHC: 32—38 %
(red cells cannot have MCHC > 38%)

15. Anaemias: Laboratory classification
On the basis of red cell indices, an anaemia may be classified as
(i) microcytic, normocytic or macrocytic, and
(ii) hypochromic or normochromic.

16. Anaemias: ETIOLOGICAL CLASSIFICATION
1. DEFICIENCY ANAEMIAS
IRON DEFICIENCY anaemia
PERNICIOUS anaemia
FOLIC ACID DEFICIENCY anaemia
2. HEMORRHAGIC ANEMIAS
CHRONIC BLOOD LOSS ;PILES
EXCESSIVE MENSES
3. HEMOLYTIC ANEMIAS
4. APLASTIC ANEMIAS

17. Iron deficiency anaemia
Iron deficiency is probably the commonest cause of anaemia in the world.
It is more common in the females than in males.
Iron deficiency results in the production of a smaller number of red cells, which are not only deficient in Hb (hypochromic), but also smaller in size (microcytic).
Thus in iron deficiency, the MCH is below 26 pg, MCHC below 32 % and MCV below 80 µ 3.

18. HYPOCHROMIC ANEMIA Normal red cells

19. Severe iron deficiency---
interferes with DNA synthesis. Hence there is a problem in :
erythropoiesis
cell division in many other tissues.
Severe iron deficiency is associated with not only severe anemia, but also with disorders of tongue (atrophic glossitis), esophagus (dysphagia) and nails (koilonychias-- spoon-like nails).
Iron deficiency can be easily treated by oral administration of Fe2+ salts.

20. Pernicious anaemia
Pernicious anaemia is caused by deficiency of vitamin B12 in the body.
Although vitamin B12 content of the diet of these patients is usually normal, the vitamin is not absorbed in the gut.
Normally, a glycoprotein (mol. wt. 45,000), known as intrinsic factor (I.F.), secreted by the gastric mucosa, helps in the absorption of vitamin B12 in the ileum.
Atrophy of gastric mucosa results in the absence of intrinsic factor, leading to malabsorption of vitamin B12.
Deficiency of vitamin B12 produces a megaloblastic bone marrow reaction ( developing red cells are megaloblasts not normoblasts) and a very severe degree of anaemia.

21. In P.A. peripheral blood,
the red cells are larger in size (macrocytes, MCV greater than 100 µ3)
but contain a normal concentration of haemoglobin (normochromic)
i.e. vitamin. B12 deficiency causes macrocytic normochromic type of anaemia.
Blood smear shows another two other characteristic features of red cells.
the cells show a wider variation in shape, i. e. all the red cells are not circular disks( poikilocytosis).
Secondly, the cell size varies from 4 µm to 12 µm , average 9.5 µm) (anisocytosis and macrocytosis). (normal : variation 6.7 to 7.7 µm, average 7.5 µm

22. MACROCYTIC ANEMIA

23. Anisocytosis

24. Red cells of different shapes

25. Besides anaemia, deficiency of vitamin B12 is associated with peripheral neuropathy and degeneration of spinal cord.
The disorders, if not treated, is invariably fatal.
Pernicious anaemia is an autoimmune disease.
The auto-antibodies destroy both the parietal and chief cells of gastric mucosa (gastric atrophy).
Pernicious anaemia can be treated by regular administration of vitamin B12 by intramuscular route.

26. Folic acid deficiency anaemia
Folic acid deficiency is fairly common during pregnancy.
It produces macrocytic normochromic type of anaemia
but there are no neurological problems.

27. Haemorrhagic Anaemias
Following an acute haemorrhage, anemia is normochromic, normocytic type.
Chronic blood loss, e.g. due to bleeding piles or excessive menstrual bleeding, leads to excessive loss of iron from the body.
Hence such patients usually show hypochromic microcytic (iron deficiency) type of anaemia.

28. Haemolytic Anaemias
Life span of red cells may be shortened by congenital defects like thalassemia and sickle cell disease,
Haemolytic anaemia may also be due to the presence of auto antibodies in the plasma, which destroy the red cells (autoimmune haemolytic anaemia).

29. SICKLE CELL ANEMIA

30. Haemolytic anaemia
Such types of anaemia are usually normocytic, normochromic type.
To overcome excessive destruction of red cells, the rate of erythropoiesis in the bone marrow is increased. That is why patients with this type of anemia show:
High reticulocyte count (10-20 %).
Increased rate of red cell destruction also leads to excessive production of bilirubin.
Therefore mild jaundice (haemolytic type) is another characteristic feature of haemolytic anaemia

31. Haemolytic anaemia: reticulocytes

32. 4. Aplastic Anaemias There is complete cessation of erythropoiesis.
It is a very serious and often fatal complication of
hypersensitivity reaction to certain drugs e.g. chloramphenicol, sulfonamides etc.
Excessive irradiation and cytotoxic drugs used in the treatment of malignant disorders also depress the bone marrow.
Besides very severe anaemia, severe leucopenia and thrombocytopenia are also present.
Death may occur due to infection or severe blood loss.
Bone marrow examination reveals presence of adipose tissue where red bone marrow is normally present, indicating cessation of haemopoiesis

33. NORMAL RED MARROW

34. MARROW : APLASTIC ANEMIA

35. POLYCYTHAEMIA (ERYTHROCYTOSIS)
The term refers to higher than normal haemoglobin concentration (above 18g/dl in men or 16 g/dl in women)
and/ or higher than normal red cell count (above 6 million/uL in men or 5.5 million/uL in women).
Polycythaemia may result from :
(i) Increased red cell mass or
(ii) Decreased plasma volume.
When elevated haemoglobin concentration/RBC count is solely due to contracted plasma volume, the condition is called relative polycythaemia.

36. Polycythaemia due to actual increase in red cell mass because of hypoxia, leading to increased production of erythropoietin, is known as secondary polycythaemia.
Polycythaemia vera (primary polycythaemia), a rare malignant condition, is discussed below.

37. Mechanism of secondary polycythaemia

38. Secondary polycythaemia
Due to hypoxia, may be seen in the following conditions:
(i) Physiological: in fetal life.
(ii) High altitude: in those residing at altitude of 10,000 feet or above.
(iii) Chronic pulmonary disorders interfering with O2 uptake in the lungs.
(iv) Congenital heart disorders with shunting of venous blood to the left side of the heart.
(v) Heavy smoking leading to high concentration of carboxyhaemoglobin in the blood.

39. Polycythaemia Vera (Primary Polycythaemia)
It is a rare disorder
There is uncontrolled over-production of mature red blood cells, white blood cells and platelets.
The circulating blood cells (unlike in leukemia) are morphologically normal.
It is basically a malignant disorder of bone marrow.
In contrast to secondary polycythaemia, patients of polycythaemia vera have very low plasma erythropoietin levels (negative feedback effect on erythropoietin production).