Anaemia

Red cell structure

Red cells lack nuclei and cytoplasmic structures such as ER and mitochondria. Exist as biconcave discs, but able to change the shape. Over 90% of cytoplasm is haemoglobin

Function of red cell

Main function is oxygen and carbon dioxide transport.

Red cell values

Haemoglobin level (Hb) Red cell count (RCC) Haematocrit (PCV)

Red cell indices

Mean corpuscular volume (MCV) Mean corpuscular haemoglobin (MCH) Mean corpuscular haemoglobin concentration (MCHC)

Anaemia
Anaemia is present when the haemoglobin level in the blood is below the lower extreme of the normal range for the age and the sex of the individual.

Clinical features of anaemia

Fatigue and weakness Pallor CVS Dyspnoea on exertion Angina murmurs and CCF *CNS

Investigation of the anaemic patient

Hb RCC PCV MCV MCH MCHC Blood picture 129-175 g/l 4.5-5.7x1012/L 40-47% 80-96fl 27-33pg 320-350g/l normochromic/hypochromic normocytic/microcytic/macrocytic

Morphological classification of anaemia

Hypochromic/ microcytic MCV MCH MCH C q q Normochromic normcytic Normal Normal normal macrocytic o o

Mechanism of anaemia
Blood loss Decreased red cell lifespan (haemolysis)
Congenital defects ( Hb SS, Spherocytosis) Acquired defect (malaria)

Impaired red cell formation

Insufficient erythropoiesis: deficiencies od Fe, Vit B12, Folate Hypoplasia of bone marrow

Pooling and destruction of red cells in an enlarged spleen (hypersplenism) Increased plasma volume (pregnancy)

Blood film examination

Red cells size shape pattern of staining inclusions association White cell number morphology Platelets number morphology

Normal

Red cell size

Microcyte

Macrocyte

Red Cell Shape

Spherocyte Poikilocyte

Elliptocyte

Irregularly contracted cells

Pattern of staining
Hypochromic Hyperchromic& polychromatic

Target cells

Clasification of anaemia
Hypochromic microcytic anaemia Normochromic and normocytic Macrocytic anaemia Aplastic anaemia- patients present as repeated oral ulceration or oropharyngeal infections

Hypochromic microcytic anaemias

Differential diagnosis Iron deficiency anaemia Thalassaemia trait Anaemia of chronic disorder Sideroblastic anaemia

Iron deficiency anaemia

Most common type of anaemia affecting throughout the world affecting about 25% of the population. Very important because
Anaemia of pregnancy as it is associated with increased low birth weight, prematurity Children with IDA have impaired psychomotor development and cognitive performance IDA pts have decreased work capacity

Cause of iron deficiency

Blood loss Increased demand Nutritional deficiency

Iron deficiency anaemia

Hypochromic, microcytic, anisocytosis, poikilocytosis, target cellsand pencil shaped poikilocytes Decreased MCV, MCH and MCHC Low serum iron, serum ferritin and increased TIBC Bone marrow aspiration shows micronormoblastic erythropoiesis with absent iron stores

Treatment of Iron deficiency

Stop blood loss Treat deficiency with
Ferrous sulphate Ferrous gluconate Oral Vit C helps absorbtion Parenteral iron Oral iron

Beta Thalassaemia trait

Hypochromic, microcytic red cells. No anisocytosis, target cells seen Low MCV and MCH, but normal MCHC (Red cell count is high) Serum iron, ferritin and TIBC may be normal Haemoglobin electrophoresis shows elevated Hb A2 level (37%)

Anaemia of chronic disorder

Hypochromic, microcytic or normochromic normocytic red cells, rouloux formation, Serum iron low Serum ferritin high TIBC low Other evidence of chronic disease eg. high ESR

Iron stain

Normal

Anaemia of chronic disorder There is a defect in the iron transfer from the bone marrow macrophages to the erythroblasts. The treatment is the treatment of the underlying disorder

Normochromic /normocytic anaemia Macrocytic anaemia

Normochromic normocytic anaemia

This could be due to anaemia of chronic disorder. Anaemia with haemo-dilution can have this appearance eg rapid blood loss, pregnancy MCV, MCH and MCHC are normal, but haemoglobin is low.

Anaemia of liver disease

Target cells Macrocytosis Acanthocytosis Due to abnormalities of lipoprotein metabolism

Anaemia of renal disease

Red cells show marked red cell crenation, bur cells or helmet cells Could be due to abnormalities of erythropoietin secretion, defects in iron metabolism

Macrocytic anaemia
* Red cells are larger than small lymphocytes. * Mean corpuscular volume is larger than 98fl

Normoblastic erythropoiesis

Megaloblastic erythropoiesis

Causes of macrocytic anaemia

Megaloblastic erythropoiesis Any abnormality affecting DNA synthesis Oval macrocytes are seen Normoblastic erythropoiesis Erythropoiesis is normal

Round macrocytes are seen Liver disease, hypothyroidism, COAD, Scurvy

Vit B12 and folate deficiency are the commonest causes

Megaloblastic anaemia
Characterised by the distinctive cytological and functional abnormalities in peripheral blood and bone marrow cells due to impaired DNA synthesis Most commomnly secondary to Vit B12 or folate deficiency Is a cause of significant ill health in the world

Metabolism of Vitamin B12

Essential for normal haemopoiesis and integrety of nervous system Act as the co enzyme in chemical reactions affecting DNA synthesis Cyanacobalamin / cobalmin family Sources: foods of animal origin; Kidney, liver, heart Absorbtion is via gastric intrinsic factor in the ileum Tissue stores in the liver 1.5 mg, adequate for about 2 years

Metabolism of Folate
Essential for normal haemopoiesis Requred for large number of reactions involving transfer of one carbon units from one compound to another Glutamates family Sources: plant & animal tissue eg: liver kidney yeast fresh green vegetables Minimal daily requirement is 100-200 Qg Absorbtion is at the duodenum and jejunum Tissue stores: liver 5-20 mg, and is adequate for 4 months

Clinical manifestations
Vitamin B12 deficiency Macrocytic magaloblastic anaemia Glossitis Peripheral neuropathy and subacute combined degeneration of the spinal cord Folate deficiency Macrocytic megaloblastic anaemia Glossitis

Causes of deficiency
Vitamin B12
Decreased intake: Nutritional deficiency Impaired absorbtion: Gastric: Pernicious anaemia Gastrectomy Intestinal: Ileal lesions Fish tape worm

Folate
Decreased intake: Nutritional deficiency Impaired absorbtion: Coeliac disease Increased demand Pregnancy, haemolytic anaemia,

Special tests in the diagnosis

Vitamin B12 Serum B12 assay Radioactive vit B12 absorbtion test: Schilling test Response to treatment Reversion of erythropoiesis to normoblastic Healing of glossitis Folate Serum folate assay Red cell folate assay Response to treatment Reversion of erythropoiesis to normoblastic Healing of glossitis

Laboratory tests in megaloblastic anaemia (findings common to both conditions)

Low haemoglobin Low red cell count MCV increased (If over 125 fl almost always Vit B12 or Folate deficiency) MCH can be increased WBC can be low- Neutropenia Platelet count can be low-Symptomless thrombocytopenia

Peripheral blood film

Oval macrocytes Hypersegmented neutrophils Neutropenia thromboytopenia

Treatment of megaloblasic anaemia

Vitamin B12 deficiency Initial dosage: 1000 micrograms of hydroxycobalamin IM injection for daily for one week Maintainance dosage 1000Qg IM once every 3 months

Folate deficiency Folic acid 5mg daily

Response to treatment
Sense of well being in 2-3 days time Return of appetite Glossitis rapidly relieved Blood: MCV gradually falls, HSN disappear in 2 weeks If diagnosis of Vit B12 or Folate deficiency is doubtful always start treatment with Vit B12 and folate simultaneously. Never treat with folate alone as neurological symptoms of Vit B12 deficiency will worsen if treated with folate alone.

Aplastic anaemia
Serious and chronic disorder Reduction in the amount of haemopoietic tissue Inability to produce normal numbers of mature cells Hypo-cellularity can be patchy

Classification
Ideopathic Secondary to drug idiosyncracy:

Anticonvulsant methylhydrantoin Antibacterial chloramphenicol Antidiabetic tolbutamide Antirheumatic gold

chemical exposure infectious hepatitis pancreatic insufficiency Constitutional : associated with inherited defects of DNA repair eg-Fanconys anaemia

Clinical features
Anaemia
Pallor, fatiguability

Neutropenia
Infections, sore throat

Thrombocytopenia
Bleeding gums Echymosis

Oral ulcerations Oropharyngeal infections

Blood film:
**Hb and Blood film Rouloux formation Macrocytic or normochromic anaemia **WBC/DC: Neutropenia/leucopenia **platelet count: Thrombocytopenia **ESR

Aplastic anaemia
Normal bone marrow Bone marrow in aplastic anaemia

Dry or Blood tap is not uncommon