Haematology Diseases PDF

# HUMAN BLOOD ## Haematology Diseases ### Blood Consists Of: - Red Blood Cells (RBCs) - White Blood Cells - Platelets - Plasma ### Hemopoiesis (The formation of blood cells) - The hemopoietic system includes the bone marrow, liver, spleen, lymph nodes and thymus. - Liver & spleen are the chief si...

# HUMAN BLOOD ## Haematology Diseases ### Blood Consists Of: - Red Blood Cells (RBCs) - White Blood Cells - Platelets - Plasma ### Hemopoiesis (The formation of blood cells) - The hemopoietic system includes the bone marrow, liver, spleen, lymph nodes and thymus. - Liver & spleen are the chief sites of hemopoiesis from 6 weeks to 7 months, when the bone marrow becomes the main source of blood cells. The bone marrow is the only source of blood cells during normal childhood and adult life. - RBCs survive 120 days, platelets around 7 days but granulocytes only 7 hours. ### Erythropoiesis - Pluri-potent stem cell - Uni-potent stem cell (CFU-E) - Colony Forming Unit - Erythrocyte - Pro-Erythroblast - Basophilic Erythroblast - Polychromatic Erythroblast - Orthochromatuc Erythroblast - Reticulocyte - Erythrocyte (Mature RBC) ### Granulocytopoiesis | Thrombocytopoiesis ------- | -------- Pluri-potent stem cell | Pluri-potent stem cell CFU-G | CFU-Mega Myeloblast | Megakaryoblast Pro Myelocyte | Megakaryocyte Myelocyte | Platelets Granulocyte (PML) | ## Normal Ranges (adults) - **Hemoglobin**: - 13.5 - 17.5 gm/dL (Male) - 11.5 - 15.5 gm/dL (Female) - **Haematocrit (PCV)**: the volume of packed RBCs in 100 ml blood - 40 - 52% (Male) - 36 - 48% (Female) - **RBCs Indices**: - **MCV (Mean Corpuscular volume):** 77 - 95 fL - $$\frac{PCV\times10}{RBCs count /cmm} = \frac{45\times10}{5} = 90 femtolitre.$$ - **MCH (Mean Cell Hb):** 27 - 32 pg - $$\frac{Hb\times10}{RBCs count /cmm} = \frac{15\times10}{5} = 30 Picogram$$ - **MCHC (Mean Cell Hb Concentration):** 32 - 36 gm/dl - $$\frac{Hb}{PCV}\times100 = \frac{15\times100}{45} = 33gm/dl$$ - **RDW (Red Cell Distribution Width):** 11.5 - 14.5% - RDW is a measure of the degree of anisocytosis (variation in RBC size). - Increased: Many types of anemia (iron deficiency, pernicious anemia, folate deficiency, thalassemia), liver disease. - **Reticulocytes**: 0.5 - 2.5% - **ESR**: 2 - 12 mm/1st hour - **WBC**: 4000 - 11000/cmm - **Neutrophils**: 50 - 70% - **Lymphocytes**: 20 - 45% - **Eosinophils**: 1 - 5% - **Monocytes**: 3 - 7% - **Basophils**: 0 - 1% - **Platelets**: 150,000 - 400,000 /cmm ## ANEMIAS ### Anemia Scheme **Definition**: Reduction in one of the following parameters: - **RBCs count**: N: 4.5 - 6 million/cmm in 8. - **Hb concentration**: N: 15 gm% (13.5 - 17.5) in 8. - **Hematocrite value (packed cell volume)**: N: 45% Females are usually 1 to 2 gm Hb & about one million RBCs per cmm less than males. (due to the effect of androgen in 8 plus the effect of menstruation) ### Pathophysiology - Hyperdynamic circulation -> short circulation time & high cardiac output. - ↑↑↑ Erythropoietin by the kidney -> ↑↑ RBCs - ↑↑ O2 delivery to the tissue (shift of O2 dissociation curve to the right): This is due to excess production of 2,3 DPG (2,3, diphosphoglycerate) which make the binding between O2 & Hb very weak. - Redistribution of the blood: blood is shifted to the vital organs e.g. brain. ### Clinical Picture **Symptoms**: (depend on the rate of reduction rather than the absolute value of Hb) - **General**: Fatigue & lassitude. - **CVS**: manifestations of low cardiac output inspite of high Cop. - **CNS**: loss of concentration, headache & dizziness. - **Genital**: Impotence, menstrual irregularities. ### Signs: - **Pallor** - **Hyperdynamic circulation**: Tachycardia, ↑S1, gallop, hemic murmur. - **Lower limb edema**: "due to hyperdynamic circulation, hypoxia & heart failure" - **Papiledema and retinal hemorrhage**: due to ↑ permeability. ### Investigations Anemia is not a diagnosis, it is an abnormal clinical finding requiring an explanation for its cause. - **I. CBC**: - **RBCs & HB**: ↓↓ with all types - **WBCs & platelets**: ↓↓ with Megaloblastic, Aplastic anemia - **Indices**: - **MCV, MCH, MCHC**: e.g. - Normal in hemolytic & aplastic anemia. - ↓ in iron deficiency anemia. - ↑ in megaloplastic anemia **except** MCHC is normal - **II. Color index**: 1 (0.9 - 1.1) **except** - **Iron deficiency anemia**: < 1 - **Megaloplastic anemia**: > 1 - **III. Bone marrow examinations**: e.g. Erythroid hyperplasia in iron deficiency, aplasia in aplastic anemia - **IV. Hepatic and renal investigations**: e.g. KFTS, LFTs. ### Treatment: - **Blood transfusion.** - **Packed RBCs.** - **Treatment of the cause**: e.g. - Fe -> in iron deficiency anemia. - Folic acid & vitamin B12 -> Megaloblastic anemia. - **Treatment of complications**: as HF (and mention) ## Classification Of Anemias ### Classification of Anemias By Pathophysiology - **I. Decreased production**: - ↓↓ Hb Synthesis: Iron Deficiency anemia, Thalassemia, Anemia of chronic disease. - ↓↓ DNA Synthesis: Megaloblastic anemia. - ↓↓ Stem Cell: Aplastic anemia. - **II. Increased destruction**: Hemolytic anemia. - **III. Increased RBCs loss**: Acute-post-hemorrhagic anemia. ### Classification of Anemias by Cell Size: - **I. Microcytic hypochromic**: - Iron deficiency anemia: defect in haem synthesis. - Thalassemia: defect in globin synthesis. - Anemia of chronic disease: defect in haem synthesis. - Sideroblastic anemia: defect in haem synthesis. - **II. Normocytic normochromic**: - Hemolytic anemia. - Aplastic anemia. - Acute-post-hemorrhagic anemia. - Anemia of chronic disease. - **III. Macrocytic**: - Vitamin B12 deficiency. - Folic acid deficiency. - Myelodysplasia. - Myxedema. - Alcohol. - Chronic liver diseases. ## Megaloblastic Anemia **Definition**: It's a hematological disorder characterized by Pancytopenia with 4 criteria: - Megaloplastic hyperplasia of the bone marrow. - Evidence of Macrocytosis. - Good response to vit. B12 & folic acid. - Neurological & G.I.T manifestations. ### Pathophysiology: - **Arrest of the division**: as vit. B12 & folic acid are essential for DNA synthesis. This will result in big cells (megaloblasts). - **Ineffective erythropoesis**: most of megaloblasts undergo intra mdullary hemolysis. - **Evidence of macrocytes**: some megaloblasts can escape the bone marrow and appear in the blood as macrocytes. - **Rapid hemolysis**: macrocytes are rapidly sequestrated by the spleen. ### Etiology: - **I. Vitamin B12 deficiency**: - Diminished intake of vitamin B12 which is present in animal products. - Decreased absorption: - **Pernicious anemia** (The most common cause) - Gasterectomy, chronic gastritis. - Malabsorption syndrome. - Ileal resection. - Chronic liver diseases: Body stores are Sufficient for 3yrs. - Transcobalamin II deficiency (rare) - **II. Folic acid deficiency**: - Decreased intake: lack of vegetables & fruits, alcoholism. - Decreased absorption: malabsorption syndrome. - Increased requirement: Pregnancy, malignancy. - Drugs: Methotrexate, phenytoin. ### Clinical Picture: - **Anemia**: see scheme - **Neurological manifestations (3p)**: Vit B12 is an important co factor in the formation of myelin sheath. - Peripheral neuropathy. - Pyramidal tract lesion. - Posterior column -> loss of deep sensations. - **gastrointestinal manifestations (3 Atrophy)**: - Atrophic glossitis. - Atrophic gastritis. - Atrophy in the intestine. ### Investigations: - **I. CBC**: - **Pancytopenia**: RBCs, Hb, WBCs & platelets: ↓↓ - **MCV, MCH, MCHC**: ↑ except MCHC is normal. - **Anisocytosis** (unequal size), **Poikilocytosis** (abnormal shapes) - **Color index**: >1 - **II. Bone marrow examinations**: Megaloplastic hyperplasia - **III. Measurement of serum B12 & folic acid**: - serum B12: < 100 pg/mL (N: > 200 pg/ml) - serum folate: < 4 ng/ml (N: 6-20 ng/ml) - **IV. Schilling test**: - Giving the patient vit. B12 (100 ug IV) to saturate body stores. - Giving patient radioactive B12 (lug) orally. - Collect patient urine /24 h and measure radioactive B12 - If vitamin B12 is absorbed, it will appear in urine. - **Low excretion**: Malabsorption. - **Normal after intrinsic factor orally**: Pernicious anemia. - **Normal after antibiotic**: Bacterial overgrowth. - **Normal after pancreatic enzymes**: Pancreatic insufficiency. - **V. Therapeutic test**: Giving small dose of vitamin B12 or folic acid -> Reticulocytosis. - **VI. Serological test**: Anti parietal cell antibodies & anti intrinsic factor antibodies may be present in pernicious anemia. - **VII. FIGLU Test**: +ve in folic acid deficiency. - Oral loading with histidine is accompanied by high urinary excretion of Formin Ino GLUtamic acid, an intermediate metabolite in the conversion of L-histidine to L-glutamic acid. (+ve FIGLU test). ### Differential Diagnosis: - **Other causes of macrocytic anemias**: - Myelodysplasia - Myxedema. - Alcohol. - Chronic liver diseases. ### Treatment - **As scheme plus replacement therapy** - **1. Vitamin B12 deficiency**: - Vitamin B12 (Hydroxycobalamine): - Intramuscular injections of 1000 ug of vitamin B12: usually given daily for the first week, weekly for the first month, and then monthly for life. - It is a lifelong disorder, and if patients discontinue their monthly therapy the vitamin deficiency will recur. - **2. Folic acid deficiency**: - Folic acid: 5 mg/day orally - Vitamin B12 is essential for the transformation of folic acid into the active form folinic acid, So large doses of folic acid may aggravate the manifestations of vitamin B12 deficiency especially neurological manifestations. # Try to learn something about everything and everything about something. - Thomas Henry Huxley