Blood

Dr. Raghuveer Choudhary

Assosiate Professor of Physiology Dr S.N.Medical College Jodhpur

Anemia is decreased red cell mass affecting tissue oxygenation

Practical - Low Hb* or Low Hematocrit*

 Anemia means a decrease in hemoglobin content,

or RBCs count,
or both of them below the normal range. Anemia leads to a decrease in blood ability to

transport oxygen to tissue cells.

Anaemia is labelled when Hb Conc is less

13 gm/dl in adult males 11.5 gm/dl in adult

Gradings of Aneamia
Mild Aneamia- Hb 8-10

females 15 gm/dl in newborns 9.5 gm/dl at 3 month of age

Gm% Moderate Aneamia- 6-8 Gm% Severe Aneamia Hb <6 Gm%

 Types & causes of anemia:

I-Blood loss anemia: A-Acute blood loss anemia: Due to severe hemorrhage. Plasma volume is replaced rapidly by the fluids present in tissue spaces. This leads to marked dilution of the blood. RBCs are replaced within 2-3 weeks. Sufficient iron gives normocytic cells but insufficient iron will produce microcytic RBCs.

 Types & causes of anemia:

I-Blood loss anemia: B-Chronic blood loss anemia: Due to repeated loss of small amounts of blood over a long period e.g.: -Gastrointestinal bleeding (peptic ulcer)/piles -Excessive menstruation. -Hemorrhagic diseases. Due to depletion in iron stores the newly formed RBCS are microcytic.

Types & causes of anemia:

II-Aplastic anemia: It results from destructione of bone marrow. Diminished erythropoisis It may result from: 1-Excessive exposure to x-rays or gamma rays. 2-Chemical toxins e.g. cancer therapy & prolonged exposure to insecticides or benzene. 3-Invasion of bone marrow by cancer cells. 4-Following infection by hepatitis. Damaged bone marrow dont produce any RBCs, so in aplastic anemia RBCS are normocytic. It is associated with decrease in WBCs & platelets.

 Fanconi anemia congenital

Direct stem cell destruction external radiation

Drugs - chloramphenicol, gold, sulfonamides, felbamate Other Toxins - Solvents, degreasing agents, pesticides

Viral infection - parvovirus B19, HIV, other

Idiopathic

 Should be suspected from an inappropriately low

reticulocyte count. Diagnosis can be confirmed by bone marrow examination.

Types & causes of anemia:

III-Hemolytic anemia:
It results from increased rate of destruction of RBCs inside the vascular system. Causes of hemolytic anemia: A-Hereditary:(intracopuscular defects) 1-Membrane abnormalities.e.g.- hereditary spherocytosis, hereditary elliptocytosis 2-Enzyme deficiency e.g. G-6-P Dehydrogenase.( Oxidation vulnerability) 3-Hemoglobin abnormalities.- sickle cell syndromes, unstable hemoglobins,methemoglobinemia 4Glycolytic defects: pyruvate kinase deficiency, 5 Thalassaemia

B-Acquired:(extracorpuscular defects)

1-Incompatible blood transfusion.(Ag-Ab reaction),erythroblastosis foetalis 2-Parasitic infection e.g. malaria. 3-Toxic agents e.g. snake venom & insect poisons. 4-Thermal e.g. several burns. 5 - Microangiopathic:Prosthetic valve 6 - Hypersplenism anemia caused by splenomegaly

Types & causes of anemia: IV-Dyshemopoietic anemia: Deficiency anemia'sWhich may be due to: 1-Iron deficiency anemia. 2-Maturation failure (megaloblastic) anemia:a-Vitamin B12 deficiency. b-Folic acid deficiency. 3-Anemia of endocrine disorders. 4-Protein deficiency anemia. 5-Anemia of renal failure.

1.

Morphological Approach Red blood cell size(MCV) Microcytic (Cells Smaller than normal size i.e. MCV< 80 fl) Normocytic (Cells Normal sized i.e. MCV = 80-100 fl) Macrocytic (Cells bigger than normal size i.e. > 100 fl) Concentration of Hb(MCHC) Normochromic (Normal Hb Concentration) Hypochromic (Decreased Hb Concentration- cells paler than normal)

 Normochromic=RBC with normal amount of

hemoglobin.
Hypochromic=RBC with low level of hemoglobin.

No hyperchromic RBC.

 Normocytic Normochromic Anemia.

Microcytic Hypochromic Anemia.

Macrocytic Hypochromic Anemia.

 Vitamin B12/Folic acid deficiency

Second most common type of anemia.

Macrocytic anemia, pancytopenia. Pernicious anaemia
autoimmune, Gastric atrophy, VitB12 def.

 Decreased Vit B12 / Folate

Decreased DNA Synthesis

Delayed maturation of erythroblasts (Nucleus) Increased cell size (macrocytes)

Normal hb content (Normochromia)

Decreased RBC number Decreased WBC number (pancytopenia)

Anemia & Pancytopenia.

Vitamin B12 and Folic acid: Essential for DNA synthesis (Thymidine triphosphate) Abnormal and diminished DNA Failure of division and maturation Macrocytic / Megaloblastic anemia

 The presence of macro

ovalocytes having an MCV >115 fl, anisocytosis, poikilocytosis and hypersegmented neutrophils suggests a megaloblastic disorder associated with a nutritional deficiency, i.e., vitamin B12 or folate deficiency.

 Essentials of Diagnosis Macrocytic anemia. Macro-ovalocytes and hypersegmented neutrophils on peripheral blood smear. Serum vitamin B12 level less than 100 pg/mL.

Other Lab tests Homocysteine Folate def. Methylmalonic acid B12 def. Intrinsic Factor Ab test very specific for pernicious anemia but only 50% sensitive Parietal cell AB test quite sensitive (90%) but not specific Schilling test

The bone marrow is hypercellular, showing evidence of abnormal proliferation and maturation of multiple myeloid cell lines. These abnormalities are most evident in the erythroid precursors with large megaloblastic erythroblasts present in increased numbers throughout the marrow.

Normal

Hypercellular

Hypocellular

Similar morphologic abnormalities can be seen in the other myeloid elements, e.g., large or giant metamyelocytes and other granulocytic precursors. This ineffective erythropoiesis is accompanied by intramedullary hemolysis causing an elevated lactate dehydrogenase and indirect bilirubin in the serum. However, the reticulocyte count is low due to the abnormal maturation process.

B12
B12
IF

Stomach

Parietal cells produce IF

Ileum IF receptors

BIF 12+IF
IF

B12

B12

Methylmalonic Acid (MMA) and Homocysteine Serum Concentrations Cobalamin and folate are cofactors in several important metabolic pathways in the cell. The hydroxylated form of cobalamin plays an important role in the metabolism of homocysteine and MMA. The conversion of homocysteine to methionine requires both vitamin B12 and folate as cofactors.

However, the metabolism of Lmethylmalonyl CoA to succinyl CoA, an enzymatic pathway involved in oxidative phosphorylation reactions within the cell, only requires vitamin B12.

Differentiating cobalamin deficiency from folate deficiency by measuring serum MMA and homocysteine levels. Both of these metabolites are elevated in cobalamin deficiency,

In folate deficiency patients, serum homocysteine levels are markedly increased, while serum MMA levels are not elevated

B12
B12
IF

Stomach

Parietal cells produce IF

Ileum IF receptors

BIF 12+IF
IF

B12

B12