blood toxicity

Toxic Responses of the Blood
Hematotoxicology is the study of the adverse effects of exogenous chemicals on blood and blood-forming tissues. Blood contains many element in addition to other organs such as bone marrow which is the site of hematopoiesis (cell production), spleen which is responsible for clearance of defective cells, and lymph nodes.
Bone marrow contains stem cells which are immature precursors for RBCs, WBCs and platelets, each are produced approximately 1-3 millions/sec., RBCs life spam is 120 days.

Hematotoxicity may be primary (direct), in which one or more blood components are affected directly, or secondary (indirect), in which the toxic effect is a consequence of other tissue injury or systemic disturbances.
Toxicology of the Erythron
The Erythrocyte
Erythrocytes [red blood cells (RBCs)] transport oxygen from the lungs to the peripheral tissues and carbon dioxide from tissues to the lung. Erythrocytes also are involved as a carrier and/or reservoir for drugs and toxins. Xenobiotics may affect the production, function, and/or survival of erythrocytes. Acute damage to RBCs or its Hb can result in anemia. Anemia results from decrease production and increase destruction of erythrocytes. The usual parameters of a complete blood count (CBC), including the RBC count, hemoglobin concentration, and hematocrit (PCV), can establish the presence of anemia. Increased destruction usually is accompanied by an increase in reticulocytes (young erythrocytes).
Two related processes contribute to the increased number of reticulocytes in humans.
First, increased destruction is accompanied by a compensatory increase in bone marrow production, with an increase in the number of cells being released from the marrow and into the circulation. Second, during compensatory erythroid hyperplasia, the marrow releases reticulocytes earlier in their life span; thus, the reticulocytes persist for a longer period in the peripheral blood.

Toxicology of the Leukon
Toxic Effects on Platelets (thrombocytes)
Toxic Effects on Fibrin Clot Formation
CO poisoning:
cyanide poisoning
Alterations in Red Cell Production
Erythrocyte production is a continuous process that is dependent on frequent cell division and a high rate of hemoglobin synthesis. Adult hemoglobin (hemoglobin A) is a tetramer composed of two ? -globin and two ?-globin chains, each with a heme residue. Abnormalities that lead to decreased hemoglobin synthesis are relatively common (e.g., iron deficiency). The synthesis of heme requires the incorporation of iron into a porphyrin ring. Iron deficiency usually results from dietary deficiency or increased blood loss. Which may potentiate the risk of developing iron deficiency anemia. Defects in the synthesis of the porphyrin ring of heme can lead to sideroblastic anemia, with its characteristic accumulation of iron in bone marrow erythroblasts. The accumulated iron precipitates within mitochondria, causing the intracellular injury.
Xenobiotics Associated with sideroblastic Anemia include: ethanol, isoniazide, pyrazinide, cycloserine, chloramphenicol, zinc and lead intoxication.


Many factors can affect blood toxicity:
1. Decrease folic acid or vitamin B 12 which are necessary to maintain the synthesis of DNA during RBCs production, their deficiency causes megaloplastic anemia. E.g. of drugs cause folic acid deficiency: methotrexate, phenytoin, primidine, carbamazepine and phenobarbital. E.g. of drugs cause vitamin B12 deficiency: colchicin, neomycin, ethanol and omeprazol.
2. Chemical toxicity to the bone marrow may cause aplastic anemia which is inability of bone marrow to proliferate, this life threatening disorder is characterized by reticulocytopenia and bone marrow hypoplasia in addition to peripheral blood pancytopenia which is a decrease in the circulating number of RBCs, WBCs and platelets. This is caused by ionization, radiation, gold, mercury, chloramphenicol, penicillin, methicillin, streptomycin, allopurinol and tetracycline.
3. Bone marrow damage may have an allergic basis involve antibodies to a precursor cells and sensitizing chemicals, e.g. chloramphenicol induced bone marrow damage may be involved in immune mechanism

Alteration in the respiratory function of hemoglobin:
Hemoglobin consist of 4 chains (tetramer): 2 ? globin and 2 ? globin chains, with a heme residue.

Reversible binding of O2 with Hb is called oxygenation.

Oxygen dissociation curve: