Chapter 11

• Hematotoxicology is the study of adverse effects of exogenous chemicals on blood and blood-forming tissues.
• Direct or indirect damage to blood cells and their precursors includes tissue hypoxia, hemorrhage, and infection.
• Xenobiotic-induced aplastic anemia is a life-threatening disorder characterized by peripheral blood pancytopenia, reticulocytopenia, and bone marrow hypoplasia.
• Idiosyncratic xenobiotic-induced agranulocytosis may involve a sudden depletion of circulating neutrophils concomitant with exposure that persists as long as the agent or its metabolites are in the circulation.
• Leukemias are proliferative disorders of hematopoietic tissue that originate from individual bone marrow cells.
• Xenobiotic-induced thrombocytopenia may result from increased platelet destruction or decreased platelet production, which lead to decreased platelet aggregation and bleeding disorders.
• Blood coagulation is a complex process involving a number of proteins whose synthesis and function can be altered by many xenobiotics.

Hematotoxicology is the study of adverse effects of exogenous chemicals on blood and blood-forming tissues. The delivery of oxygen to tissues throughout the body, maintaining vascular integrity and providing the many affector and effector immune functions necessary for host defense, requires a prodigious proliferative and regenerative capacity. The various blood cells (erythrocytes, granulocytes, and platelets) are each produced at a rate of approximately 1 to 3 million/s in a healthy adult; this characteristic makes hematopoietic tissue a particularly sensitive target for cytoreductive or antimitotic agents, such as those used to treat cancer, infection, and immune-mediated disorders. This tissue is also susceptible to secondary effects of toxic agents that affect the supply of nutrients, such as iron; the clearance of toxins and metabolites, such as urea; or the production of vital growth factors, such as erythropoietin. The consequences of direct or indirect damage to blood cells and their precursors are predictable and potentially life-threatening. They include hypoxia, hemorrhage, and infection.

Hematotoxicity may be regarded as primary toxicity, where one or more blood components are directly affected, or secondary toxicity, where the toxic effect is a consequence of other tissue injury or systemic disturbances. Primary toxicity is regarded as among the serious effects of xenobiotics, particularly drugs. Secondary toxicity is exceedingly common, due to the propensity of blood cells to reflect various local and systemic effects of toxicants on other tissues.

The production of blood cells, or hematopoiesis, is a highly regulated sequence of events by which blood cell precursors proliferate and differentiate. The bone marrow in the axial skeleton and proximal limbs is the principal site of hematopoiesis.

Whereas the central function of bone marrow is hematopoiesis and lymphopoiesis, bone marrow is also one of the sites of the mononuclear phagocyte system (MPS), contributing monocytes that differentiate into phagocytic cells in other tissues. A complex interplay of developing cells with stromal cells, extracellular matrix components, and cytokines make s up the hematopoietic inductive microenvironment. Each lineage is supported within a specific niche, and an array of cytokines and chemokines direct s a particular progenitor cell to the appropriate niche.

### The ...

Sign in to your MyAccess profile while you are actively authenticated on this site via your institution (you will be able to verify this by looking at the top right corner of the screen - if you see your institution's name, you are authenticated). Once logged in to your MyAccess profile, you will be able to access your institution's subscription for 90 days from any location. You must be logged in while authenticated at least once every 90 days to maintain this remote access.

Ok

## Subscription Options

### AccessPharmacy Full Site: One-Year Subscription

Connect to the full suite of AccessPharmacy content and resources including 30+ textbooks such as Pharmacotherapy: A Pathophysiologic Approach and Goodman & Gilman's The Pharmacological Basis of Therapeutics, high-quality videos, images, and animations, interactive board review, drug and herb/supplements databases, and more.