Disposition of Toxic Compounds

Disposition of Toxic Compounds

• Toxicants cross body membranes and enter the bloodstream via absorption.
• There's no specific system for absorption; it's similar to how essential substances (e.g., oxygen, nutrients) are absorbed.
• Key absorption sites are the gastrointestinal tract (GI), lungs, and skin.
• Biological membranes are selectively permeable; only certain substances can pass through. Factors like size, lipid solubility, similarity to body molecules, polarity, and charge determine permeability.
• Absorption mechanisms include filtration through pores (small molecules), passive diffusion (lipid-soluble molecules down a concentration gradient), active transport (specific carrier proteins, often inhibited by metabolic poisons and saturated at high substrate concentrations), and facilitated diffusion (specific carrier proteins required).
• Phagocytosis and pinocytosis transport insoluble substances through membrane engulfment.

Absorption of Toxicants via GI

• Many environmental toxicants ingested with food are absorbed in the gastrointestinal tract.
• Organic acids or bases are absorbed passively, depending on the pH of a particular part of the GI tract.
• Absorption depends on lipid solubility (unionized form).
• The stomach, with acidic environment, promotes the absorption of lipid-soluble weak acids; the small intestine, a more neutral environment, absorbs some lipid-soluble compounds slower.
• Mass action law, where the proportion of unionized form of a substance remains constant, is important for absorption.
• Surface area is a key factor in absorption, with the large surface area in the small intestine (villi and microvilli) promoting greater absorption.
• Blood flow rate also affects absorption, as it removes absorbed substances.

Absorption of Toxicants via Lungs

• Inhalation is a significant route for chemical absorption.
• Absorption of toxicants in lungs depends on factors such as the presence of gases, vapors of volatile liquids, particulates (e.g., asbestos).
• Lungs have a significant surface area with excellent blood supply.
• This fast blood flow maintains a concentration gradient across the absorption site, thus facilitating absorption.

Hematotoxicity

• Hematotoxicity studies the effects of chemicals and drugs on blood and blood-forming cells.
• Blood cell production rates vary by organism but are significant in conditions needing increased blood cell production, like inflammation.
• Damage to blood cells can lead to hypoxia, hemorrhage, and infection.
• Erythrocyte production depends on the continuous synthesis of hemoglobin.
• Xenobiotics may disrupt hemoglobin synthesis, impacting erythrocyte function, impacting globin synthesis and the balance in the synthesis between the α and β chains.

Toxicity of Liver

• The liver is a primary organ for processing absorbed toxicants; it intercepts nutrients, drugs, and waste products entering the bloodstream via portal circulation.
• Toxicants can affect transport, synthesis, and metabolism functions of the liver; including precursor or transport molecules or enzymatic processes.
• Damage can lead to impaired function, cell death, and scar tissue formation.
• Alcohol abuse, a major cause of liver damage, leads to lipid accumulation in hepatocytes (fatty liver).
• Continued abuse can lead to cirrhosis and impaired function.
• Bile production and excretion are affected in situations involving exposure to toxicants.

Toxicity of Platelets

• Platelets are crucial for blood clot formation
• Xenobiotics can interfere with platelet function and count, leading to thrombocytopenia or other issues.
• Thrombocytopenia can result from reduced platelet production or increased destruction.
• Various drugs or chemicals can affect platelet response to injury - impacting the body's ability to form a stable hemostatic plaque.
• Some chemicals interfere with platelet function mechanisms; some example include certain antibiotics and NSAIDS.

Toxicity of Leukocytes

• Leukocytes/White Blood cells are components of the immune system involved in phagocytosis (ingestion of foreign material).
• Chemical exposure can impair the ingestion process and impair hemapoiesis.
• Certain chemicals can damage DNA, affect cellular components, or influence immune-response process, leading to abnormal function, and/or potential disease states.
• Acute and chronic exposure to chemicals can severely impair the body's natural defense mechanisms from disease, by causing significant damage to the immune system.

Toxic Effects of Fibrin Clot Formation

• Fibrin clot formation is a cascade of enzymatic reactions involving multiple proteins.
• Xenobiotics can interfere with these mechanisms by affecting the level of certain blood proteins necessary for clot formation.
• Interference with vitamin K or other components involved in the formation phases in blood protein clotting or other aspects of the fibrinolytic processes can lead to serious complications.

Hepatotoxicity

• Aflatoxins, produced by Aspergillus fungi, are potent liver toxins, capable of inducing acute liver damage, long-term issues, leading to cirrhosis and liver cancer.
• α-amanitin, found in some mushrooms, is a potent inhibitor of RNA polymerase, leading to liver damage.
• Substances that affect liver detoxification processes can lead to liver damage.
• exposure to these chemicals, can result in more than one toxic event.
• Several factors affect susceptibility to these toxins, including dietary exposure and pre-existing liver conditions.

This quiz covers the processes by which toxic compounds are absorbed into the bloodstream. It explores key absorption mechanisms, sites, and the factors influencing permeability across biological membranes. Test your understanding of how toxicants interact with the body and the implications for health.