Toxicology Lecture 6: Blood Toxic Responses

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Questions and Answers

What is the study of adverse effects of chemicals on blood and blood-forming tissues called?

Hematotoxicology (correct)

Hepatotoxicology

Nephrotoxicology

Cardiotoxicology

Why is the blood considered a unique target organ?

It is a non-essential organ

It has low regenerative capacity

It is not susceptible to toxicants

It has vital functions and is highly susceptible to intoxication (correct)

What is a consequence of direct or indirect damage to blood cells and their precursors?

Arthritis

Hypoxia, hemorrhage, and infection (correct)

Diabetes

Hypertension

What is erythropoietin?

A vital growth factor Signup and view all the answers

What is the primary reason why hematotoxicity is considered a serious effect of xenobiotics?

It is among the more common serious effects of xenobiotics Signup and view all the answers

What is the term for hematotoxicity caused by damage to other tissues or systemic disturbances?

Secondary hematotoxicity Signup and view all the answers

What is a function of the blood mentioned in the text?

Maintaining vascular integrity Signup and view all the answers

Why is the liver considered important in the risk assessment of individual patient populations exposed to toxicants?

It is among the most important considerations in the risk assessment of individual patient populations Signup and view all the answers

What percentage of the circulating blood volume is composed of erythrocytes?

40-45% Signup and view all the answers

What is the primary function of erythrocytes?

To transport oxygen from the lungs to peripheral tissues Signup and view all the answers

What is a common effect of xenobiotics on erythrocytes?

A decrease in red cell mass Signup and view all the answers

What is the name of the protein component of hemoglobin?

Globin Signup and view all the answers

What is the result of an imbalance between α- and β-chain production?

Thalassemia Signup and view all the answers

Which xenobiotic is known to interfere with erythroblast heme synthesis?

All of the above Signup and view all the answers

What is the result of a deficiency in folate and/or vitamin B12?

Megaloblastic anemia Signup and view all the answers

What is necessary for the synthesis of thymidine or its incorporation into DNA?

Folate and vitamin B12 Signup and view all the answers

What is the common effect of insults that increase oxidative injury, decrease metabolism, or alter the membrane?

Decrease in erythrocyte concentration and a corresponding anemia Signup and view all the answers

Which of the following diseases is associated with significant hemolysis?

Malaria Signup and view all the answers

What is the function of NADH-diaphorase in erythrocytes?

To protect against oxidative injury Signup and view all the answers

What is the most common enzyme defect associated with oxidative hemolysis?

Glucose-6-phosphate dehydrogenase (G-6-PD) Deficiency Signup and view all the answers

What is the mechanism of immunologic destruction of erythrocytes in immune hemolytic anemia?

IgG or IgM antibodies interacting with antigens on the erythrocyte surface Signup and view all the answers

What is the effect of some drugs, such as penicillin, on erythrocytes?

They bind to the surface of the erythrocyte and elicit an immune response Signup and view all the answers

What is the effect of cytotoxic drugs, such as methotrexate, on granulocytes?

They inhibit the proliferation of granulocytes Signup and view all the answers

What is the effect of oxidative injury on erythrocytes?

It decreases the lifespan of erythrocytes Signup and view all the answers

What is the basis of platelet function?

Coordinated interaction of biochemical response pathways Signup and view all the answers

Which of the following drug groups does not affect platelet function?

Anti-diabetic drugs Signup and view all the answers

What is the effect of impaired liver function on coagulation?

Decreased production of coagulation factors Signup and view all the answers

Which vitamin is essential for the synthesis of certain coagulation factors?

Vitamin K Signup and view all the answers

What is the effect of warfarin on coagulation?

Decreases vitamin K metabolism Signup and view all the answers

What is the mechanism of idiosyncratic reactions to xenobiotics?

Formation of immune complexes with coagulation proteins Signup and view all the answers

What is the mechanism of action of oral anticoagulants like warfarin?

Interferes with vitamin K metabolism Signup and view all the answers

What is the use of heparin in hemostasis?

Treatment of acute venous thromboembolism Signup and view all the answers

What is the role of platelets in response to vascular injury?

To form a stable hemostatic plug Signup and view all the answers

What is a common side effect of intensive chemotherapy on platelets?

Thrombocytopenia Signup and view all the answers

What is the result of heparin-induced thrombocytopenia (HI)?

Platelet activation and aggregation Signup and view all the answers

What is a characteristic of thrombotic thrombocytopenic purpura (P)?

Sudden onset of thrombocytopenia Signup and view all the answers

What is the difference between hemolytic uremic syndrome (HUS) and thrombotic thrombocytopenic purpura (P)?

HUS has less severe neurologic complications Signup and view all the answers

What is a common cause of thrombocytopenia?

Decreased production or increased destruction of platelets Signup and view all the answers

What is a consequence of platelet activation and aggregation in heparin-induced thrombocytopenia (HI)?

Risk of thrombosis Signup and view all the answers

What is the result of xenobiotics interfering with platelet function?

Platelet dysfunction Signup and view all the answers

Study Notes

Hematotoxicology

The study of adverse effects of drugs and other chemicals on blood and blood-forming tissues
Ranks with liver and kidney as among the most important considerations in risk assessment of individual patient populations exposed to potential toxicants
Unique as a target organ due to:
- Vital functions (delivery of oxygen to tissues, maintenance of vascular integrity, and provision of immune functions)
- Exceptional proliferative tissue
- High regenerative capacity
- Highly susceptible to intoxication
- Supply of nutrients, clearance of toxins or metabolites, and production of vital growth factors

Consequences of Hematotoxicity

Direct or indirect damage to blood cells and their precursors can lead to:
- Hypoxia
- Hemorrhage
- Infection
Hematotoxicity can be primary (directly affecting one or more blood components) or secondary (resulting from other tissue injury or systemic disturbances)

Toxicology of the Erythron

Erythrocytes (red blood cells) make up 40-45% of circulating blood volume
Function as the principal vehicle for transportation of oxygen and carbon dioxide
Can be affected by xenobiotics, leading to:
- Decreased red cell mass (anemia)
- Increased red cell mass (erythrocytosis)
Shifts in plasma volume can alter the relative concentration of erythrocytes and be confused with true anemia or erythrocytosis

Mechanisms of Anemia

Decreased production of erythrocytes due to:
- Abnormalities in hemoglobin synthesis (e.g., iron deficiency)
- Interference with heme synthesis (e.g., isoniazid, pyrazinamide, and chloramphenicol)
- Deficiency of folate and/or vitamin B12
Increased destruction of erythrocytes due to:
- Infectious diseases (e.g., malaria)
- Oxidative hemolysis (e.g., phenol, dapsone, nalidixic acid, sulfanilamide, and nitrofurantoin)
- Immune hemolytic anemia (e.g., autoimmune hemolytic anemia, penicillin-induced hemolytic anemia)

Toxicology of the Leukon

Toxic effects on granulocytes:
- Inhibitors of mitosis (e.g., cytotoxic drugs like methotrexate, cyclophosphamide, and nitrosoureas)
Immune-mediated destruction of granulocytes

Toxicology of the Thrombocyte

Toxic effects on platelets:
- Thrombocytopenia (low platelet levels) due to decreased production or increased destruction
- Interference with platelet function
Heparin-induced thrombocytopenia (HI) and thrombotic thrombocytopenic purpura (TTP) are immune-mediated platelet destruction
Hemolytic uremic syndrome (HUS) is a disorder with clinical features similar to those of TTP

Toxic Effects on Coagulation

Decreased synthesis of coagulation proteins due to:
- Impaired liver function
- Vitamin K deficiency
Increased clearance of coagulation factors due to:
- Antibodies reacting with coagulation proteins
Toxicology of agents used to modulate hemostasis:
- Oral anticoagulants (e.g., warfarin) interfere with vitamin K metabolism
- Heparin is used for prophylaxis and therapy of acute venous thromboembolism

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Description

This quiz covers the toxic responses of the blood, a key topic in general toxicology. Learn about the effects of toxic substances on the blood system. Presented by Dr. Ban Majid Ali.