Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

Phar 303 > Hematoxicology > Flashcards

Hematoxicology Flashcards

1
Q

What is the difference between Primary Hematotoxicity and Secondary Hematotoxicity?

A

Primary: One or more blood components directly affected (common serious effect of xenobiotics, particularly drugs)

Secondary: Toxicity is a consequence of other tissue injuries or systemic disturbances

Consequences of either include hypoxia, hemmorrhage and infection

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

What are the 6 steps in Erythropoiesis?

A 
Proerythroblast (from myeloid stem cell)
Active synthesis of hemoglobin
Hemoglobin appears
Pyknosis (loss of nucleus)
Reticulocyte (still contains some RNA)
Mature erythrocyte
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

What is an erythron?

A

All stages of erythrocytes. including developin precursors

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

What three aspects of erythrocytes can xenobiotics affect?

A

Production
Survival
Function

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

What is a common effect of xenobiotics on the erythrocyte?

A

Anemia (reduction in number/volume of RBCs)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

What are the three groups the various types of annemia are divided into?

A

Caused by blood loss
Decreased or faulty RBC production
Destruction of RBCs

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

What is the healthy Hematocrit (HCT) level?

note HCT also referred to as Paced Cell Volume or PCV

A

37%-54%

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

Describe the hemoglobin molecule

A

two alpha chains, two beta chains
Each chain contains one heme
Each heme surrounds one iron ion
Each heme interacts with an O2 molecule

One hemoglobin molecule can “hold” 4 O2 molecules
280 Million Hb molecules in each RBC
Each RBC can carry more than 1 billion molecules of oxygen

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

What are 3 ways for hemoglobin to not carry oxygen properly?

A
  • Iron deficiency anemia (heme does not contain Fe)
  • Sideroblastic anemia (defect in synthesis of porphyrin ring
  • Thalassemia (disorder caused by inadequate amounts of alpha/beta chains)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

Which anemia do drugs that contribute to bleeding cause? How can you avoid this?

A

Iron deficiency anemia, reccomended increase in iron intake

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

What types of drugs contribute to iron deficiency anemia when taken chronically?

A

NSAIDs

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

How can you detect iron-deficient erythrocytes histologically?

A

Small, pale RBCs

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

How can you detect sideroblastic anemic erythrocytes histologically?

A

Prussian blue stain forms a perinuclear ring of blue granules
“sapphire neclace”

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

What causes sideroblastic anemia (usually)?

A

Exposure to toxic substances, eg Lead/Isoniazid
Pb substitutes for Zinc at ALAD step (second RLS in hemoglobin production)
Isoniazid is a potent Heme inhibitor

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

What is PLP?

A

Vitamin B6

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

What causes Decreased production of RBCs?

A

Ineffective hematopoiesis (megaloblastic anemia)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

WHat is megaloblastic anemia?

A

RBC count is low
Characterized by RBCs that are larger than normal
Can be congenital or acquired
Any defect that causes a slowing of DNA synthesis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

What is the most frequent cause of megaloblastic anemia? Why?

A

Folic acid or cobalamin (vitamin B12) deficiency

Folate/vitamin B12 are essential for DNA replication/repair

19
Q

How is Cobalamin absorbed?

A

By complexing with haptocorrin in the stomach, then transferring to Intrinsic factor-cobalamin complex in small intestine, where the complex binds to cubilin in terminal ileum

The cobelamin then reaches the liver where it enters cells or is stored in haptocorrin-cbl complices in blood

20
Q

How is Folate absorbed?

A

In duodenum/jejunum (monoglu) where it is processed and stored in liver or exported to cells

21
Q

How does alcohol cause megaloblastic anemia?

A

Decreases absorbed folate
Toxic effects on gastric mucosa and production of intrinsic factor
Affects inestinal mucosa to interfere with absorption of folic acid (jejunum) and Vitamin B12 (ileum)

22
Q

What are suicide substrates? What do they do in the context of Folate synthesis?

A

Substrate analogs that bind an enzyme and permanently deactivate the enzyme

In the folate synthesis pathway:
Fluorouracil inhibits thymidylate synthase permanently to inhibit the rate limiting step of DNA synthesis
Methotrexate inhibits dihydrofolate reductase
Neomycin antibiotics inhibit methione synthase (interferes with absorption)

23
Q

What is Aplastic anemia?

A

Stem cells are unable to generate mature blood cells (bone marrow hypoplasia)

Different forms:
Pancytopenia (deficiency in red cells, leukocytes/platelets)
Reticulocytopenia (“aplastic crisis”, low reticulocyte count)

24
Q

What causes aplastic anemia?

A

Can be inherited (rare) or Acquired:

  • Toxic chemicals (pesticides, arsenic, benzene, mercury)
  • Radiation
  • Chemotherapy
  • Medication (chloramphenicol)
25
How are we exposed to benzene? What is its most common exposure route?
Cigarettes, automobile exhaust, etc. | Ihnalation is most common exposure route
26
What are the symptoms of acute benzene toxicity?
Drowsiness, dizziness, headaches, tremors, confusion, unconsciousness
27
How does benzene cause aplastic anemia?
CYP2E/F/A oxidize it into phenol, which creates hydroquinone which can become benzoquinones, which act on ROS in bone marrow to cause toxicity
28
What is hemolytic anemia?
The destruction of RBC before their normal lifespan is over (120 days)
29
What are the two types of hemolytic anemia?
Immune and nonimmune
30
Describe the cause and effect of immune hemolytic anemia
Rare complication of drugs, antibodies (IgM or IgG) against RBCs Initiates destruction through complement/phagocytotic cells Xenobiotics can affect antibody binding to the RBC (e.g. penicillin binds RBC surface, immune response against drug-coated RBC) "Drug absorption mechanism"
31
What is another term for Non-immune hemolytic anemia? What is it associated with?
Oxidative hemolytic anemia Associated with G6PD deficiency (glucose-6-phosphate dehydrogenase) supplies NADPH Regenerates GSH when it is oxidized GPx (glutathione peroxidase) used GSH as a substrate to remove H2O2
32
What is Favism?
X chromosome linked recessive mutation (males more affected) G6PD polymorphism Denatured hemoglobin forms Heinz bodies
33
What are the beta glucosides found in beans?
Vicine and convicine
34
What happens to the beta glucosides found in beans after ingestion?
Divicine and isouramil are released after ingestion (highly reactive compounds) ROS Detoxified in a normal cell (with ample NADPH) Not detoxified in G6PD-deficient cells RBC destruction due to oxidative damage
35
What is methemoglobinemia?
The oxidation of hemoglobin involving the conversion to the ferrous Fe2+ ion in heme to the ferric Fe3+ ion Associated with anemia, tissue hypoxia and cyanosis (methemoglobinemia is not capable of binding/transporting oxygen, reduces O2-carrying capacity of blood)
36
What is the lethal level of MetHb (as a percent of Hb)?
>70% death <= 2% physiologic 2%-15% asymptomatic
37
What causes methemoglobinemia?
Nitrites, Nitrates (or inherited cytochrome b5 reductase deficiency, but rare)
38
How do you treat Methemoglobinemia?
Methylene blue Methylene blue activates a redutase which methylene blue to methylene leucoblue, whih reduces MetHb back into Hb
39
What are platelets?
Small blood cell fragments that form clots to stop bleeding Produced in the bone marrow from megakaryocytes Continuously replaced (lifespan of 9-12 days)
40
What is it called when you have abnormal platelet levels? (too much and too little)
Abnormal depletion of platelets: Thrombocytopenia Excessibe number of platelets: Therombocytosis
41
What are two possible toxic effects on platelets?
Methotrexate (antimetabolite) inhibits production from megakaryocytes DITP (drug induced thrombocytopenia) decreases production or increases destruction of platelets
42
How can penicillin be toxic to platelets?
Can act as a hapten by binding to platelet membranes and eliciting immune response that causes removal of platelets
43
What are the three procoagulants that are NOT synthesized in the liver?
Factors III, IV, and VIII
44
How does warfarin inhibit blood clotting?
By inhibiting Vitamin K epoxide reductase and vitamin K reductase

Phar 303 (19 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2025 Bold Learning Solutions. Terms and Conditions