Chapter 109 - Methemoglobinemia Flashcards

1
Q

How is methemoglobin created?

A

Iron molecule of hemoglobin is oxidixed to the ferric (Fe 3+ vs Fe 2+) state because of oxidative damage within the RBC

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2
Q

T/F: Methemoglobin increases the affinity for oxygen.

A

True

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3
Q

Which way does methemoglobin shift the oxyhemoglobin dissociation curve?

A

To the left (decreased release of oxygen to the tissues)

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4
Q

In a normal dog or cat, how much does methemoglobin account for in total hemoglobin?

A

Less than 3% of total hemoglobin

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5
Q

In a normal dog or cat, why does methemoglobin account for such a low amount of hemoglobin?

A

Because there are numerous mechanisms to prevent oxidative injury AND methemoglobin is reduced to functional hemoglobin rapidly

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6
Q

Why are RBC especially vulnerable to oxidative damage (3 reasons)?

A
  1. They carry oxygen
  2. They are exposed to various chemicals in plasma
  3. They have no nucleus or mitochondria
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7
Q

What is a benefit of having a cell without organelles?

A

Allows the cell membrane to deform to be able to pass through capillary beds

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8
Q

Name 3 oxidants that are produced in vivo.

A

H2O2, superoxide free radical, hydroxyl radicals

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9
Q

Name a powerful antioxidant produced by RBC that operates as a free radical scavenger.

A

Glutathione because it contains an easily oxidizable sulfhydryl group (SH)

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10
Q

Name mechanisms that RBC use to protect themselves from oxidative damage. (4)

A

Superoxide dismutase, catalase, glutathione peroxidase, MetHb reductase

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11
Q

On a blood smear, what is a good indicator of oxidative damage?

A

Heinz bodies

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12
Q

Why are cat RBC more susceptible to oxidative damage than dog RBCs?

A

They have 8 SH groups on the globin part of the molecule rather than 4 in the dog

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13
Q

Ghost cells are indicative of what type of hemolysis?

A

Intravascular

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14
Q

RBCs that have undergone oxidative damage are removed where?

A

Spleen macrophages

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15
Q

What is the toxic dose of acetaminophen in cats?

A

10mg/kg

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16
Q

What is the toxic dose of acetaminophen in dogs?

A

150-200mg/kg

17
Q

How is acetaminophen metabolized in the liver (4 ways)?

A

a. Conjugated to a sulfate compound by a phenol sulfotransferase- non-toxic
b. Conjugated to a glucuronide compound by uridine diphosphate-glucuconosyl transferase- non-toxic
c. Transformed and oxidized by cyp-P450- converts to reactive intermediate N-acetyl-P-benzoquinone-imine (NAPQI)
d. Deacylation by hepatic microsomal carboxyesterases to para-aminophenol (PAP)- removed by biotransformation through n-acetylation with N-acetyltransferase, conjugation with GSH or sulfation

18
Q

Why are cats more susceptible to the toxic effects of acetapminophen?

A

They lack glucuronyl transferase needed to conjugate it as well as have limited sulfate binding capacity, with only one NAT enzyme leads to decreased biotransformation and elimination of PAP

19
Q

What is the most important factor in determining morbidity and survival with acetaminophen ingestion?

A

Time from ingestion to treatment

20
Q

What is thought to be the toxic substance in skunk musk?

A

Thiols

21
Q

T/F: Nitrites and nitrates cause methemoglobinemia.

A

True

22
Q

T/F: Nitrites and nitrates cause Heinz body production.

A

False, NO (released by nitroglycerin and nitroprusside) decreases methemoglobin reductase activity

23
Q

Breeds documented to have methemoglobin reductase deficiency (9)

A

DSH, chihuahua, borzoi, english setter, cockapoo, poodle, corgi, pom, toy American eskimo dogs

24
Q

What minimum percentage does methemoglobinemia have to be to cause clinical signs?

A

20%

25
Q

What is the minimum percentage that methemoglobinemia causes death?

A

80%

26
Q

What machine can measure methemoglobin levels?

A

Co-oximeter

27
Q

What does the co-oximeter add to the sample to determine the amount of methemoglobin?

A

Cyanide- spectrophotometrically quantifies the change in absorbance at 630nm before and after the addition of cyanide which converts it to cyanmethemoglobin, a different absorbance

28
Q

If the methemoglobin levels are greater than 30%, where does the pulse ox plateau at?

A

85%

29
Q

Comparing the pulse oximeter to arterial blood gas, when should methemoglobinemia be suspected?

A

5%

30
Q

What is another reason the gap between pulse oximetry and arterial blood gas may be large?

A

Carboxyhemoglobinemia

31
Q

What is the preferred treatment for acetaminophen toxicity?

A

NAC

32
Q

How does NAC work?

A

Augments glutathione stores as it is hydrolyzed to cysteine (a component of GSH) and interacts with NAPQI to form a non-toxic conjugate and increase the fraction of acetaminophen as it’s excreted as sulfate conjugate

33
Q

What are the side effects of oral NAC?

A

Vomiting and nausea

34
Q

What are the IV side effects of NAC?

A

Phlebitis if leaked perivascularly, hypotension and bronchospasm

35
Q

How does methylene blue increase the rate of reduction of methemoglobin?

A

Using another reduction system in the RBC: NADPH dehydrogenase

36
Q

What is the side effect of methylene blue?

A

Causes oxidative damage in cats and can potentiate heinz body anemia- monitoring of hct and blood smear should be performed for 3-4 days after administration

37
Q

Why is cimetidine potentially useful in acetaminophen ingestion?

A

Inhibits P450 oxidation in the liver