Chapter 109 - Methemoglobinemia

Question 1

How is methemoglobin created?

Answer 1

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

Question 2

T/F: Methemoglobin increases the affinity for oxygen.

Answer 2

True

Question 3

Which way does methemoglobin shift the oxyhemoglobin dissociation curve?

Answer 3

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

Question 4

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

Answer 4

Less than 3% of total hemoglobin

Question 5

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

Answer 5

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

Question 6

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

Answer 6

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

Question 7

What is a benefit of having a cell without organelles?

Answer 7

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

Question 8

Name 3 oxidants that are produced in vivo.

Answer 8

H2O2, superoxide free radical, hydroxyl radicals

Question 9

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

Answer 9

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

Question 10

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

Answer 10

Superoxide dismutase, catalase, glutathione peroxidase, MetHb reductase

Question 11

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

Answer 11

Heinz bodies

Question 12

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

Answer 12

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

Question 13

Ghost cells are indicative of what type of hemolysis?

Answer 13

Intravascular

Question 14

RBCs that have undergone oxidative damage are removed where?

Answer 14

Spleen macrophages

Question 15

What is the toxic dose of acetaminophen in cats?

Answer 15

10mg/kg

Question 16

What is the toxic dose of acetaminophen in dogs?

Answer 16

150-200mg/kg

Question 17

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

Answer 17

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

Question 18

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

Answer 18

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

Question 19

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

Answer 19

Time from ingestion to treatment

Question 20

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

Answer 20

Thiols

Question 21

T/F: Nitrites and nitrates cause methemoglobinemia.

Answer 21

True

Question 22

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

Answer 22

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

Question 23

Breeds documented to have methemoglobin reductase deficiency (9)

Answer 23

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

Question 24

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

Answer 24

20%

Question 25

What is the minimum percentage that methemoglobinemia causes death?

Answer 25

80%

Question 26

What machine can measure methemoglobin levels?

Answer 26

Co-oximeter

Question 27

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

Answer 27

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

Question 28

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

Answer 28

85%

Question 29

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

Answer 29

5%

Question 30

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

Answer 30

Carboxyhemoglobinemia

Question 31

What is the preferred treatment for acetaminophen toxicity?

Answer 31

NAC

Question 32

How does NAC work?

Answer 32

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

Question 33

What are the side effects of oral NAC?

Answer 33

Vomiting and nausea

Question 34

What are the IV side effects of NAC?

Answer 34

Phlebitis if leaked perivascularly, hypotension and bronchospasm

Question 35

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

Answer 35

Using another reduction system in the RBC: NADPH dehydrogenase

Question 36

What is the side effect of methylene blue?

Answer 36

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

Question 37

Why is cimetidine potentially useful in acetaminophen ingestion?

Answer 37

Inhibits P450 oxidation in the liver