Chapter 109 - Methemoglobinemia Flashcards
How is methemoglobin created?
Iron molecule of hemoglobin is oxidixed to the ferric (Fe 3+ vs Fe 2+) state because of oxidative damage within the RBC
T/F: Methemoglobin increases the affinity for oxygen.
True
Which way does methemoglobin shift the oxyhemoglobin dissociation curve?
To the left (decreased release of oxygen to the tissues)
In a normal dog or cat, how much does methemoglobin account for in total hemoglobin?
Less than 3% of total hemoglobin
In a normal dog or cat, why does methemoglobin account for such a low amount of hemoglobin?
Because there are numerous mechanisms to prevent oxidative injury AND methemoglobin is reduced to functional hemoglobin rapidly
Why are RBC especially vulnerable to oxidative damage (3 reasons)?
- They carry oxygen
- They are exposed to various chemicals in plasma
- They have no nucleus or mitochondria
What is a benefit of having a cell without organelles?
Allows the cell membrane to deform to be able to pass through capillary beds
Name 3 oxidants that are produced in vivo.
H2O2, superoxide free radical, hydroxyl radicals
Name a powerful antioxidant produced by RBC that operates as a free radical scavenger.
Glutathione because it contains an easily oxidizable sulfhydryl group (SH)
Name mechanisms that RBC use to protect themselves from oxidative damage. (4)
Superoxide dismutase, catalase, glutathione peroxidase, MetHb reductase
On a blood smear, what is a good indicator of oxidative damage?
Heinz bodies
Why are cat RBC more susceptible to oxidative damage than dog RBCs?
They have 8 SH groups on the globin part of the molecule rather than 4 in the dog
Ghost cells are indicative of what type of hemolysis?
Intravascular
RBCs that have undergone oxidative damage are removed where?
Spleen macrophages
What is the toxic dose of acetaminophen in cats?
10mg/kg
What is the toxic dose of acetaminophen in dogs?
150-200mg/kg
How is acetaminophen metabolized in the liver (4 ways)?
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
Why are cats more susceptible to the toxic effects of acetapminophen?
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
What is the most important factor in determining morbidity and survival with acetaminophen ingestion?
Time from ingestion to treatment
What is thought to be the toxic substance in skunk musk?
Thiols
T/F: Nitrites and nitrates cause methemoglobinemia.
True
T/F: Nitrites and nitrates cause Heinz body production.
False, NO (released by nitroglycerin and nitroprusside) decreases methemoglobin reductase activity
Breeds documented to have methemoglobin reductase deficiency (9)
DSH, chihuahua, borzoi, english setter, cockapoo, poodle, corgi, pom, toy American eskimo dogs
What minimum percentage does methemoglobinemia have to be to cause clinical signs?
20%
What is the minimum percentage that methemoglobinemia causes death?
80%
What machine can measure methemoglobin levels?
Co-oximeter
What does the co-oximeter add to the sample to determine the amount of methemoglobin?
Cyanide- spectrophotometrically quantifies the change in absorbance at 630nm before and after the addition of cyanide which converts it to cyanmethemoglobin, a different absorbance
If the methemoglobin levels are greater than 30%, where does the pulse ox plateau at?
85%
Comparing the pulse oximeter to arterial blood gas, when should methemoglobinemia be suspected?
5%
What is another reason the gap between pulse oximetry and arterial blood gas may be large?
Carboxyhemoglobinemia
What is the preferred treatment for acetaminophen toxicity?
NAC
How does NAC work?
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
What are the side effects of oral NAC?
Vomiting and nausea
What are the IV side effects of NAC?
Phlebitis if leaked perivascularly, hypotension and bronchospasm
How does methylene blue increase the rate of reduction of methemoglobin?
Using another reduction system in the RBC: NADPH dehydrogenase
What is the side effect of methylene blue?
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
Why is cimetidine potentially useful in acetaminophen ingestion?
Inhibits P450 oxidation in the liver
