Dyshaemoglobinaemias

Question 1

CCM Chapter 107 - 3rd Edition

Answer 1

Dyshaemoglobinaemias

Question 2

What does o2 bind to?

Answer 2

Ferrous form of iron (Fe++) in each heme group

Question 3

What are the three most common dyshaemoglobinaemias?

Answer 3

carbon monoxide
methemoglobinaemia
sulfhemoglobinaemia

Question 4

What is the normal level of COHb in a human?

Answer 4

1%

Question 5

What elevates endogenous production of CO and COHb?

Answer 5

haemolytic anaemia, sepsis

Question 6

What determines the quantity of CO absorbed

Answer 6

RMV, duration of exposure, FiCO and FiO2

Question 7

What are the two main mechanisms resulting in CO causing pathology?

Answer 7

1. impaired oxygen delivery to tissues - CO displaces O2 on haemoglobin, has 200x the affinity. binds two of the four available heme groups in each molecule of Hb, causing a decrease in the oxygen-carrying capacity of 50%.
2. direct cellular toxicity - binding to other proteins disrupting oxidative metabolism, generative O2 free radicals. Binding to myoglobin results in hypoxia and rhabdo. binding to guanylyl cyclase causes and increase in cGMP and cerebral vasodilation and loss of consciousness

Question 8

What causes methaemoglobin?

Answer 8

Oxidative damage to the rbc results in the ferrous (Fe++) iron in heme becoming oxidised to form the ferric form (Fe+++)
Increase O2 affinity therefore causes derrangements in O2 unloading

Question 9

What amount of haemoglobin is oxidised to methHb per day normally?

Answer 9

0.5-3%

Question 10

What causes sulfhaemoglobin?

Answer 10

Most uncommon
Exposure to large amounts of sulfur drugs
Ferrous (Fe++) is oxidaised to ferric (Fe +++) and the sulfur binds with the porphyrin ring in Hb forming a green pigment.
Unable to carry O2
Irreversible. No antidote

Question 11

What mechanisms do erythrocytes have to protect themselves from oxidative damage?

Answer 11

superoxide dismutase, catalase, glutathione peroxidase, glutathione, and metHb reductase

Question 12

What are heinz bodies ?

Answer 12

Aggregates of denatured precipitated Hb molecules within erythrocytes

Question 13

What are some examples of toxins resulting in methaemoglobinaemia?

Answer 13

acetaminophen ingestion, topical benzocaine products,35 phenazopyridine (a urinary tract analgesic) ingestion, nitrites, nitrates, skunk musk,36 hydroxycarbamide,37-39 aniline (a chemical intermediate used in dyes)

Question 14

After exposure to a toxin how long does it take to form methaemoglobin?

Answer 14

mins to a few hours

Question 15

What are examples of toxins causing heinz bodies ?

Answer 15

These substances include Allium plants (onions and garlic), propylene glycol, zinc, methylene blue, crude oils, naphthalene (ingredient in moth balls),42 repeated use of propofol in cats,34 phenothiazine, phenylhydrazine, methionine (a urinary acidifier) in cats, menadione (vitamin K3) in dogs, and copper (particularly in animals with copper storage diseases)

Question 16

What is acetominophen more toxic to cats

Answer 16

Usually is metabolised by sulfate binding or glucuronyl transferase - if in large amounts or those metabolism pathways are trash (cats) then toxic compounds N-acetyl-P-benzoquinone-imine (NAPQI) and para-aminophenol (PAP) are created. NAPQI causes hepatic damage and PAP causes erythrocyte damage

Question 17

What are the clinical signs of CO toxicity

Answer 17

lethargy, depression, headache, confusion, syncope, seizures, unconsciousness, and death.2,3 Additional signs include tachypnea, tachycardia, nausea, dysrhythmias, vomiting, and cherry red mucous membranes.2,3,11 Severity of signs ranges from mild to severe and does not correlate consistently with COHb levels

Question 18

Clinical signs of methemoglobinemia/sulfhemoglobinemia?

Answer 18

The clinical presentation of patients with methemoglobinemia is consistent with decreased oxygen carrying capacity, cellular hypoxia, and shock.16 These signs begin with a metHb level of 20%

Question 19

How may dyhaemoglobinaemias be Dx

Answer 19

history
co-oximetry analysis
pulse ox to saturation gap of more than 5%

Question 20

What is the Tx for CO toxicity?

Answer 20

Elimination of CO depends on minute ventilation, duration of exposure, and the fraction of inspired oxygen.
increasing the amount of oxygen in the blood decreases the half-life of CO as dissolved oxygen competes with CO for Hb binding sites.2,3 CO is then displaced from Hb and exhaled through the lungs
Prognosis: Fair

Question 21

Treatment of oxidative damage to erythrocytes?

Answer 21

O2 not overly helpful bc most Hb maximally saturated.
Decrease toxin - charcoal, emesis, IVFT(?)