Dyshaemoglobinaemias Flashcards
(21 cards)
CCM Chapter 107 - 3rd Edition
Dyshaemoglobinaemias
What does o2 bind to?
Ferrous form of iron (Fe++) in each heme group
What are the three most common dyshaemoglobinaemias?
carbon monoxide
methemoglobinaemia
sulfhemoglobinaemia
What is the normal level of COHb in a human?
1%
What elevates endogenous production of CO and COHb?
haemolytic anaemia, sepsis
What determines the quantity of CO absorbed
RMV, duration of exposure, FiCO and FiO2
What are the two main mechanisms resulting in CO causing pathology?
- 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%.
- 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
What causes methaemoglobin?
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
What amount of haemoglobin is oxidised to methHb per day normally?
0.5-3%
What causes sulfhaemoglobin?
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
What mechanisms do erythrocytes have to protect themselves from oxidative damage?
superoxide dismutase, catalase, glutathione peroxidase, glutathione, and metHb reductase
What are heinz bodies ?
Aggregates of denatured precipitated Hb molecules within erythrocytes
What are some examples of toxins resulting in methaemoglobinaemia?
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)
After exposure to a toxin how long does it take to form methaemoglobin?
mins to a few hours
What are examples of toxins causing heinz bodies ?
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)
What is acetominophen more toxic to cats
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
What are the clinical signs of CO toxicity
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
Clinical signs of methemoglobinemia/sulfhemoglobinemia?
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%
How may dyhaemoglobinaemias be Dx
history
co-oximetry analysis
pulse ox to saturation gap of more than 5%
What is the Tx for CO toxicity?
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
Treatment of oxidative damage to erythrocytes?
O2 not overly helpful bc most Hb maximally saturated.
Decrease toxin - charcoal, emesis, IVFT(?)
