Dyshemoglobinemias Flashcards
1
Q
What is the basic structure of hemoglobin?
A
- conjugated protein- MW 64,500 daltons
- two pairs of polypeptide chains- four heme molecules attached
- purpose: tissue perfusion
- heme contains an iron complexed at the center of a prophrin ring- Ferrous state (2+) of the Fe atom carries O2
- the globin chain protects the iron moiety from inappropriate oxidation
2
Q
Redox Reactions
A
- redox reactions: always occur together
- reduction- transfer of electons to a substrate, a substrate is reduced if it gains an electron
- oxidation- extraction of electrons from a substrate, a substrate is oxidized if it loses an electron
3
Q
Carbon monoxide
A
- gas
- source: incomplete combustion of carbon containing material: methane vs. coal vs gasoline gasses (generators, house fires)
- internal production (minimal- only methyline chloride furniture stripper)
4
Q
Pharmacokinetics of CO
A
- absorption/excretion- CO gains entry through respiration, methylene chloride is converted to CO in vivo
- distribution- hemoglobin/myoglobin/other
5
Q
Risk of Exposure to CO
A
- proximity
- those that breathe faster- babies, pregnant women
6
Q
CO Pharmacology
A
- binds to hemoglobin (200-250x oxygen)
- shifts the oxygen dissociation curve to the left (tighter tissue binding)
- decrease in erythrocyte 2,3 diphosphoglycerate
7
Q
CO Mechanism
A
- mitochondria cytochrome oxidase binding- increased with hypoxia and hypotension
- nitric oxidase displaced from platelets forms peroxynitrites
8
Q
CO Effects
A
- mild- HA, N/V, dizziness
- moderate- chest pain, blurred vision, dyspnea on exertion, tachycardia, tachypnea, cognitive deficits, myonecrosis, ataxia
- severe- seizures, coma, dysrhymthmias, hypotension, MI/ischemia, skin bullae
9
Q
Late/Chronic Effects of CO Poisoning
A
- cognitive dysfunction
- dementia, psychosis, amnesia
- parkinsonism, paralysis chorea, cortical blindness, apraxia, agnosias, peripheral neuropathy, incontinence
-preceded by a lucent period of 2-40 days
10
Q
Mechanism of Late effects of CO
A
- reperfusion injury- during recovery, WBCs are attracted and adhere to the brain microvasculature (? due to cyclooxygenase dysfunction)
- WBCs release proteases, converts xanthine dehydrogenase…promoting free radical formation…leading to delayed lipid peroxidation
11
Q
Risk of late effects of CO poisoning
A
- incidence varies in the literature from 3%-14%-33%-43% at various times of follow-up and severity of illness
- adults (>30) appear to be at greater risk
- most cases of overt signs involved a loss of consciousness
- look for end organ manifestations of toxicity- CNS, cardiac, perfusion; CO level- relative importance
12
Q
Oxygen saturation in CO poisoning
A
- pulse oximetry- falsely normal (carboxyhemoglobin is read as oxyhemoglobin
- arterial blood gas- co-oximeter- will be appropriate
- calculation- will be faslsely normal because P)2 is not affected
13
Q
Treatment of CO
A
- ABCs, oxygen- shortens CO T1/2 (2-7 hr to 30-150 min)
- consider hyperbaric oxygen treatment: shortens T1/2 (4-86 min), increased O2- prevents lipid peroxidation in animal models
- 12-43% neurologic impairment with 100% oxygen alone, 0-4% treated with HBO
14
Q
Indications of hyperbaric oxygen
A
- loss of consciousness- syncope, coma, seizures
- GCS < 15 on presentation
- CO level: >10%
- myocardial ischemia, ventricular dysrhythmias
- neurologic signs 2-4 hours out
15
Q
Brain findings of CO exposure
A
-bilteral low density areas of the globus pallidus, putamen, and caudate nuclei are seldom seen