Dyshemoglobinemias Flashcards
1
Q
hemoglobin
A
- conjugated protein, MW 64.5 kDa
- two pairs of polypeptide chains in which there are 4 heme molecules attached
- for tissue perfusion
2
Q
heme
A
- contains an iron complexed at the center of a porphyrin ring
- ferrous state (2+) carries o2
- globin chain protects the iron from inappropriate oxidation
3
Q
oxidation/reduction
A
- always occur together
- reduction- gain electrons=reduced substrate
- oxidation- lose election= oxidized substrate
4
Q
carbon monoxide
A
- gas
- from incomplete combustion of carbon containing material
- gasses-methane, coal, gasoline
- various others
- internal production is minimal
5
Q
pharmacokinetics of CO
A
- absorption/excretion
- CO gains entry and exit through direct respiration- increased respiration = increased dose and increased rate of elimination
- chemical methylene chloride is converted to CO in vivo- only time CO levels will increase after removal from the source - distribution
- binds to hemoglobin, myoglobin, and other less defined tissues
* no metabolism
6
Q
CO “pharmacology”
A
- binds to Hb with 200-250 higher affinity, shifts O2 curve to the left
- decreases 2,3-BPG
* results in tissue hypoxemia, but dogs infused with toxic blood were fine- this isn’t the only thing that occurs - binds to myoglobin- direct myocardial tox
- binds to mito cytochrome oxidase- inhibits cellular respiration- effect increased with hypoxia and hypotension
- displaces NO from platelets
- forms peroxynitrites, results in free radical mediated damage thought to contribute most to CNS system long term tox
7
Q
CO acute clinical effects
A
- mild- HA, NV, dizziness
- moderate- chest pain, blurred vision, dyspnea on exertion, tachy, tachypnea, cognitive defects, myonecrosis, ataxia
- severe- seizures, coma, dysrhythmias, hypotension, MI/ischemia, skin bullae
8
Q
CO late/chronic effects
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
9
Q
mechanism of late onset effects
A
- theory
- reperfusion injury
- during recovery, WBCs are attracted and adhere to brain microvasculature (COX dysfunction??)
- WBCs release proteases, converts xanthine dehydrogenase to XO, promotes free radical formation, leading to delayed lipid peroxidation
10
Q
risk of delayed effects
A
- incidence varies in the literature from 3-14% -33%-43% at various times of follow up and severity of illness
- adults over 36 appear to be at greater risk
- most cases of over signs involve a LOC
11
Q
evaluation
A
- look for end organ manifestations of toxicity- CNS, cardiac, perfusion
- CO level has relative importance
12
Q
oxygen saturation
A
- pulse ox- falsely normal, because COHb is read as normal Hb
- arterial blood gas- Co-ox will be appropriate
- calculation will be falsely normal because pO2 is not affected
13
Q
treatment
A
- ABCs, oxygen
- shortens CO t/2 (2-7hr to 30-150 min)
- consider HBO
- shortens t/2 to 4-86 min, increased O2
- prevents lipid peroxidation in animal models
14
Q
controlled human case studies
A
- 12-43% neuro impairment with 100% oxygen alone
- 0-4% treated with HBO, small studies have done better than larger ones
15
Q
prospective randomized trial
A
- 1 hr at 2 atm 3x over 3 days + high flow 104 O2
- vs 3days high flow alone at 87
- no impact on outcome
- this was australia- they use 2, we use 2.8
16
Q
weaver trial
A
- LOC, GCS< 15, CO level >10
- myocardial ischemia, ventricular dysarrhythmias
- neuro signs 2-4 hours out
- 3 atm for 1 session than 2 atm 3x over 3 days
- oxygen and sham dive sessions to mimic study group
- impact seen on neurocognitive testing
17
Q
Indications for HBO
A
- LOC- syncope, coma, seizure
- GCS< 15 on presentation
- CO level >10%
- myocardial ischemia, ventricular dysrhythmias
- neuro signs 2-4 hours out
18
Q
other findings for CO
A
-bilateral low density areas of the globus pallidus, putamen, and caudate nuclei are seldom seen
19
Q
cyanide
A
- found in many forms
- gas-chemical warfare/industrial accidents
- crystal-requires mucous membrane or PO exposure
- jewelers, electroplating, other industries, house fires
- lactate >10 mmol/L or if patient doesn’t respond to supportive care after fire
20
Q
pharm of CN
A
- binds to cytochrom a3 on the ETC
- rapid onset of multisystem organ failure- no ATP
21
Q
treatment for CN
A
- ABCs, supportive, ACLS don’t work
- CN antidote kit/package
- hydroxocobalamin
- binds with CN to make cyanocobalamin
- HBO-maybe
22
Q
CN kit
A
- makes metHb to get rid of CN- sodium nitrite/ amyl
- thiosulfate increases metabolism of CN
- can’t use in CO poisoning, because metHb takes even more O2 carry capacity out
- H2S binds to A3 also, but is reversible
23
Q
hydroxocobalamin
A
- any smoke inhalation victim that is not improving despite supportive care including o2
- any intentional CN exposure
- B12 a+ CN= B12
- 5 g dose, can be repeated 1 time
- give with sodium thiosulfate
- potentially for nitroprusside at risk patients
24
Q
metHb
A
- heme iron oxidized to ferric 3+ form
- normal amts of 1-3%
- rate of heme oxidation increased, reduction is limited, structural abnormalities of heme
- protective mech include enzymes to reduce back to 2+, mostly NADH reductase, sometimes NADPH
25
causes of MetHb
-congenital
-infantile disposition
-external causes
Drugs:
-nitrites, sulfonamides, nitrites in infants, phenazopyridine, dapsone, local anesthetics
Toxins:
-potassium chlorate, nitrites/ in infants, aniline dye, diarrheal illness in infants (makes nitrites)
26
metHb tox
- incapacitates o2 transport
| - shifts o2 curve to left- won't release in tissues
27
metHb sx
- 0-10% asx
- 10-20% apparent cyanosis
- 20-50% dizziness, fatigue, HA, exertional dyspnea
- >50% lethargy/stupor
- >70% coma and death
28
ox sat metHb
- pulse ox- fasely and aberrantly lowered- measured as both oxy and deoxy, will fall rapidly into the high 80s
- arterial blood gas
- co-ox- appropriate
- calc-fasely normal because po2 not affected
29
MetHb treatment
- ABCs
- decontamination
- methylene blue- tetramethyl thionin chloride- specific antidote
- minor antidotes when methylene blue fails- n acetylcysteine, exchange transfusion, HBO
30
methylene blue
- cofactor of NADPH reductase
- gains electron and donates directly to metHb
- metHb reduction to 2+
31
methylene blue indication
- metHb >20-30% or sx
- cautions- hemolytic anemia from weak ox capability, painful at injection site, higher doses can cause dyspnea, restlessness, tremor, precordial pain and apprehension
32
non responders to methylene blue
- hemoglobin M disease
- G6PD def- lack generation of NADPH dependent metHb reductase
- CL salts inactivating G6PD
- sulfhemoglobinemia-acetanilid, phenacitin, nitrites, trinitrotoluene, sulfer. more benign, levels up to 10 g/dl don't cause cyanosis
- wrong diagnosis
33
sulfhemoglobinemia
- sx similar to met Hb
- metHb elevated
- lab can tease out by adding CN to blood
- treatment is supportive
34
conclusions
patients symptoms are more important than lab tests in all cases of dyshemoglobinemia and should be used in conjugation with levels
- specific antidotes are required
- timing is important
