Unit 2 - Dyshemoglobinemia Flashcards by Annette Liem

explain what hemoglobin is and its purpose

conjugated protein (64,500 D)

two pairs of polypeptide chains (4 heme molecules attached total)
for tissue perfusion

How well did you know this?

Not at all

Perfectly

what is heme’s structure?

Fe complexed at the center of a porphyrin ring

ferrous state (2+) of the Fe carries O2, CO
globin chain protects Fe moiety from inappropriate oxidation

How well did you know this?

Not at all

Perfectly

difference between carboxyhemoglobin, oxyhemoglobin, and methemoglobin?

carboxy = CO
oxy = O2
met = O2, but heme Fe in +3 form

How well did you know this?

Not at all

Perfectly

what are sources of CO?

incomplete combustion of carbon containing material
- gasses: methane VS coal VS gasoline
internal production (minimal, only if ingest/inhale methyline Cl)

How well did you know this?

Not at all

Perfectly

explain the entry/exit of CO (pharmacokinetics)

absorption/excretion
- CO gains entry through respiration
- methylene cloride is converted to CO in vivo only
distribution
- via hemoglobin, myoglobin, etc.

How well did you know this?

Not at all

Perfectly

explain CO pharmacology?

binds to Hb (200-250 x O2)

shifts O2 dissociation curve to the left
decrease in RBC 2,3-DPG

How well did you know this?

Not at all

Perfectly

explain the mechanism of CO?

mitochondrial cytochrome oxidase binding
- increased with hypoxia and hypotension
NO displaced from platelets from peroxynitrites

How well did you know this?

Not at all

Perfectly

explain the mild, moderate, and severe effects of CO?

mild: HA, nausea/vomiting, dizziness
moderate: cheset pain, blurred vision, dyspnea on exertion, tachycardia, tachypnea, cognitive deficits, myonecrosis, ataxia
severe: seizures, coma, dysrhythmias, hypotension, MI/ischemia, skin bullae

How well did you know this?

Not at all

Perfectly

what are “late/chronic effects” of CO? when do they occur?

cognitive dysfunction
dementia, psychosis, amnesia
parkinsonism, paralysis chorea, cortical blindness, apraxia, agnosias, peripheral neuropathy, incontinence

these are preceded by a “lucent” period of 2-40 days, meaning it can seem like a patient got better, but then has these effects

How well did you know this?

Not at all

Perfectly

what is the theory behind the mechanism of late effects of CO?

reperfusion injury

during recovery, WBC are attracted and adhere to brain microvasculature due to cyclooxygenase dysfunction (?)
WBCs release proteases, convert xanthine dehydrogenase to xanthine oxidase, promoting FR formation, leading to delayed lipid peroxidation

How well did you know this?

Not at all

Perfectly

at what ages are adults at greatest risk?

> 30 yo

How well did you know this?

Not at all

Perfectly

how should one evaluate CO poisoning?

look for end-organ manifestations of toxicity

CNS, cardiac, perfusion
CO level is of relative importance

How well did you know this?

Not at all

Perfectly

what is pulse oximetry in CO poisoning?

falsely normal

-carboxyhemoglobin is read as oxyhemoglobin

How well did you know this?

Not at all

Perfectly

what is arterial blood gas in CO poisoning?

co-oximeter will be appropriate

calculation will be falsely normal b/c pO2 is not affected

How well did you know this?

Not at all

Perfectly

what is treatment for CO poisoning?

ABC’s, O2 to shorten CO half-life (from 2-7 hr to 30-150 min)
hyperbaric O2 under pressure (HBO)
- shortens half-life to 4-86 minutes, increases O2
- prevents lipid peroxidaiton in animal models

How well did you know this?

Not at all

Perfectly

what are indications for HBO?

Study These Flashcards

loss of consciousness
- syncope, coma, seizures
GCS < 15 on presentation
CO level > 10%
MI, ventricular dysrhythmias
neurologic signs 2-4 hours out

what are some neuroanatomical side effects of CO?

Study These Flashcards

bilateral low density areas of globus pallidus, putamen, and caudate nuclei
-rarely seen

how does one “pick out” cyanide poisoning?

Study These Flashcards

lactate > 10 mmol/L

2. patient doesn’t respond to supportive care

what are the forms of cyanide?

Study These Flashcards

gas (usually chemical warfare/industrial accidents)
crystal (requires mucous membranes or po exposure)
- jewelers, electroplating, other industries, house fires

where does cyanide bind?

Study These Flashcards

cytochrome A3 on ETC

-rapid onset of multi-system organ failure (no ATP)

what is treatment for cyanide?

Study These Flashcards

ABCs, supportive care, ACLS, largely not successful
cyanide antidote kit/package (sodium/amyl nitrite)
hydroxocobalamin
- binds with cyanide to make cyanocobalamin (B12)
HBO +/0

when and how should one treat with hydroxocobalamin?

Study These Flashcards

any smoke-inhalation victim that is NOT improving despite supportive care including O2
any intentional cyanide exposure
- 5 g dose, can be repeated x1
- give concurrently with sodium thiosulfate
- may cause increased BP

what is the mechanism of sodium/amyl nitrite in cyanide poisoning?

Study These Flashcards

sodium/amyl nitrite makes met-Hb, so the CN (and H2S, if any) bind to met-Hb instead of cytochromes

these cyanomet-Hb or SHmet-Hb are then excreted
-cyanometHb needs thiosulfate to be excreted

define what methemoglobin is?

Study These Flashcards

heme Fe oxidized to ferric (+3) form

-normal amounts 1-3%

what is the mechanism of methemoglobinemia?

1. rate of heme oxidation increases 2. reduction of heme is limited 3. structural abnormalities of heme

what are causes of methemoglobinemia?

1. congenital 2. infantile disposition 3. external causes

how does methemoglobin exert its toxicity?

1. incapacitates O2 transport | 2. shifts O2 dissociation curve to left

``` what are symptoms of methemoglobin at: 0-10% 10-20% 20-50% >50% >70% ```

``` 0-10%: asymptomatic 10-20% apparent cyanosis 20-50% dizziness, fatigue, HA, exertional dyspnea >50% lethargy/stupor >70% coma/death ```

what is pulse oximetry in methemoglobin?

falsely and aberrantly lowered | -measured as both oxy and deoxyhemoglobin, will fall rapidly into high 80s

what is arterial blood gas in methemoglobin?

1. co-oximeter will be appropriate | 2. calculation will be falsely normal b/c pO2 is not affected

what are drugs that give methemoglobinemia?

1. nitrites (major) 2. nitrates in infants (major) 3. sulfonamides 4. phenazopyridine 5. dapsone 6. local anesthetics these cause oxidant stress

what are toxins that give methemoglobinemia?

1. nitrites (major) 2. nitrates in infants (major) 3. aniline dye 4. potassium chlorate 5. diarrheal illness in infants (make nitrites; major)

what is treatment for methemoglobinemia?

1. ABC's 2. decontamination 3. methylene blue (tetramethyl tionine chloride; specific antidote) - minor antidotes and in non-responders to methylene blue - -N-acetylcysteine - -exchange transfusion - -hyperbaric O2

explain the mechanism of methylene blue

used in treatment of methemoglobinemia - cofactor of NADPH reductase - gains electron, then donates directly to methemoglobin - methemoglobin reduction to (Fe 2+)

when is methylene blue treatment indicated?

if methemoglobin level >20-30%, or symptoms

what are cautions in using methylene blue?

1. hemolytic anemia from weak oxidizing capability 2. painful at injection site (dysuria) 3. higher doses can cause dyspnea, restlessness, tremor, precordial pain, apprehension

what are possible reasons for methylene blue non-responders?

1. hemoglobin M disease 2. G6PD deficiency - lack generation of NADPH dependent methemoglobin reducase 3. CL salts inactivating G6PD 4. sulfhemoglobinemia - more benign, levels up to 10 g/dL don't cause cyanosis 5. wrong diagnosis

what is sulfhemoglobinemia?

symptoms similar to methemoglobinemia - methemoglobin levels will be elevated - laboratory can "tease out" by adding cyanide to blood - treatment is supportive only

what are causes of sulfhemoglibnemia?

acetanilid, phenacitin, nitrites, trinitrotoluene, sulfur

Unit 2 - Dyshemoglobinemia Flashcards

(39 cards)