Dyshemoglobinemias

Question 1

hemoglobin

Answer 1

conjugated protein, two pairs of polypeptide chains with 4 heme molecules attached. purpose is to perfuse tissue.

Question 2

heme

Answer 2

iron complexed at the center of a porphyrin ring. ferrous state (2+) of the Fe atom carries O2. globin chain protects the iron moiety from inappropriate oxidation

Question 3

oxidation reduction reactions

Answer 3

redox always occurs together. GER LEO

Question 4

entry and exit of carbon monoxide

Answer 4

absorption/excretion. CO gains entry through respiration. methylene chloride is converted to CO in the body. distributed in hemoglobin and myoglobin

Question 5

CO mechanism

Answer 5

mitochondrial cytochrome oxidase binding. increased with hypoxia and hypotension. nitric oxidase displaced from platelts forms peroxynitrites.

Question 6

CO effects

Answer 6

mild: Nausea, vomiting, headache, dizzy
moderate: chest pain, blurred vision, dyspnea on exertion, tachycardia, tachypnea, cognitive defects, myonecrosis, ataxia
severe: seizures, coma, skin bullae, MI, hypotension

Question 7

CO late/chronic effects

Answer 7

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

Question 8

mechanism of late effects

Answer 8

reperfusion injury. WBCs are attracted and adhere to brain microvasculature, release stuff promoting free radical formation

Question 9

oxygen saturation

Answer 9

pulse oximetry: falsely normal. carboxyhemoglobin is read as hemoglobin. arterial blood gas calculation will be falsely normal since pO2 is not affected. co-oximeter will be appropriate

Question 10

treatment of CO

Answer 10

treat with oxygen. consider HBO (hyperbaric oxygen). prevents lipid peroxidation in some animal models

Question 11

when to give hyperbaric oxygen?

Answer 11

loss of consciousness, GCS 10%, myocardial ischemia, ventricular dysrhythmias, neurologic signs

Question 12

cyanide: how to distinguish from CO

Answer 12

lactate > 10mmol/L associated with high CN levels. patient does not respond to supportive care. if CO alone, oxygen will make it go away. with CN, no response to oxygen

Question 13

cyanide mechanism

Answer 13

binds to cytochrome A3 on the electron transport chain. rapid onset of multi-system organ failure: NO ATP!!

Question 14

cyanide treatment

Answer 14

hydroxocobalamin: binds with CN to make cyanocobalomin.

Question 15

hydroxocobalamin

Answer 15

any smoke inhalation victim that is not improving despite supportive care including O2. any intentional cyanide exposure. give a 5 gram dose. give concurrently with sodium thiosulfate

Question 16

methemoglobin

Answer 16

heme iron oxidized to the ferric (3+) form.

Question 17

methemoglobin mechanisms

Answer 17

rate of heme oxidation increased, reduction of heme is limited. structural abormalities of heme

Question 18

methemoglobinemia causes

Answer 18

congenital, infantile dispositon, external causes

Question 19

methemoglobin toxicity

Answer 19

incapacitates oxygen transport. shifts oxygen dissociation curve to the left. oxygen is less willing to provide oxygen to the tissue sites

Question 20

methemoglobin symptoms

Answer 20

0-10% asymptomatic. 10-20% cyanosis. 30-50% dizzy, headache, fatigue, dyspnea. >50% lethargy/stupor. >70% coma and death

Question 21

oxygen saturation with methemoglobin

Answer 21

pulse oximetry falsely and aberrantly lowered. arterial blood gas with co-oximeter will be appropriate, but calculation will be falsely normal due to no impact on pO2

Question 22

methemoglobinemia treatment

Answer 22

decontamination. methylene blue (specific antidote). minor antidontes and in non-responders to methylene blue include n-acetylcysteine, exchange transfusion, hyperbaric oxygen

Question 23

methylene blue mechanism

Answer 23

cofactor of NADPH reductase. gains electron and then donates directly to methemoglobin. 3+ reduced to 2+

Question 24

when to give methylene blue?

Answer 24

methemoglobin level >20-30% or symptoms. can cause hemolytic anemia, pain at injection site, and high doses can cause dyspnea, restlessness, tremor, precordial pain, and apprehension

Question 25

methylene blue non-responders

Answer 25

hemoglobin M disease, G6PD deficiency (lack generation of NADPH dependent methemoglobin reductase), CL salts inactivating G6PD, sulfhemoglobinemia, wrong diagnosis

Question 26

sulfhemoglobinemia

Answer 26

symptoms similar to methemoglobinemia. methemoglobin levels will be elevated. lab tests can tease out by adding cyanide to blood. treatment is supportive only