5.1 HEMOGLOBIN PART 2 Flashcards
What happens to hemoglobin in the lungs, where there is high O2 tension?
Hb binds O2 and transports it to tissues, where it releases O2 at low O2 tension.
What is P50 in relation to hemoglobin’s affinity for oxygen?
The partial pressure of O2 needed to saturate 50% of Hb, with a normal P50 value of 27 mmHg.
What does a rightward shift in the oxygen dissociation curve represent?
P50 > 27 mmHg, meaning lower Hb affinity for O2.
What are the two forms of hemoglobin in terms of oxygen affinity?
Relaxed (R) state: high O2 affinity | Tensed (T) state: low O2 affinity.
What are the forms of hemoglobin when oxygenated and deoxygenated?
Oxyhemoglobin (oxygenated) | Deoxyhemoglobin (deoxygenated).
What process describes CO2 diffusion into RBCs and its conversion to carbonic acid?
CO2 diffuses into RBCs, combines with water to form H2CO3, which dissociates into H+ and HCO3-.
What is the Bohr effect in CO2 transport?
H+ binds to HbO2, causing O2 to diffuse out of RBCs, shifting the oxygen dissociation curve to the right.
What is the chloride shift in CO2 transport?
As HCO3- diffuses out of RBCs, Cl- diffuses into the cell to maintain electrical neutrality.
What percentage of CO2 is carried to the lungs as plasma bicarbonate (HCO3-)?
70% of CO2 is carried to the lungs as plasma bicarbonate.
What percentage of CO2 binds with globin chains to form carbaminohemoglobin?
5% of CO2 binds with globin chains in nonoxygenated Hb.
How does nitric oxide regulate blood flow in relation to hemoglobin?
Nitric oxide binds to hemoglobin at high O2 tension (vasoconstriction) and is released at low O2 tension (vasodilation).
Dysfunctional hemoglobins unable to transport O2
dyshemoglobins
What percentage of dyshemoglobinemia cases are acquired vs. hereditary?
Majority are acquired; a small percentage are hereditary.
Hemoglobin bound to carbon monoxide (CO), normally less than 2% of total hemoglobin
carboxyhemoglobin (COHb)
Why is carbon monoxide considered a “silent killer”?
It is odorless and colorless, making it difficult to detect.
Name some sources of exogenous carbon monoxide (CO).
Gasoline motors, gas heaters, tobacco smoking, defective stoves, and industrial wastes.
What is the affinity of carbon monoxide (CO) for hemoglobin compared to oxygen (O2)?
240 times greater than O2, causing a leftward shift in the oxygen dissociation curve.
What are the symptoms of carboxyhemoglobinemia at 20%-30% COHb levels?
Dizziness, nausea, muscular weakness, headache, vomiting, confusion.
At what level of COHb do severe symptoms like asphyxiation, coma, or death occur?
50%-70% COHb
What is the typical COHb percentage in nonsmokers and smokers?
0.5% in nonsmokers, 5% in smokers.
How is COHb quantitatively measured in the lab?
Using spectrophotometry (540 nm) or gas chromatography.
What is the first step in treating CO poisoning?
Removal of the source of carbon monoxide.
What treatments are used for severe carbon monoxide poisoning?
High levels of O2 and hyperbaric O2 therapy.
At what COHb level is carbon monoxide poisoning diagnosed in nonsmokers and smokers?
> 3% in nonsmokers, >10% in smokers.
Hemoglobin where heme iron is oxidized to Fe3+, normally comprising 1% of total hemoglobin.
methemoglobin (MetHb)
Name the enzymes and substances that reduce methemoglobin (MetHb) in the body
NADH-cytochrome-b5 reductase,
ascorbic acid,
reduced glutathione, and
NADPH-methemoglobin reductase.
A disorder characterized by increased levels of MetHb due to increased production or decreased activity of NADH-cytochrome-b5 reductase.
methemoglobinemia
What causes toxic methemoglobinemia (acquired form)?
Exposure to exogenous oxidants such as nitrites, nitrates, benzocaine, aniline dyes, and drugs of abuse.
What is the pathophysiology of toxic methemoglobinemia?
Exogenous oxidants oxidize heme iron to Fe3+, impairing oxygen binding, leading to cyanosis and hypoxia due to a leftward shift in the oxygen dissociation curve.
How is toxic methemoglobinemia treated based on MetHb levels?
<30% MetHb: Removal of offending oxidant.
≥30% MetHb: Intravenous infusion of methylene blue (methylthioninium chloride).
Mutations in the gene coding for NADH-cytochrome b5 reductase, leading to diaphorase deficiency and increased MetHb.
hereditary methemoglobinemia
What are the characteristics of homozygotes with hereditary methemoglobinemia?
Homozygotes have <50% MetHb, are cyanotic, and experience mild hypoxia.
How do heterozygotes with hereditary methemoglobinemia react to oxidizing chemicals or drugs?
They may become cyanotic and hypoxic when exposed to these substances.
What therapies can reduce MetHb levels in hereditary methemoglobinemia?
Ascorbic acid and methylene blue.
What causes inherited hemoglobin M (Hb M) methemoglobinemia?
Mutations in the α, β, or γ globin genes, leading to abnormal polypeptide chains that favor iron oxidation to Fe3+.
How do patients with hemoglobin M methemoglobinemia (Hb M Disease) present clinically?
They have asymptomatic cyanosis and do not respond to methylene blue treatment.
What diagnostic methods are used to identify Hb M variants?
Hemoglobin electrophoresis, HPLC, and DNA mutation testing.
What color does blood appear in individuals with increased MetHb levels?
Chocolate brown
How are MetHb levels quantified in the laboratory?
Using spectrophotometry at 630 nm-635 nm.
What are the clinical symptoms at different MetHb levels?
<25%: Asymptomatic.
30%: Cyanosis and hypoxia.
50%: Coma and death.
How can exposure to carbon monoxide occur?
Exposure may be coincidental, accidental, or intentional (suicidal).
What happens to hemoglobin when CO binds, even at very low concentrations of CO in the air?
CO can bind to hemoglobin even if its concentration in the air is extremely low (e.g., 0.02%-0.04%).
What are the symptoms and physical findings associated with increasing levels of COHb in terms of color of blood?
Cherry red color of blood, turning the skin bright cherry red (reversible).
What are the COHb levels associated with exposure to carbon monoxide in the air?
A:
0.04% CO in air → 10% COHb (shortness of breath on exertion, impairing judgment with long exposure).
0.1% CO in air → 50%-70% COHb.
0.4% CO in air → 80% COHb.
Irreversibly oxidized and partially denatured hemoglobin due to sulfur binding
sulfhemoglobin (SHb)
What disorder is associated with sulfhemoglobin?
Sulfhemoglobinemia
What is the pathophysiology of sulfhemoglobinemia?
Exposure to sulfur chemicals or drugs leads to the incorporation of a sulfur atom into the pyrrole ring of heme, resulting in a green hemochrome.
Chemicals or drugs that may cause sulfhemoglobin
sulfonamides, phenacetin, nitrites, phenylhydrazine
How does sulfhemoglobin affect oxygen binding?
Affected heme subunits are unable to bind O2, and unaffected heme subunits have a decreased affinity for O2, causing a rightward shift in the oxygen dissociation curve, leading to cyanosis.
What color does increased sulfhemoglobin give to blood?
Mauve-lavender color.
What is formed when sulfhemoglobin combines with carbon monoxide?
Carboxysulfhemoglobin.
In which conditions has sulfhemoglobin been reported?
Severe constipation, bacteremia due to Clostridium perfringens, and enterogenous cyanosis.
How is sulfhemoglobin detected?
It cannot be detected by the cyanmethemoglobin method; its absorbance peak is between 600 nm and 620 nm.
What effect does a shift to the left have on hemoglobin’s affinity for oxygen?
Increased affinity for oxygen
What effect does a shift to the right have on hemoglobin’s affinity for oxygen?
Decreased affinity for oxygen.
How does pH affect hemoglobin’s affinity for oxygen?
Shift to the Left: Increased pH (alkaline/low H⁺)
Shift to the Right: Decreased pH (acidic/high H⁺)
How does 2,3-BPG affect hemoglobin’s state?
Shift to the Left: Decreased levels of 2,3-BPG (relaxed form)
Shift to the Right: Increased levels of 2,3-BPG (tense form)
How does carbon dioxide (CO2) affect hemoglobin’s affinity for oxygen?
Shift to the Left: Decreased CO2
Shift to the Right: Increased CO2
What effect does body temperature have on hemoglobin’s affinity for oxygen?
Shift to the Left: Decreased temperature
Shift to the Right: Increased temperature (O2 will cool off the body)
What are other causes that can shift the oxygen dissociation curve to the left?
Alkalosis,
multiple transfusions of stored blood with depleted 2,3-BPG,
Hb F (p50 = 19-21 mmHg/weak binding to 2,3-BPG leading to increased Hb affinity for O2).
What are other causes that can shift the oxygen dissociation curve to the right?
Acidosis,
high altitude,
pulmonary insufficiency,
congestive heart failure (CHF),
severe anemia.
