Hemoglobin Disorders Flashcards

1
Q

hemoglobin

A
  • large molecule made up of proteins and iron

- four folded chains of a protein called globin

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2
Q

how many hgb molecules are in one erythrocyte?

A

300 million

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3
Q

formation of hemoglobin

A
  • synthesis begins in proerythroblast and continues through reticulocyte stage
  • 2 succinyl-CoA + 2 glycine –> pyrrole molecule
  • 4 pyrrole molecules –> protoporphyrin which combines with iron to make heme
  • heme + globin combine
  • 4 subunit chains possible
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4
Q

what are the four subunit chains of hemoglobin

A

alpha
beta
gamma
delta

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5
Q

what is the most common hemoglobin?

A

hemoglobin A
2 alpha
2 beta

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6
Q

hemoglobin iron and O2 binding

A
  • heme prosthetic group containing an atom of iron
  • 4 Hgb chains so 4 iron atoms
  • each iron can bind losely with O2 making a total of 8 oxygen atoms
  • the type of Hgb chain in the hemoglobin molecule determines the binding affinity for oxygen
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7
Q

oxyhemoglobin

A

in the lungs, hemoglobin picks up oxygen which binds to the iron ions

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8
Q

deoxyhemoglobin

A
  • darker red

- blood when oxygen is dropped off

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9
Q

destruction of Hgb

A
  • RBC dies
  • Hgb released
  • liver kupffer cells phagocytose the hgb
  • iron released back into the blood and carried by transferrin to either the bone marrow for production of new RBCs or to the liver to be stored
  • porphyrin portion of Hgb is converted into biliverdin and then unconjugated bilirubin to be conjugated by hepatocytes and secreted in bile
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10
Q

methemoglobin

A
  • formed when the iron in Hgb is oxidized from the ferrous to ferric state (Fe2+ –> Fe3+)
  • cannot bind O2 and therefore cannot carry oxygen to tissues
  • normally <1% of person’s Hgb
  • in excess, blood become dark blue/brown
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11
Q

what is responsible for converting Mhgb back to Hgb?

A

NADH-dependent enzyme methemoglobin reductase

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12
Q

methemoglobin reductase pathway

A

-uses nicotinamide adenine dinucleotide (NADH) cytochrome b5 reductase in the erythrocyte from anaerobic glycoslysis to maintain heme iron in its ferrous state

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13
Q

methemoglobin and oxy-hgb dissociation curve

A
  • moves the curve markedly to the left and therefore delivers little oxygen to the tissues
  • increased affinity in the remaining heme sites that are in the ferrous state (i.e. normal Hgb holds on to O2 more)
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14
Q

30% methemoglobin

A

patients can tolerate this but normie is <1%

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15
Q

30-50% methemoglobin

A

symptoms of oxygen deprivation

  • muscle weakness
  • nausea
  • tachycardia
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16
Q

> 50% methemoglobin

A

leads to coma and death

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17
Q

methemoglobinemia 3 mechanisms

A
  • globin chain mutation (HbM) (congenital)
  • methemoglobin reductase system mutation (congenital)
  • toxic exposure to substance that oxidizes normal Hb iron that exceeds the normal capacity (acquired)
18
Q

globin chain mutation

A
  • mutations that stabilize heme iron in the ferric state, making it relatively resistant to reduction by the methemoglobin reductase system
  • patient’s blood brownish blue color and will have a cyanotic appearance
  • often asymptomatic as their methemoglobin levels rarely exceed 30% of total Hb unless exposed to a toxic dose of oxidizing agent
19
Q

impaired reductase system

A
  • mutations impairing the NADH and cytochrome B methemoglobin reductase system usually result in methemoglobinemia levels below 25%
  • affected patients may also exhibit slate gray pseudocyanosis despite normal PaO2 levels
  • exposure to agents that oxidize Hgb can produce a life-threatening methemoglobinemia
20
Q

acquired methemoglobinemia

A
  • rare, life-threatening amounts of methemoglobin accumulate exceeding its rate of reduction
  • infants have lower levels of methemoglobin reductase in their erythrocytes so greater susceptibility to oxidizing agents
  • nearly all topical anesthetic preparations have been associated with methemoglobinemia
  • benzocaine most common
21
Q

methemoglobinemia anesthetic considerations

A
  • avoid tissue hypoxia
  • admin of supplemental oxygen dose not correct low oxygen sat
  • pulse ox is unreliable
  • art line (frequent ABGs and co-oximetry)
  • blood sample is chocolate
  • correct acidosis
  • EKG - monitor for hypoxic ischemia
  • avoid oxidizing agents - LAs, nitrates, nitric oxide
22
Q

toxic methemoglobinemia treatment

A
  • supplemental oxygen

- 1-2 mg/kg of methylene blue infused over 3-5 min (may need to repeat after 30 min)

23
Q

methylene blue

A
  • acts as an electron donor for the nonenzymatic reduction of methemoglobin
  • NADPH methemoglobin reductase converts methylene blue (the oxidized form of the dye) to leukomethylene blue (the reduced form), using NADPH which requires G6PD
  • methylene blue is contraindicated in someone with G6PD deficiency
24
Q

thalassemia

A
  • inherited defect in globin chain synthesis
  • over 300 mutations
  • RBC sickling
  • Dx by Hgb electrophoresis
25
minor beta thalassemia
carrier of trait, asymptomatic
26
intermedia beta thalassemia
variable severity, mild anemia
27
major beta thalassemia
severe anemia, transfusion dependent
28
beta thalassemia
- predominant in African, Mediterranean, and Middle East - two types of alleles with different single-base mutations (B0 alleles which produce no B globulin; B+ alleles which produce reduced amounts of B globulin)
29
defective synthesis of B globulin contributes to anemia in two ways
- inadequate formation of HbA results in microcytic, poorly hemoglobinized red cells - excess of unpaired alpha globin chains form toxic precipitates that damage the membranes of erythroid precursors most of which die by apoptosis
30
alpha thalassemia
- predominant in southeast asia - deletion of one or more of the alpha globin genes - disease severity proportional to the number of alpha globin genes that are deleted - ineffective erythropoiesis and hemolysis are less pronounced than in beta thalassemia BUT ineffective oxygen tissue delivery to the tissue remains
31
thalassemia major
- life-threatening requires transfusions during 1st few years of life - 3 defects that suppress oxygen carrying capacity --> ineffective erythropoiesis, hemolytic anemia, hypochromia and microcystosis - unpaired globin aggregate and precipitate with damage the RBC - some defective RBCs die within the bone marrow and cause bone hyperplasia - altered morphology accelerate clearance-producing splenomegaly - mortality often due to arrhythmias and CHF
32
thalassemia major treatment
- transfusions to treat but often at the cost of iron overload (often need chelation therapy) - splenectomy - reduces transfusion requirements (risk of post-splenectomy sepsis) - bone marrow transplant
33
thalassemia anesthesia management
- determine severity and amount of end-organ damage - mild forms chronic compensated anemia (consider preop transfusion to Hgb >10) - severe forms - splenomegaly, hepatomegaly, skeletal malformations, CHF, intellectual disability, iron overload - risk for infection - DVT prophylaxis - risk of difficult intubation due to oral facial malformations - blood bank alerted that pt has thalassemia
34
sickle cell disease
- amino acid valine is substituted for glutamic acid at one point in each of the 2 beta chains - does increase preop morbidity and mortality
35
sickle cell trait
- only 1 beta chain affected | - does not increase preop morbidity and mortality
36
hemoglobin S
- 0.3-1.0% of African Americans - genetic defect in Hgb synthesis - precipitated hemoglobin also damages cell membrane leading to sickling crisis of ruptured cells, further decrease in oxygen tension and more sickling and RBC destruction
37
risk factors for sickle cell M&M in periop
- age - frequency of sickle cell crises - elevated Cr - cardiac conditions - surgery type
38
sickle cell preop transfusions
- controversial as to how much, when and what | - goal = increase ratio of normal Hgb to sickle Hgb
39
sickle cell anesthetic management avoid 3 H's
hypothermia hypoxia hypovolemia
40
sickle cell other anesthetic management
- good pre-med to avoid stress - high narcotic requirements - current type and cross - tourniquet (not necessarily contraindicated but can increase the risk of crisis)
41
acute chest syndrome
- looks like pneumonia on CXR - develops 2-3 days into post-op period - demands treatment for hypoxemia, analgesia, and blood transfusions - possible nitric oxide therapy - incidence is decreased if preop Hct is > 30%