hematologic - hemoglobin disorders Flashcards
Hemoglobin makeup
large molecule
made up of proteins and iron
4 folded chains of globin
an individual erythrocyte may contain about
300 million hemoglobin molecules
Normal hemoglobin beta chain made up of which amino acids
the first 6 amino acids
valine, histidine, leucine, thre, proline, glutamic acid
which amino acid is substituted in sickle cell hemoglobin beta chain
glutamic acid
synthesis of hemoglobin begins in the
proerythroblast and continues through the reticulocyte stage
2 succinyl CoA + 2 glycine yields
pyrrole molecule
4 pyrrole molcules combine to form
protoporphyrin which combines with iron to make heme
hemoglobin A has which subunits?
2 alpha and 2 beta subunits
the type of hemoglobin chain in the hemoglobin molecule determines
the binding affinity for oxygen
the oxygen combining capacity is directly related to
hemoglobin concentration and not on the number of RBCs
in the lungs hemoglobin picks up oxygen which binds to the iron forming
oxyhemoglobin
when oxygen molecules are released at the tissues oxygenated hemoglobin becomes
deoxyhemoglobin
oxygen release depends on
the need for oxygen in the surrounding tissues
shape of the oxy-hemoglobin dissociation curve is ___ and why
sigmoidal due to cooperative binding of oxygen to hemoglobin
RBC lifespan
120 days
how is hemoglobin destroyed?
liver kupffer cell phagocytose the hemoglobin and iron is released back into the blood and carried by transferrin to the bone marrow for production of new RBCs or to the liver to be stored
the porphyrin portion (pyrrole rings) of hemoglobin is converted to
biliverdin and then unconjugated bilirubin is conjugated by hepatocytes and secreted in bile
hemoglobin disorder that has altered affinity
methemoglobin
hemoglobin disorder that is a quantitative disorder of the globin chain
thalaseemia
hemoglobin disorder that is a qualitativev disorder of globin sturctures
sickle cell
methemoglobin is formed when the iron in hemoglobin is
oxidized from the ferrous (Fe2+) to the ferric (Fe3+) state
can methemoglobin bind oxygen?
no so oxygen cannot be carried to tissues
the NADH-dependent enzyme, methemoglobin reductase, is responsible for
converting MHgb back to Hgb
methemoglobin reductase pathway
uses nicotinamide adenine dinucleotide (NADH)-cytochrome b5 reductase in the erythrocyte from anaerobic glycolysis to maintain heme iron in its ferrous state
how does methemoglobin move the oxy-hgb dissociation curve?
moves the curve markedly to the left and therefore delivers little oxygen to the tissues (Left Loves)
symptoms of oxygen deprivation
muscle weakness, nausea, tachycardia
methemoglobin levels >50% leads to
coma and death
3 mechanisms of methemoglobinemia
congenital
1. globin chain mutation
2. methemoglobin reductase system mutation
Acquired
3. toxic exposure to substance that oxidizes normal hgb iron that exceeds the normal capacity
globin chain mutation definition
mutations that stabilize heme iron in the Ferric (Fe3+) state, making it relatively resistant to reduction by the methemoglobin reductase system
globin chain mutation presentation/manifestation
patient’s blood will be brownish/blue color and cyanotic appearance
patient is usually asymptomatic d/t their levels rising >30%
impaired reductase system definition
mutations impairing the NADH and cytochrome b methemoglobin reductase system usually result in methemoglobinemia levels below <25%
impaired reductase system manifestation/presentation
exhibit slate-gray pseudocyanosis despite normal PaO2 levels
exposure to agents that oxidize Hgb can produce
a life threatening methemoglobinemia
acquired methemoglobinemia definition
rare, life threatening amounts of methemoglobin accumulate exceeding its rate of reduction
infants have ____ levels of methemoglobin reductase in their erythrocytes
lower levels which puts them at great susceptibility to oxidizing agents
chemical exposure to ____ in well water can lead to methemoglobinemia
nitrates
nearly all _____ have been associated with methemoglobinemia ____ being the most common
topical anesthetic preparations, benzocaine being the most common
anesthesia considerations for methemoglobinemia
avoid tissue hypoxia, administering oxygen does not correct low oxygen saturation levels, pulse oximetry is unreliable, need an aline, blood sample may be chocolate color, correct acidosis, monitor for hypoxic ischemia, avoid oxidizing agents
examples of oxidizing agents
Local anesthetics, nitrates, and nitric oxide
toxic methemoglobinemia treatment
supplemental oxygen
1-2mg/kg methylene blue infused over 3-5minutes
may need to repeat after 30 minutes
where does methylene blue act?
through the methemoglobin reductase system and requires the activity of G6PD
methylene blue acts as an
electron donor for the nonenzymatic reduction of methemoglobin
what enzyme converts methylene blue to leukomethylene blue
NADPH methemoglobin reductase (requires G6PD)
if someone has G6PD deficiency can you give them methylene blue?
no
B thalassemia definition
inherited defect in globin chain synthesis
can be a carrier, have mild anemia, or severe anemia
B0 vs B+ allele in B thalassemia
B0 - produce no B globin
B+ - produce reduced amounts of B globin
the defective synthesis of B globin contributes to anemia in 2 ways
- inadequate formation of HbA = microcytic, poorly hemoglobinized red cells
- excess unpaired a-globin chains form toxic precipitates that damage the membranes of erythroid precursors that die by apoptosis
where is B thalassemia predominant?
african mediterranean area
where is A thalassemia predominant?
southeast asia/india
definition of A thalassemia
deletion of one or more of the a globin genes
disease severity is proportional to the number of a globin genes that are deleted
thalassemia major
life threatening
requires transfusions during 1st few years of life
what are the 3 defects that depress oxygen carrying capacity in thalassemia major
ineffective erythropoiesis
hemolytic anemia
hypochromia and microcytosis
mortality in someone with thalassemia major is usually from
arrhythmias and CHF
treatment of thalassemia major
transfusions, chelation therapy
splenectomy
bone marrow transplantation
anesthesia management in mild thalassemia
consider preop transfusion to Hgb >10
anesthesia management/considerations in severe forms of thalassemia
patients can have splenomegaly, hepatomegaly, skeletal malformations, CHF, intellectual disability, iron overload
risk for infection, need DVT prophylaxis, risk for difficult intubation d/t oro-facial malformations, make sure the blood bank is aware
sickle cell disease
the amino acid valine is substituted for glutamic acid at one point in each of the 2 beta chains
sickle cell trait
only 1 beta chain is affected
exposure of a sickled cell to low oxygen causes
crystals to form inside and elongate the RBC
sickle cell trait (does/does not) increase perioperative morbidity and mortality
does not
sickle cell disease (does/does not) increase perioperative morbidity and mortality
does
risk factors for sickle cell perioperative morbidity and mortality
age, frequency of sickle crisis’, elevated creatinine, cardiac conditions, surgery type
what is the transfusion goal for patients with sickle cell
increase ratio of normal Hgb to sickle Hgb
sickle cell disease anesthetic management/considerations
avoid the 3 H’s! (hypothermia, hypoxia, hypovolemia)
avoid stress (give versed)
high narcotic requirements
current T&C
Tourniquet - controversial could increase risk of crisis potentially
Acute chest syndrome looks like ___ on cxray
pneumonia
When does acute chest syndrome develop and what kind of treatment do they need?
develops 2-3 days postop
treatment for hypoxemia, analgesia, blood transfusions, nitric oxide therapy
incidence of acute chest syndrome is decreased if
preop Hct is >30%
