Hematologic Pathophysiology Hemoglobin DO's Flashcards
hemoglobin
large molecule made up of proteins and iron, four folded chains of a protein called globin
an individual erythrocyte may contain how many HGB molecules
300 million
HGB formation steps (5)
- synthesis begins in proerythroblast and continues through reticulocyte stage
- two succinyl CoA (formed in krebs cycle) + 2 glycine creates the pyrrole molecule
- 4 pyrrole molecules combine to form protoporphyrin which combines with iron to make heme
- heme + globin combine
- four subunit chains possible (alpha, beta, gamma, delta)
which HGB is most common and its makeup
HGB A with 2 alpha and 2 beta
which part of HGB has iron atom
heme group
how many hemoglobin chains/iron atoms per HGB molecule
4 HGB chains, 4 iron atoms
how many oxygen atoms combine with the 4 iron
8 O2 atoms
what determines binding affinity of HGB for O2
type of HGB chain in HGB molecule (directly related to Hb concentration and not on number of RBC’s)
oxyhemoglobin
(in lungs), HGB picks up O2 which binds to iron ions forming oxyhemoglobin
deoxyhemoglobin
no O2 molecules (released to tissues)
what does O2 release depend on
need for O2 in surrounding tissues
why is HGB O2 dissociation curve sigmoidal
due to cooperative binding of oxygen to HGB
lifespan of RBC
120 days
steps to HGB destruction
- RBC dies
- HGB released
- kupffer cells phagocytose HGB
- iron released back into blood and carried by transferring to either bone marow for production of new RBC’s or liver to be stored
- porphyrin portion (pyrrole rings) of HGB is converted to bilverdin and then unconjugated bilirubin to be conjugated by hepatocytes and secreted into bile
DO’s of HGB:
altered affinity:
quantitative DO of globin chains:
qualitative DO of globin structures
metHGB
thalassemia
sickle cell
metHGB
iron in HGB oxidized from ferrous (Fe2+) to ferric (Fe3+). metHGB cannot bind O2 and therefore cannot carry oxygen to the tissues.
in excess of metHGB, blood becomes dark blue/brown
methemoglobin reductase responsibility
NADH dependent enzyme responsible for converting metHGB back to HGB
methemoglobin reductase pathway
uses nicotinamide adenine dinucleotide (NADH)-cytochrome b5 reductase in erythrocyte from anaerobic glycolysis to maintain heme iron in its ferrous state
how does metHGB move the oxyHGB dissociation curve
moves curve markedly to left, delivers little oxygen to the tissues
“left loves” to hang on to their O2
-increased affinity of the remaining three heme sites that are still in the ferrous state
metHGB percentages and what they mean <1% 30% 30-50% >50%
<1%: normal
30% tolerable level up to this
30-50%: sx of oxygen deprivation can occur (muscle weakness, nausea, tachycardia)
>50% leads to coma and death
3 mechanisms/types of metHGBemia
- globin chain mutation (HbM) (congenital)
- methemoglobin reductase system mutation (congenital)
- toxic exposure to substance that oxidizes normal HGB iron (acquired)
globin chain mutation metHGBemia
mutations that stabilize heme iron in ferric (Fe3+) state, making it relatively resistant to reduction by methemoglobin reductase system
patients blood will be brownish blue color and will have cyanotic appearance
often asymptomatic as their methemoglobin levels rarely exceed 30% of total Hb unless exposed to a toxic dose of oxidizing agent
impaired reductase system
mutations impairing NADH and cytochrome b methemoglobin reductase system usually result in methemoglobinemia levels below 25%
affected patients may also exhibit slate gray pseudo cyanosis despite normal PaO2 levels
exposure to agents that oxidize HGB can produce life threatening metHGBemia
acquired metHGBemia
rare, life threatening amounts of metHGB accumulate exceeding its rate of reduction
infants have lower levels of methemoglobin reductase in their erythrocytes, greater susceptibility to oxidizing agents. (test for nitrates in well water)
nearly all topical anesthetic preparations have been associated with metHGBemia, benzocaine is most common
anesthetic considerations for methHGBemia
avoid tissue hypoxia
administration of supplemental oxygen does not correct low oxygen saturation levels
pulse oximetry is unreliable, cannot detect metHGB
arterial line- frequent ABG’s and co oximetry
blood sample- chocolate color
correct acidosis
EKG: monitor for hypoxic ischemia
avoid oxidizing agents (LA’s, nitrates, Nitric oxide)
toxic metHGBemia treatment
supplemental oxygen
1-2mg/kg methylene blue infused over 3-5 minutes
single tx usually effective, may need repeated after 30 minutes
how does methylene blue work
acts through metHGB reductase system and requires activity of G6PD
donates electron for non enzymatic reduction of metHGB (Fe3+ to Fe2+)
NADPH and methylene blue
NADPH metHGB reductase, converts methylene blue (the oxidized form of the dye) to leukomethylene blue (the reduced form), using NADPH which requires G6PD
b thalassemia (minor, intermediate, major)
inherited defect in globin chain synthesis, predominant in african mediterranean area
minor: carrier of trait, asymptomatic
intermediate: variable severity, mild anemia
major: severe anemia, transfusion dependent
dx of thalassemia
HGB electrophoresis, determines types of globin chains present
thalassemia alleles
β0: alleles which produce no B globin
B(+) alleles which produced reduced amounts of HGB
defective synthesis of B-globin in thalassemia contributes to anemia in 2 ways
1, inadequate formation of HbA results in microcytic, poorly hemoglobinized red cells and
2. excess unpaired a-globin chains form toxic precipitates that damage membranes of erythroid precursors, most of which die by apoptosis (cant properly fold without bet and alpha. damage ensues and cell wall dies
alpha thalassemia
predominant in southeast asiea
deletion of one or more of the alpha globin genes, disease severity is proportional to the number of alpha globin genes that are deleted
ineffective erythropoiesis and hemolysis are less pronounces than in B thalassemia, however, ineffective oxygen tissues delivery to the tissue remains
thalassemia major
life threatening, requies transfusions during first few years of life
3 defects which depress oxygen carrying capacity (ineffective erythropoiesis, hemolytic anemia, hypochromia and microcytosis)
unpaired globin aggregate and precipitate which damage RBC
some defective RBC’s die within bone marrow and cause bone hyperplasia
altered morphology accelerate clearance producing splenomegaly
mortality often due to arrhythmias and CHF
thalassemia major 3 defects which depress oxygen carrying capacity
ineffective erythropoiesis, hemolytic anemia, hypochromia and microcytosis
treatment of thalassemia major
transfusions to treat but often at the cost of iron overload (often need chelation therapy)
splenectomy (reduces transfusion requirements, risk of post splenectomy sepsis, deferred until >5y/o)
bone marrow transplantation (first used in 1982)
thalassemia anesthesia management
determine severity and amount of end organ damage: “how does this disease effect you”
mild forms-chronic compensated anemia. consider prep transfusion to HGB >10
severe forms: splenomegaly, hepatomegaly, skeletal malformations, CHF, intellectual disability (iron overload, cirrhosis, right sided heart failure)
risk for infection, broad spectrum antibiotics
DVT prophylaxis
risk of difficult intubation due to orofacial malformations
blood bank alerted that the patient has thalassemia (crossmatched earlier, possible antibodies r/t transfusion)
sickle cell disease
amino acid valine substituted for glutamic acid at one point in each of the 2 beta chains (effects HGB S). genetic defect, therefore, of sickle cell synthesis
sickle cell trait
only 1 beta chain is affected
sickle cell pathology
exposure of this cell to low oxygen causes crystals to form inside and elongate RBC, causes it to rupture
space change makes it impossible for RBC to pass through many small capillaries and spiked end of the crystals are likely to rupture the membrane
-precipitated HGB also damages cell membrane leading to sickling crisis of ruptured cells, further decrease in oxygen tension and more sickling and RBC destruction
-severe anemia, RBC’s are different shapes and sizes
-recurrent, painful episodes due to ischemia
sickle cell trait and perioperative morbidity and mortality
does not increase perioperative morbidity and mortality
sickle cell disease and perioperative morbidity and mortality
does increase perioperative morbidity and mortality
risk factors for perioperative morbidity and mortality r/t sickle cell disease (5)
age frequency of sickle cell crisis elevated creatinine cardiac conditions surgery type
sickle cell and preop transfusion
controversial as to how much, when, and what products
-transfusion goal is to increase ratio of normal HGB to sickle cell HGB
sickle cell disease anesthetic mangement
avoid 3 H’s: hypothermia, hypoxia, hypovolemia
good premeditation to avoid stress
high narcotic requirements
current type and cross (hard to cross match if they’ve had transfusions in the past of RBC’s)
tourniquet is controversial but if not in current crisis, they will use
acute chest syndrome
looks like PNA on CXR develops 2-3d into postop period demands tx for hypoxemia, analgesia, blood transfusions (for HGB goal >10) possible nitric oxide therapy incidence is decreased if preop Hct >30%
