Hematologic Pathophysiology Hemoglobin DO's

Question 1

hemoglobin

Answer 1

large molecule made up of proteins and iron, four folded chains of a protein called globin

Question 2

an individual erythrocyte may contain how many HGB molecules

Answer 2

300 million

Question 3

HGB formation steps (5)

Answer 3

1. synthesis begins in proerythroblast and continues through reticulocyte stage
2. two succinyl CoA (formed in krebs cycle) + 2 glycine creates the pyrrole molecule
3. 4 pyrrole molecules combine to form protoporphyrin which combines with iron to make heme
4. heme + globin combine
5. four subunit chains possible (alpha, beta, gamma, delta)

Question 4

which HGB is most common and its makeup

Answer 4

HGB A with 2 alpha and 2 beta

Question 5

which part of HGB has iron atom

Answer 5

heme group

Question 6

how many hemoglobin chains/iron atoms per HGB molecule

Answer 6

4 HGB chains, 4 iron atoms

Question 7

how many oxygen atoms combine with the 4 iron

Answer 7

8 O2 atoms

Question 8

what determines binding affinity of HGB for O2

Answer 8

type of HGB chain in HGB molecule (directly related to Hb concentration and not on number of RBC’s)

Question 9

oxyhemoglobin

Answer 9

(in lungs), HGB picks up O2 which binds to iron ions forming oxyhemoglobin

Question 10

deoxyhemoglobin

Answer 10

no O2 molecules (released to tissues)

Question 11

what does O2 release depend on

Answer 11

need for O2 in surrounding tissues

Question 12

why is HGB O2 dissociation curve sigmoidal

Answer 12

due to cooperative binding of oxygen to HGB

Question 13

lifespan of RBC

Answer 13

120 days

Question 14

steps to HGB destruction

Answer 14

1. RBC dies
2. HGB released
3. kupffer cells phagocytose HGB
4. iron released back into blood and carried by transferring to either bone marow for production of new RBC’s or liver to be stored
5. porphyrin portion (pyrrole rings) of HGB is converted to bilverdin and then unconjugated bilirubin to be conjugated by hepatocytes and secreted into bile

Question 15

DO’s of HGB:
altered affinity:
quantitative DO of globin chains:
qualitative DO of globin structures

Answer 15

metHGB
thalassemia
sickle cell

Question 16

metHGB

Answer 16

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

Question 17

methemoglobin reductase responsibility

Answer 17

NADH dependent enzyme responsible for converting metHGB back to HGB

Question 18

methemoglobin reductase pathway

Answer 18

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

Question 19

how does metHGB move the oxyHGB dissociation curve

Answer 19

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

Question 20

metHGB percentages and what they mean
<1%
30%
30-50%
>50%

Answer 20

<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

Question 21

3 mechanisms/types of metHGBemia

Answer 21

1. globin chain mutation (HbM) (congenital)
2. methemoglobin reductase system mutation (congenital)
3. toxic exposure to substance that oxidizes normal HGB iron (acquired)

Question 22

globin chain mutation metHGBemia

Answer 22

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

Question 23

impaired reductase system

Answer 23

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

Question 24

acquired metHGBemia

Answer 24

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

Question 25

anesthetic considerations for methHGBemia

Answer 25

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)

Question 26

toxic metHGBemia treatment

Answer 26

supplemental oxygen 1-2mg/kg methylene blue infused over 3-5 minutes single tx usually effective, may need repeated after 30 minutes

Question 27

how does methylene blue work

Answer 27

acts through metHGB reductase system and requires activity of G6PD donates electron for non enzymatic reduction of metHGB (Fe3+ to Fe2+)

Question 28

NADPH and methylene blue

Answer 28

NADPH metHGB reductase, converts methylene blue (the oxidized form of the dye) to leukomethylene blue (the reduced form), using NADPH which requires G6PD

Question 29

``` b thalassemia (minor, intermediate, major) ```

Answer 29

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

Question 30

dx of thalassemia

Answer 30

HGB electrophoresis, determines types of globin chains present

Question 31

thalassemia alleles

Answer 31

β0: alleles which produce no B globin | B(+) alleles which produced reduced amounts of HGB

Question 32

defective synthesis of B-globin in thalassemia contributes to anemia in 2 ways

Answer 32

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

Question 33

alpha thalassemia

Answer 33

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

Question 34

thalassemia major

Answer 34

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

Question 35

thalassemia major 3 defects which depress oxygen carrying capacity

Answer 35

ineffective erythropoiesis, hemolytic anemia, hypochromia and microcytosis

Question 36

treatment of thalassemia major

Answer 36

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)

Question 37

thalassemia anesthesia management

Answer 37

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)

Question 38

sickle cell disease

Answer 38

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

Question 39

sickle cell trait

Answer 39

only 1 beta chain is affected

Question 40

sickle cell pathology

Answer 40

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

Question 41

sickle cell trait and perioperative morbidity and mortality

Answer 41

does not increase perioperative morbidity and mortality

Question 42

sickle cell disease and perioperative morbidity and mortality

Answer 42

does increase perioperative morbidity and mortality

Question 43

risk factors for perioperative morbidity and mortality r/t sickle cell disease (5)

Answer 43

``` age frequency of sickle cell crisis elevated creatinine cardiac conditions surgery type ```

Question 44

sickle cell and preop transfusion

Answer 44

controversial as to how much, when, and what products | -transfusion goal is to increase ratio of normal HGB to sickle cell HGB

Question 45

sickle cell disease anesthetic mangement

Answer 45

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

Question 46

acute chest syndrome

Answer 46

``` 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% ```