hematologic - hemoglobin disorders

Question 1

Hemoglobin makeup

Answer 1

large molecule
made up of proteins and iron
4 folded chains of globin

Question 2

an individual erythrocyte may contain about

Answer 2

300 million hemoglobin molecules

Question 3

Normal hemoglobin beta chain made up of which amino acids

Answer 3

the first 6 amino acids

valine, histidine, leucine, thre, proline, glutamic acid

Question 4

which amino acid is substituted in sickle cell hemoglobin beta chain

Answer 4

glutamic acid

Question 5

synthesis of hemoglobin begins in the

Answer 5

proerythroblast and continues through the reticulocyte stage

Question 6

2 succinyl CoA + 2 glycine yields

Answer 6

pyrrole molecule

Question 7

4 pyrrole molcules combine to form

Answer 7

protoporphyrin which combines with iron to make heme

Question 8

hemoglobin A has which subunits?

Answer 8

2 alpha and 2 beta subunits

Question 9

the type of hemoglobin chain in the hemoglobin molecule determines

Answer 9

the binding affinity for oxygen

Question 10

the oxygen combining capacity is directly related to

Answer 10

hemoglobin concentration and not on the number of RBCs

Question 11

in the lungs hemoglobin picks up oxygen which binds to the iron forming

Answer 11

oxyhemoglobin

Question 12

when oxygen molecules are released at the tissues oxygenated hemoglobin becomes

Answer 12

deoxyhemoglobin

Question 13

oxygen release depends on

Answer 13

the need for oxygen in the surrounding tissues

Question 14

shape of the oxy-hemoglobin dissociation curve is ___ and why

Answer 14

sigmoidal due to cooperative binding of oxygen to hemoglobin

Question 15

RBC lifespan

Answer 15

120 days

Question 16

how is hemoglobin destroyed?

Answer 16

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

Question 17

the porphyrin portion (pyrrole rings) of hemoglobin is converted to

Answer 17

biliverdin and then unconjugated bilirubin is conjugated by hepatocytes and secreted in bile

Question 18

hemoglobin disorder that has altered affinity

Answer 18

methemoglobin

Question 19

hemoglobin disorder that is a quantitative disorder of the globin chain

Answer 19

thalaseemia

Question 20

hemoglobin disorder that is a qualitativev disorder of globin sturctures

Answer 20

sickle cell

Question 21

methemoglobin is formed when the iron in hemoglobin is

Answer 21

oxidized from the ferrous (Fe2+) to the ferric (Fe3+) state

Question 22

can methemoglobin bind oxygen?

Answer 22

no so oxygen cannot be carried to tissues

Question 23

the NADH-dependent enzyme, methemoglobin reductase, is responsible for

Answer 23

converting MHgb back to Hgb

Question 24

methemoglobin reductase pathway

Answer 24

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

Question 25

how does methemoglobin move the oxy-hgb dissociation curve?

Answer 25

moves the curve markedly to the left and therefore delivers little oxygen to the tissues (Left Loves)

Question 26

symptoms of oxygen deprivation

Answer 26

muscle weakness, nausea, tachycardia

Question 27

methemoglobin levels >50% leads to

Answer 27

coma and death

Question 28

3 mechanisms of methemoglobinemia

Answer 28

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

Question 29

globin chain mutation definition

Answer 29

mutations that stabilize heme iron in the Ferric (Fe3+) state, making it relatively resistant to reduction by the methemoglobin reductase system

Question 30

globin chain mutation presentation/manifestation

Answer 30

patient's blood will be brownish/blue color and cyanotic appearance patient is usually asymptomatic d/t their levels rising >30%

Question 31

impaired reductase system definition

Answer 31

mutations impairing the NADH and cytochrome b methemoglobin reductase system usually result in methemoglobinemia levels below <25%

Question 32

impaired reductase system manifestation/presentation

Answer 32

exhibit slate-gray pseudocyanosis despite normal PaO2 levels

Question 33

exposure to agents that oxidize Hgb can produce

Answer 33

a life threatening methemoglobinemia

Question 34

acquired methemoglobinemia definition

Answer 34

rare, life threatening amounts of methemoglobin accumulate exceeding its rate of reduction

Question 35

infants have ____ levels of methemoglobin reductase in their erythrocytes

Answer 35

lower levels which puts them at great susceptibility to oxidizing agents

Question 36

chemical exposure to ____ in well water can lead to methemoglobinemia

Answer 36

nitrates

Question 37

nearly all _____ have been associated with methemoglobinemia ____ being the most common

Answer 37

topical anesthetic preparations, benzocaine being the most common

Question 38

anesthesia considerations for methemoglobinemia

Answer 38

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

Question 39

examples of oxidizing agents

Answer 39

Local anesthetics, nitrates, and nitric oxide

Question 40

toxic methemoglobinemia treatment

Answer 40

supplemental oxygen 1-2mg/kg methylene blue infused over 3-5minutes may need to repeat after 30 minutes

Question 41

where does methylene blue act?

Answer 41

through the methemoglobin reductase system and requires the activity of G6PD

Question 42

methylene blue acts as an

Answer 42

electron donor for the nonenzymatic reduction of methemoglobin

Question 43

what enzyme converts methylene blue to leukomethylene blue

Answer 43

NADPH methemoglobin reductase (requires G6PD)

Question 44

if someone has G6PD deficiency can you give them methylene blue?

Answer 44

no

Question 45

B thalassemia definition

Answer 45

inherited defect in globin chain synthesis | can be a carrier, have mild anemia, or severe anemia

Question 46

B0 vs B+ allele in B thalassemia

Answer 46

B0 - produce no B globin | B+ - produce reduced amounts of B globin

Question 47

the defective synthesis of B globin contributes to anemia in 2 ways

Answer 47

1. inadequate formation of HbA = microcytic, poorly hemoglobinized red cells 2. excess unpaired a-globin chains form toxic precipitates that damage the membranes of erythroid precursors that die by apoptosis

Question 48

where is B thalassemia predominant?

Answer 48

african mediterranean area

Question 49

where is A thalassemia predominant?

Answer 49

southeast asia/india

Question 50

definition of A thalassemia

Answer 50

deletion of one or more of the a globin genes | disease severity is proportional to the number of a globin genes that are deleted

Question 51

thalassemia major

Answer 51

life threatening | requires transfusions during 1st few years of life

Question 52

what are the 3 defects that depress oxygen carrying capacity in thalassemia major

Answer 52

ineffective erythropoiesis hemolytic anemia hypochromia and microcytosis

Question 53

mortality in someone with thalassemia major is usually from

Answer 53

arrhythmias and CHF

Question 54

treatment of thalassemia major

Answer 54

transfusions, chelation therapy splenectomy bone marrow transplantation

Question 55

anesthesia management in mild thalassemia

Answer 55

consider preop transfusion to Hgb >10

Question 56

anesthesia management/considerations in severe forms of thalassemia

Answer 56

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

Question 57

sickle cell disease

Answer 57

the amino acid valine is substituted for glutamic acid at one point in each of the 2 beta chains

Question 58

sickle cell trait

Answer 58

only 1 beta chain is affected

Question 59

exposure of a sickled cell to low oxygen causes

Answer 59

crystals to form inside and elongate the RBC

Question 60

sickle cell trait (does/does not) increase perioperative morbidity and mortality

Answer 60

does not

Question 61

sickle cell disease (does/does not) increase perioperative morbidity and mortality

Answer 61

does

Question 62

risk factors for sickle cell perioperative morbidity and mortality

Answer 62

age, frequency of sickle crisis', elevated creatinine, cardiac conditions, surgery type

Question 63

what is the transfusion goal for patients with sickle cell

Answer 63

increase ratio of normal Hgb to sickle Hgb

Question 64

sickle cell disease anesthetic management/considerations

Answer 64

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

Question 65

Acute chest syndrome looks like ___ on cxray

Answer 65

pneumonia

Question 66

When does acute chest syndrome develop and what kind of treatment do they need?

Answer 66

develops 2-3 days postop | treatment for hypoxemia, analgesia, blood transfusions, nitric oxide therapy

Question 67

incidence of acute chest syndrome is decreased if

Answer 67

preop Hct is >30%