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N935 Advanced Pathophysiology > Week 3: Hematologic Pathophysiology Hemoglobin Disorders > Flashcards

Week 3: Hematologic Pathophysiology Hemoglobin Disorders Flashcards

1
Q

What does a hemoglobin consist of?

A

large molecule made of proteins and iron

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2
Q

Define globin

A

four folded chains of a protein

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3
Q

How many hemoglobin molecules are in an individual erythrocyte?

A

300 million

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4
Q

What is a pyrrole?

A

an organic compound that is characterized by a ring structure composed of 4 carbons and 1 nitrogen atom

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5
Q

What is a protoporphyrin?

A

it is the precursor of heme
it lack iron
free base

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6
Q

Describe the formation of hemoglobin from the proerythroblast to erythrocyte

A

2 succinyl-CoA molecules combine with 2 glycine amino acids to from pyrrole molecule
4 pyrrole molecules combine to form protoporphyrin
Protoporphyrin forms with iron to make heme
Heme + globin

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7
Q

How many subunit chains are possible for a globin?

A

alpha
beta
gamma
delta

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8
Q

What is the most common hemoglobin? what is its structure?

A

2 alpha and 2 beta

hemoglobin A

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9
Q

How many globin chains are in each hemoglobin and how many iron ATOMS?

A

4 hemoglobin chains

4 iron atoms

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10
Q

How many (possible) oxygen atoms are bound to a hemoglobin?

A

8 oxygen atoms

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11
Q

What determines the binding affinity for oxygen in the hemoglobin molecule?

A

type of hemoglobin chain

- the oxygen combining capacity is directly related to Hb concentration and not on the number of RBCs

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12
Q

How is oxyhemoglobin formed?

A

when hemoglobin picks up oxygen binds to the iron ion

this occurs in the lungs

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13
Q

What is the shape of the hemoglobin-O2 dissociation curve? Why?

A

sigmoidal

due to its cooperative binding of oxygen to hemoglobin

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14
Q

How is hemoglobin destructed in the liver?

A

liver kupffer cells phagocytose the hemoglobin

iron released by into blood and carried by transferrin to BM (to help with RBC production) or stored in the liver

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15
Q

What is unconjugated bilirubin?

A

when free bilirubin combines with albumin

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16
Q

Describe the steps of bilirubin production?

A 
macrophages spilt Hgb to heme and globin
heme ring open and iron released
pyrrole groups converted to biliverdin
biliverdin converted to free bilirubin
free bilirubin combines with albumin
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17
Q

What are the consequences of Hgb mutations?

A

impair globin folding or hemoglobin binding
heme will bind nonspecificallly to other regions of the globin chains
causes Heinz bodies

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18
Q

How can methemoglobin be categorized as a disorder of hemoglobin?

A

altered affinity

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19
Q

How can thalassemia be categorized by a disorder of hemoglobin?

A

quantitative disorder of globin chain

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20
Q

How can sickle cell be categorized by a disorder of hemoglobin?

A

qualitative disorder of globin structure

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21
Q

Define methemoglobin

A

formed when iron in Hb is oxidized from the ferrous to ferric state

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22
Q

What occurs in methemoglobin?

A

methemoglobin cannot bind o2 to tissues as effectively and therefore cannot carry oxygen to tissues
Holds onto O2 longer, doesn’t let go @ tissues

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23
Q

Does methemoglobin normally occur?

A

yes, but <1%

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24
Q

What converts Mhgb back to Hbg?

A

NADH dependent enzyme methemoglobin reductase

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25
Why is the pulse ox unreliable and falsely high in a patient with methemoglobin?
Methemoglobin increases absorption of light at both wavelengths (>940nm) and therefore offers optical interference to pulse ox by falsely absorbing light
26
What pathway maintains heme iron its ferrous state?
methemoglobin reductase pathway
27
What reductase maintains heme iron its ferrous state?
NADH- cytochrome b5 reductase
28
Methemoglobin shifts the Oxy-Hb dissociation curve left or right? Why?
left increases affinity in the remaining heme sites that are in ferrous state delivers little oxygen to tissues
29
what % can a patient no longer tolerate methemoglobin?
30%
30
What symptoms will occur >30% methemoglobin?
oxygen deprivation | muscle weakness, nausea tachycardia
31
3 Mechanisms/Causes of Methemoglobin
congenital or acquired congenital= globin chain mutation (hbM) or methemoglobin reductase system inhibition Acquired: toxic exposure to substance that oxidized normal Hb iron that exceeds the normal capacity
32
Globin chain mutation is
mutations that stabilize heme iron in the ferric state, making it relatively resistant to reduction by methemoglobin reductase system
33
What do patients with the globin chain mutation look like? blood color?
cyanotic appearance blood will be a blueish- brown color often asymptomatic
34
Impaired reductase system is
mutations impairing the NADH and cytochrome b methemoglobin reductase system that results in methemoglobin levels below 25%
35
Acquired Methemoglobinemia is
rare, life-threatening amounts of methemoglobin accumulate exceeding its rate of reduction
36
WHo has a greater susceptibility to oxidizing agents in methemoglobinemia?
infants because of there lower levels of methemoglobin reductase in their erythrocytes
37
What is the most common cause of acquired methemoglobin?
topical anesthetics | benzocaine
38
Implications of methemoglobinemia and anesthesia
avoid tissue hypoxia supplemental O2 will not correct low O2 frequent ABGs and co-oximetry needs arterial line chocolate color blood sample correct acidosis EKG monitor for ischemia avoid oxidizing agents: local anesthetics, nitrates, nitric oxide
39
Treatment to toxic methemoglobinemia
supplemental O2 1-2mg/kg methylene blue infused over 3-5 minutes single treatment may be okay requires activity of G6PD
40
MOA of Methylene blue in methemoglobinemia
acts as an electron donor for the non-enzymatic reduction of methemoglobin G6PD donates a proton to NADP to make NADPH. NADPH methemoglobin reductases loses it H+ to convert methylene blue to leukomethylene blue to break down methemoglobin
41
What is contraindicated in patients with G6PD deficiency?
methylene blue
42
Why do we use methylene blue in the OR?
intraoperative urologic dye confirms ureteral patency and to localize ureteral orifice for lymph node and vessel delination, and for tumor localization
43
Dose and pharmacokinetics of methylene blue
1mg/kg IV over 5-30 minutes concentration 5mg/ml 1/2 life 24 hours excreted 40% unchanged in urine
44
methylene blue
water soluble thiazine dye that promotes a non-enzymatic conversaion of metHb to hemoglobin
45
Thalassemia
an inherited defect in globin chain synthesis Beta thalassemia Alpha thalassemia minor, intermedia, major
46
HbF
2 alpha chains and 2 gamma globin chains
47
Beta thalassemia is predominant in
African, mediterranean and middle east area
48
Beta thalassemia has two types
of alleles with different single-based mutations B zero alleles which produce no beta globin beta + alleles which produce reduced amounts of beta globin
49
What are the two defective synthesis of beta globin contributes to anemia?
the inadequate formation of HbA results in microcytic, poorly hemoglobinized red cells and the excess of unpaired alpha chains form toxic precipitates that damage the membranes of erythroid precursors, most of which die by apoptosis
50
Alpha thalassemia is predominant to
southeast asia and india
51
Alpha thalassemia is
deletion of one or more alpha globin genes disease severity is proportional to the number of alpha globin genes that are deleted ineffective erythropoiesis and hemolysis are less pronounced that in b thalassemia however ineffective O2 tissue delivery still remains
52
What are the three defects that depress oxygen-carrying capacity in thalassemia major?
ineffective erythropoiesis hemolytic anemia hypochromia and microcytosis
53
Thalassemia major causes
unpaired globin to aggregate and precipate which damage the RBC some die within the BM and cause bone hyperplasia splenomegaly- d/t altered morphology from increased clearance
54
How does mortality occur in thalassemia major?
arrhythmias and CHF
55
Treatment of Thalassemia major
transfusions to treat but can cause iron overload splenectomy- reduces transfusion requirements bone marrow transplantation
56
General Anesthetic management of Thalassemia
determine severity and amount of end-organ damage risk for infection-- broad spectrum antibotics DVT prophylaxis risk of difficult intubation alert blood bank
57
Anesthetic management of Mild Thalassemia
chronic compensated anemia | consider pre-op transfusion to hgb >10g/dl
58
Anesthetic management of Severe Thalassemia
splenomegaly, hepatomegaly, skeletal malformations, CHF, intellectual disability iron overload= cirrhosis, right sided HF
59
Sickle Cell
exposure of this cell to low oxygen causes crystals to form inside and elongate the RBC space change makes it impossible for RBC to pass through small capillaries and the spiked end of the crystals are likely ruptured the membrane
60
Sickle cell disease
amino acid valine is substituted for glutamic acid at one point in each of the 2 beta chains does increase perioperative morbidity and mortality
61
sickle cell trait
only 1 beta chain effected | dose not increase perioperative morbidity and mortality
62
Sickle Cell Hemoglobin S
genetic defect of Hgb Synthesis precipitated hemoglobin also damages the cell membrane leading the sickling crisis of ruptured cells further decrease in oxygen tension and more sickling and RBC destruction severe anemia recurrent painful episodes due to ischemia
63
Sickle cells risk factors for M &M
``` age frequency of sickle crisis's elevated creatinine cardiac conditions surgery type ```
64
Sickle Cell Disease anesthetic management
``` avoid 3 h's good premed (avoids stress) high narcotic requirements current type and cross tourniquet (cautious use) ```
65
what are the 3 H's to avoid during surgery with sickle cell patients?
hypoxia hypovolemia hypothermia
66
Acute Chest Syndrome
looks like pneumonia on xray develops 2-3 days postop treatments for hypoxemia, analgesia, and blood transfusions possible nitric oxide therapy incidence is decreased if pre-op HCt is >30%
67
Key points of Anesthesia and Hgb disorders
history is important high variable approach, dependent on degree of hemolysis severe hemolysis requires transfusions avoid oxidizing medications when possible

N935 Advanced Pathophysiology (9 decks)

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