Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

Heme > Lec 5 Hemoglobin Disorders > Flashcards

Lec 5 Hemoglobin Disorders Flashcards

1
Q

On what chromosome are alpha globin genes located?

A

chr 16

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

On what chromosome are beta globin genes located?

A

chr 11

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

What 2 chains make up hemoglobin F?

A

2 alpha and 2 gamma

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

What 2 chains make up hemoglobin A?

A

2 alpha and 2 beta

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

What 2 chains make up hemoglobin A2?

A

2 alpha and 2 delta

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

When do first RBCs in embryo appear?

A

3rd wk of gestation in the yolk sac

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

Does hemoglobin F have high or low affinity for oxygen?

A

relatively high!

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

When does hemoglobin A replace hemoglobin F?

A

by about 6 months of age

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

What percent of hemoglobin is normally A2?

A

1% of adult hemoglobin

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

How many heme molecules in one hemoglobin?

A

4 heme molecules = 1 heme for each globin

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

What is the structure of heme?

A

four pyrrole groups with an Fe molec in the center

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

Where does heme synthesis occur?

A

in the mitrochondria

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

What diseases associated with deficiency of some of the enzymes in heme biosynthesis?

A

porphyrias

sideroblastic anemia

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

What are porphyrias?

A

group of metbaolic disorders in which defects in enzymes of heme synthesis –> accumulation and excretion of porphyrins = toxic compounds

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

What is defect in acute intermittent porphyria? WHat 2 things accumulate

A

deficiency of porphobilinogen [PBG] deaminase –> leads to accumulation of ALA and PBG

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

What are clinical signs of acute intermittent porphyria?

A

nervous system abnormalities –> psychosis, convulsions, ANS dysfunction, peripheral neuropathy, parlaysis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

What is the defect in porphyria cutanea tarda?

A

deficiency of urogen decarboxylase

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

What is the function of hemoglobin?

A

reversible bind O2 for delivery

  • pick O2 up in lungs and deliver to tissues postnatally
  • pick O2 from placenta and deliver to the fetus in utero
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

Does T or R state of hemoglobin have more affinity for oxygen?

A

T state = taut = low affinity

R state = relaxed = higher affinity

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

What does increased O2 affinity do to P50?

A

lower P50

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

Is ferrous [Fe2+] or ferric [Fe3+] better state for O2 unloading?

A

ferrous

if stuck in ferric = high affinity for O2 but don’t unload it

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

What part of hemoglobin binds the 2-3 DPG?

A

the beta chain N terminus region

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

What is the P50?

A

oxygen pressure at which 50% of hemoglobin is saturated with oxygen

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

What is the Bohr effect on hemoglobin O2 affinity?

A

decrease in Ph –> decrease in hemoglobin affinity for O2 –> more unloading of O22 at tissue

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

What is effect of 2,3-DPG on hemoglobin affinity for O2?

A

shifts the curve to the right = less affinity for O2

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
26
Q

What happens when you have high affinity hemoglobin? Treatment?

A

O2 bound tightly to Hgb –> lower o2 tension than normal –> increase EPO –> erythrocytosis or polycythemia

treatment = phlebotomy

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
27
Q

What happens when you have low affinity hemoglobin [familial cyanosis]? treatment?

A

hemoglobin binds O2 poorly so mostly in deoxyhemoglobin state = bluesh hue known as cyanosis
will have cyanosis even though they are not hypoxic

no treatment required

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
28
Q

What is methemoglobinemia?

A

abnormal accumulation of methemoglobin in RBC = hemoglobin in which Fe oxidized to ferric [Fe3+] state and is unable to let go

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
29
Q

What are some causes of methemoglobinemia?

A

hemoglobin M = inherited disroder where abnormal Hgb has Fe in oxidized state

exposure to oxidizing agents [nitrites]

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
30
Q

What signs of methemoglobinemia?

A

cyanosis and chocolate-colored blood

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
31
Q

What is treatment for methemoglobinemia?

A

methylene blue

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
32
Q

What happens in CO poisoning?

A

hemoglobin binds CO to form carboxyhemoglobin = high affinity hemoglobin

reddish color = cherry red skin

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
33
Q

What defect specifically causes sickle cell disease?

A

single point mutation causing substitution glutamate –> valine in position 6 of the beta globin chain

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
34
Q

What chains in hemoglobin S?

A

2 alpha and 2 beta-S

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
35
Q

Why does sickle cell promote inflammation?

A
  • polymerization of HbS disrupts RBC cytoskeleton and leads to flipping of phosphatidylserine lipids in the membrane –> negative charged glycolipids on outside + activate coagulation cascade and promote inflammation
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
36
Q

What are some factors that promote sickling of HbS?

A
  • low O2
  • infection
  • dehydration
  • acidosis
  • low levels of HbF
37
Q

What are 3 consequences of sickling HbS?

A
  • microvascular occlusions b/c sickled cells trapped in small blood vessels –> infarction and necrosis of tissue
  • chronic extravascular hemolysis b/c poorly deformable sickled cells trapped and phagocytized by macrophages in the reticuloendothelial system
  • NO depletion by free hemoglobin from intravascular RBC breakdown
38
Q

How does life span of RBCs that are sickled compare to normal?

A

shortens life span by 2-3 weeks

39
Q

What is effect of sickle cell on the spleen?

A

extravascular hemolysis within the spleen –> recurrent infarction of spleen b/c HbS stuck –> atrophy and autosplenectomy

40
Q

What are 3 complications of microvascular occlusion?

A
  • pain
  • splenic infarction
  • end organ damage to lungs, CNS, etc
41
Q

What are 3 complications of chronic extravascular hemolysis in sickle cell?

A
  • anemia
  • expansion of erythropoiesis in bone marrow
  • gallstones
42
Q

What are 4 consequences of NO depletion in sickle cell?

A
  • pulm HTN
  • stroke
  • priapism
  • leg ulcers
43
Q

What is sickle cell disease?

A

pts who are homozygous for sickle mutation

44
Q

When do clinical manifestations of sickle begin?

A

around 6 months of age; earlier than that protected by HbF

45
Q

What type of infections are people with sickle cell more at risk for?

A

encapsulated organisms like strep pneumo

46
Q

What is a tip off that pt with sickle might be undergoing aplastic crisis?

A

inappropriately low reticulocyte count

47
Q

What is splenic sequestration syndrome?

A

only occurs in children w/ functional spleens

see massive sudden intersplenic sickling –> acute severe LUQ pain, rapid increase in spleen size; abrupt fall in hematocrit + shock

48
Q

What cardiovascular complications in sickle?

A

high output CHF secondary to chronic anemia
thrombosis
stroke

49
Q

What are signs of acute chest syndrome in sickle?

A

chest pain, fever, cough, pulm infiltrate of abrupt onset due to sickling in microvasculature of lung and causing pulmonary infarction

50
Q

How do you distinguish acute chest syndrome from infection?

A

clinically indistinguishable

51
Q

What kind of gallstones do you see in sickle?

A

bilirubin gallstones from hemolysis

52
Q

What renal complications of sickle?

A

low O2 in kidney medulla –> prone to infarction from vaso-occlusion –> medullary infarcts –> impaired ability to concentrate urine; hematuria

have renal papillary necrosis and microhematuria

53
Q

What do you see on peripheral smear in sickle?

A
  • sickle shaped RBCs
  • polychromasia [reticulocytes]
  • nucleated RBCs [b/c chronic active hemolysis –> increase bone marrow activity]
  • howell jolly bodies [normally would be cleared by spleen but these pts have functional asplenia]
  • target cells
54
Q

How do you diagnose sickle?

A

hemoglobin electrophoresis + CBC

55
Q

What is treatment for sickle?

A

hydroxyurea to increase HbF and bone marrow transplant

56
Q

WHat do you see in bone marrow of pt with sickle?

A

hypercellular; erythroid hyperplasia

57
Q

What do you see on CBC in pt with sickle?

A
  • low Hbg
  • WBC may be falsely elevated if not corrected for presence of nucleated RBCs
  • high retic count
58
Q

What happens to LDH in sickle?

A

increased

59
Q

Why give folic acid to pt with sickle?

A

at risk of folate deficiency b/c they are trying to make so much more blood

60
Q

What is sickle cell trait?

A

people who are heterozygous

will have 60:40 HbA to HbS

can be clinically normal; not anemia; may be at risk for renal complications

61
Q

What is hemoglobin C disease defect?

A

mutation at residue 6 on B-globin from glutaminc acid –> lysine

62
Q

What are symptoms of hemoglobin C defect?

A

have mild hemolytic anemia w/ splenomegaly if homozygous

63
Q

What happens in patient with double heterozygote SC disease?

A

resembles mild form of sickle cell disease PLUS have splenomegaly

64
Q

How can you distinguish between patient with sickle disease and patient with SC disease?

A

SC patient will have splenomegaly; SS will not

65
Q

What is clinical course of patient with sickle-beta thalassemia?

A

depends on how much normal beta globin is produced

66
Q

How can you distinguish sickle-beta thalassemia from homozygous sickle cell disease?

A

sickle beta have splenomegaly and target cells

homozygous sickle will not

67
Q

What is the defect in beta thalaseemia?

A

beta globin synthesis decreased or absent due to point mutations in splice site and promotor sequences

68
Q

Who primarily gets thalassemias?

A

mediterranean, middle eastern, african, indian, southeast asian

69
Q

What is beta thalassemia minor?

A

heterozygote of decreased beta chain synthesis [B+]

70
Q

What is beta thalassemia major?

A

homozygote of loss of activity of B chain gene

[Bo/Bo or Bo/B+]

71
Q

What are the two major consequences of decreased beta globin synthesis?

A
  • overall decreased production of hemoglobin A –> hypochromic microcytic anemia
  • unbalanced synthesis of a and b chains –> accumulation free excess alpha chain in RBCs –> combine to form alpha tetramers that are insoluble and precipitate in RBCs = heinz bodies
72
Q

What happens to levels of HbA, HbA2, and HbF in beta thelassemia?

A

HbA decreases

HbA2 and HbF increase = compensatory mech both in and outside bone marrow

73
Q

Why do you get hepatosplenomegaly in beta thalassemia?

A

extramedullary hematopoiesis

74
Q

What are the heinz bodies of B-thalassemia made of?

A

made of hemoglobin alpha chain tetramers [a4]

75
Q

What happens to RBCs with heinz bodies in beta thalassemia?

A
  • most are prematurely destroyed in marrow = intramedullary hemolysis
  • the rest get hemolyzed in spleen = extravascular hemolysis
76
Q

What are signs of B-thalassemia major?

A

severe anemia requiring blood transfusion

increase in erythryopoiesis –> marrow expansion and extramedullary hematopoiesis

77
Q

What happens to reticulocyte count in B-thalassemia major?

A

reticulocyte count increases

78
Q

What do you see on physical exam in B thalassemia major?

A

chipmunk facies
crew cut on skull xray
hepatosplenomegally

79
Q

What do you see on smear in B thalassemia major?

A 
microcytic hypochromic RBCs
poikilocytosis
target cells
basophilic stippling
polychromasia 2ndary to increased retics
80
Q

What is treatment for B thalassemia major?

A

transfusions + iron chelation therapy
splenectomy
BM transplant

81
Q

What is the defect in alpha thalassemia?

A

deletion of one or more of the 4 alpha globin genes –> leading to decreased alpha globin synthesis and deposition of gamma-globin tetramers

82
Q

What are the consequences of decreased alpha globin chain synthesis?

A
  • reduction in conc of all hemoglobins since all contain alpha chain
  • excess free beta and gamma –> HbH [beta4] and Hb Barts [gamma4]
83
Q

What is hydrops fetalis?

A

if all 4 alpha genes are deleted –> no alpha globin + excess HbBarts [gamma x4] which cannot release O2 to tissue

incompatible with life

84
Q

What is HbH disease?

A

if 3 of 4 alpha genes are deleted –> very little alpha globin + excess B globin that forms HbH [beta x4]

HbH can precipitate in membrane of RBC –> causes extravascular hemolysis in spleen

have mild to moderate hypchromic microcytic anemia and splenomegaly

85
Q

What is alpha thalassemia minor?

A

2 alpha globin genes defective –> mild hypochromic microcytic anemia with splenomegaly

not clinically significant

86
Q

What is alpha thalassemia trait?

A

silent carrier = 1 alpha globin gene defective

asymptomatic and no anemia

87
Q

What is major cause of anemia in b-thalassemia?

A

ineffective erythropoiesis

88
Q

What is major cause of anemia in HbH disease?

A

hemolysis

Heme (20 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions