Brainscape's Knowledge GenomeTM

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


See full index

Heme/Lymph 1 > Clinical Manifestations of Hemogloinopathies and Thalassemias > Flashcards

Clinical Manifestations of Hemogloinopathies and Thalassemias Flashcards

1
Q

Hemoglobinopathies

A

Qualitative defects in primary and tertiary structure of hemoglobin
Sickle cells is an example
Rare except in malaria regions

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

Thalassemias

A

Quantitative defects in either alpha or beta globins which produce a shortage of one globin type and unbalanced excess of another

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

Hemoglobin A design

A

2 stable alpha-beta globin dimers loosely bound into a tetramer

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

Embryonic globin chain genes,

Fetal hemoglobin genes

A

Embryonic - zeta and epsilon…place taken by alpha and gamma…alpha globins present throughout life while gamma eventually replaced by beta

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

HbF genes

A

Beta globin gene turns on in 1st trimester…transition period usually completed during weeks of postnatal life

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

How to diagnose hemoglobin structural disorders

A

Hemoglobin electrophoresis or HPLC

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

Hemoglobin electrophoresis

A

Structural variants have different charge patterns…done at multiple pHs

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

HPLC

A

Liquid mobile phase of dissolved hemoglobin

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

HbS

A

HbS does not dissolve in blood plasma
Test 2 ways
1) Sodium dithionite added and plasma becomes cloudy
2) Sodium metabisulfite test where oxygen removed and RBCs will sickle

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

Sickle cell anemia

A

Hemoglobinopathy
Mutation at position 6 in beta globin primary chain
Replace glutamic acid with valine
Tower skull and leg ulcers

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

Sickle cell mutation

A

6th AA position (GAG) for glutamic acid replcaed with GTG for valine
Results in change from charged, polar hydrophilic to uncharged hydrophobic, nonpolar side chain

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

Deoxygenated sickle cell

A

Tense conformation has sticky valine that wants to bind to other valines on HbS molecules

THis is why dehydration and hypoxia cause aggregation

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

Oxygenated sickle cell

A

Adjacent HbS are not likely to aggregate

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

POlymerization of sickle cell

A

HbS line up like long, rod-like polymerized crystals

Can be undone with oxygen

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

HbS membrane effect

A

Leads to force on membrane that it eventually overcomes…overtime, the membrane retains a sickle shape even if sickle hemoglobin removed

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

Membrane performance changes

A

Malfunctioning ion transport channels permit Na and Ca influx with K, Cl and H2O efflux…leads to dehydration, RBC shrinkage, increased RBC hemoglobin concentration and more polymerization

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

Other membrane changes

A 
Iron-mediated oxidative damage to membrane structural proteins makes membrane more rigid 
Denatured HbS (Heinz bodies) damage inner leaflet and promote extravascular hemolysis 
Distortion also exposes neoepitotpes that bind IgG
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

SIckle shell shape and other things

A

Misshaped, rigid, friable, subject to stress, hemolysis and phagocytosis
Adherent to vascular endothelium
More susceptible to phagocytosis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

Sickle cell membrane pathology

A

Entagle one another
Adhere to endothelium
Interact with Igs and complement in od ways
Disturb NO biology
Stimulate - pro-coagulants, cytokines, pro-inflam molecules, free radicals

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

Vascular clumping

A

Clumping of sialic acid residues and glycophorin on membrane promoted by calcium loading and dehydration…endothelial Von Willebrand factors multimers as well as plasma fibrinogen, fibronectin, and thrombospondin may play roles

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

Vaso-occlusion

A

Entanglement and endothelial adhesion are likely at vessel bifurcations and areas of low flow or turbulence…produces ischemia and micro infarcts in many tissues

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

Bone involvement in sickle cells

A

Pain crisis, osteonecrosis of femoral head, scattered bone infarcts, predisposition to mosteomyelitis and septic arthritis

23
Q

Acute chest syndrome

A

Sequestration of sickled cells into pulmonary vasculature
Also, embolization of infarcted bone marrow
May be confused with pneumonia and often accompanies it

24
Q

Strokes

A

Increased flow velocity - increased risk
Median age 5
Strokes predispose to more strokes

25
Q

Spleen pathology and sickle cell

A

Sequestration crisis due to rapid accumulation of sickled RBCs in enlarging spleen leading to acute anemia and schock
Also progressive microinfarction leading to gradual autospelenectomy
Prone to bacterial sepsis (encapsulated like S pneumo and H influ)

26
Q

Bone marrow expansion and sickle cell

A

Chronic hemolytic anemia and increased hematopoietic drive lead to expansion of red marrow into bony spaces usually not occupied by these…leads to tower skull
Also, extramedullary hematopoiesis

27
Q

Management of sickle cell

A 
Antibiotic
Hydration and rest
Hydroxyurea (to express HbF)
Exchange transfusion 
Iron overload monitoring (becasue of chronic transfusion)
28
Q

Sickle trait

A

One mutant gene…typically HbA>50%…presence of HbA increases oxygenation and limits sickling
Sickling still possitble givne low oxygen partial pressure, unusual exertion or dehydration

29
Q

Sickle cell malaria

A

Sickling cells bearing organized are cleared by spleen

30
Q

Sickle syndromes can appear as

A

Compound heterozygotes

31
Q

Compound heterozygote sickle cell dz

A

HbS/B-thalassemia - meditteranean
HbSS with alpha thalassemia - milder anemia but similar vaso occlusion
There are many others

32
Q

HbSC dz

A

Different mutation in the same location…subs lysine for glutamic acid
HbC alone does NOT cause vaso-occlusion
Mild hemolytic anemia but don’t need tx
Significance is when found in compound heterozygous state with HbS…Milder but similar to sickle cell

33
Q

Appearance of blood in thalassemias

A

Watery

34
Q

Thalassemia naming and what happens

A

Named for deficient chain
Overall deficit of normal Hb tetramers
Excess unpaired chains lead to hemolysis or ineffective erythropoiesis

35
Q

Thal classification and how different than sickle cell

A

Mahor, intermedia, and minor

Can begin in utero with severe anemia producing marrow expansion and bony deformoities

36
Q

Normal genetics of HbA

A

4 alpha genes and 2 beta genes

37
Q

Alpha thalassemias

A

One alpha missing - plenty left over and no anemia
2 alpha missing - mild anemia but only HbA present
3 alpha mising - small HbA made but excess of beta leads to B4 tetramer called HbH which is unstable but functional…this is called HBH dz
If all 4 genes missing, then only gamma4 tetramers (Barts) and Portland are present…lethal in utero

38
Q

Alpha thal silent carrier

A

Only one gene is missing…all Hb is HbA and insignifcant amount of B left over

39
Q

Cis alpha thal trait

A

2 genes missing on one chromosome…mildly def HbA and more unpaired B left over…form is inherited from a parent with a similar genotype and half of offspring affected

40
Q

Trans alpha thal trait

A

Two genes missing but one on each chromosome…1/4 of offspring of two silent carriers would be affected and all susequent crosses with normals would be silent carriers

41
Q

If one is cis and one trans

A

Could have 3 alpha genes missing

4 if both trans

42
Q

HbH disease

A

3 alphas are missing…HbA moderately deficient and B4 tetramers are formed…recognize on Hb electrophoresis as a fast migrator

43
Q

RBCs of HbH dz

A

Reduced RBC Hb content, producing target cells

Chronic anemia provokes erythropoeisis and polychromasia

44
Q

HbH precipitates to form

A

Heinz bodies

Transfusion usually unnessecary because moderate anemia

45
Q

Result of 4 alpha missing

A

Fetal dies from high output congestive heart failure secondary to profound anemia

46
Q

B globin genes

A

Chromosome 11 each one copy

47
Q

B0 and B+

A

B0 - defective or deleted

B+ - deficient and mediterranean type

48
Q

Thalassemia major

A

Homozygous B-thalassemias
Absent or markedly decreased beta chains
Alpha chains wil form unstable precipitates that then form free radicals that contribute to hemolysis

Anemia due to decreased production and increased destruction and can be severe

49
Q

Severity of thalssemia major depends on

A

Persistence of HbF

50
Q

Cooley’s anemia

A

Homozygous B-thalassemiua
Severe anemia leading to bone marrow hyperplasia and skll and jaw malformations (crew cut)
Jaundice and splenomegaly
Growth stunted and puberty delayed
Liufelong transfusions needed and die young from iron overload

51
Q

Heterozygous B-thalaseemia

A

B-thal trait
Anemia is mild and may be silent but sometimes presents as refractory anemia in pregnancy
Small increases in HbF and HbA2 present and may be clinically silent

52
Q

Milder thalassemias mistaken often iwth

A

iron deficiency

53
Q

Summary thalassemias

A

Less Hb produced in each RBC…fewer RBC produced…excess globin chains promote oxidative damage and precip of alpha chains promotes hemolysis…speen enlarges due to all RBCs that it is cleared and hemolysis causes jaundice…massive death of RBC precurosors in bone marrow…persistent anemia leads to high output congestive heart failure…chronic hypoxia leads to organ probsd and increased EPO production leads to marrow expansion and bone deformities…***Also lead to increased GI iron absorption which, coupled with defective utilization, leads to iron overload

54
Q

Transfusion benefits and downfalls

A

Replaces O2 carrying capcity with normal donor RBCs and suppresses patients EPO drive
Each contains iron and there is no way to excrete the iron

Heme/Lymph 1 (14 decks)

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