Brainscape's Knowledge GenomeTM

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


See full index

Year 2 - MCD Haem > SCD > Flashcards

SCD Flashcards

1
Q

What is different between HbA and HbS?

A

A SINGLE aa difference in the beta-chain (missense mutation at codon 6)

Glutamic acid (polar and soluble)
is replaced by
Valine (non-polar and insoluble)

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

What does the aa difference mean for HbS?

A

It is now INSOLUBLE

HbS polymerises to form fibres - ‘tactoids’
o inter-tetrameric contacts stabilising the structure

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

What are the stages in sickling of RBCs?

A

RIGID, ADHERENT, DEHDRATED

  1. DISTORTION
    o polymerisation initially reversible with formation of oxyHbS
    o BUT is subsequently irreversible
  2. DEHYDRATION
  3. INCREASED AHDERENCE
    o to vascular endothelium
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

Link between SCD and malaria?

A

Provides a source of protection from malaria!

Up to 25% Africans and 10% Caribbeans carry the sickle gene!

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

SS?

A

Sickle cell anaemia (HOMOZYGOUS state)

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

What is encompassed under SCD?

A

Sickle cell anaemia (SS)
AND
Compound heterozygous states e.g. SC, S-beta thalassaemia

Autosomal recessive

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

What does SCD incorporate?

A

SS and ALL other conditions that lead to a disease syndrome due to sickling

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

6 overal pathogensis of SCD?

A
  1. Shortened RBC lifespan (leads to haemolysis)
  2. Blockage of microvascular circulation
  3. Lungs
  4. Urinary Tract
  5. Brain
  6. Eye
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

Shortened RBC lifespan & SCD?

A

Leads to haemolysis!

o Anaemia - partly due to reduced erythropoietic drive as HbS is a LOW AFFINITY Hb

o Gallstones - co-inheritance of Gilbert syndrome further increases risk (affect bilirubin conjugation)

o Aplastic crisis - Parvovirus B19

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

Blockage to microvascular circulation & SCD?

A
  1. INFACRTION!
    o spleen - hyposplenism (capsulated bac. can attach more)
    o bones/joins -
    • dactylitis (inflammation of bone)
    • avascular necrosis (e.g. of femoral)
    • osteomyelitis (infection of bone e.g. salmonella)
      o skin - ulcerations
  2. PAIN
  3. DYSFUNCTION
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

Lungs & SCD?

A
  1. Acute - acute chest syndrome
  2. Chronic - Pulmonary hypertension
    o Correlated w. severity of haemolysis
    o Free plasma Hb from haemolysis scavenges NO and causes vasoconstriction
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

Urinary tract & SCD?

A

o Haematuria - due to papillary necrosis

o Renal failure & Hyposthenuria
- impaired [urine]

o Priapism

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

Brain & SCD?

A

o Stroke
o Cognitive impairment

Affects 8% of SS, most common 2-9years old

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

Eyes & SCD?

A

o Proliferative retinopathy!

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

When do the clinical presentations of SCD start?

A

3-6 months after birth

This is as the switch to adult HbA from fetal has NOT occurred yet!

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

What are the clinical presentations of the early manifestations of SCD?

A

o Dactylitis

o Splenic sequestration
- undergoes enalrgement leading to cooling of blood volume & anaemia

o Infection (pnuemococcal normally)

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

What else can trigger painful SCD crises?

A 
Infection
Exertion
Dehydration
Hypoxia - due to acute chest syndrome
Psychological stress
18
Q

Laboratory features of SCD?

A
  1. Hb LOW (6-8 g/dl)
  2. Reticulocytes (immature RBCs) HIGH
    - EXCEPT in aplastic crisis
3. Film
 o Sickled cells
 o Boat cells
 o Target cells
 o Howell Jolly bodies
19
Q

2 step process to diagnose SCD?

A
  1. SOLUBILITY test

2. Electrophoresis (HPLC)

20
Q

Solubility test?

A

To diagnose SCD

  1. In presence of reducing agent, oxyHb is converted to deoxyHb
  2. Solubility deceases & solution becomes turbid
21
Q

What is an issue with the Solubility test and diagnosing SCD?

A

Does NOT differentiate between AS & SS

AS - sickle cell trait
SS - homozygous state

22
Q

What test can you do after the Solubility test to differentiate?

A

Electrophoresis (HPLC)

Separates proteins according to charge

23
Q

How can you differentiate between AS and SS using elecrophoresis?

A

Homozygous state:
o have NO HbA
o HAVE HbS
o LITTLE HbA2

Heterozygrous state:
o have BOTH HbS & HbA

24
Q

General measurement measures for people with SCD?

A

o Folic acid

  • anaemia
  • required for DNA synthesis due to the increase in RBCs
o Penicillin (prophylaxis)
 - splenic dysfunction

o Vaccination

  • splenic dysfunction
  • agaisnt capsulated bac. & influenza

o Montior spleen size

o Blood transfusion
- for acute anaemic events, chest syndrome & stroke

o Pregnancy care

25
Q

Why must you monitor spleen size when managing SCD?

A

Splenic dysfunction

Acute splenic sqeuestration can mean you get an enlarged spleen!
Often requires:
o phrophylactic therapy (against pneumococcal infection)
o transfusions (to correct anaemia)
o MAYBE splenectomy

26
Q

How should you manage if someone has a painful crisis?

A

o Pain relief - opioids

  • Diamorphine widely used
  • variation in inidividual response
  • patient-controlled analgesia

o Hydration
o Keep warm
o O2 if hypoxic

MUST exclude infection so do:

  • blood & urine cultures
  • CXR
27
Q

Current disease-modifying therapies for SCD?

A
  1. Exchange transfusion
    o Stroke
    o Acute chest syndrome
  2. Haematopoietic stem cell transplantation
    o from sibling HLA or other haplo-identical individuals
    o <16 years with SCD
    o Survival rate = 90-95%
    o Cures in around 85-90%
  3. Induction of HbF
    o HYDROXYUREA/hydroxycarbimide
    o Butyrate
28
Q

Why is treatment of SCD with hydroxyurea (hydroxycarbamide) good?

A

Induces HbF production!

HbF INHIBITS polymerisation of HbS
- that’s why infants with SCD do NOT usually develop symptoms until >3months

Patients with HIGHER HbF have:
o fewer complications
o improved survival

29
Q

Rationale behind the use of hydroxyurea (hydroxycarbamide)?

A 
o Increases HbF
o Decreases 'stickiness' of SRBCs as reduces polymerisation
 - reduces ADHESION
o Reduces WBC production by bone marrow
o Improves hydration of RBCs
o Generates NO 
 - improves blood flow
30
Q

Characterisitcs of AS (sickle cell trait?)

A

HbAS

o Normal life expectancy
o Normal blood count
o Usually asymptomatic - rarely painless haematuria (due to papillary necrosis)

Take caution w. anaesthetic use, high altitude and extreme exertion

31
Q

Sickle cell anaemia includes both HbSS and HbSC

True/False

A

FALSE

Applies specifically to the homozygous state so HbSS

Sickle cell disease encompasses all sickle cell disorders

32
Q

Sickling is due to a change in the a globin chain

True/False

A

FALSE

Beta-globin

33
Q

The molecular alteration is a deletion which protects against malaria
True/False

A

FALSE

NOT a deletion - missense (point) mutation so alters an aa changing the biophysical property of the resulting Hb

34
Q

Sickle Hb makes red cells less deformable

						True/False
A

TRUE

35
Q

Clinical manifestations may start in utero because b-globin is part of fetal Hb
True/false

A

FALSE

HbF is compsoed of ALPHA and GAMMA CHAINS so is NOT affected by

36
Q

Osteomyelitis is the name given to inflammation of a digit

True/false

A

FALSE

Osteomyelitis is a BONE infection
Digit inflammation is DACTYLITIS

37
Q

Women with HbSS have a normal life expectancy

True/false

A

FALSE

Better than males BUT still NOT normal

38
Q

Chest crises may be fatal

True/false

A

TRUE

MOST COMMON cause of death!

39
Q

Solubility tests are used to confirm sickle cell anemia if screening tests are positive

True/false

A

FALSE

Will ONLY identify for Sickle Hb presence so will NOT show if have sickle cell trait OR disease (anaemia)

40
Q

If a lady with HbAS has a partner with HbSS she should be offered genetic counselling

True/false

A

TRUE

Year 2 - MCD Haem (11 decks)

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