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Fundamentals of P > Haemolytic Anaemia > Flashcards

Haemolytic Anaemia Flashcards

1
Q

Anaemia vs haemolytic anaemia

A 
Anemia = ↓ Hb for age/gender
HA = anaemia due to ↓ RBC survival
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2
Q

RBC life cycle - brief

A

RBC prod needs = iron, B12, folate, globin chains, protoporphyrins (carry heme),

loose nucleus on the way out from BM – into circulation live for 120 days​

changes on CM identified by macrophages in liver and spleen which remove those RBCs

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3
Q

Mature RBC - metabolic pathways

A

Glycolytic pathway, hexose monophosphate shunt

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4
Q

Haemolysis - effect

A

Haemolysis = shortened RBC survival,

BM compensates w/increased RBC production

= ↑ young cells in circulation

= reticulocytosis +/- nucleated RBC

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5
Q

What is compensated haemolysis

A

RBC production able to compensate for decreased RBC life span = normal Hb​

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6
Q

What is incompletely compensated haemolysis

A

RBC production unable to keep up with decreased RBC life span = decreased Hb ​ ​

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7
Q

Clinical findings of haemolytic anaemia

A

Jaundice = unconjugated bilirubin ​
Pallor/fatigue​
Splenomegaly, increased bilirubin ​
Dark urine

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8
Q

Haemolytic crisis - define

A

Increased anaemia and jaundice with infections/precipitants​

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9
Q

Aplastic crisis - define

A

Anaemia, reticulocytopenia with parvovirus infection = rash/red cheeks, infects BM

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10
Q

Chronica haemolytic anaemia - clinical findings

A 
Gallstones – pigment​
Splenomegaly ​
Leg ulcers - free Hb scavenges NO   ​
Folate deficiency ​
(increased use) = acute hemolysis = more folate to make more RBCs
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11
Q

Haemolytic anaemia laboratory findings

A

Increased reticulocyte count = HAs unless they have parvovirus or other reason they cant make RBCs​
Increased unconjugated bilirubin ​
Increased LDH (lactate dehydrogenase) = from haemolysed RBCs​
Low serum haptoglobin​ = protein that binds free haemoglobin ​
Increased urobilinogen​
Increased urinary hemosiderin = iron from Hb that gets picked up by epithelial cells in urinary tract​
Abnormal blood film

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12
Q

Blood film for haemolytic anaemia

A

Reticulocytes - (Supravital stain)
Polychromasia​
Nucleated RBC​

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13
Q

Classifying Haemolytic Anaemias​

A

If looking at inheritance​:
Inherited​ = Hereditary spherocytosis​
Acquired​ = Paroxysmal nocturnal haemoglobinuria​

If looking at site of RBC destruction:
Intravascular​ = Thrombotic thrombocytopenic purpura​
Extravascular​ = Autoimmune haemolysis​

If looking at origin of RBC damage:
Intrinsic​ = G6PD deficiency​
Extrinsic = Delayed haemolytic transfusion reaction​

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14
Q

Describe RBC destruction

A

If extravascular (in macrophages) = into globin (broken into AAs) + iron (circulation, binds transferrin) + protoporphyrin

→ bilirubin (CO released as expired air)

→ bilirubin → (in peripheral blood) bilirubin - UC

→ bilirubin glucuronides through liver
→ stercobilinogen (faeces) → urobilinogen (urine)

Intravascular = RBC into haemoglobinaemia then methaemalbuminaemia then haemoglobinuria then haemosiderinuria

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15
Q

Vertical interaction function and defects in it

A

Stabilize lipid membrane:

Spectrin-ankyrin-band 3 interactions, Spectrin-protein 4.1R–junctional complex linkages
Skeletal proteins/-ve proteins of inner LBL

Spectrin, band 3, protein 4.2 + ankyrin = hereditary spherocytosis

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16
Q

Horizontal interaction function and defects in it

A

Support structural integrity of the red cell, including after exposure to shearing:
(involving the spectrin heterodimer associations)

Protein 4.1​ + glycophorin C​ + spectrin – HPP = hereditary elliptocytosis

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17
Q

What is hereditary spherocytosis and its effects

A

Common hereditary haemolytic anemia​
Inherited in autosomal dominant fashion (75%) ​
Defects in proteins involved in vertical interactions between the membrane skeleton and the lipid bilayer​
Decreased membrane deformability ​
Bone marrow makes biconcave RBC, but as membrane is lost, the RBC become spherical

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18
Q

Hereditary spherocytosis vs AI haemolysis distinction

A

No central pallor = same look as AI haemolysis

DAT (test) = look for AB on red cell +ve in AIH and –ve in spherocytosis

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19
Q

Clinical features of hereditary spherocytosis

A

Asymptomatic to severe haemolysis​
Neonatal jaundice​
Jaundice, splenomegaly, pigment gallstones​
Reduced eosin-5-maleimide (EMA) binding – binds to band 3​
Positive family history​
Negative direct antibody test

20
Q

Management of hereditary spherocytosis

A

Monitor​, Folic acid​, Transfusion​, Splenectomy – not in small children = important for immunity

21
Q

RBC metabolic pathways​

A

Glycolysis –energy- ATP ​
Na/K pump​
3 Na+ out 2 K+ in ​
ATP to ADP+Pi​

HMS – reducing power -NADPH/GSH​

Rapoport Luebering shunt –​

2,3 Bi-PhosphoGlycerate (2,3 BPG) – modulates O2 binding to Haemoglobin

22
Q

Role of the HMP shunt

A

Generates reduced glutathione​

Protects the cell from oxidative stress

23
Q

Effects of oxidative stress

A

Oxidation of Hb by oxidant radicals​

Resulting denatured Hb aggregates & forms Heinz bodies – bind to membrane​

Oxidised membrane proteins – reduced RBC deformability​

24
Q

What is G6PD, its spread, clinical features

A

Hereditary, X-linked disorder ​
Common in African, Asian, Mediterranean and Middle Eastern populations ​
Mild in African (type A), more severe in Mediterraneans (type B)​
Clinical features range from asymptomatic to acute episodes to chronic haemolysis

25
Q

G6PD oxidative precipitants

A 
Infections​
Fava/ broad beans​
Many drugs e.g.:​
Dapsone​
Nitrofurantoin​
Ciprofloxacin​
Primaquine
26
Q

G6PD features

A 
Haemolysis​
Film:​
- Bite cells​
- Blister cells & ghost cells​
- Heinz bodies (methylene blue)​
Reduced G6PD activity on enzyme assay​:
 - May be falsely normal if reticulocytosis
27
Q

Oxidative haemolysis definition

A

Destruction of circulating human erythrocytes exposed to oxidant stress

28
Q

Pyruvate Kinase Deficiency​ - cause and effects

A 
PK required to generate ATP​
Essential for membrane cation pumps (deformability)​
Autosomal recessive​
Chronic anaemia​
- Mild to transfusion dependent​
- Improves with splenectomy​
29
Q

Hb structure

A

Hb structure = Haem (Fe2+ + protoporphyrin IX) + globin (2ɑ + 2β)
HbA = ɑ2β2, HbA2 = ɑ2δ2 + HbF = ɑ2γ2

30
Q

Quantitative - thalassaemias = define

A

Production increased/ decreased amount of a globin chain (structurally normal)​

31
Q

Qualitative – variant haemoglobins = define

A

Production of a structurally abnormal globin chain​
HbS - ↓solubility, polymerisation
Hb Koln - ↓stability, Heinz body formation
HbC - ↓solubility, crystallisation

32
Q

Thalassaemias - define

A

Imbalanced alpha and beta chain production​

33
Q

Effect of excess unpaired globin chains

A

Excess unpaired globin chains are unstable​

  • Precipitate and damage RBC and their precursors​
  • Ineffective erythropoiesis in bone marrow​
  • Haemolytic anaemia
34
Q

Beta thalassaemias​ - chance

A

Autosomal recessive = ¼ chance​

35
Q

Diagnosis of thalassaemia trait​

A 
Asymptomatic​
Microcytic hypochromic anaemia​
Low Hb, MCV, MCH ​
Increased RBC​
Often confused with Fe deficiency​
HbA2 increased in b-thal trait –(diagnostic)​
a-thal trait often by exclusion​
globin chain synthesis (rarely done now)​
DNA studies (expensive)
36
Q

Beta Thalassaemia Major​ effect if not transfused

A

Transfusion dependent in 1st year of life

If not transfused = Failure to thrive,​ Progressive hepatosplenomegaly,​ Bone marrow expansion – skeletal abnormalities,​ Death in 1st 5 years of life from anaemia

37
Q

Side effects of transfusion

A

Side effects of transfusion = Iron overload​, Endocrinopathies​, Heart failure,​ Liver cirrhosis

38
Q

Sickle cell disease cause

A

Sickle cell = Point mutation in the β globin gene: glutamic acid → valine = Insoluble haemoglobin tetramer when deoxygenated → polymerisation​ = “Sickle” shaped cells​

39
Q

Clinically significant sickling syndromes

A

Clinically significant sickling syndromes:​ HbSS​ HbSC​ HbS-D Punjab​ HbS- O Arab​ HbS- β thalassaemia

40
Q

SCD acute complications

A 
Stroke: ischaemic & haemorrhagic
Cholecystitis​
Hepatic sequestration​
Dactylitis​
Bone pain & infarcts​
Osteomyelitis​
Leg ulcers​
Aplastic crisis​
Priapism​
Haematuria: papillary necrosis​
Splenic sequestration​
Chest syndrome​
Retinal detachment​
Vitreous haemorrhage
41
Q

SCD chronic complications

A 
Silent infarcts​
Pulmonary hypertension​
Chronic lung disease, bronchiectasis​
Erectile dysfunction​
Azoospermia​
Chronic pain syndromes
Delayed puberty​
Leg ulcers​
Avascular necrosis​
Chronic renal failure​
Retinopathy, visual loss​
Moya-moya​
42
Q

Clinical features of SCD

A 
Painful crises​
Aplastic crises​
Infections
Acute sickling:​
- Chest syndrome​
- Splenic sequestration​
- Stroke​
Chronic sickling effects:​
- Renal failure​
- Avascular necrosis bone
43
Q

Laboratory features of SCD

A 
Anaemia​
- Hb often 65-85​
Reticulocytosis​
Increased NRBC​
Raised bilirubin​
Low creatinine
44
Q

SCD diagnosis

A

Diagnosis = Solubility test​, Expose blood to reducing agent​, Hb S precipitated,​ Positive in trait and disease
Or electrophoresis to look at structure

45
Q

Autoimmune haemolysis - features

A

Idiopathic​ - cause unknown

  • Usually warm​
  • Rare cause of hemolysis precipitated by antibodies directed against blood group antigens, most commonly IgG + react with proteins on the surface of RBC at normal body temp (warm agglutinins) (IgM​ as well)

Drug-mediated​
Cancer associated​
- LPDs (Lymphoproliferative disorders)q

46
Q

Alloimmune haemolysis - features

A

Transplacental transfer:​
Haemolytic disease of the newborn:​
- D, c, L​
ABO incompatability​

Transfusion related:​
  Acute haemolytic transfusion reaction​
     - ABO​
  Delayed haemolytic transfusion reaction​
     - E.g Rh groups, Duffy​
47
Q

Non-immune acquired haemolysis​ - causes

A

Paroxysmal nocturnal haemoglobinuria​

Fragmentation haemolysis:​

  • Mechanical​
  • Microangiopathic haemolysis​
    1. Disseminated intravascular coagulation​
    2. Thrombotic thrombocytopenic purpura​

Other:​
Severe burns​
Some infections: e.g. malaria​

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