Red blood cells Flashcards

1
Q

What is anaemia?

A

Reduction in red cells or their haemoglobin content

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2
Q

What are the aetiologies of anaemia?

A
  • Blood loss
  • Increased destruction
  • Lack of production
  • Defective production
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3
Q

What substances are required for red cell production?

A
  • Metals: Iron, copper, cobalt, manganese
  • Vitamins: B12, folic acid, thiamine, Vit.B6, C, E,
  • Amino acids
  • Hormones: Erythropoietin, GM-CSF, androgens, thyroxine, SCF
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4
Q

Describe red cell breakdown

A
○ Occurs in the reticuloendothelial system
- Macrophages in Spleen, liver, lymph nodes, lungs etc
○ Globin
- Amino acids –reutilised
○ Haem 
- Iron-reutilised
- Haem – biliverdin→ bilirubin
○ Bilirubin – bound to albumin in plasma
○ From red cell breakdown -unconjugated
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5
Q

What are the functions of haemaglobin?

A
○ Gas exchange
- O2 to tissues
- CO2 to lungs
○ Oxygen dissociation curve
- Shifts as a compensatory mechanism
- “Bohr effect”
□ Acidosis
□ Hyperthermia
□ Hypercapnia
- HbF – higher O2 affinity than HbA
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6
Q

What are most congenital anaemias due to?

A

An abnormal product that breaks down in the circulation

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7
Q

Describe the genetic defects in red cell mebranes that cause congenital anaemias

A

□ Skeletal proteins are responsible for maintaining red cell shape and deformability
□ Defects in skeletal proteins can lead to increased cell destruction
□ Mutations in ankyrin >band 3 >spectrin (important)

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8
Q

Describe the genetic defects in metabolic pathways that cause congenital anaemias

A
□ Glycolysis
® provides energy
® Glucose 6-phosphate dehydrogenase
□ Pentose Phosphate shunt
® protects from oxidative damage
® Pyruvate kinase
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9
Q

Give examples of congenital anaemia membrane disorders

A

□ Hereditary spherocytosis
□ Hereditary Elliptocytosis (milder)
□ Hereditary Pyropoikilocytosis (severe but rare)
□ South East Asian Ovalocytosis

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10
Q

What causes hereditary spherocytosis?

A
□ Most common forms autosomal dominant defects in 5 different structural proteins described					® Ankyrin					
® Alpha Spectrin					
® Beta Spectrin					
® Band 3					
® Protein 4.2
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11
Q

What is hereditary spherocytosis?

A

□ Red cells are spherical

□ Removed from circulation by the RE system (extravascular)

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12
Q

What is the clinical presentation of hereditory spherocytosis?

A
□ Variable					
® Anaemia					
® Jaundice (neonatal)					
® Splenomegaly					
® Pigment gallstones
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13
Q

What is the treratment for hereditory spherocytosis?

A

® Folic acid (increased requirements)
® Transfusion (if you are ill and haemolysis is increased)
® Splenectomy (If you have a very severe condition)

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14
Q

Give examples of congenital anaemias that are due to metabolic disorders

A
  • G6PD deficiency

- Pyruvate kinase deficiency

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15
Q

What does glucose 6 phosphate dehydrogenase (G6PD) do?

A
  • Protects red cell proteins (Haemoglobin) from oxidative damage
    □ Produces NADPH - Vital for reduction of glutathione
    □ Reduced glutathione scavenges and detoxifies reactive oxygen species
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16
Q

what is G6PD deficiency?

A

□ Commonest disease causing enzymopathy in the world
® Many genetic variants
□ Cells vulnerable to oxidative damage
□ Confers protection against malaria ® Most common in malarial areas
□ X Linked
® Affects males
® Female carriers

17
Q

What is the clinical presentation of G6PD deficiency?

A
□ Variable
® Neonatal Jaundice					
® Drug, broad bean or infection precipitated jaundice and anaemia					
® Intravascular haemolysis					
® Haemoglobinuria					
® Splenomegaly					
® Pigment Gallstones
18
Q

What is pyruvate kinase deficiency?

A
® Reduced ATP					
® Increased 2,3-DPG					
® Cells rigid					
® Variable severity						
◊ Anaemia						
◊ Jaundice						
◊ Gallstones
19
Q

What are haemoglobinopathies?

A
  • Inherited abnormalities of haemoglobin synthesis
  • Reduced or absent globin chain production
    □ Thalassaemia (alpha α, Beta β, delta δ, gamma γ)
  • Mutations leading to structurally abnormal globin chain
    □ HbS (Sickle cell ), HbC, HbD, HbE, HbO Arab…..
  • Autosomal recessive inheritance
20
Q

What is sickle cell disease?

A

□ Sickle haemoglobin (HbS) composed of haem molecule and:
® 2 α chains
® 2 β (sickle) chains
□ Once a red blood cell gets rid of its oxygen it becomes sickle shaped and the never turns back

21
Q

What are the concequences of HbS polymerisation?

A

® Red cell injury, cation loss, dehydration results in haemolysis which results in:
◊ Endothelial activation
◊ Promotion of inflammation
◊ Coagulation activation
◊ Dysregulation of vasomotor tone by vasodilator ◊ Mediators (NO)
® All results in vaso-occlusion

22
Q

What are the complications of sickle cell disease?

A

® Acute chest syndrome- vasoocclusive tissue damage
® Stroke- vasoocclusive tissue damage and cerebral vasculopathy
® Pain episodes- vasoocclusive tissue damage
® Lung disease- unknown

23
Q

What is the presentation of sickle cell disease?

A
  • Retinopathy
  • Cardiomegaly -> congestive heart failure
  • Cholelithiasis
  • Renal infarcts -> haematuria
  • Bone marrow hyperplasia
  • Aseptic bone necrosis -> osteomyelitis
  • Cerebral infarcts stroke -> mental retardation
  • Pulmonary infarcts -> pneumonia
  • Splenomegaly -> Splenic atrophy (autosplenectomy)
  • Infarcts of the extremities
  • Vaso occlusion
  • Ulcer
  • Painful Vaso-occlusive crises ◊ Bone
  • Chest Crisis
  • Stroke
  • Increased infection risk
    ◊ Hyposplenism
  • Chronic haemolytic anaemia ◊ Gallstones
    ◊ Aplastic crisis
  • Sequestration crises (blood can go in but cannot get out resulting in pooling)
    ◊ Spleen
    ◊ Liver
  • Painful crisis
24
Q

What are the signs and symptoms of chest crisis?

A
  • Chest Pain
  • Fever
  • Worsening hypoxia
  • Infiltrates on CXRay
25
Q

What is the management of chest crisis?

A
  • Respiratory Support
  • Antibiotics
  • IV Fluids
  • Analgesia
  • Transfusion – top up or exchange target HbS <30%
26
Q

How are incidences of chest crisis reduced?

A

Incentive spirometry shown to reduce incidence

27
Q

What is the management for painful crisis?

A
◊ Severe pain
- often requires opiates
- Analgesia should be given within 30 mins of presentation 
- Effective analgesia by 1hour
- Avoid pethidine						
◊ Hydration						
◊ Oxygen						
◊ Consider antibiotics
28
Q

What is the life ecpectancy for people with sickle cell disease?

A

◊ US and UK cohorts survival to 18 years increased ◊ 85% in 2004 and 96% 2010

29
Q

What is the management of actue events of sickle cell disease?

A
◊ Hydration 						
◊ Oxygenation						
◊ Prompt treatment of infection						◊ Analgesia							
- Opiates
- NSAIDs
30
Q

What is the management of sickle cell disease?

A
® Lifelong prophylaxis						
◊ Vaccination						
◊ Penicillin (and malarial) prophylaxis							◊ Folic acid
® Blood transfusion						
◊ Episodic and chronic						
◊ Alloimmunisation						
◊ Iron overload					
® Disease modifying drugs						
◊ Hydroxycarbamide					
® Bone marrow transplantation					
® Gene therapy
31
Q

What is thalassaemia?

A

□ Reduced or absent globin chain production ® In alpha chain (alpha thalassaemia) ® In beta chain (beta thalassaemia)

32
Q

What is homozygous alpha zero thalassaemia?

A
  • (α0/α0 )
    ◊ No alpha chains
    ◊ Hydrops Fetalis –incompatible with life
33
Q

What is beta thalassaemia (homozygous beta thalassaemia)

A
◊ No beta chains						
◊ Transfusion dependent anaemia
- Present at 3-6 months of age
- Expansion of ineffective bone marrow
- Bony deformities
- Splenomegaly
- Growth retardation
- Life expectancy untreated or with irregular transfusions <10 years
34
Q

What is the treament for beta thalassaemia

A
  • Chronic transfusion support - 4-6 weekly
  • Normal growth and development
  • BUT - Iron overloading (must do chelation)
    ~ s/c desferrioxamine infusions (desferal)
    ~ Oral deferasirox (exjade)
    ~ Good adherence to chelation – life expectancy >40 years
    ~ Requires regular monitoring
  • Death in 2nd or 3rd decades due to heart/liver/endocrine failure if iron loading untreated
  • Bone marrow transplantation- curative
35
Q

What causes non-transfusion dependent thalassaemia?

A

A range of genotypes

36
Q

What is thalassaemia minor?

A

◊ “Trait” or carrier state ◊ Hypochromic microcytic red cell indices (small red cells)

37
Q

What are some rare defects in haem synthesis?

A

□ Defects in mitochondrial steps of haem synthesis result in sideroblastic anaemia
® ALA synthase mutations
® Hereditary (X-Linked)
® Acquired - Myelodysplasia
□ Defects in cytoplasmic steps result in porphyrias