Red Cells Flashcards
1
Q
How are red cells produced?
A
- in bone marrow
- haemocytoblast -> proerythroblast -> early erythroblast -> late erythroblast -> normoblast -> reticulocyte -> erythrocyte
- requires substances
- metals: iron, copper, cobalt, maganese
- vitamins: B12, folic acid, thiamine, B6, C, E
- amino acids
- hormones: erythropoietin, GM-CSF, androgens, thyroxine
2
Q
How are red cells broken down?
A
- broken down in reticuloendothelial system
- macrophages in spleen, etc
- 120 day lifespan
- globulin
- amino acids (reutilised)
- haem
- iron (recycled into haemoglobin)
- haem -> biliverdin -> bilirubin
- bulirubin (bound to albumin in plasma)
3
Q
What are the main genetic defects of red cells which cause congenital anaemia?
A
- membrane
- metabolic pathways (enzymes)
- haemoglobin
4
Q
How is the normal red cell membrane maintained?
A
- skeletal proteins maintain red cell shape + deformability
- skeletal proetin defects can inc. cell destruction
5
Q
What is Hereditary Spherocytosis?
A
- defects in red cell membrane structural proteins (autosomal dominant)
- ankyrin, alpha spectrin, beta spectrin, band 3, protein 2.4
- red cells are spherical
- removed from circulation by reticuloendothelial system
6
Q
What are the presentations and treatment for Hereditary Spherocytosis?
A
- anaemia
- jaundice (neonatal)
- splenomegaly
- pigment gallstones
- folic acid
- transfusion
- splenectomy (if anaemia very severe)
7
Q
What are other red cell membrane disorders?
A
- hereditary elliptocytosis
- hereditary pyropoikilocytosis
- south east asian ovalocytosis
8
Q
What are the metabolic pathways red cells are involved in?
A
- glycolysis
- pentose phosphate shunt
- glucose 6 phosphate dehydrogenase (G6PD)
- protects red cellsfrom oxidative damage
9
Q
What is G6PD deficiency?
A
- causes enzymopathy
- makes red cells vulnerable to oxidative damage
- condition gives protection against malaria
- X linked
- affects males, female carriers
10
Q
What are the presentations of G6PD deficiency?
A
- anaemia
- jaundice (neonatal)
- splenomegaly
- pigment gallstones
11
Q
What can trigger haemolysis in G6PD deficiency?
A
- infection
- broad beans
- drugs
- antimalarials
- sulphonamides + sulphones
- antibacterial
- analgesics (aspirin)
- antihelminthics
- others
12
Q
What are other red cell enzyme deficiencies?
A
- pyruvate kinase deficiency
- dec. ATP
- inc. 2,3-DPG
- cells rigid
- anaemia
- jaundice
- gallstones
13
Q
What is the structure of haemoglobin?
A
- 2 alpha chains
- 2 beta chains
- haem
14
Q
What is the function of haemoglobin?
A
- gas exchange
- O2 to tissues
- CO2 to lungs
- compensatory mechanisms for changes in PO2
- acidosis
- hyperthermia
- hypercapnia
15
Q
What is sickle cell disease?
A
- sickle haemoglobin (HbS)
- 2 alpha chains
- 2 beta (sickle) chains
- red cell injury, cation loss, dehydration
- haemolysis
- enothelial activation, promotion of inflammation, coagulation activation, dysregulation of vasomotor tone by vasodilatior mediators (NO)
- vaso-occlusion
16
Q
What are presentations of sickle cells disease?
A
- painful vaso-occlusion crises
- bone
- chest crisis
- stroke
- inc. infection risk
- hyposplenism
- chronic haemolytic anaemia
- gallstones
- aplastic crisis
- sequestration crises
- spleen, liver
17
Q
What is the treatment for a sickle cell painful crisis?
A
- opiates
- hydration
- oxygen
- consider antibiotics
18
Q
What is the management for sickle cell disease?
A
- life long prophylaxis
- vaccination
- penicillin prophylaxis
- folic acid
- blood transfusion (episodic or chronic)
- alloimmunisation
- iron overload
- disease modifying drugs
- hydroxycarbmide
- bone marrow transplant
- gene therapy
19
Q
What is thalassaemias?
A
- reduced/absent globin chain production
- mutations or deletions in alpha genes (alpha thalassaemias) or beta genes (beta thalassaemias)
- chain imbalance
- chronic haemolysis
- chronic anaemia
20
Q
What are the different types of thalassaemias?
A
- homozygous alpha zero thalassaemia
- no alpha chains
- hydrops fetalis- incompatible with life
- beta thalassaemia major
- no beta chain
- transfusion dependant anaemia
- non-transfusion dependant thalassaemia “intermedia”
- thalassaemia minor
- common
- trait or carrier state
- hypochromic microcytic red cell indices
21
Q
What are the presentation of beta thalassaemia major?
A
- severe anaemia
- at 3-6 months age
- expansion of ineffective bone marrrow
- bone deformities
- splenomegaly
- growth retardation
- life expectantcy < 10 yrs, if untreated/irregular transfusion
22
Q
What is the treatment for beta thalassaemia major?
A
- chronic transfusion support (4-6 weekly)
- normal growth + development
- iron overload
- death in 2nd/3rd decade if iron overload untreated (heart/liver/endocrine failure)
- iron chelation therapy
- s/c desferrioxamine infusions
- oral deferasirox
- good adherance to chelation
- regular monitoring (ferritin + MRI scans)
- bone marrow transplantation (curative)
23
Q
What are other haem synthesis defects?
A
- sideroblastic anaemia
- defects in haem synthesis at mitochondrial steps
- ALA synthase mutations
- hereditary
- aquired- myelodysplasia
- porphyrias
- defects in cytoplasmic steps
24
Q
What are factors that effect normal range of Hb?
A
- age
- sex
- ethnic origin
- time of day
- time to analysis of sample
25
What are reference ranges of haemoglobin?
* male 12-70 yrs (140-180)
* male \> 70 yrs (116-156)
* female 12-70 yrs (120-160)
* female \< 70 yrs (108-143)
26
What are features of anaemia?
Due to dec. oxygen delivery to tissues:
* tiredness
* pallor
* breathlessness
* ankle swelling
* dizziness
* chest pain
Related to underlying cause:
* evidence of bleeding (menorrhagia, dyspepsia, PR bleeding)
* symptoms of malabsorbtion (diarrhoea, weight loss)
* jaundice
* splenomegaly
* lymphadenopathy
27
What are red cell indices?
* MCH- mean cell haemoglobin
* MCV- mean cell volume
* can give morphological description- may be related to cause
- hypochromic microcytic
- normochromic normocytic
- macrocytic
28
What tests are indicated from each morphological description?
* hypochromic microcytic
- serum ferritin
* normochromic normocytic
- reticulocyte count
* macrocytic
- B12/folate bone marrow
29
What can serum ferritin indicate?
* low- iron deficiency
* high- thalassaemia secondary anaemia (sideroblastic anaemia)
30
What happens to absorbed iron in the body?
* bound to mucosal ferritin + sloughed off
OR
* transported across basement mebrane by ferroportin
* then bound to transferrin in plasma
* stored as ferritin- mainly in liver
31
What is the role of hepcidin in iron metabolism?
* hepcidin synthesised in liver, in reponse to inc. iron + inflammation
* blocks ferroportin to dec. intestinal iron absorption + mobilisation from reticuloendothelial cells
32
What are features of iron defciency anaemia?
* dyspepsia, GI bleeding
* other bleeding, e.g. menorrhagia
* diet
* inc. requirement, e.g. pregnancy
* atrophic tongue
* angular cheilitis
* koilonychia
\*description, NOT diagnosis, must determine cause
33
What are causes of iron deficiency anaemia?
* GI blood loss
* menorrhagia
* malabsorption
- gastrectomy
- coeliac disease
* gastric ulcer
* colon carcinoma
* gastritis
34
What is the management for iron deficiency anaemia?
* correct deficiency
- oral iron
- IV iron
- blood transfusion
* correct cause
- diet
- ulcer therapy
- gynae interventions
- surgery
35
What can reticulocyte count indicate?
* inc- acute blood loss haemolysis
* normal/dec- secondary anaemia (hypoplasia, marrow infiltration)
36
What is secondary anaemia?
* anaemia of chronic disease
* defective iron utilisation
- inc. hepcidin in inflammation
- ferritin often elevated
* identifiable underlying disease
- infection, inflammation, malignancy
37
What is haemolytic anaemia?
* accelerated red cell destruction (dec. Hb)
* compensation by bone marrow (inc. retics)
* level of Hb- balance between red cell prodcution + destruction
* haemolysis can be extra or intravascular
38
What are causes of haemolytic anaemia?
* congenital
- hereditary spherocytosis
- enzyme deficiency
- haemoglobinopathy
* aquired
- autoimmune haemolytic anaemia (extravascular)
- mechanical (intravascular)
- severe infection/DIC (intravascular)
- PET/HUS/TTP (intravascular)
39
What is the direct antiglobulin test?
* detects antibody or compliment on red cell membrane
* reagent contains either; anti-human IgG or anticomplement
* reagent bind to Ab/complement on red cell surface, causes agglutination in vitro
* implies immune basis for haemolysis
* if +ve- immune mediated haemolytic anaemia
* if -ve- non-immune mediated haemolytic anaemia
40
What are the different types of immune haemolysis and their causes?
* warm auto-antibody
- auto-immune
- drugs
- CLL
* cold auto-antibody
- CHAD
- infections
- lymphoma
* alloantibody
- transfusion reaction
41
What tests show if a patient is haemolysing?
* FBC, reticulocyte count, blood film
* serum bilirubin, LDH
* serum haptoglobin
42
What tests show the mechanism of haemolysis?
* history + examination
* blood film
* direct antiglobulin test (Coomb's test)
* urine for haemosiderin/urobilinogen
43
What is the management for haemolytic anaemia?
* support marrow function
- folic acid
* correct cause
- immunosuppression if autoimmune (steroids, treat trigger)
- remove site of red cell destruction (splenectomy)
- treat spesis, leaky prosthetic valve, malignancy, etc (if intravascular)
* consider transfusion
44
What can B12/folate assay indicate?
* megaloblastic
- B12 deficiency
- folate deficiency
* non-megaloblastic
- myelodysplasia
- marrow infiltration
- drugs
45
What are the symptoms and causes of B12 + folate deficiency?
* anaemia
* neurological symptoms
* 'lemon yellow' tinge
B12 causes:
* pernicious anaemia
* gastric/ileal disease
Folate causes:
* dietary
* inc. requirements
* GI pathology
46
What is pernicious anaemia?
* commenest cause of B12 deficiency
* autoimmune disease
* antibodies against; intrinsic factor, gastric parietal cells
* malabsorbtion of dietary B12
* symptoms take 1-2 yrs to develop
* Schilling test
47
What is the treatment for megaloblastic anaemia?
* replace vitamin
* B12 IM injection
- loading does, then 3 monthly maintenance
* oral folate replacement
* ensure B12 normal if neuropathic symptoms
48
What are other causes of macrocytosis?
* alcohol
* drugs
- methotrexate, antiretrovirals, hydroxycarbamide
* disordered liver function
* hypothyroidism
* myelodysplasia
