L15 - Haemoglobinopathies and anaemia Flashcards
Summarise erythrocyte lifecycle
- forms in red bone marrow
- circulates blood stream 120 days
- aged erythrocytes phagocytized in liver and spleen
- haem components of blood recycled
Describe how components of RBC are recycled?
- Haem components
- heme –> biliverdin –> bilirubin
- bilirubin then secreted from liver
- iron transported in blood - membrane proteins and globin proteins –> aa
Describe transport and storage of iron through body?
- travels in blood bound to transferrin protein
- stored by protein ferritin in liver
Describe the cell lineage of an RBC?
- myeloid stem cell
- proerthroblast
- reticulocyte
- erythrocyte
Anaemia definition
give examples of how anaemia may arise
deficiency in number of erythrocytes or their haemoglobin content.
e. g. either losing them quickly (haemorrhage, haemolysis)
e. g. or not making them quick enough (Fe3+, folate, B12)
Symptoms of anaemia in patients
LOADS, sorry
- yellowing of eyes (red in severe anaemia)
- skin paleness, coldness, yellowing
- SoB
- muscular weakness
- changed stool colour
- fatigue, dizziness, fainting
- low bp
- palpitations, rapid hr, angina
- spleen enlargement
Describe classification of anaemia (3)
by size of the erythrocytes.
- Microcytic
- normocytic
- macrocytic
Describe microcytic anaemia
- cause
- specific symptoms/signs
- treatment
commonest, Fe3+ deficiency.
causes: menorrhagia, GI bleed, colorectal cancer in (>50)
SS: koilonychia (spooned nails)
Tx: ferrous sulphate
Normocytic anaemia
- cause
- management
commonest causes: active/post haemorrhage, RA, chronic disease, haemolytic anaemia
management:
transfusion for severe symptoms.
Reticulocyte count and what it indicates in anaemic patients
- High corrected reticulocyte count
- appropriate response to anaemia from bone marrow
- bone marrow releasing RBCs prematurely to cover for deficit - Low corrected reticulocyte count
- bone marrow not had time to respond (acute haemorrhage)
- bone marrow failing to respond properly
- problem with bone marrow
Macrocytic anaemia
- causes
- specific signs / symptoms
- management
causes: B12 def, folate def, alcoholism
specific s&s: glossitis, paraesthesia, lemon tinge to skin, abnormal gait
tx: folate, b12 (hydroxycobalamin)
Pernicious anaemia
- autoimmune disorder.
- causes gastric mucosa atrophy.
and destruction of parietal cells. - no hence intrinsic factor IF necessary for b12 absorption.
Sickle cell anaemia
- genetic inheritance
- results from
- autosomal recessive.
- results from single glutamic acid to valine substitution at position 6 of beta globin polypeptide chain.
what causes the characteristic ‘sickle’ cell shape in sickle cell anaemia?
- when HbS deoxygenated, molecules of Hb polymerise to form tactoids
- tactoids will distort the RBC membrane
- causes sickle shape
Describe the difference between homozygotes and heterozygotes with sickle cells?
Homozyogtes
- can only produce HbS
- all beta chains abnormal
- sickle cell disease
Heterozygotes
- mixture of HbA, HbS
- asymptomatic trait
- sickle cell trait
- resistance to malaria
Crisis associated with sickle cell anaemia (3)
- Vaso-occulsive crisis
- aplastic crisis
- sequestration crisis
What is a vaso-occlusive crisis?
management
- plugging of small vessels in bone
- results in severe bone pain
- causes systemic response (t.cardia, sweating, fever)
tx
- aggressive rehydration, o2, analgesia
Aplastic crisis
- infection of adult sicklers with erythrovirus 19.
- severe erythrocyte aplasia
- low Hb, low reticulocyte count
(aplasia = failure of tissue to function properly)
Sequestration crisis
- thrombosis of venous outflow
- severe pain, loss of function
- spleen common site
- massive splenomegaly
What is thalassemia ?
- inherited
- body makes abnormal form or inadequate amount of haemoglobin
- large numbers of RBCs destroyed
Definition of haemolysis
- premature RBC destruction overloads pathways for haemoglobin breakdown
- causing modest rise in unconjugated bilirubin
- may cause jaundice
describe what happens in intravascular haemolysis?
- free haemoglobin released into plasma
- free h.globin toxic, quickly bound to haptoglobin for transportation to liver
- leads to fall in haptoglobin levels
How may haemolysis lead to black urine (if sudden) ?
recap
- free h.globin toxic, bound to haptoglobin –> liver, [haptoglobin] falls
- once haptoglobins saturated
- albumin and haemopexin bind to h.globin for transport
- if these become saturated
- free haem may appear in urine, black appearance
What is haemosiderinuria?
- renal tubular cells can absorb Hb, degrade it, store it as haemosiderin
- when these cells sloughed off –> haemosiderinuria
- always indicative of intravascular haemolysis
