5.1 Erythropoiesis Flashcards
What is haemopoiesis?
The production of blood cells and platelets.
What is erythropoiesis?
Production of erythrocytes.
How many erythrocytes do we produce every second?
2 million
Which vitamins are essential for RBC production?
- B12
- Folate
Which hormone regulates erythropoiesis?
Erythropoietin
- Produced by the kidneys, creates negative feedback loop between kidneys and blood
Where does erythropoiesis occur?
In the bone marrow
What is the life span of an RBC?
Approximately 120 days
What is haemolysis?
Destruction of RBCs
Where is erythropoietin produced?
- 90% produced by kidneys in the renal parenchyma
- 10% produced in the liver parenchyma
What are the effects of too few or too many erythrocytes?
- Too few = hypoxia
- Too many = undesirable blood viscosity
Which enzyme is important in the hameoglobin-oxygen dissociation curve?
2,3-DPG
More 2,3-DPG means Hb dissociates more easily- curve shifts right, less means dissociates less easily- curve shifts left.
What shape is the Hb-O2 dissociation curve?
Sigmoid
What happens if the Hb-O2 dissociation curve shifts left or right?
Shift to the right = oxygen more easily given to the tissues (increased DPG). Decreased affinity of Hb for oxygen.
Shift to the left = Hb holds onto oxygen and gives it away less easily (decreased DPG). Increased affinity of Hb for oxygen.
Describe the structure of an erythrocyte.
- Concave disc shape
- 8um diameter, minimum 3.5um in circulation
- Able to travel through narrow vessels
- Flexible
- Carries oxygen via Hb (2 alpha and 2 beta chains)
What is hereditary spherocytosis?
A genetic malformation affecting the red cell membrane.
Causes life long mild-moderate anaemia.
What is glucose-6-phosphate dehydrogenase deficiency?
Glucose-6-phosphate dehydrogenase is needed to reduce oxygen free radicals.
A deficiency causes early haemolysis (RBC destruction) and lead to haemolytic anaemia.
More prevalent in areas of Africa and the Middle East.
Outline the main causes of anaemia.
Underproduction:
Hereditary - haemoglobinopathies
Acquired - iron, B12 or folate deficiency, increases EPO, bone marrow failure
Increased haemolysis:
Hereditary - sickle cell anaemia, glucose-6-phosphate dehydrogenase deficiency
Acquired - immune, PNH
Acute blood loss
What Hb levels are considered anaemia in different age groups?
<150g/l : newborn
<110g/l : 3 months to puberty
<115g/l : adult female
<135g/l : adult male
What are the clinical features of anaemia?
- Shortness of breath on exertion
- Weakness, lethargy
- Headaches
- Cardiac failure, angina, confusion
- Pallor of mucous membranes
- Tachycardia
- Cardiac failure
- Jaundice (haemolysis or megaloblastic)
- Skin ulcers (sickle cell anaemia)
- Koilonychia, spoon nails (iron deficiency)
Symptoms are affected by severity, speed of onset, age, co-morbidities. Some people may be symptomless.
What laboratory investigations are carried out for suspected anaemia?
- Full blood count (MCV/MCH, WBC/platelets)
- Reticulocyte count
- Blood film
- Haematinics (B12, folate and ferritin)
How should FBC results be interpreted?
1) Check for evidence of bone marrow disease such as aplasia, infiltration or leukoplakia.
This is checked by looking for leukopenia and thrombocytopenia.
2) Do the RBCs appear big/full or little/empty? (Macrocytic/hyperchromic or microcytic/hypochromic). Both are bad.
What is the most common cause of anaemia?
Iron deficiency
How much of iron consumed is absorbed?
10%
30% in pregnancy
Which form of iron is favoured for absorption?
- Ferrous form
- Ferric form not favoured
What are the causes of iron deficiency?
- Chronic blood loss (e.g. menstrual, GI- peptic uclers)
- Increased demands (growth spurts, pregnancy)
- Malabsorption (e.g. coeliac)
- Poor diet (rare)
What are the diagnostic measures of iron deficiency?
Red cell indices:
- MCV <80fl
- MCH <27pg
Blood film:
- Hypochromic (pale), microcytic (small), pencil shaped cells
- Occassional target cells
Serum ferritin:
- <15ug/l
How is iron deficiency treated?
- Ferrous sulphate 200mg TDS for 6 months (contains 67mg iron)
Can have GI side effects. - Parenteral iron
What is folate?
- A water soluble form of vitamin B
- Found in fruit and veg
- Absorbed in small intestine
- Overcooking destroys folate
What is vitamin B12?
- A vitamin
- Normal diets contain excess B12, may see deficiency in vegans
- Deficiency can cause neurological problems: peripheral neuropathy, numbness
What is pernicious anemia?
An autoimmune condition where there is a decrease in the intrinsic factor that is usually found in the stomach to combine with vitamin B12.
This autoimmune condition causes B12 deficiency leading to anaemia.
What is pernicious anaemia?
An autoimmune condition where there is a decrease in the intrinsic factor that is usually found in the stomach to combine with vitamin B12.
This autoimmune condition causes B12 deficiency leading to anaemia.
How is a folate deficiency treated?
Folic acid prescribed.
How is a B12 deficiency treated?
Intramuscular hydroxocobalamin injection every 3 months following initial loading doses.
What are the blood group systems based on?
RBC antigens.
Nearly 30 different blood group systems and hundreds of individual RBC antigens have been described.
Clinically, the ABO and Rhesus blood group systems are most important.
Describe the ABO blood group system.
- Antigens are syntheisised by the sequential addition of sugar residues on a common precursor substance (H)
- These are IgM antibodies
- Either the A-antigen, B-antigen or O-antigen
Describe the 4 blood groups.
Group A: have A-antigen and Anti-B antibodies
Group B: have B-antigen and Anti-A antibodies
Group AB: have A and B antigens and no antibodies (univeersal recipient)
Group O: have O-antigen and antiA and anti-B antibodies (universal donor)
When is the Rhesus blood group system most important?
In pregnancy.
Describe the Rhesus system.
- Rhesus negative = doesn’t have D antigen
- Rhesus positive = does have D antigen
15% of Caucasian population are rhesus negative
Which body controls incidents related to donated blood?
Serious Hazards of Transfusion (SHOT) team