Erythropoiesis, Introduction To Microcytic Anaemias And Iron Deficiency Anaemia (IDA) Flashcards
Anaemia
Hi level below reference range for that age and sex
What 3 classes can anaemia be placed in based on RBC size
Normocytic
Microcytic
Macrocytic
How is RBC size indicated
Mean corpuscular volume
Microcytic anaemia
RBCs smaller than normal
Hypochromic
RBCs paler than normal
5 causes of Microcytic anaemia
Thalassaemia
Anaemia of chronic disease
Iron deficiency
Lead poisoning
Sideroblastic anaemia
TAILS
What is the most common cause of anaemia
Iron deficiency
What are the main roles of iron in the body
Oxygen carriers
Co factors
How is iron toxic to cells
Formation of free radicals
Why is it important to regulate iron absorbtion
Body has no iron excretion mechanism
Iron is toxic to cells
How is iron removed from the body
Lost with skin cell shedding, sweating, etc
How much iron is needed in a day
10-15 mg
Where is iron absorbed
Enterocytes in Duodenum and upper jejunum
Why is iron absorbed in the duodenum and upper jejunum
More acidic
What 2 substances can convert FE3+ to Fe2+
Vitamin c
Reductase
What is the only known iron exit protein from enterocytes
Ferroportin
What enzyme removes Fe from haem
Haem oxygenase
What protein stores iron in cells
Ferritin
What molecule transports iron around the body in the blood
Transferrin
What does DMT1 do
Transports Fe2+ into cells
What molecules can decrease iron absorption in the gut
Tannins
Phytates
Fibre
Antacids
How does vitamin c increase iron absorbtion in the gut
Prevents formation of insoluble iron compounds
Helps Reduce ferric to ferrous
What molecule is the ‘master iron regulator’
Hepcidin
How does hepcidin regulate iron absorption
Blocks ferroportin
Why is why is hepcidin released in inflammation
Prevent iron being given to bacteria/ pathogens
How is iron taken into cells (excluding enterocytes)
Receptor mediated endocytosis
What receptors allow iron to enter cells other than enterocytes
Transferrin receptors (fe bound to transferrin)
Which cells have transferrin receptors
All
Which organ has the highest amount of ferritin
Liver
Low serum ferritin is a diagnostic test for which condition
Iron deficiency anaemia
What can serum ferritin indirectly show
Total amount of iron stored in body
Which cells take up 90% of iron
Myeloid cells in bone marrow
Does erythropoiesis occur in red or yellow bone marrow
Red
Haematopoiesis
Formation of blood cellular components
Erythropoiesis
Formation of RBCs
What stem cells are involved in erythropoiesis
Hadmatopoietic stem cells
What are the steps in erythropoiesis
Haematopoietic stem cell -> common myeloid progenitor cell -> proerythroblast -> erythroblast -> reticulocyte -> erythrocyte
At what stage of maturation does a RBC lose its nucleus
Reticulocyte
Diapedesis
Blood cells squeeze through pores in capillary mebranes
How do new RBCs enter the bloodstream
Diapedesis
What peptide hormone controls erythropoiesis
Erythropoietin
Where is erythropoietin synthesised
Kidney interstitial tubules
What triggers erythropoietin secreting cells in the kidney interstitial tubules to release erythropoietin
Hypoxia
Why is erythropoietin synthesised in the kidney interstitial tubules
Oxygen levels in/around tubules not effected by blood pressure or exercise
How does erythropoietin control erythropoiesis
Increases erythroblast maturation speed
Increases proerythrocyte formation
How does erythropoietin affect haematocrit
Increase
Where are RBCs made at the 3rd week of gestation
Yolk sac
Where are RBCs mainly made at 6 wks gestation
Liver
Where do RBCs start being made at 8 wks
Spleen
When does bone marrow start to produce RBCs
3 months gestation
Which bones produce RBCs in children under 5
All bones
Which bones produce RBCs in adults over 25
Mainly membranous bones
How do RBCs make ATP
Anaerobic glycolysis
Which transporters allow glucose to enter RBCs
GLUT-1
How does anaerobic glycolysis affect the pH of a RBC
Acidifies RBC
What happens to lactic acid produced in RBCs by anaerobic glycolysis
Pumped into plasma, taken up by liver or muscle cells, and converted back to glucose
How long do RBCs live
100-120 days
What happens to senescent RBCs when they pass through the spleen
Removed from blood and engulfed by splenic macrophages in red pulp spleen
Why are old RBCs easier to trap
More rigid due to failing membrane oumps
What process breaks down RBCs
Osmotic lysis
What happens to iron in broken down RBCs
Released from haemoglobin by Haem oxygenase and re enters circulation
Reticuloendothelial system
Heterogenous population of phagocytise cells that clear immune complexes, bacteria, toxins, and old RBCs
What is the structure of the red pulp spleen
Sinuses lined by endothelial macrophages and cords
In which age group can the tip of the spleen be palpated normally
Children
Build up of what in the blood causes jaundice
Unconjugated bilirubin
What is unconjugated bilirubin bound to in the blood
Albumin
What is bilirubin conjugated with to form bilirubin diglucoronide
Glucuronic acid
What is bilirubin diglucoronide converted to
Urobilinogen
Stercogilin
Urobilin
Where is urobilinogen oxidised to urobilin
Kidneys
What gives faeces it’s brown colour
Stercobilin
What gives urine its yellow colour
Urobilin
How is iron lost from the body
Skin cell shedding
Sweating
Menstruation
Pregnancy
How much iron is stored in the liver
1000mg
What determines the signs and symptoms of anaemia
Hb level
How quickly Hb drops
Co morbidities
Anaemia symptoms
Shortness of breath
Palpitations
Headaches
claudication
Angina
Weakness
Lethargy
Confusion
Anaemia signs
Pallor
Tachycardia
Systolic flow murmur
Tachypnoea
Hypotension
Claudication
Pain
What is Koilonychia and what condition is it associated with
Spoon shaped nails
Iron deficiency
What is angular stomatitis and what is it associated with
Inflammation of corners of mouth
Iron deficiency
What is glossitis and what is it associated with
Inflammation and depopulation of tongue
Vitamin b12 deficiency
Why can thalassaemia cause abnormal facial bone development
Overactive bone marrow
Iron deficiency signs and symptoms
Tiredness
Pallor
Reduces exercise tolerance
Angina
Palpitations
Heart failure
Tachypnoea
Headache
Dizziness
Light headedness
Pica
Cold hands and feet
Epithelial changes
Pica
Cravings for non nutritive substances
Anisoctytosis
Unequal sized cells
Morphology of RBCs in iron deficiency anaemia
Microcytic
Anisocytosis
Hypochromic
Decr mean corpuscular volume
Decr mean corpuscular haemoglobin
Decr mean corpuscular haemoglobin concentration
Indices of iron status
Hb level
Mean cell volume
Mean cell Hb
Serum ferritin
Serum iron
Total iron binding capacity
Transferrin saturation
Serum/ soluble transferrin receptor concentrations
Why is iron deficiency common
Often in ferric form in food
Low bioavailability
Vegan diets
High needs when toddler, elderly, menorrhagia
Impaired absorbtion
Gastric bypass surgery
GI malignancy
How does decreased acid production or antacids decrease iron absorbtion
Acid promotes iron absorbtion
How man GI malignancies cause iron deficiency
Chronic bloodloss
When should patients with iron deficiency anaemia be urgently referred
Aged 60+
Under 60 and Rectal bleeding
Can iron supplementation help anaemia of inflammation
No
How does inflammation cause anaemia
Cytokines increase hepcidin production and inhibit erythropoietin production
How does ferritin level vary between iron deficiency anaemia and anaemia of chronic disease
<10ug/l in iron deficiency
>100ug/l in chronic disease
Causes of iron deficiency
Increased demand
Insufficient intake
Pathology
Decreased absorption
Chronic blood loss
Drugs
Genetic
When should a diagnostic trial of iron treatment be considered for treatment of iron deficiency anaemia
Premenopausal women with menorrhagia or pregnant
When should a diagnostic trial of iron treatment not be used for iron deficiency anaemia treatment
Men
Postmenopausal women
- find reasom for anaemia first eg malignancy
How is iron deficiency anaemia treated
1 daily iron tablet
What types of iron tablets are available
Ferrous sulphate
Ferrous fumarate
Ferrous gluconate
When should iron tablets be stopped in iron deficiency treatment
3 months after deficiency corrected
What are side effects of taking iron supplements
Dyspepsia
Constipation
What does an elevated sedimentation rate show
Inflammation
How is inflammation tested
Erythrocyte sedimentation test
How is inflammation anaemia treated
Treat cause of inflammation