Erythropoeisis & Anaemia Flashcards
Iron absorption Sites & stages of Erythropoiesis RBC Count Removal and recycling of senescent red cells Classification of anaemias based on RBC size Causes of iron deficiency anaemia Distinguishing between different types of iron deficiency anaemia
What is erythropoiesis?
The formation and life cycle of red blood cells
How many RBCs are replaced in an adult every second?
2.5 million
What are the stages of RBC formation before birth?
Mesoblastic stage
Hepatic stage
Myeloid stage
What is the mesoblastic stage?
3rd week before births RBCs are nucleated still and form in the yolk sac and mesothelial layers of the placenta
What happens in the hepatic stage?
Before birth, at 6 weeks erythropoiesis usually occurs in the spleen and liver
What is the myeloid stage?
Before birth, from the 3rd month onwards the bone becomes the source of RBCs
What is the average diet for iron?
15mg/day
What is the total body iron volume?
3-5g
How much iron is absorbed and excreted each day?
1g absorbed and 1g excreted
Where is most of the iron in the body?
Circulating as part of haemoglobin - 2g.
Where is the majority of iron absorbed?
Duodenum by enterocytes
How is iron absorbed in the duodenum?
Ferroportins (transporter proteins) on enterocytes allow iron movement into body
In what form can iron be absorbed?
Fe2+ ion or as part of a protein
What is the role of ferric reductase?
on the brush border of the eneterocytes and reduces Fe3+ into Fe2+
What is the function of transferrin?
Iron-binding blood plasms glycoproteins which regulate free ion levels in plasms and ECF.
What is the mechanism of transferrin?
Takes up iron from enterocytes in the form Fe3+ and transported in blood to bone marrow and other cells. Transferrin binds to transferrin receptors on erythroblasts for example and get transported into the cell via endocytosis. it then releases the iron ions which are taken up by ferritin or HB to store. The empty transferrin gets transported back to the cell surface and released to repeat.
What is ferritin?
A very large hollow polyprotein made up of 24 apoferritin subunits, stores many iron Fe3+ ions.
What is the role of ferritin?
Acts as a buffer against iron deficiency and iron overload by releasing iron into cells in a controlled way.
What is myeloid tissue?
Bone tissue
What do myeloid cells do?
Take up transferrin to allow them to deposit iron to Hb.
Where does most erythropoiesis occur?
red bone marrow
Where does erythropoiesis occur after birth up to 5 years?
In all bone marrow
Where does erythropoiesis occur between ages 5 and 20-25
Marrow of the long bones
Where does erythropoiesis occur from above the age of 25?
marrow of membranous bones - vertebrae, sternum, ribs, cranial bones and ilium
What does erythropoiesis start with?
haematopoietic stem cell/haemocytoblast
What happens to the haematopoietic stem cell/haemocytoblast?
Differentiates into a stem cell called a common myeloid progenitor/proerthryoblast
What happens to a proerythroblast?
Undergoes a series of transformations where nucleus shrinks/condenses and cytoplasm fills with Hb and nucleus is expelled so it becomes a reticulocyte and is released into the blood or stays in marrow.
What happens to reticulocytes?
Mature into erythrocytes which squeezes through pores in marrow capillary membrane into blood via diapedesis.
What produces erythropoietin?
Fibroblast interstitial cells in the kidney around the PCT.
Why does the kidney produce erythropoietin?
oxygen levels in and around the PCT are not altered by exercise or blood pressure changes and so purely determined by Hb levels. They are hypoxia sensitive so know when to stimulate EPO for more RBC production or not.
What does EPO do?
Acts on erythropoietic stem cells to increase RBC production. Increases speed of maturation of committed bone marrow cells.
Why do men have slightly higher Hb levels than women?
testosterone increase EPO production
What is the consequence for RBCs not having mitochondria?
They cannot use oxidative metabolism to make ATP
What do RBCs need ATP for?
To power sodium pumps in the membrane
Power GLUT1 transporters which take up glucose
How do RBC’s make ATP?
Anaerobic Glycolysis
Why do erythrocytes have a negative surface charge?
Glycoproteins containing siliac acid
Why is it useful that erythrocytes have a negative surface charge?
Ensures they repel each other electrostatically and don’t all stick and clump together in capillaries
What are roleaux?
Stacks of clumped RBCs
If RBCs have a negative charge how do they clump together?
Inflammatory reactions or bacteria in the blood increase fibrinogen which binds RBC membranes so they adhere.
What is ESR?
Erythrocyte sedimentation rate - increases when there are rouleaux
What does a raised ESR mean?
Non specific marker of infection
What is the life time of RBCs?
120 days
What happens to RBCs after 120 days?
Removed from the blood by macrophages and pass through spleen
How are RBCs recycled?
Spleen detects senescent RBCs by lack of deformability as more rigid. They get trapped in spleen capillaries and engulfed by spenic macrophages and broken up by osmotic lysis. Haem group removed and broken by haemoxygenase enzyme, iron atoms collected by transferrin which takes it to liver then bone marrow to re-use for new Hb.
What are you left with when an old RBC has been removed of its haem group?
BILVERDIN - greenish in colour (opened porphyrin ring minus its iron atom)
What happens to biliverdin?
Reduced to bilirubin (yellow in colour) in macrophage by biliverdin reductase
What are biliverdin and bilirubin examples of?
Antioxidants
How does bilirubin become unconjugated?
Bilirubin bound to albumin in splenic macrophages and then gets released into blood.
How does bilirubin become conjugated?
Released into blood unconjugated and reaches liver where it attaches to glucuronic acid by hepatocytes to increase its solubility
How does urobilinogen form?
Conjugated bilirubin passes in the bile to the small intestine where bacteria converts it into urobilinogen
What happens to urobilinogen?
Most passes out as feces but 10% passes back in portal vein to liver and leaves in venous blood to be recycled.
What makes urine yellow?
Recycled urobilinogen passing through kidney from liver.
What is the definition of anaemia?
Hb below reference for that age and gender
What are some symptoms of anaemia?
Tiredness, fainting, SOB, worsening angina, rapid heart beats
What are some signs of anaemia?
bounding pulse, cardiac failure, systolic flow mumur, retinal haemorrhages, rapid heart rate, pallor
What are the 3 common causes of anemiea?
Low production of RBCs
High level of destruction of RBCs
Increased loss of RBCs
What are the causes of poor production of RBCs?
Iron deficiency B12 deficiency marrow infiltration chronic disease - rheumatoid/cancer infections
Why might there be high destruction of RBCs
haemolytic anaemia
immune destruction
disorders of RBC membrane/enzyme/Hb
Define microcytic, normocytic and macrocytic.
Microcytic - <76 femtolitres so RBCs too small
normocytic - 76-96fl
macrocytic - >96 fl so RBCs too big
What is an example of microcytic anaemia?
iron deficiency
What features make up iron defiency anaemia?
microcytic RBCs
Hypochromic - reduced amounts of Hb
caused by low iron diet/reduced RBC synthesis/excess iron loss (bleeding)
Why are animals a better source of iron than plants?
Plant iron has powerful chelators which are chemicals than hold iron and prevent absorption whereas haem iron is in animals and has highest bioavailabiluty
How can you enhance absorption of iron/
Haem iron in meat ferrous salts containing Fe2+ acid stomach pH pregnancy hypoxia
How can absorption be impaired?
Non haem iron from plants ferric salts containg Fe 3+ alkaline stomach pH iron overload inflammatory disorders PPIs may reduce stomach acid so reduce absorption
What are the RF for developing iron deficiency anaemia?
age - elderly sex - females reproduction - menorrhagia GI Drugs - aspirin/NSAIDs social vegan diet pregnancy/infancy/breastfeeding
What are some causes of iron deficiency anaemia?
menorrhagia GI bleeding Gi malabsorption pregnancy growth spurts elderly vegans hookworm
How do you confirm iron defieinct anaemia?
low RBC
microcytic and hypochromic RBCS (blood film)
low serum ferritin
Low serum iron total iron binding capacity (TIBC)
How do you treat iron defieincy anaemia?
1 - improve diet
2 - ferrous sulphate tablets
3 - avoid blood transfusion
4 - continue iron supplements for 3 months once Hb is normal
How can anaemia occur normocytically?
From acute blood loss (transfusion needed)
From chronic disease
From abnormal haemolysis
