1. 2. CUES
1.1. Metabolism, absorption and transfer of iron in the body
1.1.1. What is the average iron in the human body?
1.1.2. Where in the body is iron absorbed and what transport protein aids this process?
1.1.3. How does iron exit enterocytes and what protein aids this process?
1.1.4. How does transferrin provide iron to iron deficient cells?
1.1.5. In which form is iron absorbed
1.2. Storage of iron and formation of red cells
1.2.1. What is iron stored as?
1.2.2. How is iron stored?
1.3. Maturation of proerythroblasts
1.3.1. What are the stages of proerythroblast maturation?
1.3.2. What cells form erythrocytes?
1.3.3. What do these cells look like?
1.4. Control of erythropoiesis
1.4.1. Which protein controls this process
1.4.2. What else does erythropoietin do?
1.5. Energy Metabolism of RBCs
1.5.1. Why do RBCs require ATP?
1.5.2. How does it get ATP?
1.6. Red cell cycling in the spleen
1.6.1. Why do RBCs get recycled?
1.6.2. How do they get recycled?
1.6.3. What happens to bilirubin in the blood?
1.7. Anaemia
1.7.1. Signs of anaemia
1.7.2. Symptoms of anaemia
1.7.3. Types of anaemia
1.7.4. Common cause of anaemia
1.7.5. Risk factors of anaemia
1.7.6. Definition of anaemia
1.7.7. Treatments for anaemia
1.7.8. How do we confirm iron deficiency anaemia?
2. 3. SUMMARY
2.1. Iron is absorbed in the duodenum and jejunum using the DMT-1 transport proteins in enterocytes
2.1.1. Transferrin allows iron to be transported into iron deficient cells and be stored within endosomes
2.1.2. iron is stored as ferritin in cells
2.1.3. iron can only be absorbed in haem or ferrous form
2.2. haemotopoietic stem cells are erythrocyte precursors
2.2.1. they form common myeloid/lymphocyte progenitor cells
2.2.2. proerythrocytes are a form of myeloid progenitor cells that form erythrocytes
2.2.2.1. they do this my shrinking the nucleus and packing haemoglobin into its cytoplasm
2.2.2.2. then it ejects the nucleus to form a reticulocytes that matures into a red cells
2.3. erythropoiesis is controlled by EPO
2.3.1. EPO responds to hypoxia in the proximal convoluted tubule
2.3.2. it stimulated red cells production
2.3.3. EPO can also take part in capillary formation in healing tissue
2.4. old red cells are recycled in the spleen
2.4.1. the haem group is opened and iron taken back to bone marrow to make more red cells
2.4.2. rest is reduced to bilirubin which is converted to urobilirubin and excreted in the urine
2.5. Anaemia is the deficiency of Hb that the standard levels
2.6. there are 3 types of anaemia
2.6.1. microcytic
2.6.1.1. this can be caused by iron deficiency as there is less packed haemoglobin in red cells creating smaller red cells
2.6.2. normocytic
2.6.3. macrocytic
2.7. risk factors of anaemia include age, gender, gastrointestinal issues, use of aspirin and NSAIDs etc
2.8. To confirm anaemia you should first do a full blood count, blood film, serum ferritin and TIBC
2.9. Signs and symptoms include tiredness and fatigue, palpitations, dizziness, jaundice in the skin and eyes, rapid heart rate, bounding pukse
3. 1. NOTES
3.1. Metabolism, absorption and transfer of iron in the body
3.1.1. Average diet contains 15mg of iron a day and total body iron is 3-5g
3.1.1.1. Iron absorption is helped by stomach acid, PPIs used for acid reflux can REDUCW stomach acid, thus reducing iron absorption
3.1.2. Iron is absorbed in the duodenum and jejunum
3.1.2.1. Enterocytes are simple columnar epithelial cells lining inner surface of small and large intestines and are the cells in the duodenum that absorb the iron
3.1.2.2. Enterocytes have microvilli on its surface to increase the surface area
3.1.2.3. Transporter protein DMT-1 is found in the membrane of the enterocyte to absorb iron but the iron can only be absorbed in its FERROUS form or as part of the haem group
3.1.2.3.1. Ferric reductase enzyme in microvilli can reduce ferric iron to ferrous iron so it can be absorbed
3.1.2.3.2. Iron is transported out of the enterocyte by ferroportin molecules in the basolateral membrane
3.1.2.3.3. Storage of iron
3.1.3. Iron is excreted in the faeces, nails, hair and skin flakes
3.1.4. Haemorrhage and excessive menstruation can cause iron deficiency and anaemia
3.2. Formation of red cells
3.2.1. Bone marrow is also known as myeloid tissue
3.2.1.1. Myeloid cells take up a large proportion of circulating transferrin molecules to incorporate iron into haemoglobin in the erythrocyte precursor cells
3.2.1.2. Bone marrow is soft and spongy and is divided into red and yellow marrow - erythropoiesis occurs in the RED MARROW, yellow marrow contains fat droplets
3.2.2. Sites of RBC formation IN THE FETUS
3.2.2.1. Mesoblastic Stage
3.2.2.1.1. at 3rd week
3.2.2.1.2. Nucleated red blood cells form in Yolk Sac and mesothelial layers of the placenta
3.2.2.2. Hepatic Stage
3.2.2.2.1. at 6 weeks
3.2.2.2.2. Erythropoiesis mainly in liver and spleen (8 weeks)
3.2.2.3. Myeloid Stage
3.2.2.3.1. 3 months and onwards
3.2.2.3.2. the bone marrow becomes main source of RBCs
3.2.3. RBC formation after birth
3.2.3.1. up to 5yrs
3.2.3.1.1. bone marrow in all the bones
3.2.3.2. 5-20/25 yrs
3.2.3.2.1. marrow of the long bones
3.2.3.3. 25+ yrs
3.2.3.3.1. mainly in the marrow of the membranous bones such as vertebrae, sternum, ribs, cranial bones and ilium
3.2.4. The process of RBC formation
3.2.4.1. 1. Haematopoietic stem cells / haemocytoblasts (large cells - poorly staining cytoplasm)
3.2.4.1.1. common myeloid progenitor - large nucleus, thin shell surrounding cytoplasm and nucleus stains blue in H&E stain
3.2.4.1.2. common lymphoid progenitor cells
3.2.5. Energy Metabolism of RBCs
3.2.5.1. RBCs have no mitochondria but need ATP to power sodium pumps to avoid osmotic lysis
3.2.5.2. ATP is made via anaerobic glycolysis
3.2.5.2.1. GLUT-1 transporter will transport glucose for this
3.2.5.2.2. pyruvate is converted to lactate and NAD+
3.2.5.2.3. lactate os exported to blood and converted to glucose
3.2.5.3. ESR - erythrocyte sedimentation rate
3.2.5.3.1. RBCs cannot stick together as the have a - surface charge
3.2.5.3.2. In inflammatory reactions or bacteria in the blood, fibrinogen levels in the blood increase to bind to RBCs and reduce charge allowing cells to adhere together
3.2.5.3.3. Normal ESR (female) = (Age +10)/2
3.2.5.3.4. Normal ESR (male) = (Age)/2
3.2.5.3.5. NOTE: raised ESR levels is a non-specific marker of infection in the blood
3.2.6. Red cell recycling in the spleen
3.2.6.1. Old RBCs are removed by the spleen
3.2.6.1.1. if the individual has had a splenectomy, RBCs are removed via liver and lymph nodes
3.2.6.2. Old RBCs are recognised by its rigid structure and inability to make ATP- this may cause them to get trapped
3.2.6.2.1. trapped RBCs are engulfed my splenic macrophages and broken open by osmotic lysis
3.2.6.3. haem prosthetic groups are removed from old RBCs and broken open by HAEMOXYGENASE enzyme, iron atoms from haem are collected by transferrin and taken to bone marrow to make new haemoglobin
3.2.6.4. the left over porphyrin ring without its iron atom is called BILIVERDIN which is reduced to BILIRUBIN by biliverdin reductase
3.2.6.5. unconjugated bilirubin is not water soluble and is made water soluble via two steps
3.2.6.5.1. 1. bound to albumin in macrophage to form a slightly soluble complex
3.2.6.5.2. 2. complex passed through liver and bilirubin is conjugated (joined) to gluronic acid making it a conjugated bilirubin complex which is water soluble
3.3. Anaemia
3.3.1. defines as Hb levels below reference range for that age and gender
3.3.2. the three types are
3.3.2.1. normocytic : 76-96 fl
3.3.2.2. microcytic <76 fl
3.3.2.2.1. iron deficiency can cause a microcytic anaemia
3.3.2.2.2. lack of iron in diet causes less iron to be transported in bone marrow
3.3.2.2.3. less haemoglobin (hypochromic) packed into the cells leading to smaller erythrocytes
3.3.2.2.4. decreased MCV and MCHC
3.3.2.3. macrocytic > 96 fl
3.3.3. Symptoms of anaemia
3.3.3.1. 1. insufficient oxygen in blood (hypoxaemia)
3.3.3.1.1. worsening angina
3.3.3.1.2. rapid heart rate/palpitations
3.3.3.2. 2. other factors such as red cell destruction
3.3.3.2.1. jaundice of skin and eyes
3.3.3.3. EXESSIVE TIREDNESS OR FATIGUE
3.3.3.4. fainting, dizziness
3.3.3.5. shortness of breath
3.3.4. Signs of anaemia
3.3.4.1. pallor: palmar creases/ nail bed
3.3.4.2. rapid heart rate
3.3.4.3. bounding pulse
3.3.4.4. systolic flow murmur
3.3.4.5. cardiac failure
3.3.4.6. retinal haemorrhages
3.3.5. How to confirm iron deficiency anaemia
3.3.5.1. 1. full blood count
3.3.5.1.1. low RBC number?
3.3.5.2. 2. blood film
3.3.5.2.1. microcytic/hypochromic?
3.3.5.3. 3. serum ferrtin
3.3.5.3.1. low?
3.3.5.4. 4. serum iron total iron binding capacity
3.3.5.4.1. TIBC low?
3.3.6. How to treat iron deficiency anaemia
3.3.6.1. 1. improve diet
3.3.6.2. 2. ferrous sulphate supplements
3.3.6.3. 3. avoid blood transfusion
3.3.6.4. 4. continue iron supplements for 3 months after Hb levels are normal
3.3.7. Risk Factors
3.3.7.1. Age: elderly
3.3.7.2. Sex: female
3.3.7.3. Reproductive: menorrhagia
3.3.7.4. Gastrointestinal: appetite, weight, change in bowel habit. GI tract bleeding, gastric/bowel surgery, coeliac disease, atrophic gastritis
3.3.7.5. Drugs: Aspirin, NSAIDs
3.3.7.6. Social : vegan diets
3.3.7.7. Physiological: pregnancy, infancy adolescence, breastfeeding
3.3.7.8. Pathological: hookworm infestation