Lecture 1 - Intro To anaemia Flashcards
How do RBC make energy : glycolysis
- glycolysis is the first step in the breakdown of glucose to extract energy
- does not use oxygen, and can take place under anaerobic conditions
Glycolysis two phases
1) Traps glucose molecule and uses energy to modify it: six carbon molecule splits into 2 times 3 carbon molecules
2) extracts energy from the molecules and stores it in the form of ATP and NADH using the pyruvate kinase enzyme
Survival of RBC: dealing with reactive oxygen species
- ROS convert ferrous of haemoglobin to Ferric of methaemoglobin - doesnt transfer O2
- damages the lipid membrane - short life span
- glutathione scavenges ROS
- oxidized form of gluthatione is regenerated by glutathione reductase
- Hexose monophosphate shunt generates the necessary NADPH and uses G6PD
Erythropoietin
- hormone which controls red cell production: works on red cell precursors in the bone marrow and promotes differentiation
- produced in kidney under hypoxic stress in adult
- produced in liver in the foetal and perinatal period
Definition of Anaemia
- reduction in red cell number and haemoglobin concentration of blood
- hemoglobin is the oxygen carrying pigmented proteins in red cells
- results in a reduction in the oxygen carrying capacity of the blood
Symptoms of anemia depend on:
- rapidity of onset
- general health
- severity of anemia
Symptoms of anemia
- tiredness, headaches
- dizziness
- SOB
- palpitations
- chest pain
Pallor
- conjunctivae
- palmar crease
Cardiac decompression
- tachycardia
- postural hypotension
- congestive cardiac failure
Signs of ane,ia
- angular stomatitis, glossitis, koilonychia
- jaundice
- underlying systematic illness
Useful laboratory indices in anemia
- hemoglobin
- MCV
- blood film
- Reticulocyte count
Automated counters
- haemoglobin measured by spectrophotometry at 540nm
- RBC count measured by particle counter
- MCV directly measured electronically
- MCHC calculated from haemoglobin and haematocrit
- heamatocrit calculated from red cell number and MCV
- white cells and platelets: measured optically via electrical impedence, light scatter, fluorescence and laser
Haemoglobin normal range
- male: 130-170
- female: 120-150
- higher in newborn
- pregnancy: 10-20 lower due to disproportionate rise in plasma and red cell volumes
- Mean corspuscular volume reference range
- 80-100 fl
Principles of romanowsky stain on blood film
- basic cellular elements react with acidic dye (eosin) and stain red-orange. Eg: hemoglobin
- acidic cellular elements react wit basic dye (methylene) and stain blue (eg: DNA)
Red cell development
- bone marrow proliferation and maturation is 3-5 days
- reticulocytes - bone marrow to blood: 3-4 days
- circulating mature red cell for 120 days
- vitamin B12 and folate are required for DNA synthesis and nuclear maturation
Reticulocyte
- young and immature red cells
- have residual RNA
- therefore have a blue blush
- on a blood film is called polychromasia
Reticulocyte count
- identified by staining residual RNA
- automated: residual RNA stained with flyuorescent dyes and enumerated by flow cytometry
- reference range: 50-100x10^9 g/L
Possible causes of anemia
- decreased production: deficiencies or systemic illness
- increased loss: bleeding
- shortened life span or increased destruction: haemolytic anemias, either inherited or acquired
When is anaemia due to primary bone marrow pathology
- when more than one cell line is abnormal: increased or decreased white cells and platelets
If MCV
- iron deficiency due to chronic blood loss
- inherited Hb abnormality: thalassaemias
If MCV normal
- acute blood loss
- systemic illness
- primary BM pathology
If MCV > 100 fl
- B12 and folate deficiency
- haemolysis
- liver disease
Hypochromic microcytic cells with anisopoikilocytosis
Iron deficiency anaemia
Target cells
- in liver disease
Macrocytes
- in B12 or folate deficiency
Spherocytes
- in haemolysis
Sickle cell
- sicle cell anaemia: an inherited abnormal Hemoglobin
Rouleaux
- in myeloma
- primitive white cells called blasts
- in acute leukaemia: a bone marrow disease
Increased reticulocytes means
- increased BM production
- acute hemorrhage
- reduced red cell life span: haemolysis
- response to replenished iron, B12 and folate
Normal or reduced reticulocytes means reduced BM production
- not enough iron, B12 or folate
- systemic illness
- bone marrow pathology
Further laboratory tests
- iron studies: transferrin saturation and ferritin
- B12 and folate levels
- heamollytic screen: bilirubin, LDH, haptoglobin, DCT
- tests of inherited causes of haemolysis
Systemic illness tests
- infection
- autoimmune disease: serology
- renal impairment: creatinine
- hepatic dysfunction: LFT
bone marrow biopsy
- aspirate vs trephine
- performed to confirm or exclude a suspected diagnosis
- site: posterior iliac crest or sternum, tibia in neonates
- aspirate: to assess cell number, maturation and morphology
- trephine: to assess cellularity, architecture and abnormal cellular infiltrate
Treatment of anemia
- transfusion in circulatory compromise
- replace missing iron, B12 or folate
- rectify shortened life span in case of haemolysis
- treat underlying condition
