Red Cell Disorders 1 Flashcards
Examples of Red Cell Disorders
- Iron Deficiency
-Megaloblastic Anaemia
-Haemolytic Anaemia - Inheritred / Acquired
What is Anemia?
Reduced oxygen carrying capacity causing insufficient tissue oxygenation
Symptoms of Anemia
SOB (Shortness of breath), tachycardia, paleness ect
What is a full blood count? Why do it for Anaemia?
FBC: counting of all different cell types in the blood.
Anaemia results in lack of red cells and haemoglobin
Reference range: Male 135-180 g/L and Female 115-160 g/L
Anemia - important values for RBC
Mean corpuscular volume (MCV) is important (average size and volume of a red blood cell) - normal/ reference range: 80-102 fl.
- calculated by multiplying the percent hematocrit by ten divided by the erythrocyte count
RDW (Red cell Distribution Width) also important - normal range is 11-15 fl.
- calculated by dividing the standard deviation (SD) of the mean corpuscular volume (MCV) by the MCV and multiplying by 100 to yield a percentage value to be on behalf of the RBC size heterogeneity
hereditaryAnaemia - Causes
- Blood Loss, acute and chronic, can it be distinguished by a FBC ?
- Haematinics deficiency.
- Genetic disorders of: Haemoglobin/ Red cell metabolism/ Red cell membrane
Red cell destruction (haemolysis). - Disorders affecting the bone marrow e.g. leukaemia.
- Chronic diseases e.g. renal failure.
etc.
Anemia - Classification due to red cell size
Microcytic (low MCV) - e.g. IDA, ACD, thalassaemia
Macrocytic (high MCV) -e.g. megaloblastic anaemia
Normocytic (normal MCV) - e.g. haemolytic anaemias, blood
loss, ACD
MCV reference range: 80-102 fL
Iron Deficiency Anaemia (IDA): Iron Metabolism
Used in redo reactions in most cells
-potentially toxic
-Sequested in transport and storage molecules (ferritin, haemosiderin, transferin)
Haem iron most easily absorbed
Absorption of iron involves passive diffusion and receptors
Most iron found in red cells (Hb)
IDA; most common cause of anemia worldwide
Iron metabolism - Ferritin
-Main iron storage protein
-Soluble - measured in plasma
-Found in all cells - highest concentration in liver/spleen/bone marrow
- makes iron available for critical cellular processes while protecting lipids, DNA, and proteins from the potentially toxic effects of iron.
Iron Metabolism - Haemosiderin
-Insoluble, crystalline protein
- Found predominantly in macrophages
- Stained by Prussian Blue Reactions
- Iron-storage complex that is composed of partially digested ferritin and lysosomes.
-Breakdown of heme gives rise to biliverdin and iron - body then traps this iron and stores it as haemosiderin in tissues
Iron Metabolism - Transferrin
-blood plasma glycoprotein
- responsible for ferric-ion delivery: functions as the most critical ferric pool in the body and has a cruical role in iron metabolism.
- Delivers iron to cells with transferrin receptors; e.g erythroblasts in the bone marrow and cells all over the body.
Transferrin Receptors
-Cells require transferrin receptors for uptake of iron - e,g red cells.
Hepcidin
- Protein synthesized in the liver in response to iron levels and inflammation
-Transfer to plasma depends on the requirements of the eythron for iron and available iron stores. - Hepcidin controlls this
accquiredCauses of Red Cell Disorders (Anaemia)
-Dietary
-Blood Loss: Peptic ulcer, aspirin, menorrhagia, postmenopausal bleeding, hookworms, chronic and acute
-Malabsorption: Gastrectomy, IBD, Coeliac Disease
- Increased physiological demands: Infancy, pregnancy
Symptoms of Red Cell Disorders (Anemia)
- Lethargy/ Shortness of Breath
- Koilonychia
- Angular stomatitis
- Glossitis
-Irritability and poor cognitive function in children
Diagnosis - Assessment of iron status for anemia
Bone marrow (not routine for simple IDA)
Low ferritin
Low serum iron
Increased TIBC
Increased soluble transferrin receptors (sTfR) -not routine in most labs.
Blood tested against FBC parameters such as WBC, HB, MCV, MCHC, PLT.
Diagnosis - Microcytic hypochromic anaemia
Microcytic: circulating RBCs are smaller than the usual size of RBCs
hypochromic: RBCs have decreased red color
Diagnosis: Pencil vs Target cells
Pencil cells: elongated, hypochromic RBCs, in which the long axis was more than 3 times the length of the short axis
Target cells: RBCs with a central hemoglobin- ized area surrounded by an area of pallor.
-Pallor: an abnormally pale appearance.
Treatment
Oral Iron e.g. ferrous sulphate or ferrous gluconate.
Usually required for 3-6 months or more.
Treat underlying cause.
causes of Anaemia of Chronic Disease
- Associated with inflammatory disorders (E.G malignancy and RA) due to production of inflammatory cytokines (IL-6).
- Causes of anemia often multi-factorial:
- Defective iron incorporation into developing red cells
- A reduced erythropoietin response to anaemia
- Decreased sensitivity of erythroid precursors to erythropoietin.
- Shortened red cell survival.
- Hepcidin plays a important role
Anaemia of Chronic Disease - Lab Investigations
About 30-50% are microcytic
Hb usually above 90g/L
Normocytic/mild microcytic anaemia
Rouleaux
Raised ESR/CRP
Normal/increased ferritin
Reduced serum iron & TIBC
Little or no effect on sTfR
Vitamin B12 & Folate Deficiency (Megaloblastic Anaemia)- effect on erythropoiesis
Megaloblastosis: Due to faulty DNA synthesis
Nucleus of developing erythroblast maintains primitive appearance despite maturation and haemoglobinisation of the cytoplasm
Low B12 and folate levels result in failure to convert dUMP to dTMP
Conversion of deoxyuridine monophosphate (dUMP) to deoxythimidine monophosphate (dTMP) during DNA sythesis via methyl group transfer is facilitated by vitamin B12 and folate - leads to ineffective erythropoiesis.
Role of dTMP
dTMP is subsequently phosphorylated to produce dTTP, a vital precursor for DNA replication and repair.
What do you need b12 for
B12 is only present in food of animal origin
Can take 3 -5 exhaust stores
B12 required for normal blood production and nerve function