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Blood TBL 1 - Coggle Diagram
Blood TBL 1
Physiology
Definitions
Haematocrit - volume occupied by RBCs in 100ml of blood - decreased anaemia, increased polycythaemia
Mean corpuscular volume (MCV) - average volume of single RBC - decreased microcytic anemia, increased macrocytic anemia
Mean corpuscular Hb - average mass of haemoglobin in each RBC - reduced anemia
Mean corpuscular Hb concentration - average concentration of haemoglobin in single RBC - reduced anemia
Reticulocyte percentage - decreased suggests decread haematopoiesis in bone marro, increased suggests increased haematopoiesis in bone marrow as compensatory response to anemia
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Erythropoiesis
BFU-E - erythroid cells that exhibit low sensitivity to EPO - differentiate into CFU-E
CFU-E - respond to EPO, iron, vit B12, folic acid - give rise to erythroblast
BFU-E → CFU-E → Proerythroblast → Basophilic erythroblast → Polychromatic erythroblast → Orthochromatic erythroblast → Reticulocyte → Erythrocyte (RBC)
Reticulocytes
immature RBCs formed in bone marrow
Contain cytoplasmic RNA which stains in supravital dyes giving reticular pattern
Non-nucleated, possess ribosomes and mitochondria (oxidative metabolism and heme synthesis)
Erythropoietin
Glycoprotein made primarily by kidney in response to cellular hypoxia
Triggers JAK2 signalling cascade when bound to receptors
CKD - less EPO made by kidney - normocytic and normochromic anemia, shorter survival time of RBCs
Carcinomas of kidney/liver - polycythaemia
Haemoglobin
Hb made of 4 globin proteins and 4 heme molecules
Taut - vacant O2 binding site
Relaxed - O2 bound to Hb
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Embryonic Hb - zeta and epsilon genes during 1st trimester - form Hb Gower I
Embryonic Hb- gamma gene during 1st trimester - associates with zeta to form Hb Portland
Fetal HbF - alpha genes in 1st trimester - associate with gamma to form foetal Hb
Adult HbA - beta turns on during 1st trimester - combine with alpha to form HbA (just before birth, commonsest adult Hb)
Adult HbA2 - delta turns on during 3rd trimester - combine with alpha to form HbA2 (minor adult Hb starting around time of birth)
Hemolysis
Extravascular Hemolysis
Iron removed from heme - stored in macrophage as ferritin
Globin of Hb degraded and returned tometabolic amino acid pool
Protoporphyrin component of heme degraded to bilirubin
Intravascular hemolysis
Haemoglobin-haptoglobin complex - broken RBCs release Hb into plasma - bind protein haptoglobin, complex cleared by liver
Hemopexin-heme complex - broken RBCs release heme into plasma - complex cleared by liver
Haemoglobinaemia - free Hb in blood once haptoglobin and hemopexin are depleted
Haemoglobinuria - free Hb in urine once capacity for tubular reabsorption is saturated
Pathology
Underproduction anemias
Microcytic
Iron deficiency
Microcytic hypochromic (small, pale) RBCs - may see pencil cells
MCV and MCHC are decreased
Presentations
Glossitis - reddened, swollen, smooth, shiny, tender tongue
Angular stomatitis - erosions at corner of mouth
Gastric atrophy
Koilonychia
Thalassemia
Presentations
Anemia, jaundice, chipmunk facies, bow-legged, liver and spleen enlargement, gallstones, secondary haemochromatosis
Microcytic hypochromic - decreased Hb production
Target cells - dark centre surrounded by white ring, follwoed by dark outer second ring with band of hemoglobin
Alpha thalassemia - deletions of one of 4 alpha genes
2nd trimester - foetal haemoglobin not formed as alpha genes defective - Hb Barts - loss of alpha genes, form gamma chain tetrameres - hypoxia
After birth - HbH - loss of alpha genes, beta chain tetramers formed - heinz bodies
Beta thalassemiaAfter birth - initially sifficient HbF to prevent anemia
Beta thalassemia minor - less HbA made
Beta thalassemia major - no HbA made
Production of minor adult HbA2 and HbF increases to minimise anemia
Macrocytic
Megaloblastic
Reduction in tissue folate - reduction in DNA synthesis relative to RNA synthesis - cells do not proceed from G2 to M
Cobalamin deficiency
Pernicious anemia - autoimmune condition, most common cause of vit B12 deficiency in developed countries
Anti-parietal cell autoantibodies leads to gastric atrophy and decreased IF release - decreasing B12 absorption - decreased absorption of IF-B12 complex in terminl ileum
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Hemolytic anemia
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Sickle cell disease
On deoxygenation - HbS molecules undergo conformational change allowing polymers to form via intermolecular contacts involving abonormal valine residue
Sicking of red cells initially is reversible on reoxygenation - but membrane distortion produced by each sickling episode -> influx of calcium, loss of K+ and water and damages membrane skeleton
Cumulative damage creates irreversibly sickled cells thaat rapidly undergo hemolysis
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Hereditary spherocytosis
Spherocytes are see - dark red and lack central pallor
Anion exchanger bound to cytoskeletal protein (ankyrin) - bound to noodle-shaped protein (spectrin) - forms cytoskeletal network
Patho - genetic disease due to mutation of ankyrin, spectrin, band 3/anion exchanger - splenomegaly
G6PD Deficiency
X-linked disease
G6PD/NADPH pathway is only source of GSH in RBCs that is required to mop up oxygen free radicals - RBCs damaged by oxygen free radicals - removed by macrophages in splenic and liver sinuses, destroyed in circulation
Hemolysis precipitated by oxygen stresses - RBCs destroyed faster than body can replace
Immune hemolysis
Immunoglobulins coat RBCs - IgM and IgG - complement mediated aintravascular lysis
Binding of IgG and IgM leads to opsonisation of RBCs - direct destruction by splenic macrophages - extravascular hemolysis
Hyper bilirubineamia
Increased LDH
Increased reticulocytes
Depleted haptoglobin - used for binding to free Hb in circulation
Microspherocytes - reduction in SA:V ratio
RBC agglutination - presence of IgM
Extravascular haemolysis - Ab weakly activate complement system
Intravascular haemolysis - Ab strongly activate complement system
Diagnosis - direct and indirect Coombs' test
Warm - IgG, cold - IgM
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Clinical Approach
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Normocytic/normochromic - problems of production, recent blood loss
Acute bleed, renal anaemia, marrow infiltration
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