Intro to Cardiology & RBCs

Intro to Cardiology & RBCs

1. Why needed? Diffusion: t = x2/2D t= time, x= distance, D= diffusion coefiicient

2. Blood pressure

   • Systemic circ = L ven>R atr Pulmon circ = R ven>L atr

3. Vessel structure

   • Types of Capillary
     • Fenestrated eg. glomerular capillaries
     • Continuous eg. of most tissues
       • narrow gaps betw endo cells - diffusion
     • Sinusoid/Discontinuous eg. spleen/liver/bone marrow
       • larger gaps - exchange of RBCs
     • NB. orange = glycocalyx. When damaged > atherosclerosis, diabetes (too much sugar on glycocalyx)
   • Vessel properties
   • Structure of Arteries

4. Embryology

   • Congenital heart abnormalities
     • Ventricular septal defect • Atrial septal defect • Patent foramen ovale • Coarctation (constriction) of aorta • Tetralogy of Fallot • Transposition of the arteries

5. Muscle

   • Cardiac muscle
     • Similar to skeletal muscle (eg. T-tubules, sarcoplasm etc) BUT electrical spread
       • Gap junctions (Connexons & Connexin proteins) & Intercalated Discs (contain desomosomes)
       • Whereas ^force of skeletal muscle = recruitment of more motor units
     • Excitation-Contraction
   • Vascular muscle
     • Electromechanical & Pharmacomechanical coupling

6. RBCs

   • 120 day lifespan
     • Adaptations: Biconcave ^SA gas exchange. Strong yet flexible. No internal organelles ^space for Hb
     • By far, most common cell in body
   • Erythropoiesis
     • Where?
       • In fetus: liver
         • In children: ALL bones with red bone marrow (+liver & spleen in anaemia)
           • >20yo adult: End of long bones (eg. femur/humerus), skull, vertebrae, ribs, sternum, pelvis (MAINLY red bone marrow) (+liver & spleen in anaemia)
     • Amplification & maturation
       • Enucleation is dynamic - actin moves to remove nuc from cell
     • Regulation
       • Low O2 (hypoxia, decreased O2 availability to blood, increased O2 demand by tissues)
         • Kidneys secrete erythropoietin > more erythropoiesis in bone marrow > increases O2 carrying capacity of blood
       • of proliferation and differentiation
         • Extra-cellular factors : GFs & cytokines interact with receptors on RBCs > intracellular signalling pathways
         • Intra-cellular : Transcription factors > gene expression
           • NB. Diff GFs and TFs needed at diff stages (expression of receptors varies)
     • Where takes place? Macrophage Island.
       • Macrophage helps to pull out nucleus. Engulfs nucleus and destroys it.
   • RBCs = voracious consumers taking ~90% of all body's iron
     • BUT all cells need it (CNS, Heart, Skeletal muscle sensitive to Fe deprivation)
       • SO Ferroportin iron exporter (FPN) allows giving back of Fe. (Liver, intestines, macrophages) ALSO Erythroblasts ~20% of Fe
   • Blood groups
     • 36 blood groups with over 300 antigens (important for transfusions)
       • Wrong blood grp > antigens cause body to break down foreign RBCs > iron overload > damage to organs
     • Some Blood Groups from POLYMORPHISMS in ENZYMES that add CARBOHYDRATE groups to proteins (glycosyltransferases)
       • ABO blood group antigens are carbohydrate groups on extracellular membrane lipids and proteins. The main carrier of the ABO (ABH) antigens is Band 3 (Anion transporter).
         • Specific glycosyltransferase adds H antigen A or B antigen: Gene for this glycosyltransferase has 4 nucleotide substitutions, protein differs by 4 amino acids
           • NB. Bombay blood group (rare) - don't have H antigen - problem
     • = Membrane proteins + Carbohydrates on membrane (glycosylation)
     • Some Blood Group systems from POLYMORPHISMS in MEMBRANE PROTEIN (SNPs in protein-coding gene)
       • Some mutations cause no Kidd or Duffy. Or diff aa > antibody response in blood transfusion.

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