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Physiology Midterm 2.docx

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University of Waterloo
BIOL 373
Heidi Engelhardt

Physiology Midterm 2 Diabetes • Two types: o Mellitus – sweet urine o Insipidus – bland/tasteless urine • Endocrine disorder – glucose in the urine Functions of the Kidney • Most important function of the kidney: o Salt and water balance • Regulation of extracellular fluid volume and blood pressure o When one decreases the other decreases o If too much decrease – inadequate blood flow to the essential organs • Regulation of osmolarity • Maintenance of ion balance o Keep key ions within normal range by balancing dietary intake with urinary loss o Na is the major ion that influences regulation of ECF and osmolarity • Homeostatic regulation of pH o Remove protons save bicarbonate • Excretion of waste o Endogenous:  Nitrogenous products  Breakdown of hemoglobin and hormones o Exogenous:  Drugs  Environmental toxins • Production of hormones: o Erythropoietin – regulates red blood cell synthesis o Renin – regulates blood pressure and sodium balance o Enzymes help conversion to hormones to regulate calcium balance Kidney Structures • 2 types of nephrons: o Cortical  Abdominal aorta  renal artery  arterioles  afferent arteriole  glomerulus (capillaries)  efferent arteriole  peritubular capillaries  venules  veins  vena cava o Juxtamedullary  …  afferent arteriole  glomerulus  efferent arterioles  vasa recta  … • Renal corpuscle o Bowman’s capsule + glomerulus  Bowman’s capsule just stores the glomerulus  Glomerulus is the bunch of capillaries • Distal nephron: o Distal tubule + collecting duct • Podocytes: o Foot processes wrapped around capillaries o Filtration barrier • Juxtaglomerulus apparatus o Ascending loop of henle folds back onto itself (positioned near afferent/efferent arterioles) o Paracrine communication between apparatus and afferent arteriole Kidney Function • Filtration o Movement of water and solutes into the tubules via the blood o Only occurs in renal corpuscle o Filtrate isosmotic w/ plasma – 300 mOsM  Leaving proximal tubule is also 300 mOsM – bulk reabsorption of isosmotic fluid  3 layers that prevent full filtration of plasma into lumen • Glomerulus capillary endothelium o Prevent red blood cells + some plasma proteins to pass o “fenestrated” – allows most substances to pass • Basal lamina o Prevents more plasma proteins from passing • Bowman’s capsule epithelium o Prevents the rest of plasma proteins from passing • Unique proteins: o Nephrin o podocin  Driven by : • Hydrostatic pressure o Favours fluid movement into bowman’s capsule • Colloid osmotic pressure (aka oncotic pressure) o Favours fluid movement into capillaries • Hydrostatic fluid pressure o Opposes fluid movement into bowman’s capsule  Mesangial cell: • Sticks to multiple glomerular capillaries • Alter blood flow + immune response o Why not filter out 1% only?  High filtration rate gets rid of waste quickly  Filtered  excreted are ones that don’t have specific transport mechanisms • Reabsorption o Movement of water and solutes back into the blood o Each stage (proximal  collecting duct) o Gradients (electrical/chemical) must be created by active transport o Epithethial:  Must cross apical + basolateral  ENaC – epithelium sodium channel expressed on apical side • Passive diffusion of sodium • Na /K ATPase pumps sodium across basolateral to interstitial  SGLT – sodium glucose cotransporter • Active transport (symport) • GLUT – glucose transporter o Passive diffusion of glucose to interstitial o Paracellular:  Through cell-cell junctions  Urea – passive diffusion through apical (~40% filtered urea reabsorbed in proximal) • Why reabsorbed ? o Passive so kidney has no choice o Key in nitrogen metabolism o Endocytosis of plasma proteins  Receptor mediated endocytosis of plasma proteins  Comes out as amino acids • Secretion o Removing molecules from blood back into filtrate o Everywhere except loop of henle o Depends on membrane transporters  Active transport o Secrete H /K as homeostatic means o Secrete xenobiotics/metabolic wastes o Anion secretion – OAT  Endogenous + exogenous + +  Na /K ATPase keeps intracellular sodium low  NaDC keeps intracellular dicarboxylate high • 2 degree active transport - symport • On apical + basolateral -  OAT keeps intracellular concentrations of OA high • 3 degree active transport • Only on basolateral • ~70% reabsorbed in proximal & by end of loop of henle ~90% • Distal nephron – hormone regulated to fine tune water/salt balance • Filtration fraction - % of plasma that gets filtered into tubule • Glomerular filtration rate (GFR) o Indicator of overall kidney function o 100-125 mL/min o Influenced by  Net filtration pressure  Filtration coefficient o Afferent arteriole  Increased resistance  decreased glomerular pressure = decrease GFR o Efferent arteriole  Increased resistance  build up = (backflow into glomerul(us))ar pressure increases = increase GFR o Regulation mechanisms:  Myogenic response • Changing blood pressure • “autoregulation”  Juxtaglomerular feedback • Granular cells secrete renin o Regulates salt and water balance  When levels are higher  tells macula densa  paracrine control  afferent arteriole vasoconstrict  decrease GFR • Increase in salt transport initiate feedback  Endocrine/autonomic control • Sympathetic control • Prostaglandin: o Altering filtration coefficient  Altering podocyte’s slits + shape of glomerular capillaries (mesangial cells) o vasodilation • Angiotensin II: o Changing resistance in arterioles o Vasoconstriction • Plasma clearance o Rate of which substance X disappears from the body by excretion or metabolism  mL/min o If it’s only filtered not reabsorbed or secreted + only be cleared by the kidney  tells us GFR  Inulin • Storage of carbohydrates from roots of many plants  Creatinine • Overestimates GFR (some secreted) o Glucose is 100% reabsorbed o Penicillin is secreted + fi
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