T3 L3: Formation of Urine 1

• What are the five major stages of urine formation?

  1. Glomerulus: filtration of blood
  2. Proximal tubule: reabsorption of filtrate; secretion into tubule
  3. Loop of Henle: concentration of urine
  4. Distal tubule: modification of urine
  5. Collecting duct: final modification

  
• What are the 3 major functions of the nephron?

  1. Filtration: of blood to produce a filtrate
  2. Reabsorption: of water, ions and organic nutrients from filtrate
  3. Secretion: of waste products into tubular fluid

  
• What are the characteristics of Filtration as a basic renal process?

  in glomerulus

  force for filtration:

  • blood pressure
  • different diameter of afferent and efferent arterioles

  Glomerular Filration Rate (GFR): rate at which glomerular filtrate is produced

  Can be measured clinically and used as an indicator of renal function

  
• How does glomerular filtration work?

  Filtrate passes through:

  1. Pores in glomerular capillary endothelium
  2. Basement membrane of Bowman's capsule
  3. Epithelial cells of Bowman's capsule (podocytes) via filtration slits into capsular space

  
• What are the forces acting on glomerular filtration?

  Push fluid out of glomerulus:

  • PGC: glomerular capillary hydrostatic pressure
  • πBS: Bowman's space oncotic pressure (almost 0)

  Oppose ultrafiltration:

  • PBS: Bowman's space hydrostatic pressure
  • πGC: Glomerular capillary oncotic pressure

  
• By the end of the glomerular capillary, Net filtration pressure reduced to almost 0.

  
• GFR generally remains constant even when systemic BP changes.
• Why does GFR generally remain constant even when systemic BP changes?

  autoregulation of renal blood flow
• What is Autoregulation of Renal Blood Flow (RBF)?


  local effect (not neuronal/hormonal)

  Two hypotheses:

  • Myogenic: due to response of renal arterioles stretch (Starling's law)
  • Metabolic: renal metabolites modulate arteriolar contraction, eg adenosine, NO

  
• What does GFR depend on?

  diameters of afferent and efferent arterioles

  Eg:

  • Afferent artery dilates, efferent artery constricts: increased GFR
  • eg via Prostaglandins, ANP, dopamine, NO, kinins
  • Afferent artery constricts, efferent artery dilates: decreased GFR
  • eg via Noradrenaline, endothelin, adenosine
• How can changes in GFR alter systemic blood pressure?

  drop in filtration pressure → drop in GFR → less Na enters proximal tubule → mascula densa senses the change → stimulate juxtaglomerular cells → release RENIN → angiotensin II (vasoconstrictor) → increased BP → increased filtration pressure → normal GFR

  
• What happens in the proximal tubule?

  reabsorption
• What is the driving force for reabsorption in proximal tubule?

  Na / K ATPase

  
• What does the brush border allow?

  more surface area for reabsorption

  
• How is the Na concentration of peritubular cells?

  low

  due to Na/K ATPase pumping Na out
• How is the charge of PT cells overall?

  negative

  due to presence of intracellular proteins
• How does reabsorption occur in the PT?

  Na/K ATPase → Na pumped into capillary → low Na conc in cell → Na diffuses into PT cell from lumen → Cl follows Na → water follows through aquaporin channels (AQP)
• How does the transcellular flow of water occur?

  through aquaporins (AQPS) in cell membrane
• What are the 4 major renal AQPs?

  AQP-1 : proximal tubule

  AQP-2 : collecting duct, expression controlled by ADH

  AQP-3&4 : basolateral surface of tubular cells

  
• How does glucose reabsorption from PT occur?

  co-transported with Na
• What does glucose reabsorption in PT occur through?

  two systems:

  S1 (PCT):

  • into PCT cells: SGLT2
  • out of PCT cells (into blood): GLUT2

  S3 (proximal straight tubule PST):

  • into PST cells: SGLT1
  • out of PST cells into blood: GLUT1
• Glucose is co-transported into PT cell with Na very efficiently so very little is excreted.
• How can glucose be present in urine in diabetics?

  glucose transporters become saturated

  so some glucose can't be reabsorbed and escapes into urine
• What does Tm mean in the glucose titration curve?

  maximum transport capacity of glucose (transport maxima)

  urinary excretion of glucose indicates diabetes

  
• How do SGLT2 inhibitors work in diabetes and what are some examples?

  inhibit SGLT2 transporters so glucose isn't reabsorbed into blood

  excreted in urine

  leading to overall hypoglycaemic effect

  examples: Flozins (dapagliflozin, canagliflozin, empagliflozin)

  
• What is a major side effect of SGLT2 inhibitors?

  increased risk of developing UTIs

  as glucose in urine

  bacteria use glucose for growth
• How does protein reabsorption from PT occur?

  pinocytosis (independent of Na)

  vesicle → cell → degraded by lysosomes → amino acids returned to blood

  low Tm

  proteinuria: sign of glomerular damage and impending renal failure

  
• What is secretion?

  pushing substances from peritubular capillaries into the PT

  two kinds of pumps:

  • for organic acids (eg uric acid, diuretics, antibiotics)
  • for organic bases (eg creatinine, procainamide)
• What is PAH?

  para-amino hippurate

  secreted into PT from blood

  used as a tool to measure tubular secretion