Phys 2

• Renal functions


  • Excretion of waste products
  • Maintenance of acid/base balance
  • Secretion of hormones
  • Regulation of blood pressure
• Renal failure symptoms


  • Fluid overload with edema
  • Electrolyte abnormalities
  • Anemia (end stage)
  • Reduced production of erythropoietin
  • Increase in BUN and creatinine
• Basic anatomy


  • Cortex
  • Medulla
  • Medullary pyramids (papillae)
  • Calyces
  • Renal pelvis
  • Ureter
  • Renal artery
  • Renal vein
  • Nephron
• Renal artery


  • Combined kidneys receive 20% of CO (1L /mim)
  • Blood flow from cortex to medulla
  • Medulla most susceptible to ischemia
  • Medulla has higher metabolic activity
  • Oxygen tension in medulla is low
• Nephron components


  • Renal corpuscle
  • Bowmen capsule (Glomerular capsule)
  • Glomerulus
  • Glomerular capillary wall filtration barrier
  • Visceral Epithelium (podocytes)
  • Mesangium
• Glomerular capillary wall filtration barrier


  • Fenestrated ECs
  • Endothelial Cells (EC's) form a monolayer
  • Fenestrum 70-100 nm diameter
• Glomerular basement membrane (GBM)


  • Electron dense central layer, lamina densa
  • Two thinner electron translucent layers, lamina rara externa & limina rara interna
  • Collagen IV, polyanionic proteoglycans
  • Repels anions preventing them from entering bowmen space
• Visceral Epithelium (podocytes)


  • Connect via interdigitating membranous extensions known as pedicels
  • Adjacent foot processes (pedicels) separated to create 20-30 nm filtrations slits covered by proteinacious diaphragm
  • Critical for glomerular barrier function
  • Anything greater than 5kDa is excluded from filtrate
• Mesangium


  • Mesangial cells support glomerular tuft and are contractile and phagocytic
  • Myoepithelial cells alter filtration area and rate of filtration
  • Macrophages
• Renal tubule components


  • Proximal tubule (PT)
  • Loop of Henle
  • Distal convoluted tubule (DCT)
  • Connecting tubule (CT)
  • Collecting duct
• Proximal tubule (PT) components


  • Proximal convoluted tubule (PCT)
  • Proximal straight tubule (PST)
• Loop of Henle components

  • Descending thick limb (DTL)
  • Descending thin limb
  • Ascending thick limb (ATL)
  • Thick ascending limb (TAL)
• Collecting duct components


  • Cortical collecting duct (CCD)
  • Outer medullar collecting duct (OMCD)
  • Inner medullar collecting duct (IMCD)
• Distal segments


  • Under hormonal control
  • Primary site of regulation of urine volume and concentration, sodium resorption, acid-base balance, potassium balance
• Juxtaglomerular apparatus components


  • Macular densa
  • DCT
  • Granular juxtaglomerular cells
• Granular juxtaglomerular cells


  • Part of afferent and efferent arterioles
  • Produce renin when low masses of Na+ and Cl- arrive at macula densa or low perfusion
• Afferent arteriole


  • GFR altered by dilation and constriction
  • PGs maintain patency
  • ASA may worsen renal insufficiency
• Efferent arteriole


  • GFR altered by dilation and constriction
  • More sensitive to vasoconstrictive effect of angiotensin II
  • Increases GFR
• Peritubular network


  • Supplies tubule with oxygen and nutrients
  • Reclaims fluid and other substances
• Nephron types


  • Superficial
  • Juxtaglomerular
• Juxtaglomerular nephrons


  Produce more concentrated urine
• Regulation of plasma osmolarity and water resorption

  • Antidiuretic Hormone (ADH) also known as vasopressin
• Antidiuretic Hormone (ADH)


  • Primary function to regulate the tonicity of body fluids
  • Released through the posterior pituitary as a result of plasma hypertonicity
  • Kidneys reabsorb hypotonic fluid to restore plasma isotonicity
  • Urine is concentrated and production is reduced
  • In higher concentrations promotes vasoconstriction to increase blood pressure
• Pituitary gland components


  • Anterior pituitary (adenohypophysis)
  • Posterior pituitary (neurohypophysis)
• Posterior pituitary (neurohypophysis)


  • Composed of modified glial cells (pituicytes) and axonal processes from nerve cell bodies in supraoptic & paraventricular nuclei of hypothalamus
  • Produce ADH and oxytocin
• Oxytocin


  Synthesized in Paraventricular nucleus of hypothalamus, promotes uterine contraction and milk let down, overproduction has no clinically significant symptoms
• ADH


  Synthesized in Supraoptic nucleus of hypothalamus, nonapeptide, released in response to increase plasma oncotic pressure, exercise, acts on collecting ducts kidneys promoting resorption of water
• Water resorption controlled by altering permeability of distal segments to H2O

  1. ADH binds vasopressin receptor (V2) receptor

  2. Activates adenylate cyclase to produce cAMP

  3. cAMP activates PKA

  4. AQPs inserted into cell membrane
• Aquaporins (AQPs)


  • Constitutively expressed in PT and DTL
  • ATL and TAL do not express AQP, impermeable to water
  • Principle cells in CNT, CCD, OMCD, IMCD express AQP2
  • CD contains AQP3, not dependent on ADH
• Diabetes insipidus


  ADH deficiency, risk factors include head trauma, neoplasms, inflammatory disorders of the hypothalamus, pituitary, presents with polyuria, increase in serum Na+ (hypernatremia) and osmolality, polydipsia can compensate otherwise -> fatal dehydration, managed with desmopressin or carbamazepine
• Syndrome of Inappropriate ADH secretion (SIADH)

  ADH overproduction, risk factors include ectopic production from oat cell tumors (paraneoplastic syndrome), non-neoplastic disease of the lung, injury to hypothalamus or pituitary, presents with resorption of inappropriate amounts of water from kidney, hyponatremia, total body water increased, cerebral edema, no peripheral edema, blood volume normal
• Regulation of blood volume and pressure


  • Renin angiotensinogen aldosterone axis
• Renin angiotensinogen aldosterone axis

  1. Renin protease released in response to reduction in renal perfusion, cleaves angiotensinogen to angiotensin I

  2. Angiotensin I converted to angiotensin II by ACE

  3. Angiotensin II increases BP by vasoconstriction and triggering release of aldosterone
• Aldosterone


  Increases renal resorption of Na+ and water in DCT, increases volume and CO
• Sodium and chloride resorption regulation by aldosterone


  1. Salt concentration low when fluid arrives in DCT

  2. Distal segments absorb 5% of NaCl

  3. Aldosterone binds to basolateral mineralocorticoid receptor (MR)

  4. MR internalized and transported to nucleus, complex upregulates expression of ENaC, ROMK, Na+/K+ ATPase pump within 6 hrs

  5. Basolateral Na+/K+ ATPase pump creates concentration gradient

  6. Absorption through epithelial sodium channel (ENaC)

  7. Absorption of Na+ creates negative charge in tubule, driving paracellular Cl- resorption

  8. Alpha-intercalated cells also absorbs Cl- transcellularly

  9. Aldosterone also acts immediately through serum and glucocorticoid activated kinase (SGK) to decrease degradation of ENaC and increase Na+/K+ ATPase pump activity
• Acid/Base balance


  • Bicarbonate and proton metabolism in PT
  • H+ Excretion
• Bicarbonate and proton metabolism in PT

  • PT resorbs 80% of HCO3-
  • PT secretes H+ to neutralize anion charge via a Na+/H+ exchanger (NHE3)
  • HCO3- + H+ -> H2C03 (luminal), H2C03 -> CO2 + H20 by carbonic anhydrase (IV) in microvillus boarder, CO2 + H20 enters PT cell by simple diffusion, inside cell: CO2 + H20 -> H2C03 by carbonic anhydrase (II), H2C03 -> HCO3- + H+, intracellular HCO3- resorbed across the basolateral membrane using electrogenic Na+/HCO3- cotransporter (NBCe1), Cl-/HCO3- exchanger assists in resorption in distal PT
  • Acetazolamide, a carbonic anhydrase inhibitor, impairs PT ability to resorb HCO3-
• H+ Excretion


  • PT primary site for H+ secretion
  • Distal segments of PT determine final urine and ECF pH
  • Na+/H+ exchanger (NHE3), H+ excreted powered by Na+ concentration gradient created by basolateral 3Na+/2K+ ATPase exchanger, high capacity, secretes 65% of H+ in PT
  • H+ ATPase pump, 40% H+ secretion in PT, steep H+ concentration, electrogenic
• To excrete sufficiently large H+ loads, nonvolatile acid must be excreted
• HCO3- + H+


  1. Intracellular HCO3- resorbed across the basolateral membrane

  2. Using electrogenic Na+/HCO3- cotransporter (NBCe1)

  3. Cl-/HCO3- exchanger assists in resorption in distal PT