T3 L4: Formation of urine 2

• What are the two stages of modification of tubular fluid in the Loop of Henle?

  1. Descending limb: Extraction of water
  2. Ascending limb: extraction of Na+ Cl-

  this process is more important for juxtamedullary nephrons which have longer loops of Henle.

  
• What are the characteristics of the descending limb?

  site of water extraction

  • Thin descending limb
  • flat cells, no active transport of salts
  • freely permeable to water via Aquaporin-1 channels
  • also some passive movement of water via tight junctions

  
• What are the characteristics of the ascending limb?

  site of salt extraction

  • thick ascending limb
  • tubular wall impermeable to water
  • has specialised NKCC2 co-transporters (Na, K, Cl, Cl)
  • transport: Na, K, Cl reabsorbed - NO WATER

  
• What does Furosemide target?

  NKCC2 transporter

  diuretic
• What is the osmolarity of the fluid throughout the loop of Henle?

  fluid entering from proximal tubule: isotonic → descending LOH: water reabsorbed → filtrate: hypertonic (full of salt) → ascending LOH: solutes pumped out → filtrate: hypotonic

  
• What is 'countercurrent multiplication'?

  Renal process that creates large osmotic gradient within medulla

  facilitated by NKCC2 transport in ascending limb of LOH

  permits passive reabsorption of water from tubular fluid in descending LOH

  
• What part does urea play in countercurrent multiplication?

  urea diffuses out of collecting duct into medulla down its concentration gradient

  adds to osmolarity of medullary interstitium

  drives more water out

  
• What are the components of the fluid through the LOH?

  Reabsorbed compounds (back into blood): water, Na, K, Cl, HCO3-, Ca, Mg

  Secreted (into urine): urea (from collecting duct)

  remaining fluid now enters distal tubule
• What happens in the distal tubule?

  further adjustment of urine

  active absorption and secretion of solutes:

  • Na and Cl actively reabsorbed from tubular fluid
  • in exchange for K+ / H+ ions secreted into tubular fluid
• How is Na+ exchanged in late DT and early collecting duct?

  Na+ exchanged for K+

  via PRINCIPAL CELLS

  sensitive to aldosterone
• What are the two processes that occur in the DT?

  1. Na / Cl reabsorption: entire DT
  2. Na-K exchange (via principal cells): late DT & early CD

  
• How does Na-K exchange occur in principal cells?

  when aldosterone present:

  Na+ → Na channels → into DT cells → Na/K ATPase → Na goes into blood, K into DT → K then excreted in urine through K channels
• How does aldosterone stimulate Na-K exchange in DT?

  increases expression of Na channels in principal cells

  more Na gets reabsorbed

  more water gets reabsorbed

  increased blood pressure
• What is the Juxtaglomerular Apparatus (JGA)?

  where DT is in contact with the glomerulus

  part of RAAS

  
• How does low sodium in DT cause increase in BP?

  low Na → detected by macula densa → stimulates juxtaglomerular cells → to secrete renin → activates angiotensin II → increased aldosterone secretion → increased Na reabsorption from DT → increased water reabsorption → increase BP
• How is the renal action of Aldosterone?

  lipid soluble; diffuses in

  forms R-Aldo receptor complex

  upregulates ATPase to get more sodium reabsorbed

  more water reabsorbed

  increased blood pressure
• What cells are involved in acid-base regulation in the DT and CD?

  Intercalated cells

  alpha-intercalated cells:

  • secrete acid (H+)
  • reabsorb bicarbonate
  • (make urine more acidic)

  beta-intercalated cells:

  • secrete bicarbonate
  • reabsorb H+
  • (make urine more alkaline)
• What is a non-volatile acid?

  fixed acid

  can't be turned into CO2

  excreted through kidneys

  Eg lactic acid
• What hormone controls the permeability of the collecting duct?

  ADH

  increases permeability

  increased water reabsorption
• How does ADH act in the collecting duct?

  ADH → V2 receptor → increased cAMP levels → increased AQP2 on apical surface → water reabsorbed into peritubular capillaries

  no Na involvement!
• What is the condition of a lack of ADH?

  Diabetes insipidus (water diabetes)

  treatment: synthetic ADH
• What are the two major types of Diabetes Insipidus?

  Nephrogenic:

  • kidney can't respond normally to ADH
  • treatment: Chlortalidone (diuretic), Indometacin (anti-inflammatory)

  Neurogenic:

  • lack of ADH production by brain (not enough ADH)
  • treatment: Desmopressin (ADH analogue), Vasopressin, Carbamazepine (anti-convulsive)
• What is SIADH?

  Syndrome of Inappropriate ADH

  excessive ADH release

  due tp eg head injury, unwanted side effects of drugs (eg ecstasy)

  can cause hyponatraemia and fluid overload

  Treatment: V2 receptor blockers (ADH inhibitors) eg demeclocycline
• What is the effect of maximum ADH in urine concentration?

  very concentrated urine
• What is the effect of no ADH in urine concentration?

  dilue urine

  
• What are some agents which increase ADH release?

  nicotine, ether, morphine, barbiturates

  Anti-diuretic action (urine excretion decreases)
• What are some agents that inhibit ADH release?

  alcohol

  diuretic action (urine excretion increases)
• What happens to all the water and solutes reabsorbed from the tubule?

  taken back into peritubular vessels and vasa recta surrounding the tubule