Formation of Urine Part 2

Question 1

Loop of Henle aims

Answer 1

Tubular fluid is further modified in this part of the nephron
The aim here is to recover fluid and solutes from the glomerular filtrate
The process can be divided into two stages: extraction of water in the descending limb and extraction of Na+ and Cl- in the ascending limb
This process is more important for juxtamedullary nephrons (longer loops of Henle)

Question 2

Thin Descending Limb and Thick Ascending Limb

Answer 2

Thin D limb: Cells are flat, no active transport of salts; but freely permeable to water via Aquaporin-1 channels; also some passive movement of water via tight junctions
Thick A Limb: Tubular wall is impermeable to water; But has specialised Na+/K+/2Cl- (NKCC2) co-transporters; Therefore these ions are reabsorbed

Question 3

Osmolarity in LOH

Answer 3

Fluid entering LOH from proximal tubule is isotonic (300mOsm)
Water reabsorbed out of descending LOH
By the tip of the LOH, the filtrate is hypertonic (very concentrated, 1,200 mOsm)
Solutes (e.g. Na+, Cl-) are then pumped out of the ascending LOH
By the end of the LOH, the filtrate entering the distal tubule is hypotonic (150 mOsm)

Question 4

Countercurrent Multiplication

Answer 4

Creates large osmotic gradient within medulla, facilitated by Na+/K+/Cl- transport in ascending limb
Permits passive reabsorption of water from tubular fluid in descending limb limb
Urea also plays a part:
-Active transport of NaCl contributes 600-1000 mOsm - the remainder is due to urea
Urea freely filtered at glomerulus
Some reabsorption in proximal tubule, but LOH and distal tubule relatively impermeable to urea
Urea can diffuse out of collecting duct into medulla down its concentration gradient
This adds to the osmolality of medullary interstitium

Question 5

The Distal Tubule - Na+/K+ exchange

Answer 5

The distal tubule performs further adjustment of urine:
Active absorption and secretion of solutes takes place here
o Na+ and Cl- are reabsorbed from tubular fluid - exchanged for K+ throughout the DT (K+ secreted into tubular fluid)
Na+ exchanged for K+ in late DT and early collecting duct
Involves specialised cells: principal cells - these are sensitive to aldosterone
This exchange forms part of the RAAS
Action of aldosterone (more Na+ reabsorbed, so more water moves into plasma = increased BP)

Question 6

Distal Tubule - Na+/H+ exchange

Answer 6

Na+ exchanged for H+ in DT and early collecting duct
This involves specialised cells called intercalated cells
Subtypes exist called alpha and beta intercalated cells
Alpha: secretes acid (H+) via H+/Na+ or H+/K+ exchange, involving ATPase or H+ATPase; reabsorbs bicarbonate (HCO3-)
Beta: secrete bicarbonate (HCO3-) via Pendrin; reabsorbs acid (H+)
Involved in Acid Base regulation

Question 7

The Collecting Duct - ADH

Answer 7

Permeability of the collecting duct can be considerably increased the action of ADH.
The most important hormone that regulates water balance - it is a nonapeptide with Mw of just over 1000 (Also known as ‘vasopressin’ or 8-arginine-vasopressin).
Released from the posterior pituitary subsequent to hypothalamic inputs.
Plasma half-life is 10-15 min (liver and renal metabolism).
ADH acts on vasopressin V2 receptors on basal membrane of principal cells in DT and collecting duct cells leading to activation of intracellular (aquaporin-2 or AQP2) water channels
ADH causes no net movement of solutes - only water

Question 8

Modification of Urine Volume by ADH

Answer 8

Maximal circulating ADH: CD becomes permeable to water due to maximal AQP2 insertion so water reabsorption occurs; reabsorbs up to 66 % of the water entering the collecting duct; delivery of fluid to the collecting duct is low (~ 8 L/day); urine volume can be reduced to 300 mL/day.
No circulating ADH: reabsorption of water occurs at various sites in the nephron as described previously; the collecting duct wall becomes impermeable to water due to no AQP2 so a large volume of water is excreted (up to 30 L/day).
Lack of ADH: Diabetes insipidus – treated using synthetic ADH

Question 9

Types of Diabetes Insipidus

Answer 9

Nephrogenic – due to inability of kidney to respond normally to ADH - Treatment: chlortalidone (diuretic); Indometacin (anti-inflammatory)
Neurogenic - due to lack of ADH production by the brain - Treatment: Desmopressin (ADH analogue); vasopressin; carbamezapine (anti-convulsive)
Other types: dipsogenic, gestational
Syndrome of Inappropriate ADH: Excessive release of ADH, e.g. due to head injury, unwanted effects of drugs, (e.g. ecstasy); SIADH can cause hyponatraemia and possibly fluid overload - Treatment: V2 receptor blockers (ADH inhibitors), e.g. demeclocycline, Tolvaptan

Question 10

Other substances which can affect ADH

Answer 10

ADH synthesised in hypothalamus, then stored and released from posterior pituitary
Agents which increase ADH release: Nicotine, ether, morphine, barbiturates - Anti-diuretic action (urine excretion decreases)
Agents which inhibit ADH release: Alcohol - Diuretic action (urine excretion increases)