Control Of Plasma Osmolarity

Question 1

What is Norma cell osmolarity

Answer 1

Most body fluids are isotonic to cells osmolarity 280-310 (~300) mOsm/Kg
– Exception urine

Question 2

How does osmolarity change

Answer 2

• If Water intake < water excretion = plasma osmolarity ↑ • Water intake > than water excretion = plasma osmolarity ↓ • * Body must match ingestion to excretion
– Most people on average urinate 1-1.5L/d and ingest 600-1000 mOsm/d • Urinary osmolarity therefore changes
– In normally hydrated person ~ 500-700 mOsm/Kg
– If we ingest 1000 mOsm/d they could be excreted as 100 mOsm/Kg in 10 L urine
– Or 1000 mOsm/Kg in 1 L urine
– Urine osmolarity can vary between 50-1200 mOsm/Kg • The solute concentration of urine is 1/∞ to volume of urine produced

Question 3

How do changes in water balance and changes in salt change the body fluid

Answer 3

• Disorders of water balance manifest as changes in body fluid osmolarity
– measured as changes in plasma osmolarity
– Normally plasma osmolarity ~ 280-310 mOsm/Kg (280-310 mmol/L)
– the major cation of the ECF is Na+
– ∴ ∆ Na+ ion concentration are seen
• Not a problem with Na+ balance
– Na+ balance changes volume • Problem with water balance affecting osmolarity

Question 4

What are osmoreceptos

Answer 4

• Located in hypothalamus
• Specifically in the OVLT
• Fenestrated leaky endothelium exposed directly to systemic circulation (on plasma side of Blood brain barrier)
• Sense changes in plasma osmolarity
• Signal 2O responses which are mediated via two pathways leading to two different complimentary
outcomes - both resulting in decrease in osmolarity
– Concentration of urine
– Thirst
• Cells of the supraoptic nucleus lie close to OVLT with input from baroreceptors (remember BP)

Question 5

What is the role of osmoreceptoprs when there is loss of water

Answer 5

• Under conditions of predominant loss of wate osmoreceptors in hypothalamus increase release of ADH from posterior pituitary
• ↑ of 1% in osmolarity ↑ ADH
• Secretion ADH (to ↓ renal water excretion)
• Decreased osmolarity inhibits ADH secretion
• Negative feedback loops that begin within the anterior hypothalamus
• Result is a feedback loop which stabilizes osmolarity

Question 6

How does haemodynamic changes affect osmolarity

Answer 6

• Changes in blood volume and pressure have an effect on the response to changes in osmolarity
• ↓ in ECV
– set point is shifted to lower osmolarity values and
the slope of the relationship is steeper.
• When faced with circulatory collapse the kidneys continue to conserve H20 even though this will reduce osmolarity of body fluids.
• ↑in pressure the opposite occurs.
– the set point is shifted higher and slope decreases
• Volume is more important than osmolarity if volume crashes.
If circulating volume increased, effect of ADH is blunted. Osmolarity is climbing quit high - amount of ADH substantially less. Osmolarity is high to that overall volume doesnt rise any higher. Waiting for kidneys to sort out volume.
If volume is down. Osmolarity can go very low and ADH can sill be released where cv output is compromised eg burns, haemorrhage

Question 7

Describe the efferent pathway-thirst

Answer 7

• Large deficits in water (or increase in salt) only partially compensated for in the kidney
• Ingestion is the ultimate compensation
• Stimulated by an increase in fluid osmolarity (also by reduced ECF volume)
• Salt ingestion is the analogue of thirst • Drinking is induced by increases in plasma osmolarity or by decreases in ECF volume
• Thirst increases intake of free water
• Stop when sufficient fluid has been
consumed,
– metering mechanisms are unknown? • Salt appetite
– Hedonistic appetite
– Regulatory appetite (deficiency drives need)

Question 8

What happens in terms of ash release with increased water intake

Answer 8

• Affect of thirst is increased water intake
• The stimulus for thirst response requires significant increase in osmolarity or decrease in volume (<10% changes)

• Produced by neurosecretory cells in the hypothalamus but secreted from the posterior pituitary gland
• ADH small peptide 9 AA long
– Arginine vasopressin (AVP)
– Vasopressin
– Argipressin
• Acts on the kidney to regulate the volume and osmolarity of the urine
• ADH increases the permeability of the collecting duct to
– water – urea
• Low plasma ADH = diuresis
• High plasma ADH = anti-diuresis

Question 9

What is the difference between central dibetes insipidus and nephrogenic diabetes insipidus

Answer 9

• Central Diabetes insipidus results when plasma ADH levels are too low
– damage done to hypothalamus or
pituitary gland
– a brain injury, particularly a fracture of the base of the skull
– a tumour
– sarcoidosis or tuberculosis
– an aneurysm
– some forms of encephalitis or meningitis
– and the rare disease Langerhans cell histiocytosis

• Nephrogenic diabetes
insipidus from an acquired
insensitivity of the kidney to ADH

– In both water is inadequately
reabsorbed from the collecting ducts,
so a large quantity of urine is produced – managed clinically by ADH injections or
by ADH nasal spray treatments

Question 10

What is siADH

Answer 10

• Syndrome of inappropriate antidiuretic hormone secretion or SIADH • characterized by excessive release of ADH from the PP gland or another source • dilutional hyponatremia in which the plasma sodium levels are lowered and total body fluid is
increased

Question 11

How does ADH affect expression of aquaporin

Answer 11

• No ADH stimulation means no Aquaporin 2 in apical membrane, AQP 3 and 4 on basolateral membrane only of the latter DCT and Collecting ducts
• Limited water reuptake in latter DCT, and limited in collecting duct
• Tubular fluid rich in water passes through the hyperosmotic renal pyramid with no change in water content.
• Loss of large amount of hypo osmotic (dilute) urine
• diuresis

Question 12

What is the action of the thick ascending limb

Answer 12

Thick ascending limb of the loop of Henle - action crucial • Diluting action on the filtrate
– removes solute without water and therefore increases osmolarity of the interstitium
– Block NaK2Cl (NaKCC) transporters with a loop diuretic medullary interstitium becomes isosmotic
and copious dilute urine is produced

Question 13

Describe the permeability of the descending limb to water and Na+

Answer 13

• Descending limb of long LH is highly permeable to water due to AQP – 1 water channel which
are always open • Descending limb is not permeable to Na+, therefore, Na+ remains in the descending limb of
LH and filtrate concentration (osmolarity) increases • Maximum osmolality is at the tip of LH which is 1200 mOsm/Kg

Question 14

Describe the permeability of water ad salt in the ascending limb

Answer 14

• Ascending limb of LH actively transports NaCl out of tubular lumen into interstitial fluid
• Ascending limb is impermeable to H2O
• As NaCl leaves and H2O remains, osmolality decreases in the ascending limb of loop of
Henle
• Fluid entering the DCT has low osmolality of 100 mOsm/Kg
Concentrated to dilute luminal filtrate
• As Na+ is actively transported out of ascending limb of LH, concentration increases in the interstitial fluid surrounding the loop of Henle
• This increased concentration in the interstitial fluid achieved by loop of Henle is known as
Counter Current Multiplication

Question 15

Descrbe the osmotic gradient in the medulla interstitial fluid

Answer 15

• A large, vertical osmotic gradient is established in
the interstitial fluid of the medulla • Isotonic (300 mOsm/Kg) at corticomedullary
border • Medullary interstitium is hyperosmotic up to 1200
mOsm/Kg at papilla • Gradient of increasing osmolarity • Essential mechanism
– active NaCl transport in thick ascending limb – recycling of urea (effective osmole) – unusual arrangement of blood vessels in medulla
descending components in close opposition to
ascending components

Question 16

Describe urea reabsorption

Answer 16

Urea
• Hydrophilic and does not readily permeate artificial lipid bilayers.
• ‘ineffective osmole’ in the presenc of to urea transporters that facilitate urea diffusion across most cell membranes; • In the kidney “effective osmole”
• Reflection coefficient in the PCT is approximately 0.68, intermediate between that of a completely permeable solute, such as ethanol, and that of a completely impermeant solute
• if the membrane allows certain solutes to freely cross it, then these solutes are totally ‘ineffective’ at exerting an osmotic force across this membrane
• Urea reabsorption from medullary CD • Cortical CD cells are impermeable to urea
• Movement into interstitium and diffusion back in Loop
• Under the influence of ADH fractional excretion of urea decreases and urea re-cycling increases
Urea can move thru aqp channels, urea. Can come out of CD along with water into interstitium, accumulate there, acts as an osmolarity, contributes to conc of interstitium. Urea diffuses down into ascending limb, across DCT, into CD, if ADH present, can come back in. Contributing to hypotonicity

Question 17

Describe teh countercurrent multiplier

Answer 17

See slide

Question 18

Why can loop diuretics lead to hypokalaemia

Answer 18

Loop diuretics can cause hypokalaemia - ROMK channel - allowing K+ in to filtrate on apica cells. NKCC2 inhibited. But basolateral channel still working. Increase fluid movement thrupatient. Patient pee out volume, but volume will contain a lot of potassium

Question 19

What is the role of the vasa recta briefly

Answer 19

Concentration gradient is produced by the Loop of Henle acting as a
counter current multiplier.
• BUT it is Maintained by the vasa recta acting as a counter-current
exchanger…
Osmotic gradient created would not last long if osmoles were washed out of the interstitium
• Because flow in vasa recta is in opposite direction to fluid flow in the tubule the osmotic gradient is maintained. The vasa recta acts as a counter current exchanger…

Question 20

Explain the role of the vasa recta

Answer 20

• Blood flow in renal cortex is one of the highest per gram of any tissue in the body
• Blood flow through renal medulla is low (5-10% of total RPF)
• Compromise
– need to deliver nutrients
– need to maintain medullary hyper-tonicity
• Kidney uses a hair-pin configuration for vasa recta with entry and exit through the same region of the kidney
• Thus creating a counter current exchange mechanism
• Vasa recta has no capacity for active transport sp mimics environment
• Start with osmotic stratification in medullary interstitium
• ADH is present:
– counter current multiplier gives NaCl gradient
– Also cortex to papilla gradient of urea
– In presence of ADH
Blloodin vasa recta can mimic environment surrounding. As it ecsneds into medulla. Surrounded by an interstitium of increasing conc. blood in vasa recta mimics this - takes in salt until it is equal osmolarity
Vasa recta mops up all water that ascending limp spilling out, moves it up to cortex, to leave medulla concentrate.

Question 21

Summarise the vasa recta

Answer 21

Descending limb of vasa recta
• Isosmotic blood in vasa recta enters hyperosmotic milieu of the medulla ( high conc. Na+
ions, Cl- ions + urea) • Na+, Cl- + urea diffuse into the lumen of vasa recta • osmolarity of blood in vasa recta increases as it reaches tip of hairpin loop
Ascending limb of vasa recta
• Blood ascending towards cortex will have higher solute content than surrounding interstitium • Water moves in from the descending limb of the loop of Henle