Lecture 4.1: Control of Osmolarity Flashcards
What is Osmolarity?
Concentration of osmotically active
particles in a solution
What Osmolarity of Extracellular Fluid determined by? What ion accounts most of ECF osmolarity?
- Determined by the total concentration
of solutes that cannot cross cell membranes - Na+ accounts for 90% of the ECF
osmolarity - Urea = An ‘ineffective osmole’
Plasma Osmolarity (Equation)
2 Na (mEq/L) + (Urea [mg/dL])/2.8 + (Glucose [mg/dL])/18
What are 4 Starling’s Forces?
- Hydrostatic pressure in the capillary
(Pc) - Hydrostatic pressure in the interstitium
(Pi) - Oncotic pressure in the capillary (pc )
- Oncotic pressure in the interstitium (pi )
How does [Na+] determines ECF volume?
Slide 6
Controlling Osmolarity: ECF is Hypertonic
- Respond if the ECF is hypertonic by
conserving water (thereby producing
concentrated urine) achieved by
release of vasopressin to promote anti-
diuresis - Another response is the stimulation of
thirst
Controlling Osmolarity: ECF is Hypotonic
Excrete water to produce dilute urine (diuresis) and restore ECF osmolarity
What is amount of water reabsorbed
from the tubular fluid is dependent on?
The permeability of the epithelial cells lining the connecting tubule and collecting duct
What is Arginine vasopressin?
- Peptide hormone released from
posterior pituitary - Release controlled by osmoreceptors
in hypothalamus - Also called antidiuretic hormone
What is the Action of Antidiuretics?
- An antidiuretic is a substance that
helps to control fluid balance in an
animal’s body by reducing urination,
opposing diuresis - Increased water uptake from kidneys
Vasopressin and AQP2
- Vasopressin stimulates the exocytic
insertion of aquaporin-2 (AQP2)
channels into the luminal membranes
of the principal cells of the connecting
tubule and collecting duct - When vasopressin is released,
aquaporin 2 (AQP2) channels are
inserted into the apical
membranes of the cuboidal
epithelium in the connecting
tubules and the collecting ducts
Where is AQP1 found? Function?
- Kidney (apically)
- PCT
- PST
- tDLH
- Water Absorption
Where is AQP2 found? Function?
- Kidney (apically)
- ICT
- CCT
- OMCD
- IMCD
- Water Reabsorption in response to
arginine vasopressin
Where is AQP3 found? Function?
- Kidney (basolaterally)
- Medullary Collecting Duct
- Water Reabsorption and glycerol
permeability
Where is AQP4 found? Function?
- Kidney (basolaterally)
- Medullary Collecting Duct
- Water Absorption
Via what AQPs does water enter and leave the cells of the kidney?
- Water can then enter the cells via
the AQP2 channels - And water can exit the cell through
AQP3 and AQP4 channels (which are
constitutively-expressed in the
basolateral membrane)
What happens to AQP2 is vasopressin is removed?
- With the removal of vasopressin, the
AQP2 channel is retrieved from the
apical membrane by endocytosis
What does the basolateral membrane
always contain?
- The basolateral membrane always
contains AQP-3 &4, and so is always
permeable to water - Any water that enters across the apical
membrane is thus able to pass into the
peritubular capillaries
Mechanism for Detection of Plasma Osmolarity
Hypothalamic osmoreceptors present in the supraoptic nuclei (SON) and organum vasculosum of the lamina terminalis (OVLT) of the hypothalamus detects increases in ECF osmolarity to induce thirst
What happens to Mechanism for Detection of Plasma Osmolarity if BBB is disturbed?
- The lack of a normal blood-brain barrier
in the subfornical organ (SFO) and OVLT allows
direct exposure of neurones to blood plasma - Elevations of 1-2% above normal plasma
osmolarity levels, cause the cell bodies of the
osmoreceptors to shrink, and fire an action
potential
What are Hypothalamic osmoreceptors stimulated by?
Hypertonic plasma
Cycle of Vasopressin Release (6 rough steps)
- Hypothalamic osmoreceptors are stimulated by
hypertonic plasma - Which makes the hypothalmic osmoreceptors
shrink - Mechanical stretch TRPV cation channels are
activated - Allows the influx of positive charges from the
ECF and consequent cell depolarisation - Action potentials fire to the posterior pituitary
causing release of preformed vasopressin - Osmoreceptors can also stimulate thirst to
induce a behavioural response to drink and
replace water
How is osmolarity primarily regulated?
Primarily regulated by adjusting output/urine production
What neurones produce vaspressin? Where is it contained?
- Vasopressin is produced by neurones located in
the supraoptic and paraventricular
nuclei of the hypothalamus - Vasopressin contained within secretory vesicles
Vasopressin regulates the permeability
of the……..to water
Collecting Duct
Production of DILUTE Urine
- Production of dilute urine involves the
active removal of solute from the.
tubular fluid (e.g. via the NaK2Cl co-
transporters) - This occurs in the thick ascending limb
(TAL) of the Loop of Henle - The TAL dilutes the filtrate leaving the
loop of Henle tubular fluid in TAL - Tubular fluid is further diluted in by
reabsorption of Na+in the DCT
Osmolarity of the Renal Medulla (outer to inner)
- The osmolarity of the interstitial fluid in
the renal medulla increases from the
outer renal medulla to the inner renal
medulla - Reaching 1200 mosm/l in the inner
renal medulla
What does high osmolarity mean?
Means you have more particles in your serum
What does low osmolarity mean?
Means the particles are more diluted
How is hypertonicity created in the renal
medulla? (2 Mechanisms)
- Accumulation of solutes in the ISF of
the renal medulla is required
1) Countercurrent multiplication in loop
of Henle (the ‘countercurrent.
arrangement’ of the descending and
ascending limbs, and the differential
permeability of these two limbs to
water and ions)
2) Accumulation of urea in the renal
medulla interstitium by recycling urea
from the collecting duct
What is the Descending Limb of the Loop of Henle permeable to?
- Water via AQP1
- Impermeable to solutes
What is the Thick Ascending Limb of the Loop of Henle permeable to?
- Impermeable to water
- Actively transfers solute from the tubular
lumen to the interstitial fluid via the Na+
/K+/2Cl- co-transporter
Blockade of the NaK2Cl co-transporters with ‘loop diuretics’, causes…?
The medullary interstitium to become isosmotic, and copious dilute urine is produced
Ascending limb of LoH: What is the effect of gain of NaCl in the medullary interstitial fluid on osmotic pressure?
- The gain of NaCl in the medullary interstitium
raises the osmotic pressure in the interstitium * While the osmotic pressure in the ascending
limb decreases
What happens to water in the descending tubule of LoH? Osmotic Pressure?
- Water flows out of the descending tubule by
osmosis - Thus osmotic pressure is raised in the to 400
mOsm/L
Fresh tubular fluid enters….?
From the PCT, pushing the newly-concentrated fluid (400 mOsm/L) towards the tip of the loop, and into the ascending limb
What transporters re-establishes a 200mosm/l gradient between the ascending limb and the interstitium?
The NaK2Cl pump
More concentrated tubular fluid in the thick ascending limb (TAL), allows the interstitum osmolarity to rise to…?
500 mosm/l
