Session 5: Control of Plasma Osmolarity Flashcards
What is the normal osmolality of ECF?
280-310 mOsm/kg
Roughly around 300 mOsm/kg
What is the osmolality of an isotonic fluid?
Roughly 300 mOsm/kg
What is the range of urine osmolality?
50-1200 mOsm/kg
What is the major cation of of the ECF?
Na+
What is usually the problem affecting plasma osmolality?
Water balance and not electrolytes.
Water is not isotonic but hypotonic.
What happens if you simply add water to plasma?
Water is hypotonic, this means that adding water causes the plasma to become hyposmotic. This leads to water wanting to move out of the ECF in the kidney and more diluted urine will be excreted.
Which class of nephron majorly allows the movement of water and can affect osmolality?
Juxtamedullary nephrons.
The osmolality of the protein-free blood plasma is determined by electrolytes. It is roughly 300 mOsmoles. The osmolality of the total volume of the blood plasma is 301 mOsmoles.
What is the force of that 1 mOsm called?
This is due to the pull of proteins which is called colloid osmotic pressure or oncotic pressure.
Briefly explain the concentration gradient of the nephron.
There is a vertical concentration gradient in the nephron where the osmotic gradient gradually increase as you go deeper into the kidney (cortex to medulla).
Why is the vertical concentration gradient of the nephron important?
Because it allows ADH to easily control the concentration of urine.
The collecting duct use the gradient along with hormone ADH to produce urine in varying concentrations.
What solute helps in the urine concentration mechanism?
Urea
What helps to maintain the osmotic gradient?
Vasa recta
What is the osmolality at the corticomedullary border?
Isotonic aka 300 mOsm/kg
Explain the thick ascending limb of the loop of Henle’s role in the medullary gradient.
The thick ascending limb is largely impermeable to water. This means that no water will move in this part of the kidney tubule.
It’s purpose is to remove solute without water. This leads to a hyposmotic filtrate and an increase in the osmolality of the interstitium. There are no aquaporins in this region of the tubule.
The channel responsible for the movement of ions in the thick ascending limb is NaKCC. This leads to ions moving into ICF to increase the osmolality. These ions then move into the interstitium.
Explain the action of loop diuretics like furosemide in regards to the medullary gradient.
Blocks the NaKCC transporter. This leads to no increase in osmolality of the interstitium and leaves the interstitium to be isosmotic. This means that a lot of dilute urine will be excreted.
Briefly explain what happens in the ascending limb.
Active transport of Na+ and Cl- from lumen to interstitium by NaKCC.
The ascending limb is impermeable to water.
NaCl leaves and water remains. Filtrate osmolality decreases.
Fluid entering the DCT will be hyposmotic compared to plasma.
Briefly explain what happens in the descending limb.
Highly permeable to water due to aquaporin channels which are always open.
The descending limb is impermeable to Na+ so Na+ will remain in the descending limb and osmolality of filtrate will increase.
What is the maximum osmolality of the tip of the loop of henle?
1200 mOsm/kg
What is the maximum difference in concentration gradient that can be achieved between the interstitium and the lumen?
200 mOsm/kg
Explain the counter current and its role in achieving the medullary gradient.
Active salt pump in the ascending limb establishes a 200 mOsm gradient at each horizontal level. The fluid flows forwards into the DCT a mass of 200 mOsm fluid exits into the DCT and a new mass of 300 mOsm fluid enters from the proximal tubule.
The ascending limb will the transport out more NaCl and the descending limb passive fluxes of water reestablish the 200 mOsm gradient. However this time the osmolality has increased but not the gradient.
The same thing happens where fluid flows forward several frames and the 200 mOsm gradient must be established once again.
The final vertical osmotic gradient is established and maintained by the ongoing countercurrent multiplication of the long loops of Henle.
Explain urea as an effective osmole
It is only an effective osmole in the kidneys where in the proximal tubule it can be taken up by a sodium-dependent urea transport on the apical membrane to go from the lumen into the tubular cells and then into the interstitium or the capillary.
The urea adds to the osmotic gradient.
Explain urea recycling in the nephron.
Urea is reabsorbed in the medullary collecting duct. Cortical CD cells are impermeable to urea so this only happens in the medullary part.
Urea then moves into the interstitium and diffuse back into loop of Henle.
Under the influence of ADH fractional excretion of urea decreases and urea is increasingly recycled instead.
The concentration gradient produced by the loop of henle act as a counter current multiplier. What maintains the concentration gradient?
Vasa recta
Explain the properties of the vasa recta that allows it to maintain the concentration gradient.
Capillaries are leaky because we need to supply the medullary kidney. But too high blood flow would quickly was out the concentration gradient.
This means that in the vasa recta there is:
Low flow to maintain the medullary hypertonicity.
The cells are endothelium with no active transport where movement in or out depends on passive diffusion.
Where can the vasa recta be found?
Only in the juxtamedullary nephrons running parallel to the loop of henle.
Describe the flow of the vasa recta.
Low rate of flow and its direction is also opposite to the flow of the tubular fluid.
Explain the movement of solutes and solvent in the descending vasa recta.
Runs along the ascending loop of henle.
This is highly impermeable to water so mainly solutes like Na+, Cl- and K+ will move from the thick ascending limb to the descending vasa recta as the concentration gradient in the interstitium is higher than the plasma. The slow flow allows Na+, Cl- and urea to diffuse into the vasa recta so it equilibrates at each stratified level.
This leads to the plasma of the descending vasa recta becoming increasingly hyperosmotic.
Explain the movement of solutes and solvents in the ascending vasa recta.
Runs alongside the descending limb of loop of Henle.
The descending limb is largely impermeable to Na+ and highly permeable to water.
This leads to a lot of water moving via aquaporin channels into the vasa recta as the plasma of the vasa recta has at this point been hyperosmotic as well compared to the interstitium.
Explain how osmolality can be regulated.
By osmoreceptors
Where can osmoreceptors be found?
Hypothalamus specifically in OVLT
They’re found on fenestrated leaky endothelium which is exposed directly to systemic circulation.
What do osmoreceptors sense?
Changes in plasma osmolarity.
What are the two responses of the osmoreceptors?
Altering concentration of urine by ADH
Regulating thirst sensation
Explain the regulation of osmolality.
Changes in plasma concentration by hypothalamic osmoreceptors.
This leads to ADH regulation and regulation of thirst.
ADH acts on the kidneys to regulate water excretion.
Thirst leads to water intake and increase in water.
What part of the osmoregulation pathway is activated first?
The ADH pathway.
When is the thirst sensation activated?
When there is a 10% increase in osmolality and the kidneys can’t keep up with the increase in osmolality.
What does an increase in osmolality do to ADH?
Increases ADH secretion
What does a decrease in osmolality do to ADH?
Decrease ADH secretion
Explain the response of ADH to haemodynamic changes.
Low BP due to low ECV. This does not have any change in osmolality as blood is lost (isosmotic).
Lower ECV also causes ADH to be released in order to retain the water in the body to not fall even lower.
The same goes for an increase in BP.
Volume is more important than osmolality if volume crashes.
Give examples of causes of too little ADH.
Central Diabetes insipidus
Nephrogenic diabetes insipidus
Explain central diabetes insipidus
Plasma ADH levels are too low
Damage done to hypothalamus or pituitary gland.
Leads to water be inadequately reabsorebed from the collecting ducts leading to large quantities of urine.
Causes of CDI
Brain injury like basilar skull fractures.
Tumour
Sarcoidosis or tuberculosis
Aneurysm
Encephalitis or meningitis
Explain nephrogenic diabetes insipidus
Acquired insensitivty of the kidney to ADH
Water is inadequately reabsorbed from the collecting ducts so a large quantity of urine is produced.
How is nephrogenic diabetes insipidus managed?
ADH injections
ADH nasal spray treatments
Give causes of too much ADH
Syndrome of inappropriate antidiuretic hormone secretion.
SIADH
Explain SIADH
Excessive release of ADH from the posterior pituitary gland or another source like small cell lung carcinoma.
Characterised by dilutional hyponatremia where sodium levels are lowered because the overall total body fluid increases.
Explain ADH role in the need to produce a hypotonic urine.
Decreased ADH levels leads to decreased aquaporin 2 on the apical membrane and the aquaporins on the basolateral membrane.
ADH limits the water reuptake from the DCT. More aquaporin would mean more water uptake since the filtrate at this time is hyposmotic. But downregulating the channels means that the water won’t be able to move into the interstitium quickly enough compared to the urine flow.
Large amounts of dilute urine is excreted.
Explain ADH role in need to produce a hyperosmotic urine.
ADH levels will increase and this leads to upregulation of aquaporin into the apical membrane. The basolateral membranes are already there and running and ADH only affects the apical membrane aquaporins in the collecting duct.
This allows rapid water movement from the collecting duct in its medullary region.
More concentrated urine is excreted aka lower volumes.
What is the main cause of hyponatraemia; actual low sodium or high water levels?
High water levels in 99% of the cases
What is a serum osmolality of 259 an indication of?
Not enough solute
or more likely
too much water
What is a urine osmolality of 522 an indication of?
Either too much sodium in the urine
or
more likely too little water
What can be used in order to assess whether the kidneys are doing their job?
The actual levels of sodium in the urine.
Test comes back and urine sodium is 81. This is increased.
What is the problem here?
That the kidneys are trying to reabsorb water even though there is a lot of salt.
What is the most probable diagnosis of this?
SIADH
Treatment of SIADH
Usually fluid restriction
Explain the acute symptoms of hyponatraemia.
Neurological sympomts like
Aggitation
Seizures
Nausea
Focal neurology or even coma
Does low sodium levels kill people?
Usually not. Hyponatraemia is usually a cause of something else. There are a lot of comorbidities which causes the the hyponatraemia and those are more likely to be fatal.
Explain the chronic symptoms of hyponatraemia.
Usually asymptomatic
Causes of hyponatraemia.
(Broadly)
True Na+ loss
Inbalane in ADH secretion
Drugs
Give causes of true Na+ loss
Diarrhoea and vomiting
Diuretics/Renal failure
Peritonitis
Burns
Causes of changes in ADH secretion
Heart failure
Kidney disease
Liver disease
Medication
Tumours like small cell lung carcinoma
Drugs that can cause hyponatraemia
Thiazide diuretics
SSRIs
PPIs
ACE inhibitors
Loop diuretics
Why is it important to not give Na+ too quickly to a hyponatraemic patient?
The brain will not be able to adjust to the new osmolality levels which can lead to central pontine myelinolysis or osmotic demyelination syndrome.
Why might the blood plasma still be hyperosmotic in hyponatraemia?
Because of hyperglycaemia
Causes of hyponatraemia when urine Na is <10mmol/L and patient is hypovolaemic.
GI/Skin loss
Causes of hyponatraemia when urine Na is <10mmol/L and patient is hypervolaemic.
Congenital cardiac failure
Nephrotic syndrome
Liver failure
Causes of hyponatraemia when urine Na is >20mmol/L and patient is hypovolaemic
Renal loss
Causes of hyponatraemia when urine Na is >20mmol/L and patient is euvolaemic
SIADH
Causes of hyponatraemia when urine Na is >20mmol/L and patient is hypervolaemic.
Renal failure
Main treatment of hyponatraemia
Fluid restriction
