Session 3 Flashcards
What does the vasa recta do
Absorb nutrients and solutes
Corticopapillary gradient is established by
Countercurrent multiplication (solutes)
Urea recycling
Corticopapillary gradient is maintained by
Vasa recta
What happens as you go down the descending limb of loop of henle
Increase in solute concentration, decrease in osmolality
The loop of Henle over view
- Responsible for 25% Na+ reabsorption
- Thin descending limb: permeable to water, Na+ and Cl-
- Thin ascending limb: impermeable to water, minimal Na+ and Cl- transport
- Thick ascending limb: impermeable to water, Na+K+2Cl- co transporter apical membrane
What happens at thick ascending limb for concentrated urine
Na+ pumped out
Osmolarity increases in interstitium due to gain of sodium
Osmolarity decreases in thick ascending limb due to loss of sodium
What happens as a result of sodium being pumped out of thick ascending limb
Filtrate in descending limb must equilibrate until osmolarity is same inside and outside
Water leaves LOH and Na+ and Cl- enter - tubular fluid becomes more concentrated
Overall result of loop of henle countercurrent multiplication
Vasa recta plasma descends in opposite direction to tubule
Always has lower osmolality
Always diffusion gradient from tubule to interstitium and interstitium to plasma
Thick ascending limb of Loop of Henle can maintain a difference of
200mOsm/kg between interstitium and tubular fluid
Loop of Henle normal plasma osmolality
300mOsm/kg
Maximum osmolality of interstitium
1400mOsm/kg
Fluid leaving LOH is
Hypotonic (100mOsm/kg)
5 features of vasa recta
- Hairpin arrangement- permeable to solutes and water
- Descend: absorb solutes, water lost
- Ascend: loss of solutes, reabsorb water
- Slow flow: can equilibrate at each stratification level and minimise washout
- Absorbs water released from CD in presence of ADH (maintains high osmolality of interstitium)
What does urea recycling do
Help to maintain the medullary hypertonicity
How much urea is reabsorbed in proximal convoluted tubule
50% filtered urea re absorbed
What happens to tubular concentration of urea as it goes from medulla into lumen in descending limb
Increases as it diffuses down concentration gradient (110% at base of LOH)
What happens to urea at ascending limb
Ascending limb and early DCT impermeable to urea to concentration increases as solutes and water reabsorbed
ADH causes
Urea transporter UT1 to increase expression. Urea flows down conc grad. 70% filtered urea reabsorbed by UT1 and 40% excreted
How is urea recycled
Urea secreted back into LOH and goes back up to DCT/CD and is recycled
What do diuretics do
Act on the kidney to increase the production of urine and to eliminate water from the body
3 main things diuretics do as a result of eliminating water
- Reduce plasma volume and cardiac output
- Reduce blood pressure
- Reduce oedema/ascites
What are diuretics
Drugs that increase renal excretion of sodium and water resulting in increase in urine volume
What is diuresis
Process of excretion of water in the urine
What is Natriuresis
Process of excretion of sodium in the urine
5 main classes of diuretics
- Carbonic anhydrase inhibitors
- Osmotic diuretics
- Loop diuretics
- Potassium sparing diuretics
- Thiazide and thiazide-like diuretics
How do most diuretics act
By interfering with the normal sodium reabsorption by the renal tubules resulting in Na+ and water excretion
Which diuretics act at proximal tubule
Carbonic anhydrase inhibitors
Amiloride a little bit
SGLT-2 inhibitors (not diuretics)
Which diuretics act at ascending limb of loop of Henle
Loop diuretivcs
Which diuretics act at distal convoluted tubule/ early collecting duct
Thiazide and thiazide-like diuretics
(Amiloride)
Which diuretics act at collecting duct
Potassium sparing diuretics
How do carbonic anhydrase inhibitors work
Proximal tubule, stop bicarbonate being converted into water and carbon dioxide, this inhibits sodium transport out
What do SGLT-2 inhibitors (Flozins) do
Reduce Na+ absorption in PCT
Osmotic diuretics key points
Mannitol- administered via IV
Increase water excretion with relatively little effect on Na+ (water diuresis)
Effects of osmotic diuretics
Expands the extracellular fluid volume initially, decrease blood viscosity, inhibit renin release, increase renal blood flow
Uses of osmotic diuretics
Acute renal failure due to shock or trauma
Acute drug poisoning- need to eliminate drugs that are reabsorbed from renal tubules
To lower intracranial and intra ocular pressure before ophthalmic or brain procedures
Side effects of osmotic diuretics
What do loop diuretics work on
Prevent Na+K+2CL- transporter, reduce resorption of magnesium and calcium too
What are the most potent diuretics (high ceiling)
Loop diuretics- bumetanide and Furosemine
Key points of loop diuretics
Given orally or IV
Fast onset of action
Increase urine volume
Suitable for emergency situations
When are loop diuretics useful
- Severe oedema associated with congestive heat failure, nephrotic syndrome
- Treatment for Oliguric ARF
- Treatment of hypercalcaemia
- Acute pulmonary oedema
- Acute hyperkalaemia, hypercalcaemia
- Toxicity of Br, F, and I
Side effects of loop diuretics
- Hypovolemia
- Hyponatraemia (decreased blood Na+)
- Hypokaemia (decreased blood K+)
- Hypomagnasemia
- Hypocalcae,is
- Metabolic alkalosis
- Postural hypotension
What can be done to reduce the side effect of hypokalemia with loop diuretics
Dietary K supplementation or K sparing diuretics should be used to avoid hypokalemia
How so thiazide and thiazide like diuretics work
Stop the Na+ Cl- transporter
Helps reabsorb calcium
Uses of thiazide and thiazide like diuretics
1st line antihypertensive (Bendroflumethiazide, Indapamide)
Used for treatment of :
- Essential hypertension
- Mild heart failure
- Calcimu nephrolithiasis due to hypercalciuria
- Osteoporosis
- Nephrogenic diabetes insipidus polyuria
Excretion and absorption affected by thiazide
Increase urinary excretion of: NaCl, K, Mg
Increase absorption of: calcium
Decrease excretion of: Uric acid, urinary calcium
What usually happens with aldosterone at the collecting duct
Binds to receptor
Causes increased expression of ENAC and ROMK
Get more reabsorption of sodium, greater loss of potassium
What do potassium sparing diuretics do and where do they work
Block the potassium channels so inhibits ROMK
Late DCT/CD
What do aldosterone antagonists do and where do they work
Stop aldosterone being released, reduces ENAC
Late DCT/CD
Why might you give loop diuretic at the same time as potassium sparing/aldosterone antagonist
Ensure not too much Potassium is lost
Example of potassium sparing
Amiloride
Example of aldosterone antagonists
Spironolactone
What do potassium sparing and aldosterone antagonist diuretics do
Increase urinary sodium excretion
Decrease urinary potassium excretion
Decrease H+ excretion
Uses of potassium sparing and aldosterone antagonists
Secondary hyperaldosteronism
CHF, hepatic cirrhosis, nephrotic syndrome
Treatment of hypertension (combined with thiazide or loop diuretics to correct for hypokalemia)
Potassium sparing and aldosterone antagonists are contraindicated in
Hyperkalaemia (as in chronic renal failure, K+ supplementation, Beta blockers or ACE inhibitors needed)
Liver disease (dose adjustment needed)
