Urinary: Physiology Flashcards
What are the sodium channels in the proximal tubule?
Na-H antiporter
Na-Glucose symporter
Na-AA co-transporter
Na-Pi
What are the sodium channels in the loop of henle?
NaKCC symporter
What are the sodium channels found in the early distal tubule?
NaCl symporter
What are the sodium channels found in the late distal tubule and collecting tubule?
ENaC (epithelial Na channels)
What are the histological features of the proximal tubule?
- Brush border
- Large outside diameter
- Lots of mitochondria (incredibly active)
What are the solutes transported in the 1st segment of the proximal tubule?
-Apical Na-H exchange Co-transport with glucose Co-transport with amino acid or carboxylic acids Co-transprt with phosphate
-Basolateral
3 Na-2K ATPase
NaHCO3- co transporter for acids and bases
- Aquaporin channels
- Chloride concentration increases
What are the solutes transported in the 2nd segment of the proximal tubule?
Basolateral
3Na-2K ATPase
Apical
Na+ is reabsorbed via Na-H exchanger
Paracellular and transcellular transport of Cl-
What is the overview of the function of the proximal collecting tube?
- Highly water permeable so bulk transport of water reabsorption
- Reabsorption is isosmotic with plasma
- Reabsorbs 65% water, 100% glucose and amino acids, 67% of sodium
- Driving force for reabsorption is osmotic gradient established by solute absorption, hydrostatic force in the interstitum, oncotic force in peritubular capillary due to loss of 20% filtrate at glomerulus but cells and proteins left in blood
What are the features of the thin descending limb?
- Lots of aqua porin channels
- No mitochondria
- Loose junctions
- No brush border
- Thin
- Flattened
- Passive in nature
What are the features of the thick segment of the ascending limb?
- Impermeable to water
- Many mitochondria
- No aqua porin
- Lots of active transport for sodium reabsorption
What is the function of the thick and thin descending limb?
- Paracellular reuptake of water due to increased intercellular concentrations of sodium
- Concentrates sodium and chloride ions in the lumen of the descending limb ready for active transport in the ascending
- Highly permeable to water due to AQP (1 channels always open)
- Impermebale to Na
What is the function of the thin ascending limb?
- Passive sodium reabsorption due the actions of the descending limb.
- Epethelium permits passive reabsorption by paracellular route
What is the function of the thick ascending limb?
- NKCC2 transrptoer that transports sodium, (2)chloride and potassium from lumen to cells
- Na+ ions move into the interstitum due to the action of 3Na-2K-ATPase
- ROMK channels move potassium from the cell into the lumen to allow the NKCC2 channels to work
What is the clinical significance of the thick ascending limb?
Sensitive to hypoxia due to the amount of energy use
Give an overview of the loop of henle reabsorption.
- Descending limb reabsorbs water and not NaCl
- Ascending limb reabsorbs NaCl but not water
- The tubule fluid leaving the loop is hypo-osmotic compared to plasma
Outline features of reabsorption in the distal convoluted tubule
- Hypo-osmotic fluid enters (100 mOsm/Kg)
- Active transport of 5-8% of Na+
- Water permeability is low
- Has 2 regions DCT1 and DCT1
What are the channels present in DCT1?
Apical
- NaCl enters across apical membrane via electro-neutral NCC transporter
- NCC transporter is sensitive to thiazides diuretics
Basolateral
-3Na-2K-ATPase
What are the channels present in the distal convoluted tubule 2?
Apical
- Na+ enter via ENaC
- NaCL enters by the NCC
Basolateral
- 3Na-2K-ATPase
- KCC4
Which channels are affected by amiloride diuretics?
ENaC channels
What detects changes in plasma osmolarity?
Hypothalmic osmoreceptors
What are the 2 efferent pathways to regulate plasma osmolarity and their effect?
- ADH: Acts on the kidney to control renal water excretion
- Thirst: Trigger brain for drinking behaviour to cause an effect on the water intake
Where are osmoeceptors found?
- Located in the OVLT of the hypothalamus.
- Leaky endothelium is exposed directly to the systemic circulation to sense the changes in plasma osmolarity
What physiologically inhibits ADH?
-Decreased osmolarity inhibits ADH
What happens to the osmotic and haemodynamic relationship in circulatory collapse?
- Kidney continues to conserve H2O even though this will reduce osmolarity of body fluids
- Volume is more important than osmolarity if volume crashes
Describe the efferent pathway of thirst?
- Stimulated by an increase in fluid osmolarity
- Salt ingestion is the analogue of thirst
- Large deficits in water only partially compensated for in the kidney and ingestion is the ultimate compensation.
- Stop when sufficient fluid has been consumed
What is central diabetes insipidus?
- Plasma ADH levels are too low
- Damage done to the hypothalamus or pituitary gland
- Brain injury
What is nephrogenic diabetes insipidus?
-Acquired insensitivity of the kidney to ADH
How are problems with ADH secretion managed?
- In both water is inadequately reabsorbed so a large quantity of urine is produced
- Managed clinically by ADH injections or by ADH nasal spray
What is SIADH?
Syndrome of inappropriate ADH secretion
- Characterised by excessive release of ADH from posterior pituitary gland or another source
- Dilutional hyponatraemia in which the plasma sodium levels are lowered and total body fluid is increased
What happens to the aqua porin channels when plasma osmolarity decreases?
- No ADH stimulation
- No stimulation of Aqua porin 2 in apical membrane
- AQP3 and 4 on basolateral membrane only of the latter DCT and collecting ducts and act as an exit for water entering AQP2
- Limited water reuptake in latter DCT and collecting duct
- Loss of large amount of hypo osmotic urine
- Diuresis
What happens to the aqua porin channels when plasma osmolarity increases?
- Release of ADH causes the insertion of AQP2 channels into the apical membrane
- Water moves out of the collection duct into hyper osmotic environment if there are AQP in both the apical and the basolateral epithelium of the tubule cells
What is the range for the vertical osmotic gradient in the kidney?
- 300 mOsm/kg at corticomedullary border
- 1200 mOsm/kg in medullary interstitum at papilla
What are the essential mechanisms to maintain the vertical osmotic gradient?
- Active NaCl transport in thick ascending limb
- Recycling of urea (effective osmole)
- Unusual arrangement o blood vessels in medulla descending components in close opposition to ascending components
Why is urea an effective osmole?
- Doesnt cross the membrane easily
- Urea reabsorption from medullary collecting duct
- Cortical collecting duct cells are impermeable to urea
- Movement into interstitum and diffusion back in Loop
- Under the influence of ADH fraction excretion of urea decreasing and urea re-cylcing increases
How does the vasa recta maintain the concentration gradient?
Flow in vasa recta is in the opposite redirection to fluid flow in the tube, the osmotic gradient is maintained. Vasa recta acts as a counter current exchanger.
Vasa recta can actively transport. True/False
False
What happens in the descending limb of the vasa recta?
- Isoosmotic blood in vasa recta enter hyper osmotic medullary region
- Na+,Cl- and urea diffuse into the lumen of vasa recta
- Osmolarity of the blood in vasa recta increases as it reaches tip of hairpin loop
Why is blood flow in the vasa recta slow?
Blood flow is compromised to :
- Deliver nutrients
- Maintain medulaary hyper tonicity
How does the shape of the vasa recta and loop of henle allow for the courter current exchange?
-Both hairpin configurations
What happens in the ascending limb of vasa recta?
- Blood ascending towards cortex will have higher solute content than surround interstitum
- Water moves in from the descending limb of the loop of henle
What is a diuretic?
A substance that promotes a diuresis by increase in renal excretion of water and sodium to reduce ECF volume
When are diuretic used clinically?
Conditions where sodium and water retention cause expansion of ECF volume
What is the effect of diuretics reducing ENaC activity on K+ secretion?
Reduction of K+ secretion
How do Diuretic work? (4 ways)
- Direction action on cell to block Na+ transporters in luminal membrane (Loop diuretic, Thiazide Diuretics, K+ sparing diuretics)
- By antagonising the action of aldosterone
- By modification of filtrate content
- By inhibiting activity of enzyme carbonic anhydrase
How do loop diuretics work?
- Block apical NKCC transporter
- Na and Cl not absorbed so medullary tonicity is less
- This reduces water reabsorption further down the tubule
- Leads to Na+ and water loss
Very potent diuretics
What are the effect of loop diuretics in heart failure?
Used in heart failure for treatment of symptoms
- Diuretic effect
- Vaso and veno dilation to decreased after load/preload
- Reduces symptoms but no effect on reducing mortality
What is given in acute pulmonary oedema?
-IV Furosemide
When are loop diuretics used?
- Heart failure
- Nephrotic syndrome
- Renal failure
- Cirrhosis of liver
- Hyper calcaemia
What are the effect of loop diuretics on calcium absorption?
Blockage of the NKCC channels:
- Impairs calcium reabsorption as lumen positive potential isn’t created by K+ drifting into the lumen
- More calcium is exerted in urine
- Furosemide given together with IV fluids
What are the effects of Thiazide diuretics?
- Secreted into lumen in PCT
- Block Na-Cl transporter in DCT
- Travel downstream to act at DCT
- Increase Na+ loss in urine
- Reduces Ca2+ loss in urine
When are thiazide diuretics used?
-Widely used in hypertension
ineffective in renal failure as less potent compared to loop diuretics
What are the side effects of thiazide diuretics?
- Higher incidence of hypokalaemia
- Impotence
- Gout
What are the type of K+ sparing diuretics?
Act on late distal tubule and collecting duct
- Inhibitors of ENaC (amiloride)
- Aldosterone antagonists (spironolactone)
What are the mechanism of action for potassium sparing diuretics?
- Reduces ENaC activity directly or indirectly
- Reduce loss of K+
- Both can produce life threatening hyperkalaemia especially if used with ACE inhibitors, K+ supplement or in patients with renal impairment
- Both are mild diuretics affecting only 2% of Na+ reabsorption
What are the non diuretic situations that feature the use of aldosterone antagonists?
- Reduction of mortality in heart failure (used in the long term treatment of heart failure)
- Preferred duct for ascites and oedema in cirrhosis
- Used as additional therapy in hypertension if other treatment aren’t effective
- Treatment of hypertension in Conn’s syndrome
What are ENaC blockers like amiloride used in combination with?
K+ losing diuretics
How can diuretics contribute to hypokalaemia?
- Diuretics may lead to reduced circulatory volume
- Activtion of RAAS
- Increase in Aldosterone secretion
- Increase in Na+ absorption and K+ secretion
- Hypokalaemia
How can K+ sparing diuretic cause hyperkalemia?
- Reduction in Na+ reabsorption
- Reduces potassium loss in urine as negative potential for movement of potassium isn’t created
- Hyperkalaemia
What is the reason for use of loop/thiazide diuretics and a K+ sparing diuretic in combination?
-Used to minimise changes in potassium
Thiazide/Loop diuretics can be used with only potassium supplements if necessary
What should be avoided with use of K+ sparing diuretics?
- Potassium supplement
- Impaired renal function
- Increase in risk of hyperkalaemia
Concomitant use with ACEI/ARB - regular K+ monitoring required
What is activated in nephrotic syndrome?
- Reduced circulatory volume
- RAAS activated
- Na+ and water retention
- Expansion of ECF
- More oedema
What are the adverse effects of diuretics?
- Potassium abnormalities
- Hypovolaemia especially in loop diuretic
- Hyponatraemia
- Increase in uric acid levels in blood (with Thiazides, Loop Diuretics) can precipitate attack of gout
- Metabolic effects (glucose intolerance, LDL levels)
- Thiazides (erectile dysfunction)
- Spironolactone causes gynaecomastia
How do carbonic anhydrase inhibitors work?
- Inhibits action of carbonic anhydrase in brush border and PCT cells
- Loss of HCO3- so osmolarity of lumen increases
- Can cause metabolic acidosis due to loss of HCO3- in urine
Which condition in the eye are carbonic anhydrase inhibitors useful to treat?
- Useful in the treatment of Glaucoma
- Reduces formation of aqueous humour in the eye by about 50%
What is the mechanism for osmotic diuretics?
- Acts by altering the osmolarity to affect renal water absorption
- Small inert molecule increase the plasma osmolarity thus drawing out fluid from tissues and cells
- Osmolarity of the filtrate in increased in the kidney
- Loss of water, Na+ and K+ in the urine
- Doesn’t inhibit enzymes or transport proteins
What are other substances with diuretic action?
- Alcohol (inhibits ADH release)
- Coffee (increase GFr and decreases Na+ reabsorption)
- Drugs that inhibit action of ADH on collecting ducts
What are some diseases causing diuresis?
- Diabetes Mellitus
- Cranial Diabetes Insipidus
- Nephrogenic Diabetes insipidus
- Psychogenic polydipsia
