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Name the main segments in the nephron responsible for salt and water exchange.
- There are four main segments responsible for salt and water exchange in the nephron:
- - Proximal Convoluted Tubule
- - Thick Ascending Loop of Henle
- - Distal Convoluted Tubule
- - Cortical Collecting Tubule
The main site of action of thiazide diretics is Distal Convoluted Tubule. True of False?
True. Thiazide diuretics act in the Distal Convoluted Tubule.
The main site of action of K-sparing diuretics is in the Proximal Convoluted Tubule. True of False?
- False. The main site of action K-sparing diuretics is in the Cortical Collecting Tubule.
- Carbonic Anhydrase Inhibtors (Acteazolamide) act in the Proximal Convoluted Tubule.
Thick Ascending Loop of Henle is the main site of action for loop diuretics. True or False?
True. The main site of action of the loop diuretics is in the Thick Ascending Loop of Henle.
Name three drugs that directly act on reabsorption of NaCl in the Proximal Convoluted Tubule.
Currently there is no drug directly affecting absorption of Na Cl in the PCT.
What substances are reabsorbed in the Proximal Convoluted Tubule?
- - Amino acids;
- - Glucose;
- - Numerous kations;
- - NaCl;
- - NaHCO3;
- - Weak acids (!uric acid)
What is the main site of reabsorption of Na?
The main site of Na reabsorption is the Proximal Convoluted Tubule. 60-70% of Na is reabsorbed in the PCT.
For unknown rasons Acetazolamide is highly specific for blocking Carbonic Anhydrase in the brush border of the Proximal Convoluted Tubule. True or False?
False. Acetazolamide blocks Carbonic Anhydrase in ALL tissues of the body.
What is the action of Acetazolamide in the eye and in the brain?
Acetazolamide causes decrease in the production of intraocular fluid by ciliary body and CSF by choroid plexus. This is caused throught the decrease of HCO3 absorptioin following blocking of Carbonic Anhydrase.
How Acetazolamide can be dangerous in liver failure?
In liver failre ammonia is excreted in the form of ammonia ion. Carbonic Anhydrase inhibitors cause alcalinisation of urine. This prevents formation ammonia ion from ammonia, which causes retention of ammonia in the body leading to worening of hepatic encephalopathy.
Mg and Ca are transported intor the cells of the Thick Aascending Loop of Henle via Ca/Mg co-transporter. True or False?
False. Ca and Mg ions are transported in the medullar interstitium though the intercellular gaps as a result of excessive positive charge within the tubule created by K as it is pumped out of the cell via K-selective channel in an attempt to rectify the change in intracellular polarity.
What is the mechanism of action of loop diuretics?
Loop diuretics act by blocking NKCC2 (NaK2Cl) pump, thus preventing reabsorption of NaCl.
Do loop diuretic have any effect on lungs?
Loop diuretics have potent vasodilating action on the vasculature of the lungs. the mechanism is unknown.
How NSAIDS affect use of loop diuretics?
Prostagandins are important in maintaining of glomerular filatration. NSAIDS inhibit synthesis of prostaglandins. This can affect the action of loop diuretics.
What are toxic effects of loop diuretics?
- The more important adverse efects are:
- - Ototooxicity;
- - Allergy (through the sulphonamide group);
- - Hypokalaemic alkalosis.
What is the mechanism of hypokalaemic alkalosis as a side efect of loop diuretics use?
As a result of NKCC2 block, large amiunts of Na presented in the Cortical Collecting Tubule. In an attempt to prevent large quantities of Na being excreted, the kidneys secrete K. This may be associated with loss of protons (H ions), which results in hypokalaemic alkalosis.
What proportion of Na that is reabsorbed in the various parts of nephron?
- PCT 60-70%;
- TAL 10-20%;
- DCT 5-8%;
- CCT 2-5%.
How Ca ions are transported in the Distal Convoluted Tubule?
The Ca ions absorption from the tubular lumen is governed by PTH and transport from the cell back into blood is done via Na Ca exchanger pump.
When using tiazide duretics, the maximal blood pressure lowering efect is acheived at doses higher than maximal diuretic doses. True or False?
False. The maximal blood pressure effect is acheved at lower doses than maximal diuretic effect.
What s common between loop diuretics, prostaglandin and thiazide diuretics.
Prostaglandin lowers efficacy of both loop and thiazide diuretics.
What ions Thiaside diuretics remove from the urine?
- - Na via Na Cl co-transporter;
- - Ca through the action of PTH
How Thiazide diuretics can be utilized in a patient with renal stones?
Thiazide diuretics remove Ca from the urine (mechanism governed by PTH), this effect can be used in the patient with Ca stones. The increase in Ca reabsorption is a result of decease of intracellular Na concentration caused by the use of Thiazide diuretuics as they block NCC (which decreases i ntracellular Na concentration).
What is the duration of action of Thiazide diuretics?
The duration of action of Thiazide diuretics is 6-12h, compared to up to 4h for Loop diuretics.
How K is reabsorbed from the lumen in the Distal Convoluted Tubule?
K is not transported from the lumen of DCT.
Ca and Mg ions are reabsorbed in DCT via potential driven luminal gradient created by K. True or False?
False. There is no K driven gradient in the lumen of DCT. Instead Ca is actively reabsorbed by Ca channel regulated by PTH.
Distal Convoluted Tubule is partly permeable to water. True or False?
False. DCT is impermeabe to water.
Concentration of urine gradually increases in the Distal Convoluted Tubue. True or False?
False. Concentration of urine in DCT is further decreased due to reabsorption of Na and Ca ions.
What are the mechanisms drving Ca into interstitium from the cells in the Distal Convoluted Tubule?
Ca transported by CaHATPase and CNX.
What is the mechanism behind loop and thiazide diuretic induced hypokalaemia?
By blocking Na reabsorption the diuretics increase in traluminal concentration of Na. when such highly cncentrated urine is presented at CCT, Na is actively reabsorbed with some K having to be exchanged for Na whch leads to hypokalaemia.
12-15% of Na is reabsorbed in the Cortical Collecting Tubule. True or False?
False. Only 2-5% of Na is reabsorbed in CCT.
What are adverse effects of Frusemide?
- - Hyookalaemia;
- - Hypomagnesaemia;
- - Hyponatraemia;
- - Ototoxicity;
- - Hypokalaemia metabolic alcalosis;
- - Skin reaactions, allergies;
How does Frusemide work?
Frusemide works by selectively blocking NKCC2 pump in the TAL preventing reabsorption of Na.
What is the mechanis of action behind thiazide diuretics?
Thiazide diuretics act through blocking NCC cotransporter in the DCT thus preventing reabsorption of NaCl from the lumen.
Name adverse effecs of thiazide diuretics.
- - HypoKalaemia;
- - Hypokalaemic metabolic acidosis;
- - HypoNatraemia;
- - Allergic reactions (sulpha group);
- - Carbohydrate intolerance;
- - Hyperlipidaemia;
- - HypoCalcaemia.
Is use of loop diuretics justified in hypercalcaemia?
Loop diuretics decrease transport of K ions from the cell into the lumen as a consequence of selective blockade of NKCC2. This decreases potential-driven transport of Ca and Mg ions into interstitium resulting in decrease in blood Ca level.
How loop diuretics can cause hypocalcaemia?
Loop diuretics block NKCC2. This decreases function of K-selective channels in the cell that pump K out of the cell into the lumen. Normally this results in the excessive positive charge in the lumen which causes potental driven movement of Ca and Mg into interstitium. Thus loop diuretics promote Ca and Mg loss in the urine.
Whch parts of the nephron are permeable to water?
PCT and descending part of the LoH. Normally CCT is not permeable to water, but in presence of ADH it becomes water permeable.
How does ADH changes permeability of the CCT to water?
Under the influence of ADH water permeable pores, called aquaporine are inserted in the mmbrane of the cell on the luminal side enabling water permeability.
Which parts of the nephron are not premeable to water?
Ascending part of LoH, the DCT and the CCT. The water permeability of the CCT changes in the presence of ADH, when it becomes permeable to water.
Which parts of the nephron Mannitol is active in?
Mannitol is active in the PCT and descending part of the LoH. It is also active in the CCT where it can oppose actions of ADH.
What are adverse effecs of Mannitol?
- - Hyperkalaemia;
- - Hyonatraemia;
- - Extracellular volume expansion;
- - Severe dehydration.
How Mannitol causes hypokalaemia?
Being hyperoslmolar substance, Mannitol leads to osmotic dehydration of cells with increase in intracellular K, which is eventually moved out of the cell, causing hyperkalaemia.