Renal

Question 1

Generalized resorptive defect in PCT

Answer 1

Fanconi syndrome

Question 2

hypokalemia
hypochloremia
metabolic alkalosis
normotension
elevated plasma renin level

Answer 2

Bartter syndrome

Question 3

Bartter pathophys

Answer 3

mutation involving the Na+/K+/Cl- cotransporter (NKCC2) results in salt and water loss resulting in
activation of the renin-angiotensin-aldosterone system secondary to volume depletion

renal vasoconstriction due to angiotensin II and hypokalemia leads to an increase in prostaglandin E (PGE)

Question 4

Bartter symptoms

Answer 4

failure to thrive
increased thirst
polyuria
polydipsia
vomiting

Question 5

Hypophosphatemia
Aminoaciduria
Renal glucosuria
Tubular proteinuria
Proximal renal tubular acidosis

Answer 5

Fanconi syndrome

Question 6

Autosomal recessive mutation involving the Na+Cl- cotransporter

Answer 6

Gitelman syndrome

Question 7

Gitelman symptoms

Answer 7

Hypokalemia
Hypochloremia
Metabolic alkalosis
Hypomagnesemia
Hypocalciuria
Normotension

Question 8

Hypercalciuria in Barttter. T/F?

Explain

Answer 8

True

Question 9

Where do loop diuretics work?

Answer 9

Inhibit Na+-K+2CI- channel in the thick ascending limb of loop of Henle.
By preventing Na+ and K+ reabsorption into the renal mediilla, they abolish the hypertonicity of the medulla (so urine cannot be concentrated in the collecting ducts). This results in marked diuresis.
They also increase Ca2+ excretion because they reduce the lumen positive potential in the loop of Henle

Question 10

Where do thiazide diuretics work

Answer 10

Inhibit Na+-Cl~ symporter, thereby blocking Na+ and Cl- reabsorption in the distal convoluted tubule. NaCl is excreted along with water into the urine. They also increase Ca2+ reabsorption.

Question 11

Spironolactone vs triamterene and amiloride

Answer 11

Spironolactone: Competitive antagonist at the aldosterone receptor in
collecting tubule (indirectly inhibits Na+ reabsorption).
Triamterene and amiloride: Directly block Na+ channels in the collecting tubule.

Question 12

At PCT, what follows sodium

Answer 12

At luminal border, sodium moves along gradient (simple diffusion)

At basolateral border, sodium moves against gradient (primary active transport using ATP) to be reabsorbed

Cl- (electroneutrality)
H20 (osmosis)
Glucose (Na+Glu co-transport) 
amino acids
ca2+ (Na+Ca2+ co-transport) 
HCO3-

Question 13

At PCT, what goes against sodium

Answer 13

H+

through Na+H+ exchanger

Question 14

What do you know about Liddle syndrome

Answer 14

Extremely rare
Age of onset: childhood
Etiology: autosomal dominant mutation in the SCNN1B and SCNN1G genes on chromosome 16p → structural alteration in the β and γ subunits of the epithelial sodium channel (ENaC) in the collecting duct

Pathophysiology: structural alteration in the ENaC → ENaCs cannot be degraded by ubiquitin proteasomes → increased number of ENaCs in the collecting duct → increased reuptake of water and sodium (pseudohyperaldosteronism) → hypertension with low renin production and hypokalemia

Clinical features
Hypertension

Diagnostics
Hypokalemia
Metabolic alkalosis
Decreased renin and aldosterone levels

Confirmatory test: genetic testing

Treatment: lifelong oral potassium substitution with potassium-sparing diuretics that directly block ENaCs in the collecting duct (e.g., amiloride, triamterene

Question 15

Spironolactone effective with Liddle syndrome?

Answer 15

The potassium-sparing diuretic spironolactone (an aldosterone receptor antagonist) is not effective in Liddle syndrome because the increased sodium channel activity is not caused by aldosterone.

Question 16

Amiloride MOA

Answer 16

same as triamterene

Question 17

Triamterene MOA

Answer 17

A potassium-sparing diuretic that acts by direct inhibition of the epithelial sodium channels in the distal convoluted tubule and the collecting duct leading to reduced Na+ reabsorption and reduced K+ secretion as well as increased diuresis.

Question 18

Gitelman syndrome

Answer 18

Prevalence: 1/40,000
Age of onset: ≥ 6 years; diagnosis is usually made in adolescence or adulthood

Etiology: autosomal recessive defect in the SLC12A3 gene on chromosome 16p → impaired function of the thiazide-sensitive sodium-chloride cotransporter in the distal convoluted tubule → impaired Na+ and Cl- reabsorption → mild natriuresis → mild volume depletion → mild RAAS activation

Clinical features
Fatigue, muscle weakness
Muscle cramps and/or tetany
Mild polyuria
Chondrocalcinosis
In some cases, mild hypotension

Diagnostics
Metabolic alkalosis
Severe hypokalemia
Hypercalcemia 
Hypomagnesemia 

Confirmatory test: genetic testing
Treatment
Mainstay of therapy: lifelong oral potassium substitution with potassium-sparing diuretics (spironolactone, amiloride)

Question 19

Bartter syndrome

Answer 19

Definition: a group of rare genetic disorders (autosomal recessive) that affect chloride reabsorption in the ascending limb of the loop of Henle

Prevalence: 1/1,000,000

Pathophysiology: failure to reabsorb Cl- from the ascending loop of Henle →
Failure to reabsorb Na+ → natriuresis (salt and water loss) → volume depletion → activation of the renin-angiotensin-aldosterone system (RAAS) →
Renal vasoconstriction → rise in the levels of prostaglandin E in an attempt to counter renal vasoconstriction → growth inhibition
↑ Aldosterone levels → enhanced K+ and H+ excretion → hypokalemia and metabolic alkalosis
↓ Paracellular reabsorption of calcium → hypercalciuria → hypocalcemia, nephrocalcinosis, renal stones

Clinical features
Antenatal symptoms: polyhydramnios, preterm delivery
Severe polyuria and polydipsia → life-threatening volume depletion and hypotension
Muscle atrophy, weakness, cramps, carpopedal spasm
Failure to thrive, developmental delay
Dysmorphic facies , strabismus, and sensorineural deafness
Symptoms of renal colic may occur during as a result of calcium stones.

Diagnostics
Laboratory diagnostics
Hypokalemia and metabolic alkalosis
Hypercalciuria 
Hyperuricemia (∼ 50% of cases)
Response to thiazide and loop diuretics 
Normal response to thiazide diuretics 
Blunted response to loop diuretics 
Confirmatory test: genetic testing
Treatment
Mainstay of therapy: lifelong oral potassium substitution with potassium-sparing diuretics (spironolactone, amiloride) 
Spironolactone, an aldosterone antagonist, is preferred over amiloride, an epithelial sodium channel (ENaC) inhibitor.