Renal Flashcards
Generalized resorptive defect in PCT
Fanconi syndrome
hypokalemia hypochloremia metabolic alkalosis normotension elevated plasma renin level
Bartter syndrome
Bartter pathophys
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)
Bartter symptoms
failure to thrive increased thirst polyuria polydipsia vomiting
Hypophosphatemia Aminoaciduria Renal glucosuria Tubular proteinuria Proximal renal tubular acidosis
Fanconi syndrome
Autosomal recessive mutation involving the Na+Cl- cotransporter
Gitelman syndrome
Gitelman symptoms
Hypokalemia Hypochloremia Metabolic alkalosis Hypomagnesemia Hypocalciuria Normotension
Hypercalciuria in Barttter. T/F?
Explain
True
Where do loop diuretics work?
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
Where do thiazide diuretics work
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.
Spironolactone vs triamterene and amiloride
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.
At PCT, what follows sodium
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-
At PCT, what goes against sodium
H+
through Na+H+ exchanger
What do you know about Liddle syndrome
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
Spironolactone effective with Liddle syndrome?
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.
Amiloride MOA
same as triamterene
Triamterene MOA
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.
Gitelman syndrome
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)
Bartter syndrome
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.
