Flashcards in 19. Renal tubular defects Deck (41):
Renal tubular defects - types
1. Fanconi syndrome
2. Bartter syndrome
3. Gitelman syndrome
4. Liddle syndrome
5. Syndrome of apparent minelocorticoid excess
Fanconi syndrome- pathophysiology
Generalized reabsorptive defect in early proximal convoluted tubule
Fanconi syndrome --> .... (result in )
increased amino acids, glucose , HCO3- and PO4- ---Metabolic acidosi (proximal renal tubular acidosis)
causes of Fanconi syndrome
1. hereditary defects ( wilson disease, tyroseninemia, glycogen storage disease, cystinosis)
3. multiple myeloma
4. nephrotoxins/ drugs ( expired tetracyclines, ifosfamide , cisplatin, tenofovir, lead poisoning)
nephrotoxins/ drugs that cause Fanconi syndrome
expired tetracyclines, ifosfamide , cisplatin, tenofovir, lead poisoning)
Bartter syndrome- pathophysiology ( and result in)
Reabsorptive defect in thick ascending loop of Henle --> affects Na+? K+?2CL- contrasporter
Bartter syndrome .... (result in )
2. metabolic alkalosis
Situation that mimics Bartter syndrome
chronic loop diuretic use
Loop diuretics - deugs
4. Ethacrynic acid
Bartter syndrome - mode of inheritance
Gitelman syndrome - pathophysiology
Reabsorptive defect in distal convoluted tubule
Gitelman syndrome - mode of inheritance
situation that mimics Gitelman syndrome
lifelong thiazide diuretics
Gitelman syndrome---> .... (results in )
Gitelman syndrome vs Bartter syndrome according to severity
Bartter syndrome is more sever
Liddle syndrome - pathophysiology
gain of function mutation --> increased Na+ reabsorption in collecting tubules ( high activity of epithelial channels)
situation that mimics Liddle syndrome
hyperaldosterinism ( but aldosterone is nearly undetectable)
Liddle syndrome - mode of inheritance
AD ( gain function mutation)
Liddle syndrome --> .... (result in )
3. metabolic alkalosis
4. low aldosterone
Liddle syndrome - treatment
Syndrome of apparent minelocorticoid excess - pathophysiology
hereditary deficiency of 11β-hydroxysteroid dehydrogenase which normally converts cortisol ( can activate mineralocorticoid receptors) to cortizone ( inactivate on mineralocoticoid receptors) in cell containing minrealocortioid receptors --> increased mineralocoirticoid activity
Syndrome of apparent minelocorticoid excess - manifestations
3. metabolic alkalosis
4. Low erum aldosterone levels
situation that mimics Syndrome of apparent minelocorticoid excess
glycyrrhetinic acid ( present in licorice ) which blocks activity of 11β-hydroxysteroid dehydrogenase
Licorice, is the root of
Glycyrrhiza glabra from whic a sweet flavour can be extracte ( wide variety of candies or sweets)
apparent minelocorticoid excess - treatment
corticosteroids --> decreases endogenous cortisol production --> decrease mineralocorticoid receptor activation
• A man has hypertension. Serum studies: hypokalemia and metabolic alkalosis. Aldosterone is low. Could this disorder be acquired?
Yes, these findings are consistent with 11β-hydroxysteroid dehydrogenase deficiency (SAME), which may be acquired from glycyrrhetic acid
• A patient with Wilson disease has a low body pH. Urine studies show elevated protein and glucose. Where in the kidney is the likely defect?
A PCT reabsorptive defect causes HCO3-, PO43-, amino acid, and glucose losses in urine (this is Fanconi syndrome [due to Wilson disease])
• A man with lymphoma received an excess of cyclophosphamide at his last chemotherapy session and now has a metabolic acidosis. What happened?
The nephrotoxic cyclophosphamide has caused Fanconi syndrome (reabsorptive defect in the PCT that results in metabolic acidosis)
• Bartter syndrome is a reabsorptive defect in the thick ascending loop of Henle. Which cotransporter does it affect?
The Na+/K+/2Cl- cotransporter
• Gitelman syndrome is a defect of ____ reabsorption in the DCT.
• A man with an autosomal recessive disorder presents with hypokalemia and a high body pH but a normal urine calcium level. Diagnosis?
Gitelman syndrome (high calcium in the urine is seen with Bartter syndrome)
• A chronic hypertension patient has low K+ levels. He has an autosomal dominant kidney disorder affecting the collecting tubules. Treatment?
Amiloride (the patient has Liddle syndrome)
• Liddle syndrome is an increase in Na+ reabsorption in the ____ tubules of the kidneys.
• A patient has hypokalemia and a metabolic alkalosis. Aldosterone is low, blood pressure is high. Is this an ion channel issue?
Yes (this combination of findings is consistent with Liddle syndrome, with abnormally increased renal sodium channel activity)
• A black licorice addict has hypertension, low K+, and a metabolic acidosis. To what hereditary deficiency is this condition similar?
A hereditary deficiency of 11#946;-hydroxysteroid dehydrogenase (syndrome of apparent mineralocorticoid excess)
• Name some causes of Fanconi syndrome.
Hereditary (Wilson disease, tyrosinemia, glycogen storage), ischemia, multiple myeloma, toxins/drugs (old tetracyclines, tenofovir), lead
• What are the prominent serum and urine electrolyte abnormalities seen in Gitelman syndrome?
Hypokalemia, hypomagnesemia, metabolic alkalosis (blood), and hypocalciuria (urine)
• What are the prominent serum and urine electrolyte abnormalities seen in Bartter syndrome?
Hypokalemia, metabolic alkalosis (blood), and hypercalciuria (urine)
• What are the prominent serum electrolyte abnormalities seen in Liddle syndrome?
Hypokalemia and metabolic alkalosis