Acquired and Congenital Tubular Function Defects & RTA

Question 1

What location of the nephron is disrupted with Fanconi syndrome?

Answer 1

Proximal tubules

Question 2

Reabsorptive disturbances associated with Fanconi syndrome

Answer 2

Filtered glucose, amino acids, uric acid, phosphate, and bicarbonate are passed into the urine instead of being reabsorbed

[not considered to be a defect in a specific channel, but moe a general defect in function of the proximal tubules]

Clinical features include polyuria, polydipsia, hypovolemia, hypophosphatemic rickets (kids), osteomalacia (adults), growth failure, type 2 RTA, hypokalemia, hypophosphatemia/phosphaturia, glycosuria, proteinuria, hyperuricosuria

Question 3

What location of the nephron is disrupted with Bartter syndrome?

Answer 3

Classic Bartter’s syndrome is associated with defect in Cl- channel in TAL

[other types of Bartter’s may affect other channels but all affect the TAL]

Question 4

Reabsorptive disturbances associated with Bartter syndrome

Answer 4

Reduced urine concentrating and diluting capacity

Question 5

How is Bartter syndrome similar to a class diuretics?

Answer 5

Symptoms of Bartter syndrome are identical to those of patients taking loop diuretics

— normal to low BP, polyuria/polydipsia, elevated plasma renin and aldosterone, hypokalemia, hyponatremia, hypocalcemia, hypomagnesemia, hypochloremic metabolic alkalosis, hyperglycemia, hyperuricemia, increased cholesterol and triglycerides, and ISOTONIC urine

Question 6

What location of the nephron is disrupted with Gitelman syndrome?

Answer 6

Distal Convoluted Tubule

[usually mutation in gene coding for NaCl cotransporter in DCT]

Question 7

Reabsorptive disturbances associated with Gitelman syndrome

Answer 7

Diluting capacity reduced

[concentrating capacity is normal/near normal]

Question 8

How is Gitelman syndrome similar to a class diuretics?

Answer 8

Gitelman syndrome mimics chronic use of thiazide diuretics

— polyuria/polydipsia, hypokalemia, hyponatremia, hypercalcemia, hypomagnesemia, hypochloremic metabolic alkalosis, hyperglycemia, hyperuricemia, increased cholesterol and triglycerides, can dilute OR concentrate urine

Question 9

What location of the nephron is disrupted with Liddle syndrome?

Answer 9

Collecting duct

[ENaC channels not degraded correctly]

Question 10

Reabsorptive disturbances associated with Liddle syndrome

Answer 10

Since ENaC channels are not degraded correctly, there is increased Na reabsorption with K+ loss

leads to severe HTN associated with low plasma renin activity, low aldosterone, metabolic alkalosis, and hypokalemia

Question 11

Contrast Liddle syndrome with hyperaldosteronism (Conn syndrome)

Answer 11

Liddle syndrome = pseudohypoaldosteronism — There is a failure of response to aldosterone leading to renal tubular acidosis and hyperkalemia; levels of aldosterone are actually elevated d/t lack of feedback inhibition

Conn syndrome = true hyperaldosteronism —> increased K+ secretion and resulting hypokalemia

Question 12

Site of dysfunction, severity of acidosis, and potassium disturbance associated with RTA type 1

Answer 12

Distal tubules — impaired distal H+ secretion by alpha-intercalated cells

Most severe acidosis of all types of RTA; plasma bicarb often < 10 mEq/L, urine pH typically > 5.5

Plasma K+ is usually low but may be corrected by alkali therapy [hypokalemia]

Question 13

How would you clinically differentiate Gitelman from Bartter syndrome?

Answer 13

Gitelman generally more benign (can dilute or concentrate urine) while Bartter patient urine is isotonic

Bartter tends toward hypocalcemia/hypercalciuria (opposite of Gitelman)

Failure to respond to loop diuretics = Bartter syndrome

Failure to respond to thiazide diuretics = Gitelman syndrome

Question 14

Site of dysfunction, severity of acidosis, and potassium disturbance associated with RTA type 2

Answer 14

Proximal tubules — impaired HCO3 reabsorption

Acidosis is less severe than type 1 because pt can still acidify urine to pH ~5.3; plasma HCO3 typically 12-20 mEq/L due to distal compensation

Plasma K+ is usually low and worsened by alkali therapy [hypokalemia]

Question 15

Site of dysfunction, severity of acidosis, and potassium disturbance associated with RTA type 4

Answer 15

Adrenals — lack of aldosterone or failure of kidney to respond to it (hypoaldosteronism, decreased excretion of NH4+, hyperkalemia inhibits NH3 synthesis)

Acidosis is mild, with normal anion gap when present; urine pH typically < 5.5, plasma HCO3 typically > 17 mEq/L

Hyperkalemia

Question 16

Clinical criteria for dx of RTA

Answer 16

Acidemia
Normal anion gap
Normal serum creatinine
No diarrhea