Saturday, November 10, 2012

Inherited tubulopathies:


Inherited tubulopathies:

These disorders are characterized by electrolyte disturbances (particularly potassium).

Bartter’s syndrome: 

This is autosomal recessive characterized by renal salt wasting, polyuria, polydipsia, impaired urinary concentrating ability, hyperreninemic, hypokalemic metabolic alkalosis and mild hypomagnesemia. There is defect in three transporters/channels in loop of Henle, NKCC2 (type I) or ROMK1 (type II) and basolateral pump CLC-Kb (type III).

Gitelman’s syndrome: 

This is also autosomal recessive disorder characterized by hypokalemic, hyperreninemic, hypomagnesemic, metabolic alkalosis presenting latter in life than in batters syndrome. The molecular defect is in the thiazide sensitive NCCT transporter and biochemistry can therefore mimic the effects of thiazide use.

Liddle’s syndrome: 

This is autosomal dominant disorder characterized by hypokalemic, hypomagnesemic metabolic alkalosis but there is hypertension and hyperreninism. The disease is due to activating mutation which increases sodium transport through ENaC channel with increase in K and H loss.

Isolated abnormalities of tubular function:

Glycosuria: Glucose is freely filtered but reabsorbed completely in PCT. If plasma glucose concentrations rise or if GFR increases (as in pregnancy), then the capacity of PCT to reabsorb filtered glucose is exceeded and glycosuria occurs.

In hereditary glycosuria patients excrete glucose in urine at normal plasma glucose concentrations. There are two types of hereditary renal glycosuria (type A and B). The absorption of glucose in PCT is Na dependent by Na-D-glucose cotransport on luminal cell to transport glucose and by facilitated transport by GLUT2 on basolateral membrane which enable glucose to exit off the cell. In intestine there is Na-D-glucose cotransporter (SGLT1) and in kidney there is SGLT2. Mutation in gene for SGLT2 can cause hereditary renal glycosuria. Mutation affecting GLUT2 which facilitates transport of glucose, galactose and fructose across the basolateral membrane are another cause of renal glycosuria (Fanconi-Bickel syndrome).
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