Lecture Notes on Inherited Disorders: Bartter's Syndrome, Gitelman Syndrome, and Liddle's Syndrome

Summary

In this lecture, we discussed inherited renal disorders, specifically Bartter's Syndrome, Gitelman Syndrome, and Liddle’s Syndrome. These disorders affect different parts of the nephron and lead to unique clinical symptoms and biochemical abnormalities.

Bartter's Syndrome

• Genetics and Pathophysiology: Autosomal recessive condition with a defect in the thick ascending loop of Henle.
• Functionally Affected Component: Sodium-potassium-chloride co-transporter on the luminal side; responsible for reabsorption of sodium, chloride, and potassium.
• Clinical Manifestations:
  • Salt wasting leading to polyuria and dehydration.
  • Hypokalemia leading to metabolic alkalosis.
  • Decreased glomerular filtration rate (GFR) increases renin and aldosterone levels causing more severe hypokalemia.
  • Hypercalciuria can lead to nephrocalcinosis.
  • Failure to thrive in children, antenatal polyhydramnios, dehydration, renal rickets, and potentially sensory-neural deafness.

Gitelman Syndrome

• Genetics and Pathophysiology: Autosomal recessive condition manifesting in late childhood with defects in the distal collecting tubule.
• Functionally Affected Component: Sodium chloride co-transporter and TRPM-6 transporter, which is essential for magnesium reabsorption.
• Clinical Manifestations:
  • Similar to Bartter's with salt wasting, polyuria, dehydration, and metabolic alkalosis.
  • Notably, there is severe magnesium wasting leading to decreased serum magnesium levels.

Differences Between Bartter's and Gitelman Syndromes

• Location of Defect:
  • Bartter's Syndrome: Thick ascending loop of Henle.
  • Gitelman Syndrome: Distal collecting tubule.
• Specific Effects:
  • Hypercalciuria and nephrocalcinosis are prominent in Bartter's Syndrome.
  • Low serum magnesium levels are a key feature of Gitelman Syndrome.
• Mnemonic Aids:
  • For Bartter's (B before G): Thick ascBending Loop (“Before” Distal Collecting Tubule in Gitelman).
  • Hypercalciuria from Bartter's can be remembered as B and C in "Barter's and Calcium."
  • Low magnesium levels in Gitelman can be recalled from G and M in "Gitelman and Magnesium."

Liddle's Syndrome

• Genetics and Pathophysiology: Autosomal dominant disorder characterized by a gain of function in epithelial sodium channels.
• Clinical Manifestations:
  • Increased reabsorption of sodium and water leading to hypertension.
  • Unlike Bartter's and Gitelman, dehydration is absent due to hypertension.
  • Negative feedback on renin leading to low renin levels.
• Treatment: Amiloride is used.

These notes cover the essential differences and characteristics of each syndrome, focusing on their genetic basis, affected nephron segment, clinical manifestations, and biochemical features.