Renal Tubular defects and acidosis Flashcards
What are the Renal Tubular defects and where do they occur in the nephron?
- Fanconi syndrome - PCT
- Bartter syndrome - TAL of LoH
- Gitelman syndrome - DCT
- Liddle syndrome - Collecting ducts
- Syndrome of Apparent Mineralocorticoid Excess (SAME) - Collecting ducts
What Renal Tubular Defects cause decreased reabsorption?
- Fanconi syndrome
- Bartter syndrome
- Gitelman syndrome
What Renal Tubular defects cause increased absorption and hypertension?
- Liddle syndrome
- Syndrome of Apparent Mineralocorticoid Excess (SAME)
What hormone is responsible for the reabsorption of calcium in the distal tubules?
PTH
What are distinguishing features between Bartter and Gitelman syndrome?
Both present with Met alkalosis and hypokalemia. Bartter is more severe
Bartter has hypercalciuria (decreased Ca2+ in serum)
- Whereas Gitelman has hypocalciuria (increased serum calcium)
- Gitelman presents with hypomagnesemia
What renal tubular defect is autosomal dominant?
Liddle syndrome
What is Liddle syndrome treated with?
Amiloride
What is Fanconi Syndrome due to a defect in and what does this lead to?
PCT defect
- Increased excretion of all substances reabsorbed by PCT: AA, glucose, HCO3-, PO43-
- Metabolic acidosis (RTA type 2)
- Hypophosphatemia (retardation, rickets, osteopenia)
- Hypokalemia
- Volume depletion also common
What can cause Fanconi syndrome?
- Hereditary defects (Wilson disease, tyrosinemia, glycogen storage disease)
- Ischemia
- Multiple Myeloma
- Nephrotosxins/drugs - Ifosfamide, cisplatin
- Lead poisoning
What is the defect in Bartter syndrome?
In TAL of LoH
- Effects Na+/K+/2Cl- cotransporter
- Similar to loop diuretic use
What lab results does Bartter syndrome give?
Met alkalosis
- Hypokalemia
- Hypercalciuria (hypocalcemia)
What is Gitelman syndrome due to a defect in?
NaCl in DCT
What lab finding is consistent with every Renal tubular defect?
HYPOkalemia
What Renal Tubular Defect has Metabolic acidosis with hypotension and hypokalemia?
Fanconi Syndrome
What is Liddle syndrome due to?
gain of function mutation
- Decreased Na+ channel degradation
- Increased Na+ reabsorption in collecting tubules
How can you differentiate between Renal Tubular defects (such as Liddle and SAME) with a hyperaldosteronism?
Present nearly identically however RT defects have almost undetectable levels of aldosterone
What is Liddle syndrome treated with?
Amiloride
What enzyme is responsible for SAME?
11Beta HSD (Hydroxysteroid dehydrogenase) - Deficiency or blockage of activity
What substance can cause SAME?
Glycyrrhetinic acid
- Present in licorice
- Blocks activity of 11B HSD
What does 11B HSD do?
- Cortisol acts on mineralocorticoid receptors
- 11B HSD converts cortisol to cortisone making it inactive thus decreasing mineralocorticoid receptor activity
What are the different types of Renal Tubular Acidosis (RTA) and what part of the nephron is affected?
- RTA type 2 - Proximal Tubule
- RTA type 1 - Distal Tubule
- RTA type 4 / Hyperkalemic tubular acidosis - Collecting Duct
What is RTA type 2?
Defect in HCO3- reabsorption
- Increased excretion of HCO3- in urine
- Met acidosis
Urine may be acidified by alpha-intercalated cells in CD but not enough to overcome HCO3- excretion
What can cause RTA type 2
- Fanconi syndrome
- Multiple Myeloma
- Carbonic Anhydrase inhibitors
What is the serum K+ level in each type of RTA?
- Type 2/Proximal RTA - Decreased K+
- Type 1/Distal RTA - Decreased K+
- Type 4 / Hyperkalemic tubular acidosis - Increased K+
