Renal Flashcards
Secondary causes of membranous nephropathy (5)
- Autoimmune (eg: SLE)
- Infection (Hep B/C, syphilis)
- Meds (NSAIDS)
- Cancer
- Allogeneic stem cell transplantation
How do you differentiate from primary and secondary MN on biopsy?
In secondary MN, the target antigen is extrinsic to the podocyte and reaches GBM via circulation.
This often results in generation of subendothelial and mesangial deposits in addition to subepithelial deposits which are characteristic in MN.
In primary MN, dominant Ig is igG4 subclass, while as other IgG subclasses predominate in most cases of secondary MN.
Most common renal manifestations of Sjogren’s syndrome
Interstitial nephritis (often associated with distal RTA)
MPGN in rare cases
Glomerular disease in Sjogren’s syndrome is rare
What are the two major acid buffers in the renal tubules?
Why are they required?
Ammonia (NH3) and Phosphate.
Average daily acid lose for a typical western diet is 1mmol/kg. These hydrogen are secreted via the collecting duct (through H ATPase and H/K ATPase).
If these acids are not buffered, daily excretion of 50-70 mmol of acid in 1 L of urine will require urine pH of less than 2.5, and pH gradient between the cell interior and the tubular lumen of 100000:1, which is biologically impossible. Therefore you need buffers as urine pH can only go down to 4.5-5.
How does the kidney handle the potassium?
Almost all filtered potassium is reabsorbed by the proximal tubule and LoH.
Any potassium in the final urine is actively secreted by the distal nephron, particularly the connecting tubule and the principle cells of the CCT.
Distal potassium secretion is affected by two factors.
- Aldosterone
- Distal delivery of sodium and water (sodium reabsorption makes lumen electronegative and thus cause passive secretion of potassium from tubular cell into the lumen)
What constitutes distal tubule?
Distal tubule denotes the region of the nephron that extends downstream from the macula densa to the confluence of another tubule (ie, collecting system)
Consists of two nephron segments
- Distal convoluted tubule (early and late)
- Connecting tubule
Late distal tubule is more sensitive to effect of aldosterone.
How is sodium reabsorbed through the DCT?
DCT1 - via thiazide sensitive NCC (electroneutral absorption of Na and Cl)
DCT2 - amiloride sensitive ENaC (sodium only)
As a result of DCT2’s role in absorbing sodium only, the lumen fluid becomes progressively electronegative as it travels further down the line, which then becomes important for potassium secretion by the distal tubule (via voltage dependent ROMK)
Action of aldosterone
- Acts on mineralocorticoid receptor of the principal cells of the distal tubule and collecting duct
- Upregulates Na/K ATPase pump in the basolateral side, pumping 3Na/2K out, allowing favourable gradient for Na reabsorption - Upregulates ENaC in the collecting duct and allows sodium reabsorption
- Reabsorption of Na through ENaC results in K secretion through ROMK
- Stimulates H secretion via the H+ ATPase in the intercalated cells of the cortical collecting tubule
- Upregulates NCC in the DCT
Causes of hypoaldosteronism
Most commonly due to reduced aldosterone production.
- Hyporeninemic hypoaldosteronism
- Renal disease most often due to diabetes
- NSAIDS (reduce renal renin secretion which is mediated in part by prostaglandins, and also impair angiotensin II induced release of aldosterone)
- Calcineurin inhibitors - ACEI/ARB use
3 Chronic heparin therapy (impairs aldosterone synthesis - Primary adrenal insufficiency
- Severe illness
Examples of aldosterone resistance includes inhibition of ENaC (due to use of spironolactone, antibiotics such as trimethoprim)
How do you diagnose hypoaldosteronism?
- Enquire about drugs (NSAIDs, ACEI/ARB, calcineurin inhibitor, heparin etc)
- Check PRA, serum aldosterone and serum cortisol (better to test after administration of a loop diuretic or three hoursi n the upright position, which will increase renin and aldosterone release in individuals()
Hyporeninemic hypoaldosteronism - low PRA, low serum aldosterone, normal cortisol
Primary adrenal insufficiency - low serum aldosterone and cortisol, HIGH PRA (due to volume depletion/hypotension)
When does the risk of metabolic acidosis start to increase with decreasing GFR?
Generally below <40 ml/min.
In earlier CKD, residual nephrons are able to increase their ammonia production to be used as the major cation buffer.
Titratable buffers such as phosphates do not decrease until late CKD due to multiple reasons (higher urinary phosphate level due to higher serum level, high FGF-23 level etc)
What effect does hyperkalaemia have on acid-base balance?
Hyperkalaemia reduces NH3 production and consequently decreases buffering effect of the kidney, resulting in net acid excretion reduction.
Bartter and Schwartz criteria for SIADH
- Hypotonic hyponatremia (serum osmolality <275)
- Euvolaemia
- Less than maximally dilute urine
- Elevated urine sodium
- Absence of advanced kidney/heart or liver disease
- Alternate causes such as hypothyroidism, addisons and diuretic use all excluded
Why can potassium restrictive diet ultimately lead to hypokalaemia, when sodium restrictive diet does not lead to hyponatremia?
The normal kidney can excrete urine virtually free of Na+ in the setting of dietary Na+ restriction. By contrast, ∼15 mEq/d of K+ continues to be excreted in response to a K+-free diet. For this reason, dietary restriction of K+ alone can potentially lead to hypokalemia over time.
How does hypomagnesemia lead to hypokalaemia?
Usually intracellular Mg inhibits K secretion through the ROMK in the distal tubule.
This Mg effect is only overcome by Aldosterone stimulated Na reabsorption through the ENaC.
Low intracellular Mg leads to persistent potassium excretion
