What about these X linked diseases in kidney !

From board stand point, Alport syndrome and  Fabry disease are important AND both these disorders are X linked.

Alport syndrome : Mutation in COL4A5 gene (Thin membrane disease is a structural anomaly secondary to mutation in COL4A3 and COL4A4)

Fabry disease : Mutation in alpha galactosidase A gene.

There are autosomal variants of these diseases and can rarely affect females but not tested in the boards usually!

Dent’s disease – familial nephrolithiasis is also X linked.

ADPKD  is autosomal dominant (as the name implies) – 40% associated with liver cysts, 5% associated with AVM . It is not cost effective to do screening for AVM in all patients with ADPKD. However, if there is a family history of Hemorrhagic stroke (where the risk of AVM goes up to 20%), Screening is recommended !

Medullary sponge kidney is usually a developmental anomaly but can have a hereditary predisposition!

Yuvaraj

1) C – ANCA vasculitis treatment  – prednisone and Cyclophosphamide. There is plasmapheresis in the choice . If they specifically ask for initial therapy, then prednisone and plasmapheresis could be considered. This patient did not have pulmonary hemorrhage and was not sick !

2) B – Fabry disease. This is an X linked recessive disease which predominantly affects male ! Deficiency of Alpha galactosidase A causes accumulation of sphingolipids(glycolipids and in this disease specifically galactoacylcerebrosidase) in blood vessels , nerves kidney and heart. The manifestations are neurological(pain and tingling in extremities, progressive CKD-especially in 3 decade, Cardiac hypertrophy, abdominal pain(accumulation of sphingolipids in blood vessels supplying intestines) and skin rash(especially around the umbilicus)

3) D – Sickle cell/Tylenol/NSAID combination should raise suspicion about papillary necrosis

4)A – Arterial line is negative pressure and is causes dialysis catheter to flatten out!

5) B – most common cause of intradialytic hypotension is diastolic dysfunction. I was tempted to choose pericardial effusion given the stem of the case .

6) E – Hyperglycemia- very common cause of PD ultrafiltration failure since it decreases the solute gradient dramatically!

7) C – Isolated scrotal swelling should raise concerns about patent processes vaginalis in a new PD patient

8) E  -Gentamycin toxicity- hypomagnesemia

9) C – Cyclosporine toxicity causes hirsutism

10) B – Increased urine oxalate -pathogenesis for calcium oxalate stone in Chron’s disease

Hope the explanation helps!

Yuvaraj

Hypokalemia is associated with alkalosis and Hyperkalemia is associated with acidosis! We have heard about this but did ‘t know if this had mechanistic/pathogenetic significance until we heard Dr.Weiner’s lecture today.

Hypokalemia increases ammonia production in proximal tubule which is absorbed into the interstitium in the ascending loop of Henle through NKCl cotransporter (since the concentration of ammonia is several hundred folds higher than potassium in hypokalemic state). The ammonia  decreases the activity of ENaC in the principal cell , which decreases potassium excretion(this is favourable in hypokaleic state since K is conserved by this) and ammonia combines with proton secreted in the alpha intercalating cell thereby increasing net acid excretion.

In short, hypokalemia signals the cortical collecting duct to decrease potassium excretion by increasing the production of ammonia.

Hyperkalemia decreases ammonia production in proximal tubule and the net acid excretion is decreased.

It was interesting to know the cause of hyperkalemia in acidosis!

This explanation based on ammonia generation hypothesis holds good only in chronic acidosis and not in acute acidosis such as DKA and lactic acidosis.