tubular disorders

Question 1

examples of chloride responsive vs chloride resistant metabolic alkalosis

Answer 1

chloride responsive - usually due to loss of H e.g. vomiting /diuretic
low urine chloride

chloride resistant - loss of HCO3 e.g. other renal loss / hyperaldosteronism
high urine chloride

Question 2

type I RTA
- examples
- where
- whats the defect
- urine pH
- urine anion gap
- plasma K
- urine Ca

Answer 2

• genetic mutations, SLE/Sjogrens, lithium / lipo ampho
• distal tubule
• cannot excrete H from alpha intercalated cells
• urine pH high >5.5
• urine anion gap high - suggest production ammonia
• hypokalaemia
• more urine Ca, so high risk stones

Question 3

type II RTA
- examples
- where
- whats the defect
- urine pH, and WHY
- urine anion gap
- plasma K
- urine Ca

Answer 3

• ifos, aminoglycosides, cisplat
• PCT
• can’t absorb HCO3
• urine pH acidic <5.5, as DCT can still acidify urine
• urine anion gap - negative because more HCO3 lost
• hypokalaemia
• normal urine Ca, no stones

Question 4

what kind of acidosis does RTA cause?

Answer 4

hyperchloraemic NAGMA

Question 5

type IV RTA
- urine pH
- plasma K
- urine Ca

Answer 5

• urine pH >5.3
• hyperkalaemia
• urine Ca normal

Question 6

type IV RTA - examples of causes

Answer 6

1) aldosterone deficiency / resistance
2) severe hypovolaemia
3) SLE
4) meds - lithium / lipo-ampho

Question 7

What is Fanconi syndrome? key features?

Answer 7

generalised PCT dysfunction type II RTA - characterised by:
- aminoaciduria
- phosphaturia
- proteinuria
- glycosuria

Question 8

causes of fanconi syndrome

Answer 8

Drugs: cisplat, ifos, aminoglycosides, valproate
genetic: Wilson’s, Dent, Marfan’s, Ehlers-Danlos, Lowe
metabolic (galactosaemia, tyrosinaemia, cystinosis)
endocrine: vit D disorders from chronic hypocalcaemia
Environmental: heavy metals

Question 9

how does RTA I vs II respond to treatment? what about K in each with treatment?

Answer 9

HCO3 is mainstay of treatment
RTA I responds promptly. K corrects.
RTA II responds slowly because of marked bicarb diuresis with therapy, so need greater doses. K worsens.

Question 10

most common cause of renal Fanconi’s

Answer 10

cystinosis

Question 11

clinical manifestations of RTA I vs II

Answer 11

RTA I
a. Growth failure in the 1st year of life
b. Additional symptoms
i. Polyuria + Dehydration (from sodium loss)
ii. Anorexia, vomiting and constipation
iii. Hypotonia

RTAII
slightly older, infancy/later life
growth failure

Question 12

many of the genetic causes of RTAI associated with what defect?

Answer 12

SNHL

Question 13

two methods to diagnose cystinosis

Answer 13

• Cystine crystals in the cornea
• Leukocyte cysteine content = elevated; confirms diagnosis-

Question 14

how to treat cystinosis

Answer 14

Cysteamine – which binds to cystine and converts it to cysteine (both oral and eye)

Question 15

What is Lowe syndrome and how is it related to renal tubular disorder?

Answer 15

X linked disorder of OCRL1 gene causing classic triad of: congenital cataracts, mental retardation, fanconi’s

Question 16

causes of type IV RTA

Answer 16

• Aldosterone deficiency
• RAAS blockage
• Drugs – spironolactone, amiloride, lithium, calcineurin inhibitors
• Pseudohypoaldosteronism (collecting duct resistance to aldosteronism)
• aldosterone unresponsiveness e.g. pyelo, obstructive uropathy (more common)

Question 17

Bartter: location and mutation

Answer 17

‘barta’: Thick ascending loop
AR of NKCC2

Question 18

metabolic abnormalities of Bartter

Answer 18

like frusemide:
volume loss
hypokalaemia
hypocalcaemia + hypercalcuria > stone risk
hyperrenin and hyperaldosteronism, elevated PGE (esp in antenatal)
high aldosterone > H+ excretion + HCO3 absorption > metabolic alkalosis

Question 19

Gittelman: location and mutation

Answer 19

DCT
AR Na/Cl co-transporter

Question 20

metabolic abnormalities of Gittelman

Answer 20

like thiazides:
volume loss from Na loss in urine
RAAS activation *but not too much volume loss so RAAS normal values > hypoK and metabolic alkalosis
hypocalcuria (unclear why)
hypoMg (unclear why)

Question 21

types of Bartter and their distinct mutations

Answer 21

first NAh thats shit
second, the rom coms
they give me a kick, they’re classic
go forth with bdsm
lastly i rest my case

I = NKCC2 (SLC12A1): antenatal, severe salt wasting and polyhydramnios
II = ROMK (KCNJ1): antenatal transient hypokalemia and acidosis in neonatal period
III = CIC-Kb (CLCKB): modest salt wasting, no nephrocalcinosis
IV = Barttin (BSND): early neonata, with severe salt wasting
V = CaSR (CaSR)hypocalcaemia

Question 22

types of Bartter according to age of onset

Answer 22

Antenatal Bartter syndrome (type I, II, and IV) (hyperPgE)
- neonatal/infancy, more severe
- Perinatal onset = polyhydramnios, neonatal salt wasting, severe episodes of recurrent dehydration

Classic Bartter syndrome (type III) = childhood with FTT and recurrent episodes of dehydration

Question 23

recurrent episodes of dehydration and growth failure more associated with Barrter or Gittleman

Answer 23

Barrter

Question 24

mx for nephrogenic DI

Answer 24

1. maintain lots of free water access
2. reduce solute in diet
3. medications
   - thiazides (don’t know how)
   - amiloride (don’t know how)
   - indomethacin