Renal--Hereditary Renal Tubular Disorders

Front 1

What are signs indicating genetic defects in tubular function?

Back 1

Chronic dehydration, salt wasting, and acidosis --> Poor Growth

Front 2

Renal tubular transport dysfunctions are typically what types in the PT and DT?

Back 2

PT--transport protein OR generalized
DT--specific receptor

Front 3

What happens when cubulin and megalin are defective?

Back 3

Defect results in defective reabsorption of LMW proteins in the PT

Front 4

What are the three effects of RFS?

Back 4

Alteration of membrane perm., reduction of Na-coupled transport, and decreased transporter activity/endocytotic recycling pathway

Front 5

What are some clinical features of RFS?

Back 5

Rickets in children and osteomalacia in adults, growth retardation, polyuria, hypokalemia, dehydration, and LMW proteinuria

Front 6

What is Dent disease?

Back 6

X-linked disorder in CLCN5 that codes for an endocytic protein that regulates recycling of cubulin and megalin--YOU DON'T PROPERLY SCAVENGE LMW PROTEINS THAT GOT FILTERED

Front 7

What are the three nuclear gene defects associated with RFS?

Back 7

CYSTINOSIS(defective lysozomal cysteine transport leading to increased intracellular cysteine
Dent disease
X-linked hypophosphatemic rickets

Front 8

What are the inherited disorders of the TAL and DT?

Back 8

Bartter-Gitelman spectrum and Mg wasting disorders

Front 9

What is antenatal Bartter's variant? How is it diagnosed?

Back 9

Presents in utero/early infancy with prematurity and polyhydramnios and severe growth delay, severe polydypsia/polyuria, and NORMAL SERUM Mg
VERY HIGH Ca++ excretion/nephrocalcinosis
Diagnose by measuring high urinary prostaglandins as well as impaired urinary concentration

Front 10

What is classic Bartter variant? How is it diagnosed?

Back 10

Compared to antenatal it is a milder phenotype that presents in early infancy--growth delay, polyuria/polydyspsia, DECREASED SERUM Mg DUE TO HYPERMEGNESURIA, urine calcium excretion normal/high, and URINARY CONCENTRATION IS IMPAIRED

Front 11

What disease looks like chronic loop usage? Chronic thiazide usage?

Back 11

Loop--Classic Bartter's
Thiazides--Gitelman's

Front 12

The mildest form of Bartter's syndrome is due to what problems? What is pathopneumonic for this form? What causes the severe form?

Back 12

Mild = Mutations in BL Bartin protein(Cl- transport) characterized by a lack of hypercalciuria
Severe--Defect in triple transporter

Front 13

What are the four grand results of triple transporter knockout in Bartter's?

Back 13

Metabolic alkalosis and hypokalemia--due to increased NaCl delivery to the DT
Normotension, blunted vascular response to AT2 and Norepi--INCREASED PROSTAGLANDIN E2/KALIKREIN
Hyposthenuria--Increased PGE2 and metabolic alkalosis impair vasopressin stimulated urine concentrating process
Hypercalciuria and hypermagnesiuria--Reduced Vte driven PARA

Front 14

What does increased PGE2 in Bartter's cause?

Back 14

Blunts the vascular response to ATII and Norepi--this exacerbates via feedback loop the further worsening of Na/Cl transport
Hyposthenuira--due to impairment of vasopressin stimulated urin concentration

Front 15

What is the therapy for barter's syndrome?

Back 15

Saline rehydration, K+ supplement, indomethacin to block PGE pathway

Front 16

What are the metabolic features of Gitelman?

Back 16

Salt wasting CAUSES hypokalemic alkalosis, and hyperreninemia
Excessive Mg+ loss CAUSES secondary hypokalemia, and alkalosis

Front 17

What are the three grand results of NaCl transporter knockout in Gitelman?

Back 17

Metabolic alkalosis/hypokalemia--Increased NaCl delivery to distal nephron
Hypocalciuria--cell hyperpolarization due to Cl- BL efflux
Hypermagnesiuria--DECREASE IN Na+ DEP. Ca++ REAB

Front 18

Where does most Mg++ reab occur?

Back 18

In the TAL--mostly PARA

Front 19

What is Gordon Syndrome?

Back 19

Blood pressure disorder from a single gene defect(AD)
Pseudohypoaldosteronism Type II
WNK kinase knockout = continuous reab of Na+ and so none is left to create a gradient for aldosterone and H/K secretion
HYPERKALEMIA and Non-AG Met. acidosis

Front 20

What transporters do WNK kinases regulate?

Back 20

NaCl and KCl cotransporters in the DCT
ENaC and ROMK in the CD

Front 21

PHA Type 1 AR causes what effects? What causes PHA Type 1 AR?

Back 21

Massive renal salt wasting and consequential hyponatremia
High Na+ in salt/sweat/stool
Severe hyperkalemia and associated metabolic acidosis
High plasma renin and aldosterone
THIS DISEASE IS CAUSED BY ENaC LOSS OF FUNCTION(gene defects)

Front 22

PHA Type 1 AD involves what defect and has what effects?

Back 22

It's less severe than AR
It involves a haploinsuff. of mineralcorticoid receptors responsible for upregulating ENaC
Effects: renal salt wasting, hyperkalemia, metabolic acidosis

Front 23

What is Liddle Syndrome?

Back 23

Dysregulation of the ENaC--causes low renin HTN

Front 24

What is GRA?

Back 24

Glucocoritcoid remediable aldosteronism from altered gene--causes low renin HTN

Front 25

What is Apparent Mineralcorticoid Excess?

Back 25

Defect in cortisol degradation

Front 26

Define RTA Type 1

Back 26

Type 1 is DISTAL--defect in collecting tubule's ability to excrete H+ that is associated with hypokalemia and risk for calcium-containing kidney stones

Front 27

Define RTA Type 2

Back 27

Type 2 is PROXIMAL--defect in proximal tubule bicarb reabsorption that is associated with hypokalemia and hypophosphatemic rickets

Front 28

Define RTA Type 4

Back 28

Type 4 is HYPERKALEMIC--hypoaldosteronism or lack of collecting tubule response to aldosterone that is associated with hyperkalemia and inhibition of ammonium excretion in the proximal tubule
It leads to decreased urine pH due to decreased buffering capacity

Front 29

What is a complication of Type 1 RTA and what is a treatment?

Back 29

Nephrocalcinosis
Treat with bicarb supplement

Front 30

What is the most common complication of RTA Type 2? What is the treatment?

Back 30

Rickets in children
Massive amounts of bicarb

Front 31

How does nephrogenic diabetes insipidus present?

Back 31

Insens. of the DT to ADH causes SEVERE polyuria leading to megaureter, megacystitis, and flow uropathy

Front 32

What will nephrogenic diabetes insipidus respond to?

Back 32

Combination of thiazide/amiloride + diuretics/indomethacin

Front 33

What are the genetic features of diabetes insipidus?

Back 33

X-linked and usually AR
Underlying defect is in AVPR2 or aquaporin 2 channel(binding domain responsible for generating cAMP to trigger aquaporin release)