Disorders of the Distal Tubule

Question 1

Bartter’s syndrome pathogenesis

Answer 1

Defect in Cl- reabsorption in the NK2C cotransporter, or K+ channel ROMK, or Cl- channel, or Barttin (needed to insert Cl channels)

Question 2

Bartter’s syndrome is similar in effect to which kind of diuretic?

Answer 2

Loop

Question 3

In Bartter’s syndrome, which ions will be altered and how so?

Answer 3

Hypochloremia
Hypokalemia
Hyponatremia

Question 4

What happens to levels of aldosterone and renin in Bartter syndrome?

Answer 4

Both up

Question 5

What tissue changes occur in Bartter’s syndrome and why?

Answer 5

Hyperplasia of juxtaglomerular apparatus due to elevated prostaglandin activity

Question 6

How is Bartter’s inherited?

Answer 6

AR

Question 7

What are some S/S for neonatal Bartter syndrome?

Answer 7

Fetal polyuria causing polyhydramnios
Amniotic fluid - elevated PGE2
Salt wasting at birth
Calcium stones and hypercaliuria

Question 8

Gitelman’s Syndrome is similar to which diuretic?

Answer 8

Thiazides

Question 9

How is Gitelman’s inherited?

Answer 9

AR

Question 10

Gitelman’s effects on ion levels

Answer 10

Hypomagnesemia
Hypokalemia
Hypocalciuria

Question 11

What kind of acid-base disorder to Bartter’s syndrome patients usually have?

Answer 11

Hypochloremic metabolic alkalosis

Question 12

Gitelman’s defect

Answer 12

Mutated Na/Cl cotransporter in DCT

Question 13

What is the typical age of presentation for Bartter’s and for Gitelman’s?

Answer 13

Bartter’s is young

Gitelman’s is adults

Question 14

Explain Gitelman’s pathogenesis

Answer 14

Defective Na/Cl symporter in DCT causes increased distal Na delivery, increasing K secretion and H secretion (leading to hypokelamia and alkalosis). The distal delivery increase also increases excreted sodium, leading to RAAS activation.

Question 15

Gitelman’s S/S

Answer 15

Hypomagnesemia
Hypokalemia
Hypocalciuria
Hypochloremic metabolic alkalosis

Question 16

Is Gitelman’s or Bartter’s more severe and why?

Answer 16

Bartter’s is more severe because more sodium wasting since earlier in tubule

Question 17

Liddle syndrome defect

Answer 17

Gain of function of ENaC leading to constitutive activation

Question 18

Liddle syndrome treatment

Answer 18

Salt restriction and diuretics

Question 19

Liddle syndrome inheritance

Answer 19

AD

Question 20

Liddle syndrome S/S

Answer 20

Hypertension
Low renin
Low aldosterone
Hypokalemia
Metabolic alkalosis

Question 21

What are some causes of hypokalemia?

Answer 21

Diuretics
Hyperaldosteronism (1 or 2ndary)

Question 22

What are some causes of hyperkalemia?

Answer 22

Hypoaldosteronism

Pseudohypoaldosteronism

Question 23

What does the TTKG measure?

Answer 23

estimates the ratio of potassium in the lumen of the CCD to that in the peritubular capillaries

Question 24

What are the expected values for TTKG for hypo- and hyperkalemia?

Answer 24

Hypokalemia: 8

Question 25

What is a primary cause of hyperaldosteronism?

Answer 25

Adrenal tumors

Question 26

What are some secondary causes of hyperaldosteronism?

Answer 26

Dehydration Bartter Gitelman

Question 27

What is the defect in glucocorticoid-remediable hyperaldosteronism?

Answer 27

Recombination of 11BHSD and aldosterone synthase

Question 28

GRA pathogenesis

Answer 28

Fusion protein produces hybrid molecule that binds aldosterone receptors in times of stress, causing low renin hypertension and hypokalemia

Question 29

GRA treatment

Answer 29

Glucocorticoids

Question 30

Apparent mineralocorticoid excess pathogenesis

Answer 30

Mutant kidney enzyme 11BHSD causes increased cortisol in kidney which cross-reacts to activate aldosterone receptor. Leads to low renin hypertension and hypokalemia, and treated with glucocorticoids

Question 31

S/S of PHA Type I

Answer 31

Hyperkalemia Hyponatremia HYPOTENSION thru volume depletion

Question 32

PHA Type I defects -2

Answer 32

AD mutant mineralocorticoid receptor or AR ENaC always off mutation

Question 33

PHA Type I treatment

Answer 33

NA supplementation Lots of fluids K-binding resins

Question 34

PHA Type II S/S

Answer 34

Hyperkalemia Hyperchloremic metabolic acidosis HYPERTENSION Low RAAS

Question 35

PHA Type II treatment

Answer 35

thiazide diuretics

Question 36

PHA Type II defect

Answer 36

Mutated WNK1 and WNK4 which regulate Na/Cl cotransporter (thiazide target)

Question 37

What are some types/causes of elevated anion gap acidosis?

Answer 37

Ketoacidosis Lactic acidosis Inborn metabolic errors Poisons like methanol and ethylene glycol

Question 38

What are some causes of normal gap acidosis?

Answer 38

GI loss of bicarb through diarrhea Exogenous Cl? **Renal tubular acidosis

Question 39

Type II renal tubule acidosis

Answer 39

Associated with Fanconi syndrome | Proximal tubule damage

Question 40

Type I renal tubule acidosis

Answer 40

Distal tubule | Very rare

Question 41

Type IV renal tubule acidosis

Answer 41

Hyperkalemic | Aldosterone deficiency or unresponsiveness

Question 42

What are some tests for RTA?

Answer 42

Fractional excretion of bicarbonate Urine pH Urine anion gap Urine vs blood pCo2

Question 43

What are the expected values of fractional bicarb excretion for the different types of RTA?

Answer 43

Proximal RTA (II): <5-10%

Question 44

What are the expected values of urine pH for the different types of RTA?

Answer 44

``` Proximal RTA (II): 5.5 Hyperkalemic (IV): either ```

Question 45

What is the formula for urine anion gap

Answer 45

Na + K - Cl

Question 46

What would urine anion gap analysis show for the types of RTA?

Answer 46

All would show positive value (normal gap)

Question 47

How is U-B pCO2 used to differentiate between types of RTA?

Answer 47

Proximal RTA: normal of >10 Type I and IV: abnormally low bicarb clearance Low values mean lots of bicarb combined with the excess H and was turned into H20 + CO2

Question 48

Explain a quick differential diagnosis for the types of RTA

Answer 48

Is there Fanconi? Type II Is there hyperkalemia? Type IV If neither one, then it is Type I

Question 49

Defect in Type IV RTA

Answer 49

``` Mineralocorticoid deficiency Tubular dysfunction from obstruction or lupus Aldosterone resistance (pseudohypo...) ```

Question 50

Does RTA have a negative or normal anion gap?

Answer 50

Normal anion gap acidosis