2.2.2 Renal Tubular Disorders

Question 1

What is the underlying cause associated with Nephrogenic Diabetes Insipidus?

Answer 1

Mutations in the vasopressin receptor

Defective AQP

Failure in AQP targeting mechanisms

No response following ADH stimulation

Question 2

Gitelman’s syndrome is caused by what?

Answer 2

Defects in the distal tubule caused by alteraltions to thiazide sensitive co-transporters or the TRPM6

Question 3

What is an environmental cause of Nephrogenic Diabetes Insipidus?

Answer 3

Lithium

Question 4

What are some symptoms of Gitelman’s syndrome?

Answer 4

Hyponatremia

High Urine K+

Hypercalcemia

Normotensive

Question 5

What are the clinical signs and symptoms of Nephrogenic Diabetes insipidus?

Answer 5

Polyuria

Polydipsia

Risk of dehydration

Dilute urine with low osmolarity

Question 6

Bartter’s syndrome is caused by what?

Answer 6

Changes in the NKCC, ROMK1, or Barttin proteins within the Loop of Henle

Question 7

What can be a result of defective proton secretion?

Answer 7

This can occur in the proximal and distal/collecting tubule.

In the proximal tubule H+ is secreted by the Na/H exchanger

In distal and collecting tubules H+ is secreted by ATPases

Question 8

Proximal tubule transporter abnormalities can include what?

Answer 8

Glucose, amino acids, and phosphate is absorbed by apical Na+ co-transporters

Protons secreted by the Na+ proton exchanger

Chloried follows the paracellular pathway and bas-dependent exchangers

Organic anions are secreted by Na-dependent and independent OAT transporters

Question 9

What is the defect in proximal tubular acidosis?

Answer 9

Apical Na/H exchanger

or

basolateral Na/bicarbonate transporter

Question 10

What is the defect in distal renal tubular acidosis?

Answer 10

Apical proton ATPases

Question 11

What are the genetic forms of Fanconi’s syndrome?

Answer 11

Question 12

What are the symptoms associated with Liddle’s syndrome?

Answer 12

Increased ECF

Hypertension

Decreased renin-aldosterone

Hypokalemia

Metabolic alkalosis

Question 13

What are the symptoms of Bartter’s Syndrome?

Answer 13

High renin aldosterone

Hypochloremia

Polyuria

Poor muscle tone

Heart repolarization abnormalities

Question 14

What are the mutated genes associated with nephronophthisis?

Answer 14

NPH1, 2 and 3 - coding for Nephrocystin

Question 15

What are some environmental causes of Gitelman’s syndrome?

Answer 15

Thiazides

Question 16

Explain as you would to a 5 year old what ADPKD is.

Answer 16

Question 17

What are the genetic causes of Fanconi’s syndrome?

Answer 17

Cystinosis

Galactosemia

Glycogen storage disease

Question 18

What are some environmental causes of Fanconi Syndrome?

Answer 18

Exposure to heavy metals

Expired tetracyclins, gentamicin

Toluene and derivatives

Question 19

How does nephrogenic diabetes insipidus differ from non-nephrogenic?

Answer 19

Non-nephrogenic diabetes insipidus consists of:

Defective ADH production

Excessive Water intake

Question 20

What are the signs of proximal and distal renal tubular acidosis?

Answer 20

Kidney stones

Hypercalcuria

Metabolic acidosis

Question 21

What are the mutated genes in adult PKD?

Answer 21

PKD1 or PKD2

Question 22

What are the two types of tubulopathies?

Answer 22

Mutations of the renal transport system

Acquired defects: Pharmaceutical agents or injury and inflammation

Question 23

What is Fanconi’s syndrome?

Answer 23

Fanconi syndrome is a generalized reabsorptive defect of the proximal tubule.

The clinical features of proximal renal tubular acidosis are:

Polyuria, polydipsia and dehydration

Hypophosphatemic Rickets (in children) and osteomalacia (in adults)

Growth failure

Acidosis

Hypokalemia

Hyperchloremia

Other features are:

Hypophosphatemia/Phosphaturia

Glycosuria

Proteinuria/Aminoaciduria

Hyperuricosuria

There are different diseases underlying Fanconi syndrome. They can be inherited as well as acquired.

Question 24

What are the major Kidney cystic diseases?

Answer 24

Question 25

What is the major pathogenesis of ADPKD and cyst formation?

Answer 25

Renal epithelial cells have an apical cilium.

The primary cilium of renal tubular cells has been proposed to function as an antenna that senses fluid flow in the lumen. The shear stress from bending the cilium activates the polycystins. These are composed of two polypeptides, Polycystin 1 and 2, which forms a complex at the ciliar plasma membrane that functions as a calcium channel. Once activated, the polycystins allow calcium entrance in the cells. Once in the cytoplasm, this calcium acts on intracellular stores to produce additional release of calcium. The amplified signal regulates different processes in the cells, including cell growth and differentiation by influencing gene transcription. It has also been proposed that the intracellular calcium can regulate K+ channels in the apical membrane of the cells.

Alterations in the polycystins results in their lack of function and polycystic kidney disease. This is the most common inherited disease of the kidney, characterized by the formation and development of numerous fluid-filled cysts that distort the structure and impair the function of the kidneys. Eventually the disease progresses to end-stage renal disease and renal failure.

Question 26

What are the mutated genes associated with Child PKD?

Answer 26

PKHD1 - coding for Fibrocystin

Question 27

The defect associated with Liddle’s syndrome is associated with what?

Answer 27

Genetic mutations in ENac subunits that allows them to be uncontrolled