2.2.2 Renal Tubular Disorders Flashcards
What is the underlying cause associated with Nephrogenic Diabetes Insipidus?
Mutations in the vasopressin receptor
Defective AQP
Failure in AQP targeting mechanisms
No response following ADH stimulation
Gitelman’s syndrome is caused by what?
Defects in the distal tubule caused by alteraltions to thiazide sensitive co-transporters or the TRPM6
What is an environmental cause of Nephrogenic Diabetes Insipidus?
Lithium
What are some symptoms of Gitelman’s syndrome?
Hyponatremia
High Urine K+
Hypercalcemia
Normotensive
What are the clinical signs and symptoms of Nephrogenic Diabetes insipidus?
Polyuria
Polydipsia
Risk of dehydration
Dilute urine with low osmolarity
Bartter’s syndrome is caused by what?
Changes in the NKCC, ROMK1, or Barttin proteins within the Loop of Henle
What can be a result of defective proton secretion?
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
Proximal tubule transporter abnormalities can include what?
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
What is the defect in proximal tubular acidosis?
Apical Na/H exchanger
or
basolateral Na/bicarbonate transporter
What is the defect in distal renal tubular acidosis?
Apical proton ATPases
What are the genetic forms of Fanconi’s syndrome?
What are the symptoms associated with Liddle’s syndrome?
Increased ECF
Hypertension
Decreased renin-aldosterone
Hypokalemia
Metabolic alkalosis
What are the symptoms of Bartter’s Syndrome?
High renin aldosterone
Hypochloremia
Polyuria
Poor muscle tone
Heart repolarization abnormalities
What are the mutated genes associated with nephronophthisis?
NPH1, 2 and 3 - coding for Nephrocystin
What are some environmental causes of Gitelman’s syndrome?
Thiazides
Explain as you would to a 5 year old what ADPKD is.
What are the genetic causes of Fanconi’s syndrome?
Cystinosis
Galactosemia
Glycogen storage disease
What are some environmental causes of Fanconi Syndrome?
Exposure to heavy metals
Expired tetracyclins, gentamicin
Toluene and derivatives
How does nephrogenic diabetes insipidus differ from non-nephrogenic?
Non-nephrogenic diabetes insipidus consists of:
Defective ADH production
Excessive Water intake
What are the signs of proximal and distal renal tubular acidosis?
Kidney stones
Hypercalcuria
Metabolic acidosis
What are the mutated genes in adult PKD?
PKD1 or PKD2
What are the two types of tubulopathies?
Mutations of the renal transport system
Acquired defects: Pharmaceutical agents or injury and inflammation
What is Fanconi’s syndrome?
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.
What are the major Kidney cystic diseases?
What is the major pathogenesis of ADPKD and cyst formation?
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.
What are the mutated genes associated with Child PKD?
PKHD1 - coding for Fibrocystin
The defect associated with Liddle’s syndrome is associated with what?
Genetic mutations in ENac subunits that allows them to be uncontrolled
