Renal Tubular Disorders

Question 1

Renal Blood flow is

Answer 1

1250 ml/min

Question 2

Proximal Tubule

Answer 2

Busy, metabolically active cells to reabsorb and excrete things out via active transport

Many mitochondria (Na gradient generated by Na/K ATPases)

Vulnerable to hypoxia (as need lots of oxygenated blood)
Vulnerable to toxicity

Question 3

Renal Glycosuria (PCT disorder)

Answer 3

Sodium glucose transporter 2 (SGLT2) fails to reabsorb glucose so glucose present in urine

These transporters can be manipulated and blocked so more sugar is excreted- can be used in type 2 diabetes treatment

Also SGLT2 inhibitors used in heart failure and kidney disease.

Question 4

Aminoaciduria: Cystinuria

Answer 4

Renal basic amino acid transporter (rBAT) fail to reabsorb the amino acid cystine so present in urine.
Leads to stone formation. Also causes renal colic.

Treated by high fluid intake so there is lower concentration.

Can alkalinise the urine which makes it harder to crystallise.

Also can use chelation (binds to cystine to stop it getting into urine) - eg penicillamine, captopril

If none of these work, surgery to remove stones.

Question 5

Hypophosphataemic rickets

Answer 5

X-linked hypophosphateaemic rickets (XLH)
A proteases is dependent on the co-transporter so
Causes bow-legged deformity, impaired growth

Treated by phosphate replacement

Question 6

Carbonic anhydrase catalyses what reactions?

Answer 6

H2CO3 –> H+ + HCO3- in the tubular cells

H2CO3 —> H2O + CO2 in the tubular lumen

Question 7

Disorders of carbonic anhydrase

Answer 7

Genetic defects cause a mixed proximal /distal renal tubular acidosis.

Acetaxolamide inhibits causing mild diruetic effect and induces a metabolic acidosis

Used to treat altitude sickness

Question 8

Proximal (Type 2) renal tubular acidosis

Answer 8

Na/H antiporter defect so failure to reabsorb bicarbonate.
Causes acidosis, impaired growth.
Treated by bicarbonate supplementation.

Question 9

Fanconi Syndrome (PCT dysfunction)

Answer 9

Possibly due to failure to maintain Na gradient

Clinical features include all PCT disorders (Glycosuria, aminoaciduria, phosphaturic rickets, renal tubular acidosis)

Caused by genetics, myeloma, lead poisoning, cisplatin

(This is different to Fanconi anaemia)

Question 10

Loop of Henle

Answer 10

Generates medullary conc gradient

Active sodium reabsorption in thick ascending limb

Question 11

Thick ascending limb function

Answer 11

Many channels involved to move calcium and magnesium into blood via chloride sodium and potassium ion channels. (check this is correct)

Question 12

Barrter’s syndrome

Question 13

Distal Tubule and collecting duct

Answer 13

DT allow fine tuning of sodium reabsorption, potassium and acid-base balance

CD mediates water reabsorption and urine concentration

Question 14

Gitelman’s syndrome

Answer 14

Defect in NCCT (thiazide sensitive chloride channel) causes failure of the sodium-chloride cotransport in DT
Hypokalaemic alkalosis due to volume contraction, impaired Mg absorption, increased Ca reabsorption.

Causes polyuria, polydipsia and tetany.

Question 15

Actions of aldosterone

Answer 15

Steroid hormone which increases expression of ENaC and Na/K ATPase

Question 16

Distal (type 1) renal tubular acidosis

Answer 16

Luminal H+ ATPase or H+/K+ ATPase defects.

Means there is a failure of H+ excretion and urinary acidification.

Can be genetic.

Question 17

Liddle’s syndrome

Answer 17

Activating mutation of ENaC so sodium channels always open so constant aldosterone like effect.

Treated by blocking ENaC with Amiloride

Question 18

Hyperkalaemic distal (type 4) renal tubular acidosis

Answer 18

Low aldosterone levels, reduced generation of electrochemical gradient means failure of H+ and K+ excretion.

Common in elderly patients with diabetes.

Treated with diuretics of fludrocortisone

Question 19

Nephrogenic diabetes insipidus

Answer 19

defect in vasopressin V2 receptor or aquaporin 2 water channel. This means there is a failure of water reabsorption in CD.

Causes polyuria, polydipsia, hypernatremia.

(used to tell between insipidus diabetes by tasting the urine! Insipidus means tasteless as very diluted.)