Renal tubular Acidosis (Frequently asked topic in various PG Entrance Examinations)

The word acidosis refers to the tendency for RTA to lower the blood’s pH. When the blood pH is below normal (7.35), this is called acidemia. The metabolic acidosis caused by RTA is a normal anion gap acidosis.

There are 4 types,only 3 are clinically important.Type 3 is Combined proximal and distal type,RTA type 3 is uncommon and seen only in children.

Type 1 (Distal RTA)-Distal RTA (dRTA) is the classical form of RTA, being the first described.

Underlying Defect-Selective deficiency in H+ secetion in Distal nephron by the alpha intercalated cells.

Electrolyte imbalance-Hypokalemic Hyperchloremic Metabolic acidosis

Despite acidosis urinary PH can not be acidified and is always above 5.5,

Etiology-Renal stone,amphotericin.cirrhosis and collagen vascular disease

Treatment-Potassium Citrate

Complication-Nephrolithiasis  (related to alkaline urine, hypercalciuria, and low urinary citrate)

Type ONE=stONE

Type 2 (Proximal rRTA) MOST COMMON TYPE OF RTA IN CHILDREN

Underlying Defect-Defect in proximal tubules’s ability to adequately reabsorb filtered HCO3 ions.

Electrolyte imbalance-Hypokalemic,Hyperchloremic Metabolic acidosis

The distal intercalated cells function normally, so the acidemia is less severe than dRTA and the urine can acidify to a pH of less than 5.3

Etiology-Carbonic Anhydrease inhibitors (acetazolamide,Diamox) ,Fanconi’s syndrome

Treatment-Potassium Citrate

Complications-Rickets,Osteomalacia

Di-hard Fan of Type 2

Type 3 

In some patients, their RTA shares features of both Distal RTA and Proximal RTA.

A transient phenomenon in infants and children with dRTA (possibly in relation with some exogenous factor such as high salt intake) and is no longer observed.

This form of RTA has also been referred to as juvenile RTA.

Underlying Defect-inherited carbonic anhydrase II deficiency

Type 4-MC type RTA IN ADULTS

Underlying Defect-Hyporeninemic hypoaldosteronsim leads to defect in Na absorption,H+ and K+ excretion,Dcrease ammoniagenesis and Increase K+

Electrolyte Imbalance-Hyperkalemic,Hyperchloremic Metabolic acidosis

Etiology-MC found in Diabetic nephropathy,tubulointerstitial reanal disease and hypertensive nephrosclerosis.

Aldosterone deficiency (hypoaldosteronism)- Primary vs. hyporeninemic

Aldosterone resistance-
Drugs: NSAIDs, ACE inhibitors and ARBs, Eplerenone, Spironolactone, Trimethoprim, Pentamidine

Treatment-Furosemide,Kayexalate

Complications-Hyperkalemia

Image

Image

Advertisements

MODY : MATURITY ONSET DIABETES OF YOUNG ( AIIMS MAY 2O13 )

Q1] Most common mutation found MODY…..[AIIMS 2013]
[A] HNF 4 alpha
[B] Glucokinase
[C] HNF 1 alpha
[D] HNF 1 beta

OR

Q2] Most common mutation leading to full blown diabetes in  MODY…..
[A] HNF 4 alpha
[B] Glucokinase
[C] HNF 1 alpha
[D] HNF 1 beta

IMPORTANT POINTS : Maturity Onset Diabetes of Young (MODY)

[1] Diabetes due to a single gene defect leading to defect in beta cell function without beta cell loss.

[2] Four salient points defining MODY

[a] Autosomal dominant with high penetrance.

[b] Early onset < 25 years

[c] No obesity

[d] No islet cell autoantibodies and NO insulin resistance syndrome

*******TYPE 1 DIABETES MELLITUS  is a autoimmune disease were beta cell destruction is caused primarily by T cell. Also note that autoantibodies against beta cell  r present in 70% of patients.

[3] MODY accounts for 1- 5 % of all diabetes cases.

About 50 % cases of MODY are caused by mutation in gene that codes for GLUCOKINASE . Another 40 % of cases are caused by 5 genes that encodes transcription factors nvolved in pancreatic development or insulin regulation. [ ref ; MEDICAL GENETICS 4ed/page 252 ELSEVIER PUBLICATION].

GLUCOKINASE mutations result in stable, mild fasting hyperglycaemia with a threshold for glucose-stimulated insulin release typically 6·6–7·2 mmol/l. Complications are rare, and generally glucokinase-related diabetes does not require any therapy ie MODY 2 doesnt usually leads to  full blown diabetes. [Ref : MEDSCAPE]

Most common MODY leading to full blown diabetes = MODY 3.

This is all i could get on this topic. The ans to this q remains a controversy for me as im yet to find a reference of any other text book stating MODY 3 to be commner( Though various internet references are mentioning MODY 3 to be commner ) .Now u r free to chose ur ans , answer to q2 is no doubt MODY 3 but answer to q1 =? . Most would go with MODY 3 even for q1. 🙂

[4] FORMS OF MODY

[a] MODY 1 = HNF 4 alpha

[b] MODY 2 = GLUCOKINASE

[c] MODY 3 = HNF 1 alpha

[d] MODY 4 = IPF 1 ( insulin promoting factor )

[e] MODY 5 = HNF 1 beta

[f]  MODY 6 = Neuro D1

[5] MODY 2 = It is associated with a mild form of nonprogressive hyperglycemia that is usually managed with diet alone. Individuals with GCK MODY rarely have overt symptoms of diabetes, and diabetes-associated complications are rare.

[6] MODY 1 , MODY 3 , MODY 5 = Full blown diabetes

[7] IPF 1 GENE = [A] If heterozygote mutation = MODY 4

[B] If homozygote mutated state = pancreatic agenesis.