DR. SHAFIQ AHMAD

1. DR. SHAFIQ AHMAD TMO MEDICAL “B” UNIT. LRH, PESHAWAR

2. Case History A Nineteen years old thin boy presented with six months history of pain both the lumber areas with generalized abdominal cramps and body aches. He was also experiencing difficulty in walking, along with epigastric pain and occasional vomiting for the last two months. No h/o loose motion, joints pains and fever. A month ago he was again hospitalized in DHQ Nowshehra for vomiting and partially responded to anti-emetic and PPI.

3. ON EXAMINATION He was a thin lean boy of average height, afebrile and normotensive. Systemic examination was unremarkable. Gait was normal although he was complaining of pain during walking and on standing from sitting position.

4. INVESTIGATION FULL BLOOD COUNT • Hb 13gm % • TLC 7500/mm3 with normal differential count • Blood Urea 50mg % • S.Creatinine 1.1mg% • S.Calcium 8.5mg% • S.Amylase 171 U/L • Urine microscopy NAD

5. ABDOMINAL ULTRA SOUND Bilateral nephrocalcinosis

6. Serum Electrolytes & Arterial Blood Gases Analysis • S.Na+ 139meq/L • S.Cl - 113meq/L • S.K+ 3.4meq/L • PH 7.34 • PCO2 35.5mmHg • HCO3 18.4mmol/L

7. Ammonium chloride challenge test0.1 gm/kg Ammonium chloride was given orally and urinary and plasma pH recorded every two hrs. There was no drop in urinary pH below 5.4 tough the plasma pH fell to 7.30. This test confirmed the diagnosis of…….

8. DIAGNOSIS Type I distal Renal Tubular hypokalemic, hyperchloremic metabolic acidosis

9. RENAL TUBULAR ACIDOSIS • Definition : Its a systemic acidosis, resulting due to impaired ability of the Renal tubules to “ ACIDIFY” the urine normally and there will be little or no over all reduction in the Renal function test. The disease is characterized by • Hypokalemic,Hyperchloremic, metabolic acidosis with Normal Serum Anion Gape [ Na+ ( Cl+HCo3)]

10. DISEASE PRESENTATION Disease can present in different ways depending upon which aspect of Renal acid handling has been effected. • There may be defect in HCo3 reabsorption in P.C.T • Decrease Amoniogensis in D.C.T. • There may be defective proton secretion.

11. CLASSIFICATION • Type I • Type IImay be inherited or acquired • Type IV : is acquired and associated with decrease Aldasteron level or tubular Hypo responsiveness to Minerlocorticoids. • Type III (distal RTA):

12. DISTAL RTA / TYPE I characterized by: Hypokalemic , Hyperchloremic metabolic acidosis . Excess Bicarbonaturia Inability to decrease urinary PH below 5.5 all this happens because: • Of either excessive backward diffusion of H+ from lumen to the blood or….. • Inadequate transport of H+ ions.

13. ETIOLGY • CONGENITAL • Familial • Marfan syndrome • Ehler Danlos syndrome • Sickle cell disease • Hereditary elliptocytosis

14. ACQUIRED • PRIMARY may be idiopathetic • SECONDARY Various systemic diseases can lead to distal RTA

15. HYPERGAMMAGLOBULNAEIMIC STATES • Amylodosis • Cronic liver disease • Cryglobulinaemia AUTO IMMUNE DISEASE • Sjogoren’s syndrome • Thyroiditis • Auto immune hepatitis • Primary bilary cirrhosis • SLE

16. DRUGS • Amphotericine – B • Lithium • NSAID • Lead NEPHROCALSINOSIS • Chronic hyper calciurea • Medullary spongy kidney • Chronic Pyleonephritis RENAL TRANSPLANT REJECTION

17. SYMPTOMS and COMPLICATIONS: • Anorexia • Fatigue • Renal colic • Polyuria/ polydypsia • Bone pain and weakness ( due to rickets in children and osteomalacia) • Constipation • Recurrent UTI • Renal failure

18. INVESTIGATION • Electrolyte Decrease K+ , increase in Chloride • Arterial Blood Gases Analysis. Decrease in ph HCo3 less than 21 mmol/L • Urine analysis • urinary PH never below 5.5 • Decrease urinary NH4 • Increase in Ca+ • Decrease citrate level • Ammonium chloride challenge test.

19. Treatment • Treat the cause: • NaHCo3 supplement: enough Alkali should be given to filtrate the daily metabolic acid load. Usual range is 0.5 to 2mmol/kg/d. • NaHCo3 and shohls solution ( Na+ citrate 1 mmol + citric acid 1mmol) • Potassium Alkali • Thiazide Diuretic : may reduce plasma Vol and then increase PCT reabsorption and HCo3 • Vitamin D:

20. TYPE II RTA • Less common than type I • Occurs as a part of generalized disorder of P.C.T , function , presenting as • Hyper chloremic acidosis • Other features of Fanconi syndrome that is glycosuria , Aminoacidurea , phosphaturea

21. MECHANISM The main defect is failure to secrete adequate H+ ions or selective defect in the P.C.T ability to reabsorb filtered HCO3. About 90% of filtered bicarbonate is absorb by P.C.T, D.C.T has a limited ability to absorb bicarbonate . When to much bicarbonate is left in the filtrate is delivered to D.C.T, that is over whelming the absorptive capacity of D.C.T, the tubules dose not function adequately and leads to bicarbonate Urea.

22. Eventually the distal delivery of filtered HCO3 declines because the Plasma HCO3levels drops as a result of progressive Urinary loss. When Plasma HCO3 level drops to 15—18 mmol/L,the distal Nephrone will start function normally, as lower filtered load of HCO3 can be reabsorbed by P.C.T resulting in normal delivery of HCO3 to D.C.T and able to absorb all the HCO3 . At this point HCO3 Urea disappears and Urinary PH can be acidic.

23. ETLOGOY CONGENITAL Hereditary Autosomal Dominant • cystinosis • Galactosaemia • Wilson Disease • von –Greke’s Disease • Hereditary fructose intolerance

24. Acquired • Auto immune :with increase immunoglobulin e.g sjorgren,s syndrome • Drugs : acetazolamide (by inhibiting carbonic anhydrase) lead , tetracyline , copper . • Others : hyper parathyroidsim , amyloidsis, nephrotic syndrome Dysprotenanic slate i.e. myloma

25. SYMPTOMS • Polyurea • Polydypsia • Muscle weakness rare ( caused by Hypokalemic Myopathy) • Bone pain from ricket/osteomalacia –rare.

26. INVESTIGTION • FBC--- normal • UREA – Creatinin – normal S.Electrolytes S.K+ decrease Cl- increase . Decrease in Ca++ . Decrease phosphate . ABGs Decrease PH ,Decrease HCo3 URINE ANALYSIS PH increase 5.5 Aminoacidurea protein positive

27. TREATMENT • Large doses of Alkali i.e. 5-15 mmol/kg/day. Because it is rapidly excreted . • Potassium Citrate may be required • Thiazide diuretic with low salt diet reduces the amount of HCo3 required .

28. TYPE FOUR RTA This type also called HYPER KALAMIC DISTAL RTA or HYPORENIMIC HYPOALDESTERONISM --- acquired disorder

29. ETIOLOGY • Chronic interstitial nephritis • Diabetic nephropathy • Primery adrenal disease for example ADDISONS • Hereditary inborn error of steroid synthesis but it is rare • Drugs : AC inhibitor, heparin , trimethoprim , NSAID, spirnolactone. • Obstructive uropathy • Sickle cell disease

30. MECHANISM weather there is decrease Aldasteron level or Renal Resistance to the effect of Aldasteron , it reduces the ability of distal Nephrone to secret H+ ions. Hyperkalaemia is directly due to loss of Aldasteron action . This causes suppression of Renal production of NH4 which further exacerbates the Acidosis

31. SYMPTOMS • Polyurea , Polydypsia • Lion pain if reflux uropathy is present

32. INVESTIGATION S.Electrolyte S.Na + - normal ( decrease if Addison ) Increase S.K+ PH + decrease Bicarbonate decrease Ca++ Normal

33. TREATMENT Aim: To decrease K+ as acidosis usually improve once Hyperkalemic block of NH4 production is removed • Low potassium diet • Minerlocorticoids supplements i.e. FLUDROCORTISONE 0.1---- 0.2 mg/day This Minerlocorticoids replacement should not be the approach for the patients with hypertension or heart failure history

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