Acid/Base Saleem Bharmal 1/6/2009

HPI: 75 year old M with PMHx of DM, HTN, CKD (baseline Cre 3.0), bladder cancer s/p resection and orthotopic neobladder who was initially admitted for workup of intermittent chest pain. On admission labs patient was noted to be in acute on chronic renal failure with a Cre of 4.9 and was noted to have a serum HCO3 of 7. Patient at time of admission described some shortness of breath and weakness. He denied any diarrhea, recent illness or nausea/vomiting. He did state that he his urine contained more mucous which in the past represented possible infection of the neobladder. Patient wife straight cath neobladder daily and flushes it. Per patient wife he has a night bag to collect urine and is usually full in the AM, but she noticed over the last few night the amount of urine in the bag has progressively declined.

Past Medical History IDDM CKD stage IV, baseline Cre 3.0 Bilateral Renal Artery stenosis; s/p RAS stent to R CAD s/p stent S/P bladder resection for neoplasm and orthotopic neobladder Anemia COPD (FEV1 65%) Hyperlipidemia

Outpatient Medications Aspirin Plavix Imdur NPH Diltiazem Labetalol Ranitidine Valsartan Repaglinide Albuterol Spiriva Vit D Zocor KCL 20meq daily Lasix 20mg daily prn (for leg swelling)

Physical Exam T 97.2 P 87 BP 157/55 R 16 O2Sat 97% Wt 66 kg Gen: Elderly male in NAD. Pt did not appear short of breath of tachypnic HEENT: MMM, no elevated JVD appreciated Heart: S1/S2 no murmurs Pulm: Clear to auscultation b/l, no crackles or wheeze Abd: soft, NT ND; + bowel sounds, medial surgical scar well healed Ext: +1 pitting edema in LE bilaterally up to the knees Neuro: AAOx3

Admission Labs and Studies WBC 10.7/HGB 8.3/HCT 25.7/PLT 99 Na 140/K 4.7/CL 119/HCO 7/BUN 103/Cre 4.9/Gluc 112/Ca 8.0 Anion Gap: 14 Urinalysis: Yellow/clear/neg gluc/neg bili/neg ketones/ SG 1.011/trace blood/pH 7.0/prot 30/neg nit/+ leuk/4-8 WBC/1-3 RBC CXR: No evidence of focal consolidation, vascular congestion, or pleural effusions

Brief Hospital Course Once admission labs were obtained ABG was drawn which revealed: ABG: 7.11/20.0/157/HCO3 6.0/lact 0.3 (This shows a primary metabolic acidosis with appropriate respiratory compensation)

Brief Hospital Course Given the elevated creatinine patients ARB and lasix were held. He had urine electrolytes sent as well as renal ultrasound done: Urine: Na 18 K 40 Cl 8 Cre 95 Osmolality 327 Calculated urine anion gap: (18+40) – (8) = + 50 Renal U/S: No hydronephrosis; R 10cm L 9.6cm

Brief Hospital Course Given the low urine Na and decreased urine output it was suspected that patient’s acute on chronic renal failure could be secondary to prerenal azotemia from intravascular volume depletion. Patient was started on 3amp NaHCO3 in d5W (134 meq NaHCO3) at 75ml/hr and started on bicitra tabs 30ml po bid. NaHCO3 gtt was then increased to 125ml/hr and Bicitra increased to 30ml q6.

Brief Hospital Course With IVF his Cre improved and returned to baseline of 3.0 over 3 days. HCO3 gtt was stopped after two days and serum HCO3 increased to 20. He was maintained on oral Bicitra. A urine culture was sent, given WBC on U/A and increased mucosal discharge from bladder, which grew back positive for Klebsiella Pneumoniae

Differential of etiology of metabolic acidosis Patient from, previous labs, at baseline appeared to have an underlying metabolic acidosis with a serum HCO3 between He was also noted to have a chronic hypokalemia requiring him to take KCL supplementation. Patients underlying metabolic acidosis could be from CKD, neobladder, Type I RTA (not type II RTA as urine pH 7.0 prior to getting HCO3 load). During admission patient had a more severe metabolic acidosis than his baseline which could be attributed to acute renal failure and or UTI in setting of neobladder.

Neobladder and other urinary diversion and reconstructions Ureterosigmoidostomy: First surgical technique used, ureters are implanted into the sigmoid colon and the anal sphincters were relied upon to provide continence. No longer used as complications include chronic UTI and decline in renal function, hyperchloremic acidosis, and development of secondary cancers in the sigmoid colon Ileal loop conduit: Urine is directed from the ureters through a segment of isolated ileum to the surface of the abdominal wall. Urine is collected continuously via ostomy. Orthotopic neobladder: Internal reservoirs that are connected to the native urethra and rely upon the external striated sphincter for continence. Reservoirs are constructed from a segment of detubularized intestine (usually ileum) anastomosed to the native urinary outflow tract

Metabolic Acidosis from Ureteral Diversions Hyperchloremic metabolic acidosis can result from reabsorption of excreted metabolites through the intestinal mucosa. Colon has an anion exchange pump with luminal chloride being reabsorbed as bicarbonate is secreted Colon can also absorb ammonium, which is derived both from the urine and from urea-splitting bacteria. This patient was found to have Klebsiella UTI which can cause hydrolysis of urea into ammonium and hydroxyl ions. Severe acidosis is a major problem usually only for ureterosigmoidostomy. It is less frequent in the other procedures because they limit the amount of time that urine is in contact with bowel mucosa. In one series of 363 men with ileal neobladders, only 1 percent developed severe metabolic acidosis, although nearly one-half required some form of alkalinizing treatment due to mild acidosis.

Utility of Urine Anion Gap in this situation? Urine: Na 18; K 40; Cl 8 Calculated urine anion gap ([Na])+([K])-[Cl]: (18+40) – (8) = + 50 Urine anion gap = unmeasured anions – unmeasured cations In the setting of metabolic acidosis excretion of NH4+ (unmeasured cation) should increase if renal acidification is intact resulting in a negative value. Urine anion gap that is positive in a setting of non (high) anion gap acidosis suggests impaired H+ and NH4+ excretion which can be seen in renal failure, or type 1 and type 4 RTA

Utility of Urine Anion Gap in this situation? However in this case measurement of urine anion gap could be misleading because patient has neobladder and also may have had volume depletion. Volume Depletion: Volume depletion causes increased proximal Na retention. This causes decreased distal Na+ delivery to which impairs distal acidification (similar to Type I RTA). Distal delivery of Na+ can be reabsorbed by principal cells and can cause an electronegative luminal gradient which promotes H+ secretion. Neobladder: Colon has anion exchange pump with luminal chloride being reabsorbed as bicarbonate is secreted. This may result in lower urine Cl measurement which would give you a positive urine anion gap and may also explain the elevated urine pH in setting of metabolic acidosis.

Worsening metabolic acidosis in setting of renal failure Decreased GFR results in decreased titratable acid in the urine Decreased ammonia production and ammonium excretion Impaired ability of HCO3 reabsorption