Hrev_master [Emergency Care Journal 2015; 11:4837] [page 9] Cause of respiratory paralysis: kidney, not the lung Laxmikant Ramkumarsingh Tomar, Mukul P. Agarwal, Surender Rajpal, Amitesh Aggarwal Department of Medicine, University College of Medical Sciences (University of Delhi), Delhi, India Abstract Hypokalemia is a common electrolyte abnor- mality and if neglected, it may be fatal. This type of electrolyte abnormality is seen in distal renal tubular acidosis (RTA). Respiratory paralysis in distal RTA due to hyokalemia is a rare clinical entity described in the literature. Here we dis- cuss one such case: a 25-year-old female pre- sented with complaints of acute onset symmetri- cal weakness of bilateral lower limbs that rapidly progressed to involve trunk, upper limb and neck. Later on, she developed respiratory paraly- sis and was put on mechanical ventilation. Diagnosis of distal RTA with hypokalemia was made and managed successfully. Introduction Distal renal tubular acidosis (RTA) is a rare renal disorder, characterized by normal anion gap, hyperchloremic acidosis and hypokalemia, and failure to secrete acid into the urine. Respiratory paralysis due to distal RTA is an even rarer phenomenon and should be distinguished from familial periodic paraly- sis (FPP), as management of disease can increase the severity of the other. Case Report A 25-year-old female presented with acute onset weakness of both lower limbs for eight hours prior to admission. Onset of weakness started with both lower limbs within half an hour of getting up in the morning. It rapidly progressed to involve trunk, upper limbs and neck in the matter of six to eight hours. Weakness was symmetrical in pattern, first involved distal muscles, later on proximal ones and associated with heaviness in calf prior to onset of weakness. She had no history of fever, vomiting or diarrhea. There was no symptom or signs suggestive of hyperthyroidism or hypothyroidism. Patient denied any history of heavy meal intake, exposure to cold or heavy exercise prior to this weakness. No past histo- ry of dry eyes, dry mouth, dry skin, rash, photo- sensitivity, alopecia, jaundice, blood transfu- sion could be elicited. There was no history of hypertension, diabetes mellitus or past expo- sure to chemicals and toxins or any drug intake. No history of similar weakness previ- ously was elicited. Family history was unre- markable. At the time of presentation, she was con- scious, oriented. She was afebrile, pulse rate was 86/min and blood pressure was 113/72 mm Hg. Neurological examination showed flaccid limbs (power 0/5) with decreased tone in all limbs. The deep tendon reflexes and neck hold- ing were absent. Rest of systemic examination was normal. In the evening, the patient was found to have developed heaviness and droop- ing of both eyelids without involvement of extraocular muscles and pupillary sparing, fol- lowed by labored breathing and was found to be using accessory muscles of respiration. Her single breath count was 10. She was intubated and mechanically ventilated. Routine blood group chemistry revealed hemoglobin 9.7 g/dL, total leukocyte count 11,400 /mm3, blood urea 39 mg/dL, serum cre- tanine 1 mg/dL, serum sodium 145 mEq/L, serum potassium 1.6 mEq/L, blood sugar 84 mg/dL, corrected serum calcium 7.3 mg/dL, phosphorus 3.1 mg/dL, serum albumin 3.1 g/dL, intact parathyroid hormone 78 pg/mL (normal range: 7-65 pg/mL) and vitamin D levels were within normal limits. Her arterial blood gas analysis (ABG) pH 6.99, HCO3– 15.3 mE/L, pCO2 67 mm Hg, chloride 108 mEq/L, and anion gap 9. Urinary examination revealed pH 7.8 and positive urinary anion gap. Antinuclear antibodies (ANA), HbSAg, anti HCV, thyroid profile, anti SS-A & anti SS-B tests were nega- tive. There were hypokalemic changes, U waves and ST depression in electrocardiogram (ECG) (Figure 1). X ray kidney ureter bladder (KUB) showed bilateral renal calculi (Figure 2). Abdominal sonography showed normal size kidney with bilateral renal calculi. In the view of the above findings of acute flaccid quadriparesis, metabolic acidosis, hypokalemia, hypocalcemia, alkaline urine, a diagnosis of distal (type I) renal tubular acido- sis leading to hypokalemic paralysis was made. Patient was managed on intravenous potassi- um chloride in 20% mannitol, syrup potassium citrate and oral sodium bicarbonate. Her ECG changes were reverted (Figure 3). After being mechanically ventilated for two days, she made unprecedented recovery in terms of recovery of motor weakness, in the order of: diaphragm, ocular muscles causing ptosis, distal lower limb, neck, upper limb, trunk, proximal lower extremity. Discussion Distal RTA is a disorder of tubular acid transport. It is characterized by a normal anion gap hyperchloremic metabolic acidosis, with hypokalemia and failure to acidify urine below 5.5 despite systemic acidosis. It differs from uremic acidosis which is associated with a high anion gap. Kalita and colleagues showed that out of 52 patients with hypokalemic periodic paralysis, only seven (13.5%) had distal RTA.1 Only few cases are reported in the literature that showed respiratory paralysis due to hypokalemia in distal RTA. Distal RTA is of two types: inherited or acquired. Autosomal-reces- sive form presents in infancy, whereas autoso- mal-dominant form may not present until young adulthood.2 Acquired forms of distal RTA may be due to drugs like amphotericin B, toluene toxicity, infections like pyelonephritis or hepatitis and autoimmune diseases like Sjogrens syndrome or lupus.3,4 It often presents as hypercalciuria, nephrocalcinosis, rickets or osteomalacia, and growth retardation in chil- dren with progress to short stature in adult life.During stressful condition or fever in RTA, acidosis and hypokalemia may be life threaten- ing. Ventricular fibrillation and even nocturnal death have been reported with RTA.5 Emergency Care Journal 2015; volume 11:4837 Correspondence: Laxmikant Ramkumarsingh Tomar, Department of Medicine, University College of Medical Sciences (University of Delhi), Dilshad Garden, 110095 Delhi, India. Tel: +91.9650082899. E-mail: drlaxmikantucms@yahoo.com Key words: Renal tubular acidosis; Hypokalemia; Respiratory paralysis. Contributions: LRT, total workup of patient done while patient was admitted and during her follow up; MPA, final draft of paper and help in manage- ment of patient; SR, help in management of patient; AA, contribution in writing of the manu- script; all the authors have seen the final manu- script and approved it for submission. Conflict of interest: the authors declare no poten- tial conflict of interest. Received for publication: 23 November 2014. Revision received: 16 January 2015. Accepted for publication: 19 January 2015. This work is licensed under a Creative Commons Attribution 3.0 License (by-nc 3.0). ©Copyright L.R.Tomar et al., 2015 Licensee PAGEPress, Italy Emergency Care Journal 2015; 11:4837 doi:10.4081/ecj.2015.4837 Non co mmerc ial us e o nly [page 10] [Emergency Care Journal 2015; 11:4837] Inhibition/dysfunction of certain ion exchangers and certain antibodies in distal renal tubular cells causes less H+ secretion in distal renal tubular cells and leads to metabolic acidosis:6-8 absence or nonfunctioning H+- ATPase in the apical part of renal tubule caus- es decrease of H+ excreation from intercalated cells; deficiency or malfunctioning of cytoplas- mic anion-exchanger 1 (HCO3/Cl-ATPase) in the basal membrane prevents HCO3 resorption and less H+ formation and excretion; higher antibody titres against carbon anhydrase II diminishing H production for secretion. The electronegative gradient that was gen- erated by distal sodium resorption is therefore compensated by enhanced K excretion in the principal cells in order to balance electronega- tivity. Also, the metabolic acidosis can lead to less sodium absorption in the proximal tubule due to low glomerular filtrated bicarbonate that creates a hyperreninaemic hyperaldos- teronism state ultimately leads to distal sodi- um reabsorption and potassium wasting. The diagnosis was mainly made by serum electrolytes, ABG, urinary pH, 24-hour urine citrate and calcium, ECG and USG. In general, if the test is non-conclusive an acid load test can often be performed. The mainstay of treat- ment for distal RTA is to replenish potassium and bicarbonate levels with intravenous and oral potassium chloride or potassium citrate and oral sodium bicarbonate respectively. Close differential diagnosis is FPP. It should be distinguished clinically by history and also on the basis of ABG. The onset in FPP is before the age of 16, with history of episodic flaccid weakness and these episodes are precipitated by carbohydrate-rich meals, emotional or phys- ical stress, alcohol ingestion, and cold expo- sure. There is rarely involvement of ocular, bulbar, and respiratory muscles.9 There is redistribution of K+across the cell membrane in skeleton muscle due to mutation in two genes i.e. voltage-gated calcium or sodium channel (CACNA1S and SCN4A).10 Therefore, administration of sodium bicarbonate in FPP causes intracellular shift of potassium into cells and further produces hypokalemia. Acetazolamide and oral potassium supplement is the treatment modality for FPP. Generally, correction of the serum pH and bicarbonate levels reduces renal potassium wasting by diminishing distal sodium delivery, but sometimes mild hypokalaemic state can persist and can be corrected by simultaneous potassium supplementation. Administration of acetazolamide in distal RTA is contraindicated as it produces more hypokalemia. Case Report Figure 1. Electrocardiogram showed ST depression and U waves suggestive of hypokalemic changes. Figure 2. X ray abdomen showed bilateral renal calculi. Figure 3. Electrocardiogram changes reverted after correction of hypokalemia. Non co mmerc ial us e o nly [Emergency Care Journal 2015; 11:4837] [page 11] Conclusions Every patient with hyperchloremic metabol- ic acidosis associated with unexplained hypokalemia should be assessed for RTA, as hypokalemia may cause quadriparesis or it may end up in a life threatening complication like respiratory paralysis. This should also be differentiated from FPP especially during acute attack, as management of one disease increases the severity of the other. References 1. Kalita J, Goyal G, Bhoi SK, et al. Comparative study of thyrotoxic periodic paralysis from idiopathic hypokalemic periodic paralysis: an experience from India. Ann Indian Acad Neur 2012;15:186- 90. 2. Karet FE. Inherited distal renal tubular acidosis. J Am Soc Nephrol 2002;13:2178- 84. 3. McCurdy DK, Frederic M, Elkinton JR. Renal tubular acidosis due to ampho- tericin B. New Engl J Med 1968;278:124- 30. 4. Carlisle EJ, Donnelly SM, Vasuvattakul S, et al. Glue-sniffing and distal renal tubular acidosis: sticking to the facts. J Am Soc Nephrol 1991;1:1019-27. 5. Brenner BM. The kidney. 7th ed. Philadelphia, PA, USA: Saunders; 2004. 6. Christensen KS. Hypokalemic periodic paralysis secondary to renal tubular acido- sis. Eur Neurol 1985;24;303-5. 7. Walsh S, Turner CM, Toye A, et al. Immunohistochemical comparison of a case of inherited distal renal tubular aci- dosis (with a unique AE1 mutation) with an acquired case secondary to autoim- mune disease. Nephrol Dial Transplant 2007;22:807-12. 8. Han JS, Kim GH, Kim J, et al. Secretory- defect distal renal tubular acidosis is asso- ciated with transporter defect in H(+)- ATPase and anion exchanger-1. J Am Soc Nephrol 2002;13:1425-32. 9. Takemoto F, Hoshino J, Sawa N, et al. Autoantibodies against carbonic anhy- drase II are increased in renal tubular aci- dosis associated with Sjogren syndrome. Am J Med 2005;118:181-4. 10. Sternberg D, Maisonobe T, Jurkat-Rott K, et al. Hypokalaemic periodic paralysis type 2 caused by mutations at codon 672 in the muscle sodium channel gene SCN4A. Brain 2001;124:1091-9. Case Report Non co mmerc ial us e o nly