2A 38y/o woman with periodic weakness & vomiting Dr.EtminanDr.Saeedi
3Case Peresentation CC:periodic weakness & vometing PI:She presented with complaining periodic weakness & vometing of from 6months before.Approximately 6month ago she complains N/V without headache,vertigo,dysphagia,chest pain,abdominaln pain & dysuria .but she complains of anorexia ,flunk pain,constipation ,bloating,no related with feeding. She has 4kg Wt loss in duration 6month ago.Her weakness was related with vomiting,periodic & in proximal muscle.weakness no progress at afternoon
4PMH:Due to new symptoms she had history of several admission ,surgical consult&endoscopy but she had not any improvement & referred to this center,,,In past history she had renal colic & nephrolithasis & ESWLshe has not history of other problem or surgical in past medical
6Familial historyThere is not history of disease or cancer in her family
7Social & habitual history No smoking or using opiumShe distributed her social communication because this problem
8R .O.S:NO headache,vertigo or hearing lossNO hair loss,ulcer in mouth or photo senNO dry mouth or eyeNO dysphagia or odinoohagiaNO chest pain or dyspneaNO abd pain but constipation & bloating &flunk painNO problem in mens or dysuria but frequency &nacturiaNO sweeling of joint or stiffness
9She complains muscle pain but no bone pain& unable to perform specific tasks, such as climbing stairs or combing hair.NO complain of changing color hands in cold waret or skin problems
10Physical Exam She was ill but not toxic & not in acute distress T:37.1 Ax at night BP: 110/80, PR: 89, RR :21O2 sat: 95%pale no ichteric no tenderness on PNsNo lymphadenopathyTemporal wastingNo HoarsenessNo up jvp &no thyromegaly
11Chest examination Revealed equal bilateral breath sounds, with no wheezes & bilateral clearShe had a normal S1&S2 sound and no murmurs.
12Abdomenwas soft and nontender, with no masses or hepatosplenomegaly.no CVA tendernessExtno peripheral edemaand no rash, telangiectasia, or other skin changesno clubbing.joints revealed no warmth, swelling, erythematic, tender prox muscle
13Nourologic exam:Cranial & prieferal ner NL No ptosis,gag nlDTR +2Muscle force: upper(prox4/5 dist5/5)lower(prox3/ dis5/5)
14Problem list:A 38y/o woman with periodic weakness & vomiting about 6 month before that vometing no related with feeding but related with weakness constipation bloating.Weakness is in prox muscle,tender.
24ENDOSCOPY:NLAbd CT: nephrocalcinosis both kidnyAbd sono:diffuse nephrocalcinosis in both kidney(Nephrocalcinosis is characterized by the deposition of both calcium oxalate and calcium phosphate paranchyma and tubules).
30Problem list:A 38y/o woman with periodic weakness & vomiting 6 month before, that no related with feeding but related with weakness constipation bloating.Weakness is in prox muscle,tender.K:2/ metabolic acidosis AG:nl urine PH:8 ca:8/1 p:1/8 nephrocalcinosis CXR
38Severe muscle weakness or rhabdomyolysis . The pattern of weakness in hypokalemia is similar to that associated with hyperkalemia. Weakness usually begins in the lower extremities, progresses to the trunk and upper extremities, and can worsen to the point of paralysis.In addition to causing muscle weakness, severe potassium depletion (serum potassium less than 2.5 meq/L) can lead to muscle cramps, rhabdomyolysis, and myoglobinuria . Potassium release from muscle cells during exercise normally mediates vasodilation and an appropriate increase in muscle blood flow . Decreased potassium release due to profound hypokalemia can diminish blood flow to muscles during exertion, leading to ischemic rhabdomyolysis . A potential diagnostic problem is that the release of potassium from the cells with rhabdomyolysis can mask the severity of the underlying hypokalemia or even lead to normal or high values.
39Respiratory muscle weakness Involvement of gastrointestinal muscles, resulting in ileus and its associated symptoms of distension, anorexia, nausea, and vomiting.
40Cardiac arrhythmias and ECG abnormalities — A variety of arrhythmias may be seen in patients with hypokalemia. These include premature atrial and ventricular beats, sinus bradycardia, paroxysmal atrial or junctional tachycardia, atrioventricular block, and ventricular tachycardia or fibrillation . Hypokalemia produces characteristic changes on the ECG although they are not seen in all patients. There is depression of the ST segment, decrease in the amplitude of the T wave, and an increase in the amplitude of U waves which occur at the end of the T wave . U waves are often seen in the lateral precordial leads V4 to V6.
41Renal abnormalities — Prolonged hypokalemia can cause multiple structural and functional changes in the kidney . These include:Impaired concentrating abilityIncreased ammonia productionIncreased bicarbonate reabsorptionAltered sodium reabsorptionHypokalemic nephropathyElevation in blood pressureGlucose intolerance — Hypokalemia reduces insulin secretion, which may play an important role in thiazide-associated diabetes. However, worsening glucose tolerance is much less common in the era of low-dose thiazide therapy (eg, 12.5 to 25 mg of hydrochlorothiazide)
42 Nephrocalcinosisis associated with conditions that cause hypercalcemia, hyperphosphatemia, and the increased excretion of calcium, phosphate, and/or oxalate in the urine. HypocitraturiaHypercalciuria with hypercalcemiaHypercalciuria without hypercalcemiaHyperphosphaturia
43Hypercalcemia and hypercalciuria : Primary hyperparathyroidismSarcoidosisVitamin D therapyMilk alkali syndromeWilliams' syndromeCongenital hypothyroidism
44Hypercalciuria without hypercalcemia : Distal (type 1) renal tubular acidosis — Distal (type 1) renal tubular acidosis (RTA) is the most common cause of nephrocalcinosis (particularly in children) due to hypercalciuria without hypercalcemia . Distal RTA results in a systemic acidosis that requires increased buffering of acid by bone, with the subsequent release of bone calcium and phosphate. Metabolic acidosis is also associated with hypocitraturia, which can promote calcium precipitation in the tubules.The reported prevalence of nephrocalcinosis in patients with distal RTA ranges from 60 to 80 percent .Medullary sponge kidney
45Loop diureticsBartter syndromeChronic hypokalemia — Hypercalciuria and nephrocalcinosis have been observed in chronic hypokalemic states including primary aldosteronism and Liddle's syndrome . Nephrocalcinosis and chronic hypokalemia are also seen in distal (type 1) renal tubular acidosis and Bartter syndrome but, as noted above, hypercalciuria is thought to be primarily responsible. Support for this hypothesis comes from the observation that chronic hypokalemia in Gitelman syndrome, which involves a mutation in the thiazide-sensitive sodium-chloride cotransporter in the distal tubule, is associated with hypocalciuria and the absence of nephrocalcinosis .
46Hyperphosphaturia — Hyperphosphaturia with or without hypercalciuria is a risk factor for nephrocalcinosis. Hyperphosphaturia may occur with or without hyperphosphatemia. Hyperphosphaturia and hyperphosphatemia plus acute renal failure are observed in tumor lysis syndrome and after ingestion of oral sodium phosphate bowel preparations. These acute disorders are typically characterized by microscopic nephrocalcinosis, and are discussed elsewhere.Hyperphosphaturia in the absence of hyperphosphatemia (ie, phosphate wasting), usually results from inherited tubulopathies, although acquired forms may be observed in the setting of malignancy or renal transplant.
47Hyperoxaluria —Hyperoxaluria may also be secondary to the increased enteric absorption of oxalate . Fat malabsorption is the most common cause of increased oxalate absorption .Secondary hyperoxaluria may also be due to the chronic ingestion of excessive amounts of oxalate precursors, such as vitamin C, or of foods rich in oxalic acid such as rhubarb, parsley, cocoa, nuts, or star fruit
52DISTAL (TYPE 1) RTA — Distal (type 1) RTA is characterized by an impaired capacity for hydrogen ion and therefore ammonium secretion in the collecting tubules. The impairment in hydrogen ion secretion is manifested as an abnormally high urine pH (5.5 or higher) during systemic acidosis.Distal RTA results from one of several defects in distal hydrogen ion secretion.Decreased proton pump (H-ATPase) activityIncreased luminal membrane permeability with backleak of hydrogen ionsDiminished distal tubular sodium reabsorption which reduces the electrical gradient for proton secretion
53Clinical manifestations — The clinical manifestations of distal RTA vary depending upon the underlying etiology. The recessive forms present in infancy, the dominant form later in life, and acquired distal RTA may occur at any age based upon the timing of renal tubular injury.Recessive form :Severe hyperchloremic metabolic acidosis (serum bicarbonate levels may decrease below 10 meq/L)Moderate to severe hypokalemia (serum potassium ≤ 3.0 meq/L)NephrocalcinosisVomitingDehydrationPoor growthRicketsBilateral sensorineural hearing loss in some cases with mutations of the gene that encodes B1 subunit of the H-ATPase pumpDominant form — In comparison with recessive distal RTA, dominant distal RTA is usually associated with milder disease, and presents later in life (often in adolescence and adulthood). The most common initial finding is renal stone or nephrocalcinosis. Patients typically have mild or no acidosis, mild to moderate hypokalemia, and rarely bone disease or poor growth .