A Case of Bartter's Syndrome
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A Case of Bartter's Syndrome

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  • ypoklaemia

A Case of Bartter's Syndrome A Case of Bartter's Syndrome Presentation Transcript

  • DR.G.BALAJI PROF.DR.G.SUNDARAMURTHY’S unit- M6
    • 40 year male presented with weakness of both lower limbs of 4 hours duration.
    • Sudden onset, involving both lower limbs simultaneously.
    • He feels the limbs are lifeless.
    • No h/o involvement of upper limbs, trunk muscles, neck muscles.
    • No h/o any sensory disturbances.
    • No bowel or bladder disturbances.
    • No h/o trauma, back pain, fever , myalgia.
    • No h/o diarrhoea, vomiting, abdominal pain.
    • No h/o dysuria, hematuria, oliguria.
    • No h/o headache , blurring of vision, syncope attacks, seizures
    • no h/o chest pain cough, dyspnea, palpitations, hemoptysis.
    • No h/o any heavy meals.,exercise
    • Past history:
    • Not a case of DM, SHT, IHD, PT, Bronchial asthma.
    • No h/o drug intake , fever, diarrhoea.
    • No similar episodes in the past.
    • Left upper limb amputated above elbow following a trauma.
    • Personal history:
    • Alcohol consumer. last consumption 5 days ago.
    • No h/o smoking, drug addiction, extra marital , or premarital affairs.
  • Acute paraparesis
    • Guillain- Barre syndrome
    • Cns-
    • para sagittal meningiomas
    • Anterior cerebral artery ischemia
    • Superior sagittal or cortical venous thrombosis
    • Acute hydrocephalus
    • Spinal cord
    • Intra spinal lesion in mid thoracic level
    • Spinal lesions-
    • Compressive lesions- ivdp, tumour abscess or hematoma, malignancy.
    • Vascular- spinal cord infarction, av fistula,
    • Transverse myelitis.
    • ( no sensory loss or upper level of lesions.)
    • Cauda equina lesions:
    • Trauma, mid line disc herniation, intra spinal tumour- sphincter is affected.
    • Anterior horn cell disease- polio
    • Guillain- Barre syndrome
    • Myopathy.
    • Periodic paralysis
  • examination
    • Pt conscious, oriented, afebrile
    • Obeys commands.
    • Not dyspneic or tachypneic.
    • No Icterus/ cyanosis/ clubbing/ pedal edema/ lymph node enlargement.
    • Pulse: 80/ min regular, normal volume and character. All peripheral pulses felt equally in all 4 limbs.
    • BP: 110/70 mm Hg in RUL.
    • RR: 14 /min , abdomino thoracic.
    • CVS: S1, S2 heard. No murmurs.
    • RS: NVBS. No added sounds
    • P/A: soft non tender,
    • No organomegaly, no free fluid.
    • No mass.
  • Central nervous system
    • Higher functions :
    • Pt is conscious, oriented to time, place and person.
    • Speech intact.
    • Memory normal.
    • CRANIAL NERVES :
    • Normal.
    • Motor system
    • upper limb right left- amputated
    • Bulk normal
    • Tone normal
    • Power 4/5
    • Reflexes:
    • DTR biceps +
    • triceps +
    • supinator +
    • Superficial abdominal +
    • Lower limbs right left
    • Bulk normal normal
    • Tone reduced reduced
    • Power 1/5 1/5
    • Reflexes
    • knee absent absent
    • Ankle absent absent
    • Plantar no response no response
    • No axial muscle weakness
    • SENSORY SYSTEM
    • Touch,Pain , temperature : present
    • Vibration, joint position: present.
    • Cortical sensation: intact.
    • Spinal vibration: present
    • Cerebellum ;
    • Upper limbs: no cerebellar signs
    • Lower limbs; could not be examined.
    • GAIT:
    • Could not be examined.
    • Skull and spine – NORMAL.
    • SPINAL VIBRATION – present at all levels
    • Problems
    • (Apparent) paraparesis of sudden onset- hours
    • Areflexia in lower limbs
    • Bowel and bladder : not involved
    • Sensations- intact.
    • No spinal tenderness.
    • No signs of increased ICT.
    • AIDP- Guillain Barre syndrome
    • Channelopathies- Hypokalemic periodic paralysis
  • Investigations
    • CBC:
    • Hb- 14.5 g
    • TC- 5400
    • DC: P- 64, L-36
    • ESR- 6/12
    • PCV: 42%
    • Platelets- 1.5 lakhs.
    • RFT:
    • UREA- 26 mg
    • Creatinine- 1.1 mg
    • Urine routine-
    • Albumin- nil
    • Sugar- nil,
    • deposits- nil
    • Pus cells- nil
    • Chest X-RAY: normal
    • ECG - flat P wave, U wave, prolonged QT interval.
    • ELECTROLYTES:
    • Sodium: 137 meq/l
    • Potassium- 1.3 meq/l
    • Chloride- 88 meq/l
    • Bicarbonate- 33 meq/l
  • diagnosis
    • Hypokalemia -?cause
    • Treatment
    • IV Potassium- 20 meq of KCl.
    • Oral KCl- 25 ml/ hr.
    • Patient regained power in lower limbs.
    • Reflexes returned.
    • Pt was able to walk.
    • HYPOKALEMIA:
    • REDUCED INTAKE
    • RENAL WASTING - most common cause
    • TRANS CELLULAR SHIFT.
  • Hypokalemia
    • plasma K+ concentration <3.5 mmol/L,
    • CAUSES:
    • I. Decreased intake  ( Seldom a sole cause for K+ depletion) 
        • A. Starvation
        • B. Clay ingestion (Geophagia – binds dietary K+ and Fe)
    •   II. Redistribution into cells   
    • A. Acid-base    
    • 1. Metabolic alkalosis ( 1.K+ redistribution into cell 2.Excess renal loss)   
    • B. Hormonal    
    • 1. Insulin (Stimulation of Na H antiporter and secondary activation of NA K ATP ase pump)
    • 2. beta-Adrenergic agonists (1.Directly induces cellular uptake of K+ 2.Stimulates insulin secretion)
    • 3. alpha-Adrenergic antagonists
    • C. Anabolic state  (D/T K+ shift into newly formed cells)  
      • 1. Vitamin B12 or folic acid ( RBC production)
      • 2. Granulocyte-macrophage colony stimulating factor (white blood cell production)
      • 3. Total parenteral nutrition  
    •   D. Other   
      • 1. Pseudo hypokalemia
      • 2. Hypothermia
      • 3. Hypokalemic periodic paralysis (Calcium Channelopathy)
      • 4. Barium toxicity
  • pseudohypokalemia
    • Prevented storing the blood sample on ice or rapidly separating the plasma from the cells.
    • e.g., acute myeloid leukemia
    • …..low measured plasma K+ concentration d/t white blood cell uptake of K+ at room temperature
    • III. Increased loss   
    • A. Non renal    
        • 1. Gastrointestinal loss (1.diarrhea – per se loss of K+)…profuse diarrhea, villous adenomas, VIP oma, laxative abuse 2.Vomitting - mainly d/t ^ renal K+ excretion caused by volume depletion and metabolic alkalosis)
        • 2. Integumentary loss (sweat ) (ECF contraction…Aldosterone secretion )
    • B. Renal
    • 1.Increased distal flow :
    • diuretics
    • osmotic diuresis
    • salt-wasting nephropathies
    • 2. Increased secretion of potassium     
    • I. Mineralocorticoid excess:
    • Primary hyperaldosteronism (ca, Conn's , hyperplasia)… low plasma renin activity
    • Secondary hyperaldosteronism (1.malignant hypertension, 2.renin-secreting tumors –RCC, Ovarian Ca, Wilm’s tumor, 3.renal artery stenosis, 4.hypovolemia)… Hyperreninemia
    • Bartter's s .. (Na K 2 Cl pump mutation…Volume depletion…hyperaldosteronism…K+ secreted
    • Apparent Mineralocorticoid excess (licorice, chewing tobacco, carbenoxolone) …cortisol occupies the aldosterone receptor for action…cortisol to cortisone does not occur d/t 11 beta HSDH deficiency/inhibition …– low renin and aldosterone
    • Congenital adrenal hyperplasia ( D/T non aldosterone Mineralocorticoids – corticosterone, deoxycorticosterone)
    • Cushing's s .. (cortisol formed overwhelms the activity of 11 beta HSDH)
    • II. Distal delivery of non-reabsorbed anions:
    • vomiting …HCO3 in urine
    • nasogastric suction
    • proximal (type 2) renal tubular acidosis
    • diabetic ketoacidosis …Beta OH butyrate
    • glue-sniffing (toluene abuse) …Hippurate
    • penicillin derivatives …(1.Secrete K+; 2. Osmotic diuresis)  
    • III. Other:
    • Amphotericin B …( ^ distal nephron K+ permeability)
    • Liddle's syndrome … (ENaC up regulation in CCD…negative Electrical gradient in lumen…H+ & K+ secretion)
    • Hypomagnesaemia …(Resistant to treatment)
  • Genetic disorders
    • Hypokalemic periodic paralysis
    • Bartter's syndrome
    • Gitelman's syndrome
    • Liddle's syndrome
    • Apparent mineralocorticoid excess
    • Glucocorticoid-remediable hyperaldosteronism
  • APPROACH TO HYPOKALEMIA HYPOKALEMIA urine potassium < 25 mEq/day urine potassium >30 mEq/day
  • Urinary conservation +
  • Urinary conservation -
  •  
  • Lab values
    • Sodium-134 meq
    • Potassium- 1.46 meq
    • Chloride- 84.3 meq
    • Bicarbonate- 33.2 meq
    • Serum calcium- 9.3 meq
    • Magnesium- 2.0 mg
    • Urine specific gravity- 1.030
    • USG ABDOMEN-
    • normal sized kidneys.
    • CMD Present.
    • Normal echoes.
    • X- RAY KUB
    • No evidence of any calculus.
  • ABG 1 st day 2 nd day PH 7.52 7.48 HCO3 32.6 36.6 PCO2 40.5 50.1 PO2 80.4 74 ANION GAP 13.5 10.3 SO2 97 95.4
    • THYROID:
    • T3 -125.82
    • T4-9.68
    • TSH-1.472.
    • ENT opinion- normal .
    • No hearing loss.
    • LFT:
    • Serum proteins- 6.3 gms
    • Albumin- 4.3 gms
    • Globulins-2.0 gms
    • 24 HR urine excretion-
    • sodium- 322meq (100-260)
    • Potassium-144 meq (25-100)
    • Chloride- 516.6 meq ( 110-250)
    • Calcium-418.6 mgm (<300 mg/day)
    • Hypokalemia- 1.4 meq
    • Metabolic alkalosis : ph- 7.54
    • Normal calcium- 9.3 meq
    • Normal magnesium- 2.o meq
    • Normal blood pressure- 110/70 mm HG.
    • URINE chloride-516 meq
    • Urine potassium-144 meq
  •  
  • Final diagnosis
    • Bartter’s syndrome-
    • Type- 111
  • BARTTER’S SYNDROME
    • Autosomal recessive
    • Fn of thick ascending LOH affected
    • Inactivating mutations of one of 4 genes encoding membrane proteins (Types I to IV)
    • Gain of function mutation in extracellular Ca ion sensing receptor (CaSR)… variant of Bartter presenting with Hypocalcemia (AD inheritance)
  • Bartter’s syndrome types
    • Type I : mutation in the gene for Na K 2Cl cotrasporter (NKCC2) + on the apical membrane of LOH
    • Type II : mutation in the gene for ATP regulated K channel (ROMK)
    • Type III : mutation in the basolateral voltage gated Cl channel (ClC – Kb)
    • Type IV : mutation in the BSND protein (barttin) that activates beta subunit for ClC Kb and ClC Ka . Associated with deafness
    • Type V : Gain of function mutation in the CaSR gene … + with Hypocalcemia
    • …. First four types are autosomal recessive : type V is autosomal dominant
  •  
  • Clinical features
    • Present in antenatal period
    • or in neonates( III can + in early childhood)
    • Antenatal …
    • Polyhydramnios & Preterm labour
    • Postnatal …
    • Polyuria , Polydipsia ,Growth retardation , Dehydration , Nephrocalcinosis (universal in I & II ; only in 20% of III) , Muscle weakness , Fatigue
    • Systemic features include fever, vomiting, diarrhea +…
    • Probably all are d/t PG mediation
    • fever can be d/t dehydration
    • vomiting d/t hypokalemic paralytic ileus.
    • TYPE IV : Sensorineural deafness specific detected as early as 1 month of age : also CRF progression in childhood is common
  • Biochemical abnormalities
    • Hypokalemic metabolic alkalosis
    • Hyperreninemic hyperaldosteronism
    • Normal blood pressure
    • Inappropriate urine excretion of K +
    • Inappropriate urine excretion of Cl –
    • Hypercalciuria
    • Normo magnesemia
    • Urinary PG ^ed in majority
    • Blunted response to loop diuretics
  • Nephrocalcinosis + + +- + + - Polyhydramnios + + + + - - FTT + + + + - - Growth Retardation + + + + - - Polyuria + + + + + - Polydipsia + + + + + - Muscle cramps/pain - - - - + +- Chondrocalcinosis - - - - - +- SN hearing loss - - - + - - Hypocalcemia - - - - + - FEATURES B I B II B III B IV B V GM
  • Treatment
    • Restore plasma K to about 3.5 mmol/l
    • K+ supplementation / Spironolactone / Amiloride
    • PG inhibitor like indomethacin 2 mg/day in divided doses …in infants have reduced incidence of growth retardation
  • Differential diagnosis
    • 1.Gitelman’s syndrome
    • ( Differentiated by Hypocalciuria + : Hypomagnesaemia +)
    • 2.Vomiting
    • (Differentiated by Urinary Cl < 20 meq/L)
    • 3.Abuse of loop diuretics
    • (H/O drug intake + or assaying the expected drugs in urine)
    • …. All are observed in older patients
  •  
  • American journal of medicine : vol 61: issue 1 :1985
    • A patient with Bartter's syndrome in whom the disease was recognized at 52 years of age has been described in….
    • Adult onset Bartter diagnosed at the age of 40 yrs
    • Korean journal of medicine : vol 10 : number 4 :1995
    • Male who had not been diagnosed as Bartter syndrome type IV until 28 yr because of a mild clinical manifestation. The patient also had congenital deafness .
    The Journal of Clinical Endocrinology & Metabolism : Vol. 88 : Number 2 : 2003
    • Deaf daughter of consanguineous parents, who was referred for the first time at the age of 20 , because of refractory hypocalcaemia
    • Antenatal polyhydramnios +
    • Polydipsia and polyuria. The patient's height and weight reached, respectively, 165 cm and 70 kg
    Oxford journal of medicine : vol 22 : number 1 : 2006
    • Thank you