a case of bartter's syndrome
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 paraparesisGuillain- Barre syndromeCns- para sagittal meningiomasAnterior cerebral artery ischemiaSuperior sagittal or cortical venous
thrombosisAcute hydrocephalusSpinal cordIntra 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- polioGuillain- Barre syndromeMyopathy.Periodic paralysis
examinationPt conscious, oriented, afebrileObeys 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 soundsP/A: soft non tender, No organomegaly, no free fluid.No mass.
Central nervous systemHigher 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 leftBulk normal normalTone reduced reducedPower 1/5 1/5Reflexes knee absent absentAnkle absent absentPlantar no response no
response
No axial muscle weaknessSENSORY SYSTEMTouch,Pain , temperature : present Vibration, joint position: present.Cortical sensation: intact.Spinal vibration: present
Cerebellum;Upper limbs: no cerebellar signsLower 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-
hoursAreflexia in lower limbsBowel and bladder : not involvedSensations- intact.No spinal tenderness.No signs of increased ICT.
AIDP- Guillain Barre syndromeChannelopathies- Hypokalemic periodic
paralysis
InvestigationsCBC:Hb- 14.5 gTC- 5400DC: P- 64, L-36ESR- 6/12PCV: 42%Platelets- 1.5 lakhs.RFT:UREA- 26 mgCreatinine- 1.1 mg
Urine routine- Albumin- nilSugar- nil,deposits- nilPus cells- nil
Chest X-RAY: normal
ECG- flat P wave, U wave, prolonged QT interval.
ELECTROLYTES:Sodium: 137 meq/lPotassium- 1.3 meq/lChloride- 88 meq/lBicarbonate- 33 meq/l
diagnosis
Hypokalemia -?cause
TreatmentIV 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 INTAKERENAL WASTING- most common causeTRANS CELLULAR SHIFT.
Hypokalemia plasma K+ concentration <3.5 mmol/L,
CAUSES: I. Decreased intake ( Seldom a sole cause
for K+ depletion) A. StarvationB. 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: diureticsosmotic diuresis salt-wasting nephropathies
2. Increased secretion of potassium
I. Mineralocorticoid excess: Primary hyperaldosteronism (ca, Conn's ,
hyperplasia)…low plasma renin activitySecondary 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 urinenasogastric suction proximal (type 2) renal tubular acidosis diabetic ketoacidosis …Beta OH butyrate glue-sniffing (toluene abuse) …Hippuratepenicillin 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 1. Hypokalemic periodic paralysis 2. Bartter's syndrome 3. Gitelman's syndrome 4. Liddle's syndrome 5. Apparent mineralocorticoid
excess 6. Glucocorticoid-remediable
hyperaldosteronism
APPROACH TO HYPOKALEMIA
HYPOKALEMIAHYPOKALEMIAHYPOKALEMIAHYPOKALEMIA
urine potassium < 25 mEq/dayurine potassium < 25 mEq/day urine potassium >30 mEq/dayurine potassium >30 mEq/day
Urinary conservation +
Urinary conservation -
Lab valuesSodium-134 meqPotassium- 1.46 meqChloride- 84.3 meqBicarbonate- 33.2 meqSerum calcium- 9.3 meqMagnesium- 2.0 mg
Urine specific gravity- 1.030
USG ABDOMEN- normal sized kidneys.CMD Present.Normal echoes.
X- RAY KUBNo evidence of any calculus.
ABG1st day 2nd 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 -125.82T4-9.68TSH-1.472.
ENT opinion- normal .No hearing loss.
LFT:Serum proteins- 6.3 gmsAlbumin- 4.3 gmsGlobulins-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 meqMetabolic alkalosis : ph- 7.54Normal calcium- 9.3 meqNormal magnesium- 2.o meqNormal blood pressure- 110/70 mm HG.URINE chloride-516 meqUrine potassium-144 meq
Final diagnosis Bartter’s syndrome- Type- 111
BARTTER’S SYNDROMEAutosomal recessiveFn of thick ascending LOH affectedInactivating 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 typesType 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 featuresPresent in antenatal period or in neonates( III can + in early childhood)Antenatal … Polyhydramnios & Preterm labourPostnatal … 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 abnormalitiesHypokalemic metabolic alkalosisHyperreninemic hyperaldosteronismNormal blood pressureInappropriate urine excretion of K +Inappropriate urine excretion of Cl –HypercalciuriaNormo magnesemiaUrinary PG ^ed in majorityBlunted response to loop diuretics
NephrocalcinosisNephrocalcinosis ++ ++ +-+- ++ ++ --
PolyhydramniosPolyhydramnios ++ ++ ++ ++ -- --
FTTFTT ++ ++ ++ ++ -- --
Growth RetardationGrowth Retardation ++ ++ ++ ++ -- --
PolyuriaPolyuria ++ ++ ++ ++ ++ --
PolydipsiaPolydipsia ++ ++ ++ ++ ++ --
Muscle cramps/painMuscle cramps/pain -- -- -- -- ++ +-+-
ChondrocalcinosisChondrocalcinosis -- -- -- -- -- +-+-
SN hearing lossSN hearing loss -- -- -- ++ -- --
HypocalcemiaHypocalcemia -- -- -- -- ++ --
FEATURESFEATURESB B II
B B IIII
B B IIIIII
B B IVIV
B B VV
GMGM
TreatmentRestore plasma K to about 3.5 mmol/l K+ supplementation / Spironolactone /
AmiloridePG inhibitor like indomethacin 2 mg/day in
divided doses …in infants have reduced incidence of growth retardation
Differential diagnosis1.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 American journal of medicine : vol 61: issue 1 :19851 :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 Korean journal of medicine : vol 10 : number 4 :19954 :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 : Oxford journal of medicine : vol 22 : number 1 : 2006number 1 : 2006
Thank you