approach to hypokalemia
TRANSCRIPT
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Approach to Hypokalemia
Ranjita Pallavi
Internal Medicine
PGY-2
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Renal Vs Extra renal loss
Urinary K+: > 20 mEq/L – Renal loss
Urinary K + : < 20 mEq/L – Extrarenal loss
TTKG : Transtubular Potassium Gradient ( Urine K+ / Plasma K+ ) ( Urine Osm / Plasma Osm )
TTKG : Renal loss : > 4 Extra renal loss : < 4
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RENIN HIGH ALD HIGH
RENIN LOW ALD HIGH
LOW RENIN LOW ALD
RAS Primary Hyperaldosteronism NORMAL CORTISOL :
Malignant HTN Glucorticoid remediable HTN Apparent mineralocorticoidexcess
Renin Secreting Tumor
Liddles syndrome
LicoriceDOC
LOW CORTISOL :
Adrenogenital syndrome 11 beta hydroxylase deficiency17 alpha hydroxylase deficiency
HIGH CORTISOL :
Familial Glucocorticoid ResistanceEctopic ACTHSevere Cushings Syndrome
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PRIMARY ALDOSTERONISM
Primary Aldosteronism with an Adrenal Tumor
Primary Aldosteronism without an Adrenal Tumor
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WHEN TO SCREEN?
Recommended in Hypertensive Patients with one of the following:
Hypokalemia Severe, resistant or relatively
acute hypertension Adrenal incidentaloma
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PRIMARY ALDOSTERONISM WITH AN ADRENAL TUMOUR
Aldosterone producing adrenal adenoma( rarely adrenal carcinoma)
Also known as Conn’s Syndrome Usually unilateral M:F: 1:2 Commonly seen between 30-50
years ~1% patients present with
hypertension
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PRIMARY ALDOSTERONISM WITHOUT AN ADRENAL TUMOUR
Idiopathic hyperaldosteronism and/or nodular hyperplasia
The adrenal are either normal in appearance or more commonly reveal Bilateral(10%) or rarely, unilateral(<1%) micro- or macronodular adrenal hyperplasia
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THE CRITERIA FOR DIAGNOSIS OF PRIMARY ALDOSTERONISM
Diastolic hypertension without edema
Renin hyposecretion that fails to increase appropriately during volume depletion
Aldosterone hypersecretion that does not suppress appropriately to volume expansion
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METHOD OF SCREENING
Aldosterone conc/Renin activity ratio Considered positive if ratio > 20,
usually > 30 In addition, the aldosterone conc.
Should be > 15 ng/dL
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DIAGNOSIS
Aldosterone > 15ng/dL Aldosterone/renin ratio > 30 Confirmation with Na+ suppression
test Imaging of the adrenal glands Adrenal Vein sampling 18-OH Corticosterone levels may
help differentiate hyperplasia from adenoma
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Aldosterone Suppression Tests
IV Saline suppression 500 ml 0.9% NaCl/hr for 4 hours OR 500 ml 0.9% over 30
mimutes, then 500ml/hr for 2 hours Draw PAC at time 0, 120 and 150 minutes Suppression if PAC< 8.5 ng/dL(<6 normal> 10 PA)
Oral sodium chloride suppression test 10 gms NaCl dily for 4 days On Day 4, collect 24 hour urine aldosterone, sodium
Suppression if aldosterone< 14 mcg and sodium > 200 eEq/24 hours
Fludrocortisone suppression test High salt diet and large doses of fludrocortisone over a 4 day
hospitalization
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ADRENAL VEIN SAMPLING
Considered gold standard to distinguish adenoma and hyperplasia
Usually done under ACTH infusion Looking for localization of
aldosterone increase Very useful when no abnormalities
seen on imaging or bilateral nodules
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LIDDLE’S SYNDROME
Clinical features include: Hypertension Hypokalemia with renal K+ wasting Metbolic alkalosis and Suppressed plasma renin activity Autosomal Dominant
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Primary abnormality in renal tubule that enhances Na+ reabsorption: a defect in the cyutoplasmic domain of the epithelial Na+ channel that results in gain of fuction activating mutation of the channel
Amiloride and Triamterene are specific inhibitors of this channel, treatment with these agents corrects the electrolyte abnormalities and ameliorates the hypertension.
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Mechanism of action
Cortisol Aldosterone
Cortisone (inactive)
11B-Hydroxysteroid dehydrogenase (11β-HSD)
Mineralocorticoid Receptor (MR)
Glycyrrhetinic Acid
11β-HSD
Cortisol
Cortisol nmol/L
Aldosterone pmol/L
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Bartter and Gitelman Syndromes
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Bartter syndrome genotype-phenotype correlations
Genetic Type Defective Gene Clinical Type
Bartter type I NKCC2 Neonatal
Bartter type II ROMK Neonatal
Bartter type III CLCNKB Classic
Bartter type IV BSND Neonatal with deafness
Bartter type V CLCNKB and CLCNKA Neonatal with deafness
Gitelman syndrome NCCT Gitelman syndrome
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Indirect loss of NaHCO3 in glue sniffing.
Groeneveld J et al. QJM 2005;98:305-316
The Author 2005. Published by Oxford University Press on behalf of the Association of Physicians. All rights reserved. For Permissions, please email: [email protected]
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Functional evaluation of proximal bicarbonate absorption
Fractional excretion of bicarbonate Urine ph monitoring during IV administration
of sodium bicarbonate. FEHCO3 is increased in proximal RTA >15%
and is low in other forms of RTA.
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Functional Evaluation of Distal Urinary Acidification and Potassium Secretion
Urine ph Urine anion gap Urine osmolal gap Urine Pco2 TTKG Urinary citrate
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Urine ph
In humans, the minimum urine pH that can be achieved is 4.5 to 5.0.
Ideally urine ph should be measured in a fresh morning urine sample.
A low urine ph does not ensure normal distal acidification and vice versa.
The urine pH must always be evaluated in conjunction with the urinary NH4+ content to assess the distal acidification process adequately .
Urine sodium should be known and urine should not be infected.
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Urine anion gap (UAG)
Urine anion gap = [Na+] + [K+] – [Cl-]
Normal: zero or positive Metabolic acidosis: NH4+ excretion increases (which is
excreted with Cl-) if renal acidification is intact
GI causes: “neGUTive” UAG Impaired renal acid excretion (RTA): positive or zero
Often not necessary b/c clinically obvious (diarrhea)
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Urine anion gap
There are, however, two settings in which the urine AG cannot be used.
When the patient is volume depleted with a urine sodium concentration below 25 meq/L.
When there is increased excretion of unmeasured anions
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Urine osmolal gap
When the urine AG is positive and it is unclear whether increased excretion of unmeasured anions is responsible, the urine ammonium concentration can be estimated from calculation of the urine osmolal gap.
UOG=Uosm - 2 x ([Na + K]) + [urea nitrogen]/2.8 + [glucose]/18.
UOG of >100 represents intact NH4 secretion.
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Urine Pco2
Measure of distal acid secretion. In pRTA, unabsorbed HCO3 reacts with
secreted H+ ions to form H2CO3 that dissociate slowly to form CO2 in MCT.
Urine-to-blood pCO2 is <20 in pRTA. Urine-to-blood pCO2 is >20 in distal RTA
reflecting impaired ammonium secretion.
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TTKG TTKG is a concentration gradient between
the tubular fluid at the end of the cortical collecting tubule and the plasma.
TTKG = [Urine K ÷ (Urine osmolality / Plasma osmolality)] ÷ Plasma K.
Normal value is 8 and above. Value <7 in a hyperkalemic patient
indicates hypoaldosteronism. This formula is relatively accurate as long
as the urine osmolality exceeds that of the plasma urine sodium concentration is above 25 meq/L
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Urine citrate
The proximal tubule reabsorbs most (70-90%) of the filtered citrate.
Acid-base status plays the most significant role in citrate excretion.
Alkalosis enhances citrate excretion, while acidosis decreases it.
Citrate excretion is impaired by acidosis, hypokalemia,high–animal protein diet and UTI.
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Renal Tubular Acidosis
First described clinically in 1935
Confirmed as a renal tubular disorder in 1946
Designated as RTA in 1951
Refers to disorders affecting the overall ability of the renal tubules either to secrete hydrogen
ions or to retain bicarbonate ions
All types produce hyperchloremic metabolic acidosis
with a normal anion gap.
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Proximal RTA
Proximal RTA (Type 2) Caused by an
impairment of HCO3- reabsorption in the proximal tubules
Most cases occur in the context of Fanconi’s syndrome
Isolated proximal RTA is rare.
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DISTAL RTA
Impairment of distal acidification
Inability to lower urine pH maximally below 6.0 under acid load
Pathomechanism is inability to secrete H+ adequately (secretory defect or classic distal RTA)
Gradient defect Voltage dependent
defect In children mainly a
genetic defect of the H+ pump
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Adolsterone
Water
K+
Na
Na+
H+
Cl-RTA IV:
Hypoaldosteronism or pseudohypoaldosteronism
H20
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Proximal RTA
Distal RTA RTA IV
Type of Acidosis
Hyperchloremic metabolic acidosis
Hyperchloremic metabolic acidosis
Hyperchloremic metabolic acidosis
Serum Potassium
low low high
Urine pH
< 5.5 >5.5 < 5.5
Urine bicarbonate loss