Hendrata Erry Andisari

Department of Medicine Faculty of Medicine

Hang Tuah University- Ramelan Hospital Surabaya
K+ is dominant intracellular cation in the body

Regulation of K+ homeostasis is achieved through :

•K shift
•Renal K+ excretion
•Extrarenal loss
•Intake
 Extracell fluid Intracell fluid

200
Plasma Interstitial fluid

150

Cell Membrane
Caviler
Cl- Cl- K+ Others
100 fosfat
Na+ Na+

HCO3- PO4
50
HCO3- Na+
HCO3-
K+
PO4 K +
PO4 Cl-
0

Electrolyte composition in human body fluid

FKUI, Gangguan keseimbangan air-elektrolit dan asam basa, 2007
 Disturbance of these homeostasis

Hyperkalemia Hypokalemia
 Hyper and hypokalemia disrupt action potential formation
and promote various clinical sypmtoms and physical findings
based on the following :

Neuromuscular Inhibition of
dysfunction normal cell enzymatics
• Disorders of K+ balance are associated with
significant morbidity and mortality due to effects on
a number of neuromuscular and cellular function
• Rapid recognition and treatment of these K+
disorders is required to avoid serious morbidity and
mortality
Approach to the Potassium Disorders

Disorders of potassium homeostasis can be classified

into four categories.
These categories include :
1.Change in renal elimination Renal

2.Altered intake
3.Altered cellular distribution Extrarenal
4.Increased losses (stool, sweat)
Overview of potassium handling in the nephron
Schmitz PG,
Renal an Integrated Approach to Disease, 2012
Initial step in the evaluation of potassium
disorders is,
determination of renal excretion of potassium
•24 hrs urine potassium is the gold standard, but
• Inconvenient
• delays the diagnosis
•Supplanted by
• Transtubular Potassium Gradient (TTKG)
Transtubular Potassium Gradient (TTKG)
• The TTKG has supplanted the 24-hour collection in
the initial evaluation of potassium disorders.
• The TTKG has proven to be both convenient and
reliable
• The TTKG equals the ratio of potassium
concentration at the end the cortical collecting duct
to the plasma potassium concentration.
• Normal value of TTKG is 3-6 and its equal with
20-40 meq/L of serum potassium level
• Therefore, it is a semi quantitative reflection of the
driving force for potassium secretion in the kidney
• Normally, the TTKG is elevated in hyperkalemic
states and reduced in hypokalemic states
• An abnormal TTKG implies deranged renal
elimination of potassium
The TTKG is easily measured at the bedside,
using simple urine and plasma chemistries

K 
  Bloodosm 
TTKG   urine

 x  
K blood   Urineosm 
• Normal : 3-6 equal with K urine 20-40 meq/L
• Hiperkalemia 
• Hipokalemia 

Schmitz PG, Renal an Integrated Approach to Disease, 2012

 Serum Potassium Concentration

Low (<3.5 mEq/L) High (>5.5 mEq/L)

Calculate TTKG Calculate TTKG

<3.0 ** >6.0 **

Yes No Yes No

Extrarenal Renal Extrarenal Renal

Initial approach to the evaluation of potassium disorders

Schmitz PG, Renal an Integrated Approach to Disease, 2012
 Hypokalemia (TTKG < 3)

Decreased intake Cellular shift GI loss

Geophagia Alkalosis GI loss

Insulin/Glucose
2-agonists
Cell proliferation
Periodic paralysis

Approach to hypokalemia with an

appropriately renal response
Schmitz PG, Renal an Integrated Approach to Disease, 2012
 Hypokalemia (TTKG3)

Blood pressure

High Normal or low

Renin Blood pH

High Low Low High

RAS Aldosterone RTA Vomiting

Diuretics
Bartter’s syndrome
High Low Gitelman’s syndrome

Primary hyperaldosteronism Cushing’s syndrome

GRA Congenital adrenal hyperplasia
AME
Approach to hypokalemia caused by an increase in renal potassium excretion
Schmitz PG, Renal an Integrated Approach to Disease, 2012
CLINICAL MANIFESTATION
Impaired neuromuscular function :
Cardiac disturbance :
• various atrial and ventricular arrhythmias
(U wave in ECG, in K level <2.0 meq/L))
• may be fatal in patients on digoxin therapy
Renal manifestation
• Polyuria
• Hypokalemic nephropathy
Reilly RF, Acid-Base, Fluids & Electrolytes, 2007
CLINICAL MANIFESTATION (con’t)
Other organ/system
• respiratory failure
• Ileus

Metabolic perturbations
• hyperglycemia from decreased insulin release
• impaired hepatic glycogen and protein synthesis
TREATMENT OF HYPOKALEMIA
Estimates of the total body potassium deficit :
K concentration Deficit
30 – 3.5 100 – 300
2.5 – 3.0 300 – 600
< 2.5 > 600
TREATMENT OF HYPOKALEMIA (con’t)
• Oral KCl 40 – 80 mEq/day if K concentration 2.5 – 3.5 mEq/L
• IV KCl 50 meq in 500 NS, maximal rate 20 meq/hr,
if K concentration < 2.5 mEq/L
• combination oral and IV can be use if needed

Continuous cardiac monitoring is desirable

Correction of the cause of hypokalemia is

a part of therapy
 Diagram of Approach to Hyperkalemia

Hyperkalemia

Pseudohyperkalemia Cell Shift

• Test tube hemolysis • Insulinopenia
• Thrombocytes Urine K+ excretion • B2-adrenergic
• Leukocytes TTKG blockade
• Acidernia
• Hyperkalemic
periodic paralysis
• Succinylcholine
• Hyperosmolality
/ DKA
TTKG = Transtubular K+ gradient
• Exercise

Reilly RF, Acid-Base, Fluids & Electrolytes, 2007

 Hyperkalemia (TTKG > 6)
Ekstra renal

Increased intake Cellular shift

Fruits Vegetable Pseudohyperkalemia

Acidosis
Insulin deficiency
-blockers
Digoxin
Tissue necrosis
Periodic paralysis

Approach to hyperkalemia with appropriately increased

renal of potassium
 Hyperkalemia (TTKG < 6)
Renal

Hypoaldosteronism Reduced Na+ uptake Low GFR

Spironalactone Decreased ECV Acute and chornic

NSAIDs Triamterene kidney disease
Heparin Amiloride
ACE-In
ARB
Renin inhibition
Type 1 PHA
Type 2 PHA
Adrenal insufficiency
Hyporeninemia

Approach to hypokalemia with impaired renal excretion

Schmitz PG, Renal an Integrated Approach to Disease, 2012
Clinical manifestations
• Often asymptomatic
• Neuromuscular disturbance (K > 6.5 meq/L)
• Distal parasthesia
• Generalized muscle weakness
• Ascending flaccid paralysis
• Ventilatory failure

• Sudden cardiac death (K > 7-7.5 meq/L)

ECG changes
• K+ 5 - 6 meq/L
• 50% no ECG changes

• peaked T, shortened QT

• K+ 6 - 7 meq/L
• Prolonged QR, AV dissociation AV

• Flattening and loss P

• Widening QRS complex

• K+ > 7 – 8 meq/L - VT
 Serum potassium Typical ECG Possible ECG abnormalities
appearance
Mild (5.5-6.5 mEq/L) Peaked T waves
Prolonged PR segment

Moderate (6.5-8.0 mEq/L) Loss of P wave

Prolonged QRS complex
ST-segment elevation
Ectopic beats and escape rhytms

Severe Proggresive widening of QRS complex

Sine wave
Ventricular fibrilation
Asystole
Axis deviations
Bundle branch blocks
Fascicular blocks

Typical ECG appearance on hyperkalemia stages

(Mayo clinic proceedings. 2007. 82 (12) (1553-1561)
Pseudo Hyper K
• Caused by released of K from damage cell in vitro
------ 1-2 meq/L artifactual release
• Hemolysis
• Thrombocytosis
• Leukocytosis
• Familial psudohyper K
 Management of hyperkalaemia
1. Acutely:
• Calcium gluconate 10%, 10 ml i.v.
• D 50W, 50 ml i.v. plus regular insulin, 10 IU i.v.
• Sodium bicarbonate, 1 mol/l, 50 ml i.v.
• Salbutamol, 0.5 mg i.v.
• Haemodialysis (only in exceptional situations)

Nephrol Dial Transplant (2004) 19: 2163–2166

 Management of hyperkalaemia
2. Chronically
• Discontinue all potentially triggering factors,
e.g. stop K+-sparing diuretics, etc.
• Consider loop diuretics (provided that renal
function is relatively well maintained)
• Consider giving K+-exchange resin (p.o. or p.r.)
• Consider giving synthetic mineralocorticoids
(e.g. fludrocortisone) in cases of
mineralocorticoid deficiency.

Nephrol Dial Transplant (2004) 19: 2163–2166

Management
Hyper K >6.5 meq/L : medical emergency
- therapy should begin immediately
1. Stabilization of cardiac membrane
- 10 ml Ca gluconas 10% over 2-3 min into large vein
- evident within minutes and lasts for 30 to 60 min
- represents a temporizing measure only
- plasma K concentration is unaltered
Management (con’t)
2. Transcellular redistribution
a. Insulin and dextrose
--- activated insulin receptor stimulates N+/K+-ATPase
driving cellular uptake of K
- 1 iu insulin setiap 5 gr glukosa
- each 10 iu insulin can expected to lower K by 0.5-1.5
meq/l within 15 min, lasting 2-4 hrs
b. Sodium bicarbonate
- increasing the pH of ECF (100 mmol over 1-2 hrs)
- when hyper K associated by severe inorganic acidosis
c. Salbutamol
- meter dose inhaler, nebulized, intravenous
 Management (con’t)
3. Removal of excess
- Loop diuretic
- Cation exchange resin (kayexalate)
- Hemodialysis or CRRT
- Laxantia (MgS04)

Monitoring of K+ concentration is most important

β2-adrenergic agonists
•In patients with ESRD has been demonstrated
•Allon et al : 10 or 20 mg of nebulized albuterol, decreased
plasma K
• Within 30 min and the effect sustained for at least 2
hr.
• Minimal increase in heart rate.
• Safety concern because the dose used are 4-8 times
those prescribe for the treatment of acute asthma.
• Has additive effect to insulin
 Cation-exchange Resin

For Chronic Hyperkalemia

Is a cross-linked polymer with negatively charged
structural units .
The resin can exchange bound Na or Ca for cations
including K+
•Na = sodium exchange resin (Kayexalate)
•Ca = calcium exchange resin (Calcium resonium)
Cation-exchange Resin
Conflicting data have been reported regarding
the effectiveness of exchange resin in lowering serum
potassium levels.

The major complications :

•Constipation
•Intestinal (colon) necrosis
•Bowel perforation (reported rates of 0.27 % to 1.8%)
•Hypokalemia
• Exchange resins with or without laxative agents
should not be used exclusively to treat acute
hyperkalemia because of their slow onset of action.
• Exchange resins with sorbitol should not be used as
a first-line therapy for hyperkalemia
 Summary of Clinical Treatment of Hyperkalemia
Treatment Dose Onset Time Mechanism

Ca gluconate Stabilize
10–20 mL IV 1–5 min 30–60 min
(10%) membranes
Insulin and 10–20 U of IV insulin 30 min
4–6 h Cell uptake
glucose and 25 g of glucose
20 mg in 4 mL
Albuterol 30 min 1–2 h
normal saline in Cell uptake
(β2-agonist)
nebulizer
Terbutaline
0.7 mg/kg SQ 20–30 min 1–2 h Cell uptake
(β2-agonist)
Na bicarbonate 50–75 mEq IV 5–10 min 2–12 h Cell uptake
Na polystyrene 30–45 g oral 2–4 h
4–12 h GI excretion
sulfonate 50–100 g enema
Hemodialysis 1–2 mEq/L K bath — 2–8 h Removal
Abbreviations: IV, intravenous; U, units; GI, gastrointestinal; SQ, subcutaneou

Reilly RF, Acid-Base, Fluids & Electrolytes, 2007

 SUMMARY
• Potassium is dominant cation in the body.
• Regulation of K homeostasis is achieved through K shift, renal
handling, extrarenal loss and intake
• Disorders of K balance are associated with significant
morbidity and morality due to effects on a number of
neuromuscular and cellular function
• Have been explained about diagnostic approach, clinical
manifestation and management of hypokalemia and
hyperkalemia.
• Rapid recognition and treatment, followed by smart
monitoring is required to avoid serious morbidity and
mortality
TRI HITA KARANA

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