Post on 10-Sep-2014
Dyskalemia A Pathophysiological Approach
Dr. Mubarak S. AlGhamdi
Senior Resident
Internal Medicine, KFMC
Saudi Arabia
Transcellular Shift
-Alkalosis
-Insulin
-B-adrenergics
-A-adrenergic antaggonists
-Acidosis
-B-antagonists
-Hyperosmolarity
Intracellular K+
* Organic acids (lactate, BHP) are not associated with shifts
* In hyperosmolar state, the movement of K out of the cell along with water due to Solvent Drag
ATP
Tubular Lumen
(urine)
2K+
3 Na+
Na+
H+
Proximal Tubule
Capillary Lumen (blood)
Proximal Tubule Epithelial Cell
NHE
K+ Ca+2 Mg+2 ,
PO4, AA, Glu
Paracellular Pathway
Proximal RTA
Diffusion
Diffusion: The movement of solutes from a higher to a lower solute concentration area.
Convection: The movement of solutes with a water-flow,“solvent drag”
Convection
Thick Limb - Loop of Henle Sodium ReabsorptionAscending Thick Limb of the Loop of Henle epithelial cell
ATP
Tubular Lumen
(urine)
Capillary Lumen (blood)
2K+
3 Na+
Na+
K+
ROMK
channel
K+
K+ recycling
Na+ Ca+2 Mg+2 Paracellular Pathway
+-
2 Cl-
Cl-
NKCC2
CaSR
Loop Diuretics
Bartter’s Syndrome
+-
Bartter’s Syndrome
ATP
Tubular Lumen
(urine)
2K+
3 Na+
Na+
Cl-
Cl-
Distal Tubule Sodium Reabsorption
Capillary Lumen (blood)
K+
Distal Tubule Epithelial Cell
NCCT
Thiazide Diuretics
Gitelman’s Syndrome
Gitelman’s Syndrome
Barrter vs Gitelman
ATP2K+
3 Na+Na+
Capillary Lumen (blood)
K+
Collecting Tubule Sodium Reabsorption
Tubular Lumen
(urine)
K+
+
Collecting Tubule Epithelial Cell
Principal Cell
ENaC
ROMK
Amiloride, Triamterene, Trimethoprim, Pentamidine
Liddle’s Syndrome
Distal U
rinary F
low --
Nonabsorbable Anions
-Bicarbonaturia
-BHP (DKA)
-Penicillin
-Hippurate (glue-sniffing)
ATP
Tubular Lumen
(urine)
2K+
3 Na+
Na+
Cl-
Collecting Tubule
Capillary Lumen (blood)
Distal Tubule Epithelial Cell
WNK kinase
ENaC
Aldosterone
Spironolactone, Epleronone
Pseudohypoaldosteronism I
Gordon’s Syndrome
AKA: Pseudohypoaldosteronism II, Chloride Shunt Syndrome
+
+
Cortisol Cortisone 11b OHSD II
MR
SAME Licorice
Hypokalemia
Plasma K < 3.5 mmol/L
Causes of Hypokalemia
• Decreased intake (unusual)– Ingestion of clay (geophagia)
• Transcellular shift (acute hypokalemia)– Hormones (insulin, B-
adrenergics)
– Metabolic alkalosis
– Hypokalemic periodic paralysis (familial, thyrotoxic)
• GI Loss– Diarrhea, laxatives, villous
adenoma,
– NGT suction & vomiting lead to renal K+ loss.
• Renal Loss– Diuretics
– Bartter’s, Gitelman’s, Liddles’s syndromes
– Bicarbonaturia, ketoaciduria
– Hyperaldosteronism
– Hypercortisolism
– SAME, Licorice
• Miscellaneous– Low magnesium
– Pseudohypokalemia (↑RBC, ↑WBC)
* K in stool is 5-10 mmol in 100-200 mL, thus, high volume diarrhea can cause hypokalemia.
* K in gastric content is 5-10 mmol/L, thus you need ~ 30-80 L of vomitus to achieve K deficit of 300-400 mmol.
HypokalemiaClinical Manifestations
→ Neuromuscular effects : hyperpolarization, lower excitability- weakness, paresia, myalgia, fatigue- hypo/areflexia- paralyis, rhabodmyolysis, dyspnea- smooth muscle : GI tract, urinary bladder
→ Cardiac effects : delay in ventricular repolarization- ECG (T flat, depressed ST, U wave)- arrhythmia (reentry currents during prolonged repolarization)- ↑ sensibility to toxic drugs (digoxin)
→ Renal effects : nephrogenic diabetes insipidus, Interstitial nephritis, ↑ ammoniagenesis
→ Glucose intolerance : ↓ insulin secretion β-cell
→ Blood pressure : ↑ (low K+ diet) or ↓ (Gitelmann)
→ Growth defect : impaired protein metabolism – GH release
EKG in Hypokalemia
Peaked T wave Flat P, ↑PR, ↓ST, peaked T Atrial standstill, ↑QRS Sine wave
Flattened T-wave Presence of U-wave ST depression
Estimation of potassium deficit
Hyperkalemia Plasma K > 5 mmol/L
Causes of hyperkalemia
• Pseudohyperkalemia
• High intake
• Reduced GFR
• Transcellular shift– Insulin deficiency
– B-blockers
– Metabolic acidosis
– Hyperosmolarity
– Hyperkalemic periodic paralysis
• Decreased renal K excretion– Addison’s disease
– RTA IV
– Aldosterone receptors blockade (aldactone, eplerenone).
– ENaC blockade (amiloride, triameterene)
– Gordon’s syndrome
– Tubulointerstitial disorders
– Drugs
• Miscellaneous– Cell lysis (rhabdomyolysis,
TLS).
HyperkalemiaClinical Manifestations
• Cardiac– Abnormal electrocardiogram– Atrial/ventricular arrhythmias– Pacemaker dysfunction
• Neuromuscular– Paresthesias– Weakness– Paralysis
• Renal electrolyte– Decreased renal NH4+ production– Natriuresis
• Endocrine– Increased aldosterone secretion– Increased insulin secretion
EKG in Hyperkalemia
Peaked T wave Flat P, ↑PR, ↓ST, peaked T Atrial standstill, ↑QRS Sine wave
Management of Hyperkalemia
• Antagonize the cardiac effect of hyperkalemia– 10% Calcium gluconate 10 cc over 5-10 min– Can be repeated after 5 min if EKG changes persist– Except if the patient on digoxin– Onset 1-3 min, duration 30-60 min
• Induce intracellular K+ shift;– HRI 10-20 IU IV ± 25-50 cc D50%
• Onset 30 min, duration 4-6 hrs– Nebulized albuterol 10-20 mg or 0.5 mg IV
• Onset 30 min, duration 2-4 hrs– Na Bicarb IV if acidotic 50 mEq over 2 min
• External removal;– Renal
• IVF + diuretics• Fludrocortisone 0.05 – 0.1 mg
– GI• Na or Ca resonium ± sorbitol (15 gm PO or 50 gm rectal with tap water)
– Onset 1-2 hrs, duration 4-6 hrs– Dialysis: immediate onset
Risk of colonic necrosis & perforation in post-op with Ca resin & sorbitol enema
Dyskalemia Quizzes
Q1
• A 25-year-old man is found to have BP 160/90 and K 2.8 in pre employment clinical check up.
• On further questioning, the physician discovered that the patient is drinking a lot of licorice
What is the most likely explanation of his condition?
1. Mutation in ENaC
2. Mutation in ROMK
3. Inhibition of 11-OHSD type 2
• Primary hyperaldosteronism
Role of 11-OHSD type 2
Adapted from Ellison
Cortisol
Aldo
Cortisol
Cortisol
AldoMR
GR
Cortisone
11 OHSD
SAME or Licorice
MR
Cortisone
11 OHSD
ENaC
Na,K-ATPase
Q2
• A patient with hypertension is found to have hyperkalemia and low PRA & PAC.
• Which ONE of the following would be consistent with these findings?– Gordon’s syndrome– Licorice ingestion– Liddle’s syndrome – Gitelman’s syndrome– RAS
Gordon’s Syndrome
• Aka: PHA II, chloride shunt syndrome, familial hyperkalemic hypertension.
• AD
• Mutation in WNK (1,4).
• High BP, ↑K+, acidosis, normal renal function, ↓ PRA
• Short stature, stiff spine, limbs deformities.
• Rx. Thiazides diuretics
Q3
• A 35-year-old nurse presents with chronic acidosis that is difficult to manage.
• Labs disclosed:– Na 143, K 2.8, Cl118, BUN 18 Cr 65, ABG 7.38/31/15 – Urinalysis nl, spot urine for lytes: Na 40, K5, Cl150
• Which disorder best describes this patient clinical syndrome?– Diuretic abuse– Laxative abuse– RTA I– RTA II– RTA IV
Urinary Anion Gap
• UAG = [Na+]+ [K+] - [Cl-]
• Provides a rough index of urinary ammonium excretion.
• A negative UAG suggests GIT loss of bicarbonate (eg diarrhoea)
• A positive UAG suggests impaired renal distal acidification (ie renal tubular acidosis).
• Remember ‘neGUTive’ - negative UAG in bowel causes.