Dyskalemia

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.