Dyskalemia

A Pathophysiological Approach
Dr. Mubarak S. AlGhamdi Senior Resident Internal Medicine, KFMC Saudi Arabia

Transcellular Shift

Intracellular K+

-Alkalosis -Insulin -B-adrenergics -A-adrenergic antaggonists

-Acidosis -B-antagonists -Hyperosmolarity

* 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

Proximal Tubule
Tubular Lumen (urine)
Proximal Tubule Epithelial Cell

Capillary Lumen (blood)

Na+
Proximal RTA NHE ATP

2K+ 3 Na+

H+

K+ Ca+2 Mg+2 ,

Paracellular Pathway

PO4, AA, Glu

Diffusion

Diffusion: The movement of solutes from a higher to a lower solute concentration area.

Convection

Convection: The movement of solutes with a water-flow, solvent drag

Thick Limb - Loop of Henle Sodium Reabsorption

Tubular Lumen (urine)
Ascending Thick Limb of the Loop of Henle epithelial cell

Capillary Lumen (blood)

Na+
Loop Diuretics Bartters Syndrome

NKCC2

2K+
ATP

2 ClK+

3 Na+

K+ recycling

CaSR

K+

Cl-

+
Na+ Ca+2 Mg+2

ROMK channel

- +

Paracellular Pathway

Bartters Syndrome

Distal Tubule Sodium Reabsorption

Tubular Lumen (urine) Distal Tubule Epithelial Cell
NCCT Thiazide Diuretics Gitelmans Syndrome

Capillary Lumen (blood)

Na+
ATP

2K+ 3 Na+

Cl-

K+

Cl-

Gitelmans Syndrome

Barrter vs Gitelman

Collecting Tubule Sodium Reabsorption

Tubular Lumen (urine)
Amiloride, Triamterene, Trimethoprim, Pentamidine

Collecting Tubule Epithelial Cell Principal Cell

ENaC

Capillary Lumen (blood)

2K+
ATP

Na+

3 Na+

Liddles Syndrome

K+
Nonabsorbable Anions -Bicarbonaturia -BHP (DKA) -Penicillin

K+

-Hippurate (glue-sniffing)

Distal Urinary Flow

ROMK

Collecting Tubule
Tubular Lumen (urine) Distal Tubule Epithelial Cell
ENaC

Capillary Lumen (blood)

Na+
ATP

2K+

Cl+ Gordons Syndrome

AKA: Pseudohypoaldosteronism II, Chloride Shunt Syndrome

3 Na+

WNK kinase
+ MR

Aldosterone

Spironolactone, Epleronone Pseudohypoaldosteronism I Cortisone 11b OHSD II SAME Licorice Cortisol

Hypokalemia
Plasma K < 3.5 mmol/L

Causes of Hypokalemia
Decreased intake (unusual)
Ingestion of clay (geophagia)

Renal Loss
Diuretics Bartters, Gitelmans, Liddless syndromes Bicarbonaturia, ketoaciduria Hyperaldosteronism Hypercortisolism SAME, Licorice

Transcellular shift (acute hypokalemia)

Hormones (insulin, Badrenergics) Metabolic alkalosis Hypokalemic periodic paralysis (familial, thyrotoxic)

Miscellaneous
Low magnesium Pseudohypokalemia (RBC, WBC)

GI Loss
Diarrhea, laxatives, villous adenoma, NGT suction & vomiting lead to renal K+ loss.
* 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.

Hypokalemia Clinical 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 -cell Blood pressure : (low K+ diet) or (Gitelmann) Growth defect : impaired protein metabolism GH release

EKG in Hypokalemia
Flattened T-wave Presence of U-wave ST depression

Peaked T wave

Flat P, PR, ST, peaked T

Atrial standstill, QRS

Sine wave

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

Addisons disease RTA IV Aldosterone receptors blockade (aldactone, eplerenone). ENaC blockade (amiloride, triameterene) Gordons syndrome Tubulointerstitial disorders Drugs

Miscellaneous
Cell lysis (rhabdomyolysis, TLS).

Hyperkalemia
Clinical 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 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 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

Induce intracellular K+ shift;

External removal;

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 11b-OHSD type 2

Primary hyperaldosteronism

Role of 11b-OHSD type 2

SAME or Licorice
11b OHSD

Cortisone

Cortisol
Cortisol

GR
ENaC Na,K-ATPase MR

Cortisol
11b OHSD

Cortisone

MR
Aldo

Aldo
Adapted from Ellison

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?
Gordons syndrome Licorice ingestion Liddles syndrome Gitelmans syndrome RAS

Gordons 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.