Chemical pathology II - Potassium Flashcards by Max Kam

How is K transported across intra-cellular and extra-cellular space?

Na/K ATPase pump

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Effect of acid/base balance on serum K concentration?

Acid-base status cause transcellular
shifts for neutrality:

 HyperK (and hypermagnesemia) = acidosis

 HypoK (and hypomagnesemia) = alkalosis

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Effect of insulin on serum K conc?

Insulin promotes cellular uptake of glucose together with K (and magnesium and phosphate)

> > > > serum hypoK

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Effect of adrenaline/ catecholamine and thyroxine on serum K conc.?

Adrenaline (catecholamines), thyroxine stimulate cellular K+ uptake via Na+/K+-ATPase

> > > > serum HypoK

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Effect of aldosterone on serum K conc. and acid/base balance?

Aldosterone action&raquo_space; renal H+, K excretion and
Na+ absorption at collecting ducts

> > alkalosis, hypokalemia, hypernatremia (e.g. Conn
syndrome)

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Define serum and plasma K level for hyperkalemia

 Plasma K >5.0 mmol/L; or
 Serum K >5.5 mmol/L

Serum K higher because platelets release K in clotting

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Can K conc. from arterial be used to define hyperK?

(not centrifuged = cannot detect if its hemolyzed = not reliable)

Always gives higher K value than serum and plasma K conc

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4 clinical manifestations of HyperKalemia?

Vague muscle weakness
Flaccid paralysis
Cardiac arrhythmia
Paresthesia (burning or prickling sensation in hands)
Non-specific: malaise, vomit, nausea

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Define the ECG changes with Hyper K at 6-7, 8-10, 11, 12mmol/L

(not important)

 6-7mmol/L = tall, peaked T waves
 8-10mmol/L = aberrant QRS complexes
 11mmol/L = fusion of QRS and T waves
 10-12 mmol/L = ventricular fibrillation

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Define 4 extra-renal causes of HyperK

*****

Pseudohyperkalemia (factitious hyperkalemia)
Tumor lysis syndrome, tissue necrosis (trauma, burns, rhabdomyolysis): K leak from cells
Hyperkalemic periodic paralysis (autosomal dominant disorder)
drug history (IV / oral K therapy, Potassium-sparing diuretics, Digoxin/digitalis)

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4 causes of pseudohyperkalemia

Extra-renal cause of HyperK

1) Hemolysed specimen (check hemolysis index):
- Elevated PO4, K, CK, AST, LDH, uric acid, Mg
- Decreased alkaline phosphatase, amylase, GGT

2) EDTA contamination (EDTA contains K; check calcium – should be low)
3) Thrombocytosis, leukocytosis(check complete blood picture, e.g. leukemia)
4) Aged samples(check sampling date and time; do the test ASAP to minimize K leakage from cells)

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Compare hyperK and hypoK periodic paralysis clinical presentation

(Extra-renal cause of HyperK)

1) Hyperkalemic periodic paralysis: Acute onset of muscle weakness:
 Precipitated by exercise, cold, hyperK
 Spontaneously resolves over a few hrs

2) Hypokalamic periodic paralysis:
Attacks of flaccid paralysis (lasting 6-24 hours):
 Precipitated by rich carbohydrate diet (stimulates insulin secretion&raquo_space; hypoK)
 Spontaneously resolves

Both autosomal dominant

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List 4 drugs that can cause serum HyperK

Extra-renal cause of HyperK

 IV / oral K therapy

 Potassium-sparing diuretics affect renin and aldosterone

 Digoxin/digitalis (inhibits H-K-ATPase pump&raquo_space; inhibit intracellular K+ uptake&raquo_space; hyperkalemia)

Insulin (rapid K uptake in cells)

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3 risk factors for digoxin overdose?

 Elderly (renal failure)
 Hypothyroidism (more sensitive to side effects of digoxin)
 HypoK

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Precaution with diabetics using insulin and K conc. imbalance?

Insulin activates Na+/K+-ATPases in many cells

> > flux of potassium into cells cause hypokalemia

insulin drip must be given together with K to avoid lethal hypokalemia

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3 renal causes of HyperK?

Acute renal failure/ injury
End-stage Renal failure
Diabetic ketoacidosis

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High plasma creatinine + HyperK

Dx?

renal failure (acute or end-stage renal failure)

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Low plasma HCO3 + high anion gap + HyperK

Dx?

diabetic ketoacidosis
(metabolic acidosis causes transcellular shift >>  hyperkalemia)

or Renal failure

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2 endocrine causes of HyperK?

Explain mechanisms

Addison’s disease (primary adrenal insufficiency: no mineralocorticoid/aldosterone = hyperK)
Congenital adrenal hyperplasia - 21-hydroxylase deficiency (decreased synthesis of cortisol,
aldosterone = hyperK)

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How to use renin and aldosterone levels to d/dx HyperK causes? (4)

(kidney impairment, extrarenal causes, mineralcorticoid resistance, aldosterone dediciency)

Normal renin and aldosterone = extra-renal cause of HyperK
High renin and high aldosterone = Minceralcorticoid resistance/ secondary hyperaldosteronism (keep releasing aldosterone, no negative feedback to renin)
High renin and low aldosterone = Selective aldosterone deficiency (renin cant stimulate aldosterone release)
Low renin and low aldosterone = Prostaglandin inhibition

Outline the flow of tests to d/dx hyperkalemia

1) Exclude all extra-renal causes of HyperK
2) Check plasma HCO3 and anion gap: low HCO3 + High anion gap = Kidney failure or Diabetic ketoacidosis
3) Check plasma creatinine: high = kidney failure
4) Check ACTH stimulation: No/ poor response = Addison’s disease or 21-hydroxylase deficiency (CAH)
5) Spot renin and aldosterone testing

List some causes of prostaglandin inhibition (Low renin and low aldosterone)

indomethacin (NSAID inhibits prostaglandin and
renin production)
interstitial nephritis
syndrome of hyporeninemic hypoaldosteronism
elderly with diabetes mellitus and mild renal impairment

List some causes of mineralocorticoid resistance (secondary hyperaldosteronism) - High renin and high aldosterone

Interstitial nephritis, obstructive uropathy, amyloidosis, SLE

Pseudohypoaldosteronism (congenital)

List some causes of selective aldosterone deficiency ( High renin and low aldosterone)

 Congenital: affects aldosterone synthase

 Acquired: heparin inhibits aldosterone synthesis

Action plan for moderate and severe hyperK?

Moderate: <5.5mmol/L = go through diagnostic flow chart Severe: > 6.5mmol/L = do an ECG Save urine K +/- other blood samples before treatment Test profiles for Renal failure, Diabetic Ketoacidosis

Case 1:  F/65y, HT, DM. OPD FU  Collection time: 15/4/2011 14:05  Arrival time: 16/4/2011 10:13 ``` Plasma:  Na 140 (132-144 mmol/L)  K 5.5 (3.2-4.8 mmol/L)  Urea 5 (3.0-8.0 mmol/L)  Cr 125 (60-120 μmol/L) ``` Dx?

Slightly elevated creatinine + Hyper K = mild renal impairment However, the sample is assessed very late >> hemolysis might increase K conc. >> Cannot determine hyperK

``` F/65y  Plasma:  Na 140 (132-144 mmol/L)  K 5.5 (3.2-4.8 mmol/L)  HCO3 15 (23-28 mmol/L)  Urea 5 (3.0-8.0 mmol/L)  Cr 100 (60-120 μmol/L) ``` Dx?

HyperK Low HCO3 - metabolic acidosis Check anion gap > high anion gap = Renal failure or diabetic ketoacidosis Check glucose for DM and insulin use = Extra-renal HyperK cause

``` Case 3:  M/48, known DM, found Loss of consciousness Plasma:  Na 132 (132-144 mmol/L)  K 6.5 (3.2-4.8 mmol/L)  Urea 23 (3.0-8.0 mmol/L)  Cr 323 (60-120 μmol/L)  Glucose 18 mmol/L  Urine ketone ++ ``` K deficit despite hyperK Dx?

High glucose - poor DM control High creatinine - Think renal failure or diabetic ketoacidosis HyperK High Urea High urine ketone K deficit despite hyperK - serum only accounts for 1% total body K Renal failure causing diuresis, passing too much K

Case 5:  Baby/1 day old, ambiguous external genitalia, hypotensive... ``` Plasma:  Na 118 (132-144 mmol/L)  K 6.5 (3.2-4.8 mmol/L)  Urea 9.5 (3.0-8.0 mmol/L)  Cr 60 (30-50 μmol/L) ```

Low Na > cannot drive Na/K-ATPase > cannot excrete enough K >> congenital adrenal hyperplasia

Case 7a:  M/70y, CRF with renal transplant 10 years ago, FU OPD ```  Na 140 (132-144 mmol/L)  K 9.5 (3.2-4.8 mmol/L)  Urea 5 (3.0-8.0 mmol/L) – normal RFT  Cr 110 (60-120 μmol/L) – normal RFT  Ca 0.56 (2.20-2.60mmol/L) ``` Dx?

Severe hyperK | But low Ca + Hyper K = EDTA contamination

Case 7b:  M/27, leukemia, just post-chemotherapy ```  Na 140 (132-144 mmol/L)  K 9.5 (3.2-4.8 mmol/L)  Urea 5 (3.0-8.0 mmol/L)  Cr 125 (60-120 μmol/L)  Ca 0.56 (2.20-2.60 mmol/L)  High PO4, urate ``` Dx?

tumour lysis syndrome

``` Case 7c:  M/58  Plasma:  Na 140 (132-144 mmol/L)  K 6.5 (3.2-4.8 mmol/L)  Urea 5 (3.0-8.0 mmol/L)  Cr 100 (60-120 μmol/L) Comments: sample mishandled before analysis ``` Dx?

HyperK caused by hemolysis >> misleading results >> Test for free Hb in the blood to indicate hemolysis cause

Why is serum K always higher than plasma K?

Serum platelets lysis release K

``` Case 8:  M/18y, sudden onset of paralysis, but resolves after few hours Plasma:  Na 140 (132-144 mmol/L)  K 5.5 (3.2-4.8 mmol/L)  Urea 5 (3.0-8.0 mmol/L)  Cr 100 (60-120 μmol/L) ``` Dx?

– hyperkalemic periodic paralysis

Hypokalemia: | Define plasma and serum levels

 Plasma K <3.0mmol/L |  Serum K <3.5mmol/L

Symptoms of hypoK

 Anorexia, nausea  Polyuria, polydipsia  Muscle weakness

2 metrics used to d/dx HypoK?

Paired spot urine K Plasma HCO3-

Outline the flow of diagnosis for HypoK

Plasma HCO3- normal or increased (metabolic alkalosis/ hyperkalemic alkalosis) a) Urine K <20-40 mmol/L = non-renal loss - Inadequate intake, intracellular shift, - extra-renal loss (CHRONIC diarrhea, laxative abuse, PREVIOUS diuretics, colon villous adenoma) b) Urine K >20-40 mmol/L = renal loss: - Vomiting, emetics, - CURRENT diuretics, - Conn's syndrome, Cushing's syndrome, - Leukemia, - Mg depletion, - Gentamycin - High ACTH + High cortisol - Small cell lung cancer Plasma HCO3- decreased (metabolic acidosis) a) Urine K <20-40 mmol/L = Acute diarrhea b) Urine K >20-40 mmol/L = renal loss: Renal tubular acidosis type I and II; Carbonic anhydrase inhibitor

Causes of Plasma HCO3- normal or increased +Urine K >20-40 mmol/L

Urine K >20-40 mmol/L = renal loss: - Vomiting, emetics, - CURRENT diuretics, - Conn's syndrome, Cushing's syndrome, - Leukemia, - Mg depletion, - Gentamycin

Causes of Plasma HCO3- normal or increased +Urine K < 20-40 mmol/L

Urine K <20-40 mmol/L = non-renal loss - Inadequate intake, intracellular shift, - extra-renal loss (CHRONIC diarrhea, laxative abuse, PREVIOUS diuretics, colon villous adenoma)

Electrolyte imbalance for acute diarrhea?

Plasma HCO3- decreased (metabolic acidosis) Urine K <20-40 mmol/L = Acute diarrhea Serum HypoK

Electrolyte imbalance for chronic diarrhea?

Plasma HCO3- normal or increased (metabolic alkalosis/ hyperkalemic alkalosis) Urine K <20-40 mmol/L- extra-renal loss - CHRONIC diarrhea Serum HypoK

Electrolyte imbalance for vomiting

Plasma HCO3- normal or increased (metabolic alkalosis/ hyperkalemic alkalosis) Urine K >20-40 mmol/L = renal loss: Vomiting Serum HypoK

Common causes of hypoK

Diuretics Vomiting/ diarrhea Mg deficiency Mineralocorticoid excess Glucocorticoid excess Renal tubular acidosis

Which body fluid contains the most K

Urine - 50mmol/L Diarrhea fluid - 40-100mmol/L Saliva - 15mmol/L Gastric, pancreatic juice - 10mmol/L

Case 9:  M/3mo, pyloric stenosis with refractory vomiting ``` Plasma:  Na 140 (132-144 mmol/L)  K 2.5 (3.2-4.8 mmol/L)  HCO3 30 (23-28 mmol/L)  Urea 5 (3.0-8.0 mmol/L)  Cr 100 (60-120 μmol/L) ```

HCO3 is high HypoK >> Vomiting of gastric juice causes alkalosis and loss of K

Case 10:  M/65, chronic smoker, weight loss and dry cough for 3 months ```  Na 140 (132-144 mmol/L)  K 2.6 (3.2-4.8 mmol/L)  Urea 7 (3.0-8.0 mmol/L)  Cr 110 (60-120 umol/L)  Further investigations:  Urine K 102 mmol/L (high)  Cortisol 2424 umol/L  ACTH increased  CXR – lung mass ```

Urine K >20 HypoK High ACTH > High cortisol D/dx: ectopic ACTH production (common in small cell lung cancer) Cushing syndrome

Case 11:  F/70y, CA stomach on chemotherapy ``` Plasma:  K 2.3 mmol/L (3.5-5.0)  Ca 1.86 mmol/L (2.25-2.55)  PO4 0.56 mmol/L (0.6-1.2)  ALB 30 g/L (30-52)  Hypocalcemia refractory to replacement ```

Chemotherapy: check Mg, especially if cisplatin cause severe hypomagnesemia <0.3mmol/L: Cisplatin Inhibit PTH action >>> hypoK, hypoCa