Interpreting clinical laboratory data

Graeme Vernon

Austin Health Drug Information

Outline

• Clinical pharmacy perspective

• Most common tests

• Case summaries

• Reference

– Jeff Hughes (editor). Case studies in clinical

practice. Use of laboratory test data,

Pharmaceutical Society of Australia, 2004.

Clinical pharmacy approach

• Lab data mainly for diagnostic use

– pharmacists do not diagnose

• Focus on tests relevant to pharmaceutical care

– understanding a diagnosis

– avoiding adverse outcomes from drug therapy

– monitoring therapy

– recognising adverse drug reactions

Normal ranges

• Normal range assumes a Normal distribution of

results

– ‘abnormal’ if > 2 standard deviations from mean

• Reference range

– normal range from a defined population

»hospital population

»pregnant women

»Infants, children

Important tests

• Sodium

• Potassium

• Creatinine

• Liver function

• Blood counts

• Glucose

• Calcium

• Magnesium

Sodium

• Serum levels 135–145 mEq/L

• Extracellular cation

• Osmolality depends on sodium, urea and glucose

concentrations

• Renal excretion

– angiotensin, aldosterone, renin, vasopressin

Hyponatremia

• Mild (125–135 mEq/L)

• More likely to be symptomatic < 125 mEq/L

– headache, lethargy, nausea, dizziness, confusion,

agitation, muscle twitching or cramps, psychosis,

seizures

– cerebral edema, coma (severe hyponatremia only)

Causes of hyponatremia

• Increased extracellular fluid volume (ECF)

– renal failure

– edema treated with diuretics

• Normal ECF

– syndrome of inappropriate antidiuretic hormone (SIADH)

– serum osmolality, urine osmolality, urine sodium

• Reduced ECF

– excess diuresis (renal sodium loss)

– gastrointestinal loss (vomiting, diarrhea)

Drug causes of hyponatremia

• SIADH

– stimulate central ADH release

– e.g. carbamazepine, SSRIs, chlorpromazine

• Increased ADH activity (kidneys)

– NSAIDs, amiloride

• Sodium and water removal

– diuretics

Hypernatremia

• Less common drug-related problem

• Symptoms

– thirst (may dissipate)

– confusion, neuromuscular excitation, seizures,

coma

– depend on rate of sodium rise

Causes of hypernatremia

• Reduced ECF

– diarhea, vomiting, burns, diuretics (sodium loss)

• Normal ECF

– diabetes insipidus (renal water loss due to reduced

ADH release)

– nephrogenic diabetes insipidus

» induced by hypercalcemia or hypokalemia

• Increased ECF

– hypertonic sodium (IV infusions, TPN)

– mineralocorticoids, Cushing’s syndrome

Drug causes of hypernatremia

• Nephrogenic diabetes insipidus

– lithium, foscarnet, amphotericin, demeclocycline

• Renal water loss

– loop diuretics, mannitol, overuse of osmotic laxatives

• Increased renal sodium

– fludrocortisone, corticosteroids

• Inceased body sodium

– hypertonic saline, sodium bicarbonate, sodium salts,

hypertonic saline enemas

Potassium

• Serum levels 3.5–5.0 mEq/L

• Intracellular

– 50–60 mEq (~2%) extracellular

– acute regulation - intracellular flow

»alkalosis, insulin, beta-2 stimulants shilf K into cells

– chronic regulation - renal elimination

Hypokalemia

• Cramping, paralytic ileus, constipation, hypotension, arrhythmias, tetany, muscle paralysis, respiratory failure

• Apparent potassium loss

– metabolic alkalosis, insulin, beta stimulants

• True loss

– reduced intake, GI loss, fluid loss (burns)

– hyperaldosteronism, Cushing’s syndrome

– magnesium deficiency

Drug causes of hypokalemia

• Intracellular shift

– adrenaline, salbutamol

• Renal loss

– thiazide, loop diuretics

– fludrocortisone, carbenoxolone, high-dose glucocorticosteroids

– amphotericin, cisplatin

• GI loss

– laxative abuse

Hyperkalemia

• Signs/symptoms > 6 mEq/L

• Cardiovascular

– hypotension

– ECG changes, bradycardia

– increase risk of digoxin toxicity

• Neuromuscular

– weakness

Drug causes of hyperkalemia

• Increased load

– potassium supplements

• Cellular shift

– beta-blockers, digoxin toxicity

• Reduced renal elimination

– ACE inhibitors, ARAs

– lithium, NSAIDs, amiloride, trimethoprim

Creatinine

• Serum levels (adults)

– 0.3–1.2 mg/dL, 0.03–0.11 mmol/L

• Formed from creatine in the liver

– 98% of creatine present in muscle

• Eliminated mainly by renal filtration

• Serum levels reflect both muscle mass and kidney

function

Creatinine clearance

• Better indicator of renal function

• Calculated from urine creatinine/24 hours

• Estimated from Cockcroft and Gault method

– age, lean body weight, serum creatinine

– (140 - age) x IBW ‚ (72 x serum creatinine in mg/dL)

– valid only for steady state

• Degrees of renal impairment

– mild 50–75 mL/min

– moderate 20–50 mL/min

– severe < 20 mL/min

Liver function tests

• Bilirubin (total)

– < 1 mg/dL (< 20 micromol/L)

• Alkaline phosphatase (ALP) < 120 U/L

– bile duct cells, bone, intestine

• Aspartate aminotransferase (AST) < 45 U/L

– liver cells, heart, kidney, muscles

• Alanine aminotransferase (ALT) < 36 U/L

– mainly liver cells

• Gamma glutamyl transpeptidase (GGT) < 60 U/L

– liver cells (cholestasis, alcohol, drugs)

LFTs in different forms of jaundice

Type Cause Bilirubin ALP AST/ALT

GGT

Pre-hepatic Hemolysis ↑unconjugated

N N

Intra-hepatic

damage

Hepatitis,

drugs

↑

mostly conjugated

N - ↑ ↑ ↑

Cholestasis Biliary

cirrhosis

↑

mostly conjugated

↑ N - ↑

Blood examination

• Hemoglobin

– male: 130–170 g/L, female: 115–155 g/L

• White cells

– 4–11 x 109/L

– neutrophils, 2–7.5 x 109/L

– lymphocytes, monocytes, eosinophils, basophils

• Platelets

– 150–400 x 109/L

• Red cell count, volume, etc.

Hematology terms

• Leucopenia - low total white cell count

• Granulocytopenia - low granulocyte* count

– *neutrophils, eosinophils, basophils

• Neutropenia - low neutrophils

• Agranulocytosis - severe granulocytopenia

• Thrombocytopenia - low platelets

• Aplastic anemia - absence of erythrocytes,

leucocytes and platelets

Glucose

• Fasting glucose

– diabetes unlikely < 100 mg/dL (5.6 mmol/L)

– diabetes likely > 125 mg/dL (7.0 mmol/L)

• Random glucose

– risk of hypoglycemia < 65 mg/dL (3.6 mmol/L) and

using insulin or sulfonylureas

– normal levels, 70–110 mg/dL (4–6.5 mmol/L)

before meals or 70–145 mg/dL (4–8 mmol/L) after

meals

• Hypoglycemia < 40 mg/dL (2.2 mmol/L)

Glycolated hemoglobin

• Glycolated = glycosylated hemoglobin (HbA1c)

• Glucose binds slowly to this type of hemoglobin in red blood cells.

• Steady state (formation, decomposition, destruction) with about 3.0 to 6.5% being HbA1c

• Diabetics have higher average blood glucose and therefore a higher proportion of HbA1c

• Indication of mean BGL over previous 4–8 weeks

– aim for 7% or less

Calcium

• Serum 8.4–10 mg/dL (2.1–2.6 mmol/L)

– adjust for calcium binding to albumin

» increased serum concentration of ionised (active) calcium

with low albumin levels

– Ca (corrected) =

Ca (measured) + [(4.0 - albumin) x 0.8]

where albumin concentration is in g/dL

Hypocalcemia

• Corrected serum calcium < 8.4 g/dL (2.1 mmol/L)

– Finger numbness, paresthesia, tetany and muscle

cramps

– CNS depression, confusion, hallucinations,

seizures

– ↓ myocardial contractility; arrhythmias,

bradycardia, hypotension

Hypercalcemia

• Corrected serum calcium > 10 g/dL (2.55 mmol/L)

– symptoms > 11 g/dL (2.85 mmol/L)

» life threatening > 14 g/dL (3.5 mmol/L)

– weight loss, vomiting

– muscle fatigue, lethargy, coma

– psychosis

– ↓ renal function

Magnesium

• Serum 1.4–2.0 mEq/L (0.7–1.0 mmol/L)

• Hypomagnesemia < 1.4 mEq/L (0.7 mmol/L)

– ↑ muscle reflexes, cramps

– disorientation, psychosis, seizures

– arrhythmias

Hypermagnesemia

• Serum magnesium > 2 mEq/L (1.0 mmol/L)

– 2–4 mEq/L (1–2 mmol/L)

»vomiting, skin flushing, weakness, ↓ consciousness

– 3.4–5.0 mEq/L (1.7–2.5 mmol/L)

» loss of tendon reflexes, muscle weakness

– 5.0–6.0 mEq/L (2.5–3.0 mmol/L)

»hypotension, vasodilation

– 8.0-10 mEq/L (4.0–5.0 mmol/L)

»arrhythmias (inc. AF)

– > 10 mEq/L (5.0 mmol/L)

»asytole, heart block, ventricular failure, coma, death

Case studies

• Acute renal failure

• Hyponatremia

• Jaundice

• Aplastic anemia

• DVT treatment