Comprehensive Metabolic Panel, Plasma

Glucose is the primary circulating monosaccharide and main cellular fuel. Plasma concentration is tightly regulated by insulin, counter-regulatory hormones (glucagon, cortisol, growth hormone), and hepatic glycogenolysis and gluconeogenesis. Fasting glucose reflects the balance of endogenous production and insulin-mediated uptake, while post-prandial values show the response to dietary carbohydrate.

Fasting glucose is the cornerstone of diabetes screening and diagnosis; impaired fasting glucose (100–125 mg/dL) defines prediabetes, and values ≥126 mg/dL on two occasions confirm diabetes. Non-fasting glucose helps assess overall glycaemic control but is less standardised for diagnosis. Hypoglycaemia (typically <70 mg/dL) prompts evaluation for insulin excess, adrenal insufficiency, or other causes.

Urea is the main nitrogen-containing end-product of protein catabolism, synthesised in the liver and excreted by the kidneys. BUN reflects protein intake, hepatic urea synthesis, and renal urea clearance, making it sensitive to both renal function and volume status. It is reabsorbed passively in the proximal tubule, so it rises disproportionately in pre-renal states.

BUN is a screening marker for renal dysfunction and a key component of the BUN:creatinine ratio, which helps distinguish pre-renal (ratio >20) from intrinsic renal azotaemia. Elevated BUN is seen with dehydration, high protein intake, upper gastrointestinal bleeding, and kidney disease; low BUN may reflect malnutrition, liver disease, or overhydration.

Creatinine is a breakdown product of creatine phosphate in skeletal muscle, produced at a relatively constant rate and filtered by the glomeruli with minimal tubular reabsorption. Its plasma concentration depends on muscle mass, production rate, and glomerular filtration rate (GFR), making it the most widely used endogenous marker of kidney function.

Serum creatinine is the foundation of estimated GFR calculations (CKD-EPI, MDRD), which stage chronic kidney disease. Rising creatinine signals acute kidney injury or progression of CKD. The BUN:creatinine ratio adds context: a ratio >20 suggests pre-renal azotaemia, while an elevated creatinine with a normal ratio points to intrinsic renal disease.

eGFR is calculated from serum creatinine, age, sex, and race (though race-based adjustment is being phased out in favour of race-free equations). It estimates the volume of plasma filtered by the glomeruli per minute, indexed to body surface area, and is the single best summary measure of kidney function.

eGFR is the basis for CKD staging: ≥90 is normal or hyperfiltration; 60–89 is mild reduction (stage 2 if kidney damage is present); 30–59 is moderate (stage 3); 15–29 is severe (stage 4); <15 is kidney failure (stage 5). Serial eGFR tracks disease progression and guides decisions about nephrology referral and renal replacement therapy.

Sodium is the dominant extracellular cation and the primary determinant of plasma osmolality and extracellular volume. Its concentration is tightly regulated by antidiuretic hormone (vasopressin), which adjusts renal water reabsorption, and by the renin–angiotensin–aldosterone axis, which modulates sodium reabsorption and vascular tone.

Hyponatraemia (<136 mmol/L) is the most common electrolyte disorder, caused by free water excess relative to sodium (hypervolaemic, euvolaemic, or hypovolaemic) or rarely by true sodium depletion; it can produce confusion, seizures, and coma if severe or acute. Hypernatraemia (>145 mmol/L) indicates free water deficit and is often seen with dehydration, diabetes insipidus, or hyperosmolar states.

Potassium is the principal intracellular cation, with only about 2% of total body potassium in the extracellular space. Plasma concentration is regulated by renal excretion (aldosterone-mediated) and by shifts between intracellular and extracellular compartments driven by insulin, catecholamines, acid–base status, and cell turnover. Excitable tissues—cardiac and skeletal muscle, nerves—are exquisitely sensitive to changes in extracellular potassium.

Hypokalaemia (<3.5 mmol/L) causes muscle weakness, arrhythmias (flattened T waves, U waves, prolonged QT), and can precipitate rhabdomyolysis; common causes include diuretics, gastrointestinal losses, and hyperaldosteronism. Hyperkalaemia (>5.0 mmol/L) risks life-threatening arrhythmias (peaked T waves, widened QRS, ventricular fibrillation) and is seen with renal failure, potassium-sparing diuretics, ACE inhibitors, and tissue breakdown.

Chloride is the major extracellular anion, moving with sodium to maintain electrical neutrality and playing a key role in acid–base homeostasis. Its concentration is influenced by renal handling (parallel to sodium in many tubular segments), gastrointestinal losses, and reciprocal changes with bicarbonate in metabolic acid–base disorders.

Hypochloraemia (<98 mmol/L) is seen with vomiting (loss of HCl), diuretic use, and metabolic alkalosis. Hyperchloraemia (>107 mmol/L) accompanies metabolic acidosis (normal-anion-gap or hyperchloraemic acidosis), often from diarrhoea or renal tubular acidosis. The anion gap—calculated as [Na − (Cl + HCO₃)]—is central to acid–base diagnosis and uses chloride as one of its three inputs.

The total CO₂ measurement on a metabolic panel is predominantly bicarbonate (HCO₃⁻), with a small contribution from dissolved CO₂ and carbonic acid. Bicarbonate is the body's main buffering anion, regulated by renal reabsorption and regeneration in response to acid–base disturbances, and by respiratory control of PCO₂.

Low CO₂ (<22 mmol/L) indicates metabolic acidosis or respiratory alkalosis with renal compensation; high CO₂ (>29 mmol/L) reflects metabolic alkalosis or compensated respiratory acidosis. Interpreting CO₂ requires integration with the anion gap, chloride, and clinical context—or ideally arterial or venous blood gases for a complete acid–base picture.

Calcium is the most abundant mineral in the body and circulates in three forms: ionised (the physiologically active fraction), protein-bound, and complexed with anions. Total calcium reflects all three; ionised calcium is the definitive measure but requires special handling. Calcium homeostasis is controlled by parathyroid hormone, vitamin D, and calcitonin, which regulate intestinal absorption, renal excretion, and bone remodelling.

Hypercalcaemia (>10.5 mg/dL) is most often caused by primary hyperparathyroidism or malignancy and presents with stones, bones, abdominal groans, and psychiatric moans. Hypocalcaemia (<8.5 mg/dL) produces neuromuscular irritability (Chvostek and Trousseau signs, tetany, seizures) and is seen with hypoparathyroidism, vitamin D deficiency, chronic kidney disease, and hypoalbuminaemia (which lowers total but not ionised calcium).

Albumin is the most abundant plasma protein, synthesised exclusively by the liver with a half-life of approximately 20 days. It maintains oncotic pressure, transports hormones, fatty acids, bilirubin, and drugs, and serves as a readily mobilised amino-acid reserve. Plasma albumin concentration reflects synthesis rate, distribution volume, and losses (renal, gastrointestinal, or into third spaces).

Hypoalbuminaemia (<3.5 g/dL) is a marker of chronic illness, malnutrition, liver disease, nephrotic syndrome, protein-losing enteropathy, and acute inflammation (negative acute-phase protein). It is associated with oedema, impaired drug binding, and worse outcomes across many conditions. Hyperalbuminaemia is rare and usually reflects dehydration or laboratory error.

Total protein is the sum of albumin and globulins (immunoglobulins, acute-phase proteins, transport proteins, and others). It provides a crude overview of protein nutritional status, hepatic synthetic function, and the presence of inflammation or monoclonal gammopathies. The albumin:globulin ratio (calculated as albumin divided by [total protein minus albumin]) helps interpret shifts.

Hypoproteinaemia (<6.0 g/dL) is seen with malnutrition, liver disease, nephrotic syndrome, and protein-losing states; it contributes to oedema. Hyperproteinaemia (>8.3 g/dL) can reflect dehydration or, if marked, a monoclonal protein (myeloma, MGUS); serum protein electrophoresis is the next step. The albumin:globulin ratio is typically 1.1–2.5; a low ratio suggests inflammation or immunoglobulin excess.

Bilirubin is the yellow breakdown product of haem, mostly from senescent red cells. Unconjugated (indirect) bilirubin is lipid-soluble, bound to albumin, and taken up by hepatocytes, where it is conjugated with glucuronic acid to form water-soluble direct bilirubin, which is excreted in bile. Total bilirubin is the sum of conjugated and unconjugated fractions.

Hyperbilirubinaemia (>1.2 mg/dL) manifests as jaundice when total bilirubin exceeds approximately 2.5 mg/dL. Predominantly unconjugated elevation points to haemolysis, Gilbert syndrome, or Crigler–Najjar syndrome; conjugated (direct) hyperbilirubinaemia indicates hepatocellular injury or cholestasis. Total bilirubin is interpreted alongside direct bilirubin, ALT, AST, and ALP to classify the pattern of liver or biliary disease.

Alkaline phosphatase is a hydrolase enzyme found in liver (canalicular membrane), bone (osteoblasts), intestine, placenta, and kidney. Serum ALP reflects mainly hepatic and bone isoenzymes in adults. Hepatic ALP is induced by cholestasis and rises when bile flow is impaired; bone ALP increases with osteoblastic activity (fractures, Paget disease, bone metastases).

Elevated ALP is the hallmark of cholestatic liver disease—biliary obstruction, primary biliary cholangitis, drug-induced cholestasis—and of increased bone turnover. Isolated ALP elevation prompts fractionation or correlation with GGT (which is liver-specific) to distinguish hepatic from bone sources. Low ALP is rare and can be seen with hypophosphatasia, malnutrition, or hypothyroidism.

Aspartate aminotransferase is a transaminase enzyme present in liver, heart, skeletal muscle, kidney, brain, and red cells, existing in cytosolic and mitochondrial isoforms. When cells are injured, AST leaks into the circulation. Its plasma half-life is shorter than ALT's, so AST rises and falls more rapidly in acute injury.

AST is a marker of hepatocellular injury but is less liver-specific than ALT because it is abundant in heart and muscle. The AST:ALT ratio helps narrow the differential—ratios <1 are typical of steatotic liver disease and viral hepatitis, while ratios ≥2 suggest alcohol-related liver injury or cirrhosis. Very high AST (>1000 U/L) is seen with acute viral hepatitis, ischaemic hepatitis, or drug-induced liver injury.

Alanine aminotransferase is a cytosolic enzyme concentrated in hepatocytes, with small amounts in kidney and muscle. It catalyses the transfer of an amino group from alanine to alpha-ketoglutarate. Because of its liver specificity, ALT is the most sensitive marker of hepatocellular injury, and its longer half-life compared to AST means elevations persist for several days.

ALT is the first-line marker for hepatocellular damage. Isolated ALT elevation is common in metabolic dysfunction-associated steatotic liver disease; marked elevations suggest acute viral, toxic, or ischaemic hepatitis. The AST:ALT ratio adds context: <1 in MASLD and viral hepatitis, ≥2 in alcohol-related injury. Serial ALT is used to monitor chronic liver disease and hepatotoxic therapy.

The BUN:creatinine ratio compares two nitrogenous waste products with different renal handling. Creatinine is filtered and minimally reabsorbed, so it tracks GFR closely. Urea is filtered and passively reabsorbed, particularly in volume-depleted states when tubular flow slows. A high ratio therefore indicates disproportionate urea retention, typically from reduced renal perfusion.

A BUN:creatinine ratio >20 suggests pre-renal azotaemia (dehydration, heart failure, hypotension) or upper gastrointestinal bleeding (protein load from digested blood). A ratio <10 can be seen with low protein intake, liver disease (reduced urea synthesis), or severe overhydration. Normal ratios do not exclude kidney disease; they simply indicate that BUN and creatinine are rising proportionately.