Appendix B · Normal Laboratory Reference Values
Read this first
The values in this appendix are educational reference figures assembled to help you reason about physiology. They are not a clinical or diagnostic reference. Every laboratory issues its own method-specific reference intervals, and those — printed on the report in front of you — are the ones that govern patient care. Where this appendix and a real laboratory report disagree, the report is right and this appendix is wrong.
All patients described in this book are fictional composites.
B.1 How to Read a Reference Range
Most students treat a reference range as a boundary between health and disease. It is not, and the difference between those two ideas is the single most useful thing in this appendix.
A reference interval is a statistical construction
A laboratory establishes a reference interval by measuring an analyte in a defined reference population — typically 120 or more ostensibly healthy volunteers, screened to exclude known disease — and then reporting the central 95% of the results. For an analyte whose values follow a Gaussian distribution, that is the mean plus or minus 1.96 standard deviations. For a skewed analyte, such as most enzymes, it is the interval between the 2.5th and 97.5th percentiles of the observed data.
Notice what that construction does. It defines "normal" as what most healthy people do, and then it deliberately cuts off the outer 5%. Therefore, by definition, one healthy person in twenty falls outside the reference range for any given analyte — 2.5% above and 2.5% below. Being outside the range is not evidence of disease. It is the expected experience of a substantial minority of perfectly well people.
Now do the arithmetic that follows from this, because it changes how you order tests. A comprehensive metabolic panel reports 14 analytes. If each is independent and each has a 95% chance of falling inside its range in a healthy person, then the probability that all fourteen are inside is 0.95 to the fourteenth power, which is about 0.49. Roughly half of perfectly healthy people will have at least one "abnormal" flag on a routine metabolic panel. Add a complete blood count and a lipid panel and you are near certainty.
This is why untargeted testing generates work rather than information, and why the discipline that matters is not knowing the ranges but knowing the question. You order a test because a specific result will change what you do next. If no result would change anything, the test generates only a number to explain away.
WHY ONE HEALTHY PERSON IN TWENTY FALLS OUTSIDE
frequency
▲
│ ╭───────╮
│ ╭──╯ ╰──╮
│ ╭─╯ ╰─╮
│ ╭─╯ ╰─╮
│ ╭─╯ ┌─────────┐ ╰─╮
│ ╭─╯ │ CENTRAL │ ╰─╮
│ ╭─╯ │ 95% │ ╰─╮
│ ╭──╯ │ of the │ ╰──╮
│ ╭──╯░░░░░░░░░░░░░│ healthy │░░░░░░░░░░░░░╰──╮
│ ╭──╯▒▒▒░░░░░░░░░░░░░│ populat.│░░░░░░░░░░░░░░░░╰──╮
│╭─╯▒▒▒▒▒░░░░░░░░░░░░░░└─────────┘░░░░░░░░░░░░░░░░▒▒▒╰─╮
└┴───────┴─────────────────────────────────────┴───────┴──►
▒▒▒▒▒▒▒▒│ │▒▒▒▒▒▒▒▒
2.5% │◄──────── REFERENCE INTERVAL ──────►│ 2.5%
"LOW" │ mean − 1.96 SD │ "HIGH"
flagged │ to │ flagged
but well │ mean + 1.96 SD │ but well
2.5th percentile 97.5th percentile
═══════════════════════════════════════════════════════════════════
CONSEQUENCE 1 A single flagged value is weak evidence of anything.
CONSEQUENCE 2 P(all normal) on an n-analyte panel = 0.95^n
n = 1 → 95% n = 14 → 49%
n = 7 → 70% n = 20 → 36%
CONSEQUENCE 3 The interval says nothing about THIS patient's usual
value. A result at the 50th percentile of the
population can be far from the 50th percentile of the
person. The TREND beats the single point.
Figure B.1 — A reference interval is the central ninety-five percent of a healthy population.
Described: A symmetric bell-shaped frequency distribution of an analyte measured in a healthy reference population. The central portion of the curve, containing ninety-five percent of the area, is bracketed and labeled as the reference interval, running from the 2.5th percentile on the left to the 97.5th percentile on the right, equivalent to the mean minus 1.96 standard deviations to the mean plus 1.96 standard deviations. The two tails outside the brackets are shaded and each labeled 2.5 percent, marked "flagged but well" — these are healthy individuals whose results will be reported as low or high purely because of where the interval was drawn. Beneath the curve, three consequences are stated: a single flagged value is weak evidence of anything; the probability that all results on a panel of n independent analytes fall inside their intervals is 0.95 raised to the power n, which gives 95 percent for one analyte, 70 percent for seven, 49 percent for fourteen, and 36 percent for twenty; and the interval says nothing about an individual patient's own usual value, so the trend across serial measurements carries more information than any single point.
Ranges belong to a method, not to nature
The same analyte measured by two different assays can legitimately produce two different numbers with two different intervals. Alkaline phosphatase, creatinine, and every hormone immunoassay are notorious for this. Two hospitals across the street from one another may report different reference ranges because they use different instruments, calibrators, antibodies, and units. There is no universal "normal creatinine" floating free of a measurement method.
The practical rule is simple and absolute: use the interval printed on the report you are holding, and be cautious comparing a value from one laboratory with a value from another, particularly for hormones and tumour markers.
Ranges belong to a population
Reference intervals shift, sometimes dramatically, with:
- Age. Alkaline phosphatase in a 14-year-old in a growth spurt runs two to three times the adult upper limit, because growing bone is full of osteoblasts and osteoblasts are full of this enzyme — a normal finding that looks like liver disease if you use adult numbers (Chapter 6). Neonatal creatinine for the first days of life reflects the mother's value, not the baby's. Hemoglobin falls through infancy to a physiological nadir around two to three months.
- Sex. Hemoglobin, hematocrit, creatinine, ferritin, and urate all run higher in men, largely because of testosterone-driven erythropoiesis and greater muscle mass.
- Pregnancy. Plasma volume rises about 45% while red cell mass rises only about 25%, so hemoglobin falls by dilution and a value that would be anemia outside pregnancy is normal within it. Alkaline phosphatase rises two- to fourfold from placental production. Glomerular filtration rate rises roughly 50%, so creatinine and urea fall, and a creatinine of 1.0 mg/dL in the third trimester is distinctly abnormal. Fibrinogen and D-dimer rise. TSH ranges are trimester-specific (Chapter 28).
- Altitude. Chronic hypoxia drives erythropoietin release, so hemoglobin and hematocrit rise with residential altitude. A lifelong resident of a town at 3,100 m normally runs a hematocrit several percentage points above a sea-level reference interval, and applying the sea-level interval would label an entire population polycythemic (Chapter 22).
- Time of day and posture. Cortisol peaks around waking and troughs near midnight, so a cortisol value is meaningless without the time it was drawn. Serum iron and testosterone are also strongly diurnal. Standing for 30 minutes concentrates protein-bound analytes by roughly 10% relative to lying down, because fluid shifts out of the vasculature.
- Ancestry. Historical estimating equations for glomerular filtration rate included a coefficient for Black race, derived from average differences in measured creatinine generation. The 2021 CKD-EPI creatinine equation removed it, on the grounds that race is a social rather than a biological variable and that the coefficient systematically overestimated kidney function in Black patients, delaying referral and transplant listing. This is a good example of a reference standard being a scientific and social choice at the same time.
The point that matters: normal for the population, abnormal for the person
Here is the example to carry with you. A serum creatinine of 1.1 mg/dL (97 µmol/L) sits inside almost every adult reference interval.
In a muscular 25-year-old man weighing 90 kg, that value is unremarkable. His estimated glomerular filtration rate is well above 90 mL/min/1.73 m². His kidneys are fine.
In a frail 80-year-old woman weighing 45 kg, the identical value implies an estimated GFR in the region of 45 mL/min/1.73 m² — stage 3a chronic kidney disease. Her kidneys have lost roughly half their filtering capacity.
Same number, same laboratory, opposite meaning. The reason is mechanistic and worth stating carefully. Creatinine is produced at a nearly constant rate by the non-enzymatic breakdown of creatine phosphate in skeletal muscle, and it is cleared almost entirely by glomerular filtration. Serum creatinine is therefore a ratio of production to clearance. The young man generates a great deal of creatinine and clears it briskly; his steady-state concentration is 1.1. The elderly woman has perhaps a third of his muscle mass and generates far less, so to sit at the same concentration her clearance must be correspondingly poorer. Low production hides poor clearance. Cross-reference Chapter 26, where the relationship between GFR, creatinine, and the estimating equations is developed properly.
Two corollaries follow immediately.
- A doubling inside the range is still a doubling. A creatinine that rises from 0.5 to 1.0 mg/dL over four days has never left the reference interval, and it means the glomerular filtration rate has roughly halved. The relationship between creatinine and GFR is a rectangular hyperbola, so early loss of function produces almost no change in creatinine and late loss produces a great deal. Never read a creatinine without its previous value.
- The individual's own baseline is the best reference interval available. The technical name for this idea is the reference change value: the difference between two serial results that exceeds what analytical imprecision and normal biological variation could produce. In practice, laboratories implement a crude version of it as a delta check, flagging results that have moved implausibly far from the patient's last one.
Pre-analytical errors — the results that are not real
Before you interpret a strange value, ask whether the specimen produced it.
| Pre-analytical event | What it does to the result | Give-away |
|---|---|---|
| Hemolysis in the tube | Raises potassium, LDH, AST, magnesium, phosphate; lowers haptoglobin | Pink or red serum; the lab usually comments |
| Tourniquet left on > 1 min, fist pumping | Raises potassium (muscle release), calcium, protein-bound analytes | Isolated unexplained hyperkalemia in a well patient |
| Drawn above a running IV | Dilutes everything; wildly raises whatever is in the fluid (glucose, sodium, potassium) | Implausible combination, e.g. glucose 600 with sodium 120 |
| EDTA (purple-top) contamination | Markedly raises potassium; crushes calcium and magnesium to near zero | Potassium 9 with calcium 4 in a patient who looks fine |
| Not fasting | Raises triglycerides and glucose | Triglycerides 400 in an otherwise normal panel |
| Prolonged standing before draw | Concentrates albumin, calcium, and everything protein-bound by ~10% | Whole panel shifted up slightly |
| Delayed processing | Glucose falls ~5–7% per hour (glycolysis by red cells); potassium rises | Low glucose with no clinical hypoglycemia |
| Cold storage of a potassium sample | Raises potassium (sodium-potassium pump stops, potassium leaks out) | Sample sent from a distant clinic |
The one-sentence version of Bayes
A test result does not tell you the probability of disease. It modifies the probability you already had.
Sensitivity is the fraction of people with the disease who test positive; specificity is the fraction without it who test negative. Neither tells you what you want to know, which is the probability of disease given the result. That depends on the pre-test probability — how likely the disease was before you tested. A D-dimer of 700 ng/mL in a breathless post-operative patient with a swollen calf means something very different from the same number in an asymptomatic 78-year-old, because D-dimer is sensitive but not specific: it is good at ruling pulmonary embolism out when the pre-test probability is low, and nearly useless at ruling it in.
This is why the phrase "just order the test and see" is a false economy. A test ordered without a question returns a number without a meaning.
B.2 Complete Blood Count with Differential
Cross-reference: Chapter 17 (Blood).
| Analyte | Conventional (US) | SI | High suggests | Low suggests |
|---|---|---|---|---|
| White blood cells | 4,500–11,000 /µL | 4.5–11.0 ×10⁹/L | Infection, inflammation, corticosteroids, stress, leukemia | Marrow failure, chemotherapy, overwhelming sepsis, HIV |
| Red blood cells (M) | 4.5–5.9 ×10⁶/µL | 4.5–5.9 ×10¹²/L | Polycythemia, chronic hypoxia, dehydration | Anemia, bleeding, hemolysis |
| Red blood cells (F) | 4.0–5.2 ×10⁶/µL | 4.0–5.2 ×10¹²/L | — | — |
| Hemoglobin (M) | 13.5–17.5 g/dL | 135–175 g/L | Polycythemia, altitude, smoking, dehydration | Anemia of any cause |
| Hemoglobin (F) | 12.0–16.0 g/dL | 120–160 g/L | — | — |
| Hematocrit (M) | 41–53% | 0.41–0.53 | Roughly 3 × hemoglobin; same causes | Same causes |
| Hematocrit (F) | 36–46% | 0.36–0.46 | — | — |
| MCV | 80–100 fL | 80–100 fL | B12/folate deficiency, alcohol, hypothyroidism, reticulocytosis | Iron deficiency, thalassemia, chronic disease, lead |
| MCH | 26–34 pg | 26–34 pg | Macrocytosis | Hypochromia, iron deficiency |
| MCHC | 31–37 g/dL | 310–370 g/L | Hereditary spherocytosis; spurious with lipemia | Iron deficiency |
| RDW | 11.5–14.5% | same | Mixed populations: early iron/B12 deficiency, post-transfusion | — |
| Platelets | 150,000–400,000 /µL | 150–400 ×10⁹/L | Reactive (infection, iron deficiency, post-splenectomy), myeloproliferative | Marrow failure, consumption (DIC, TTP), splenic sequestration, drugs |
| MPV | 7.5–11.5 fL | same | Young platelets: peripheral destruction | Marrow production failure |
| Neutrophils | 40–70%; 1,800–7,800 /µL | 1.8–7.8 ×10⁹/L | Bacterial infection, stress, steroids, tissue necrosis | Chemotherapy, viral, drug reaction, marrow failure |
| Bands (immature) | 0–5% | — | A "left shift" — acute bacterial infection or marrow stress | — |
| Lymphocytes | 20–45%; 1,000–4,800 /µL | 1.0–4.8 ×10⁹/L | Viral infection, pertussis, CLL | Steroids, HIV, immunodeficiency |
| Monocytes | 2–10%; 200–950 /µL | 0.2–0.95 ×10⁹/L | Chronic infection (TB), recovery phase, autoimmune | — |
| Eosinophils | 0–6%; 0–450 /µL | 0–0.45 ×10⁹/L | Allergy, parasites, drug reaction, adrenal insufficiency | Acute stress, steroids |
| Basophils | 0–2%; 0–200 /µL | 0–0.2 ×10⁹/L | Myeloproliferative disease, hypersensitivity | — |
| Reticulocytes | 0.5–2.5% of RBC; 25,000–75,000 /µL | 25–75 ×10⁹/L | Marrow responding: hemolysis, blood loss, treated deficiency | Marrow not responding: deficiency, aplasia, renal failure |
The absolute neutrophil count is what matters, not the percentage. ANC = total WBC × (neutrophils% + bands%). Neutropenia is an ANC below 1,500/µL; below 500/µL is severe neutropenia, at which point the patient cannot mount a normal inflammatory response and a fever becomes a medical emergency regardless of how well they look — there may be no pus, no infiltrate on the chest film, and no local redness, because all three are made of neutrophils.
MCV classifies anemia before any other test. Microcytic (< 80 fL): iron deficiency and thalassemia lead the list. Normocytic (80–100 fL): acute blood loss, anemia of chronic disease, early iron deficiency, renal failure. Macrocytic (> 100 fL): vitamin B12 or folate deficiency, alcohol, hypothyroidism, and — importantly — reticulocytosis, since reticulocytes are large. Pair MCV with the reticulocyte count and you have separated production failure from destruction or loss before you have ordered a single specialized test.
B.3 Basic and Comprehensive Metabolic Panel
Cross-reference: Chapters 26 (Urinary) and 27 (Fluid, Electrolyte, and Acid-Base Balance).
| Analyte | Conventional (US) | SI | High suggests | Low suggests |
|---|---|---|---|---|
| Sodium | 135–145 mEq/L | 135–145 mmol/L | Water deficit (not salt excess): dehydration, diabetes insipidus | Water excess: SIADH, heart/liver/renal failure, diuretics |
| Potassium | 3.5–5.0 mEq/L | 3.5–5.0 mmol/L | Renal failure, acidosis, cell lysis, ACE inhibitors, hemolyzed sample | Diuretics, vomiting/diarrhea, alkalosis, insulin, hyperaldosteronism |
| Chloride | 98–107 mEq/L | 98–107 mmol/L | Non-anion-gap acidosis, saline loading | Vomiting, diuretics |
| Bicarbonate (total CO₂) | 22–28 mEq/L | 22–28 mmol/L | Metabolic alkalosis; compensation for respiratory acidosis | Metabolic acidosis; compensation for respiratory alkalosis |
| Anion gap | 8–12 mEq/L | same | Lactate, ketones, uremia, toxic alcohols, salicylate | Hypoalbuminemia (correct it), paraproteins |
| BUN (urea nitrogen) | 7–20 mg/dL | 2.5–7.1 mmol/L | Renal impairment, GI bleeding, catabolism, dehydration | Liver failure, malnutrition, pregnancy, overhydration |
| Creatinine (M) | 0.7–1.3 mg/dL | 62–115 µmol/L | Reduced GFR; also high muscle mass, creatine supplements | Low muscle mass, amputation, advanced liver disease |
| Creatinine (F) | 0.6–1.1 mg/dL | 53–97 µmol/L | — | — |
| BUN : creatinine ratio | 10:1 to 20:1 | same | > 20:1 → pre-renal (hypovolemia) or upper GI bleed | < 10:1 → intrinsic renal disease, malnutrition |
| Glucose (fasting) | 70–99 mg/dL | 3.9–5.5 mmol/L | Diabetes, stress, steroids, pancreatitis | Insulin excess, adrenal insufficiency, sepsis, liver failure |
| Calcium (total) | 8.5–10.5 mg/dL | 2.12–2.62 mmol/L | Hyperparathyroidism, malignancy, immobility, thiazides | Hypoparathyroidism, vitamin D deficiency, renal failure, low albumin |
| Calcium (ionized) | 4.65–5.28 mg/dL | 1.16–1.32 mmol/L | The physiologically active fraction — unaffected by albumin | — |
| Magnesium | 1.7–2.2 mg/dL | 0.70–0.90 mmol/L | Renal failure, magnesium therapy | Alcohol, diuretics, PPIs, diarrhea — often with refractory hypokalemia |
| Phosphate | 2.5–4.5 mg/dL | 0.81–1.45 mmol/L | Renal failure, tumour lysis, hypoparathyroidism | Refeeding syndrome, hyperparathyroidism, alcohol |
| Total protein | 6.0–8.3 g/dL | 60–83 g/L | Dehydration, myeloma | Malnutrition, liver disease, protein loss |
| Albumin | 3.5–5.0 g/dL | 35–50 g/L | Dehydration only | Liver failure, nephrotic syndrome, inflammation, malnutrition |
| Globulin | 2.3–3.5 g/dL | 23–35 g/L | Chronic infection, myeloma, autoimmune | Immunodeficiency |
| Total bilirubin | 0.3–1.0 mg/dL | 5–17 µmol/L | Hemolysis, hepatocellular injury, obstruction, Gilbert syndrome | — |
| Direct (conjugated) bilirubin | 0.1–0.3 mg/dL | 2–5 µmol/L | Obstruction or hepatocellular disease — the liver did conjugate it | — |
| AST | 10–40 U/L | 0.17–0.67 µkat/L | Liver, muscle, heart, hemolysis | — |
| ALT | 7–56 U/L | 0.12–0.93 µkat/L | Liver — the more liver-specific of the two | — |
| Alkaline phosphatase | 30–120 U/L | 0.5–2.0 µkat/L | Biliary obstruction, bone turnover, growth, pregnancy | Hypophosphatasia, malnutrition |
| Uric acid (M / F) | 3.4–7.0 / 2.4–6.0 mg/dL | 202–416 / 143–357 µmol/L | Gout, tumour lysis, renal failure, thiazides | Drugs, SIADH |
| Osmolality (measured) | 275–295 mOsm/kg | same | Dehydration, hyperglycemia, toxic alcohols | Water excess, SIADH |
Three formulas worth memorizing.
- Anion gap = Na⁺ − (Cl⁻ + HCO₃⁻). Normal 8–12 mEq/L. The gap is the unmeasured anions, mostly albumin. Because albumin is the main contributor, a low albumin masks a real gap: corrected AG = measured AG + 2.5 × (4.0 − albumin in g/dL). A patient with an albumin of 2.0 g/dL and an apparently normal gap of 11 actually has a corrected gap of 16.
- Corrected calcium = measured total calcium + 0.8 × (4.0 − albumin in g/dL). About 40% of serum calcium is bound to albumin, so hypoalbuminemia lowers total calcium without lowering the ionized, physiologically active fraction. When it matters, measure the ionized calcium directly rather than correcting.
- Calculated osmolality = 2 × Na⁺ + glucose/18 + BUN/2.8 (conventional units), or 2 × Na⁺ + glucose + urea in mmol/L. The osmolal gap is measured minus calculated; a gap above about 10 mOsm/kg implies an unmeasured osmole in the plasma, classically ethanol, methanol, ethylene glycol, or mannitol.
B.4 Lipid Panel
Cross-reference: Chapters 19 (Vessels) and 21 (Nutrition and Metabolism).
| Analyte | Conventional (US) | SI | Notes |
|---|---|---|---|
| Total cholesterol | mg/dL | ÷ 38.67 = mmol/L | Sum of all lipoprotein cholesterol |
| LDL cholesterol | mg/dL | ÷ 38.67 = mmol/L | The principal atherogenic particle |
| HDL cholesterol | mg/dL | ÷ 38.67 = mmol/L | Inversely associated with risk |
| Triglycerides | mg/dL | ÷ 88.57 = mmol/L | Fasting sample preferred if > 400 |
| Non-HDL cholesterol | = total − HDL | — | All atherogenic particles in one number |
| Lipoprotein(a) | < 30 mg/dL (< 75 nmol/L) | — | Genetically determined; measure once in a lifetime |
| Apolipoprotein B | < 90 mg/dL | — | One apoB per atherogenic particle — a particle count |
Risk-category cutoffs.
| Category | Total cholesterol | LDL | HDL | Triglycerides |
|---|---|---|---|---|
| Optimal | — | < 100 mg/dL (2.6 mmol/L) | ≥ 60 mg/dL (1.6) — protective | — |
| Desirable / normal | < 200 mg/dL (5.2 mmol/L) | 100–129 (2.6–3.3) near optimal | 40–59 M, 50–59 F | < 150 mg/dL (1.7 mmol/L) |
| Borderline high | 200–239 (5.2–6.2) | 130–159 (3.4–4.1) | — | 150–199 (1.7–2.2) |
| High | ≥ 240 (6.2) | 160–189 (4.1–4.9) | Low: < 40 M (1.0), < 50 F (1.3) | 200–499 (2.3–5.6) |
| Very high | — | ≥ 190 (4.9) — consider familial hypercholesterolemia | — | ≥ 500 (5.6) — pancreatitis risk |
The Friedewald estimate. Most laboratories do not measure LDL directly; they calculate it:
LDL = total cholesterol − HDL − (triglycerides ÷ 5) (conventional units) LDL = total cholesterol − HDL − (triglycerides ÷ 2.2) (SI, mmol/L)
The triglyceride term estimates the cholesterol carried in VLDL. The estimate fails when triglycerides exceed 400 mg/dL (4.5 mmol/L), because the fixed ratio no longer holds, and it underestimates LDL at low LDL values. When triglycerides are high or the LDL is very low, ask for a direct LDL or use non-HDL cholesterol, which requires no assumptions at all.
B.5 Arterial Blood Gas and Acid–Base
Cross-reference: Chapters 22 (Respiratory) and 27 (Fluid, Electrolyte, and Acid-Base Balance).
| Analyte | Conventional (US) | SI | High suggests | Low suggests |
|---|---|---|---|---|
| pH | 7.35–7.45 | same | Alkalemia | Acidemia |
| PaCO₂ | 35–45 mm Hg | 4.7–6.0 kPa | Hypoventilation (respiratory acidosis) or compensation for metabolic alkalosis | Hyperventilation (respiratory alkalosis) or compensation for metabolic acidosis |
| PaO₂ | 80–100 mm Hg (room air) | 10.7–13.3 kPa | Supplemental oxygen | V/Q mismatch, shunt, hypoventilation, diffusion limitation, low FiO₂ |
| HCO₃⁻ (calculated) | 22–26 mEq/L | 22–26 mmol/L | Metabolic alkalosis or renal compensation | Metabolic acidosis or renal compensation |
| Base excess | −2 to +2 mEq/L | same | Metabolic alkalosis | Metabolic acidosis |
| SaO₂ | 95–100% | 0.95–1.00 | — | Hypoxemia; note the sigmoid dissociation curve makes SaO₂ insensitive above PaO₂ 80 |
| Lactate | 0.5–2.2 mmol/L (4.5–19.8 mg/dL) | same | Tissue hypoperfusion, sepsis, metformin, seizures, ischemic bowel | — |
| A–a gradient | (age ÷ 4) + 4 mm Hg | same | Shunt, V/Q mismatch, diffusion defect | — |
| Venous pH / PvCO₂ | 7.32–7.38 / 42–50 mm Hg | — | A venous gas is adequate for pH and CO₂ trend; it cannot assess oxygenation | — |
The alveolar gas equation gives the alveolar oxygen tension you should compare with the measured arterial value:
PAO₂ = FiO₂ × (Patm − 47) − (PaCO₂ ÷ 0.8)
At sea level breathing room air, that is 0.21 × (760 − 47) − PaCO₂/0.8, or about 150 − 1.25 × PaCO₂. The A–a gradient is PAO₂ − PaO₂. A normal gradient with hypoxemia means the problem is hypoventilation or low inspired oxygen; a widened gradient means the lung itself is failing to transfer oxygen.
Expected compensation for the four primary disorders
Compensation is predictable, which is what makes it useful: if the measured compensation differs from the predicted, a second acid–base disorder is present.
| Primary disorder | Direction | Expected compensation | Time course |
|---|---|---|---|
| Metabolic acidosis | HCO₃⁻ ↓, pH ↓ | Winter's formula: expected PaCO₂ = 1.5 × [HCO₃⁻] + 8 ± 2 | Minutes to hours (respiratory) |
| Metabolic alkalosis | HCO₃⁻ ↑, pH ↑ | PaCO₂ rises 0.7 mm Hg for each 1 mEq/L rise in HCO₃⁻ above 24 | Hours; limited by hypoxic drive, rarely exceeds 55 mm Hg |
| Respiratory acidosis, acute | PaCO₂ ↑, pH ↓ | HCO₃⁻ rises 1 mEq/L per 10 mm Hg rise in PaCO₂ | Immediate (cell buffering) |
| Respiratory acidosis, chronic | PaCO₂ ↑, pH near normal | HCO₃⁻ rises 3.5 mEq/L per 10 mm Hg rise in PaCO₂ | 3–5 days (renal) |
| Respiratory alkalosis, acute | PaCO₂ ↓, pH ↑ | HCO₃⁻ falls 2 mEq/L per 10 mm Hg fall in PaCO₂ | Immediate |
| Respiratory alkalosis, chronic | PaCO₂ ↓, pH near normal | HCO₃⁻ falls 4–5 mEq/L per 10 mm Hg fall in PaCO₂ | 2–3 days |
Why acute and chronic differ. The acute response is chemical buffering inside cells, which is immediate but weak. The chronic response is renal — altered bicarbonate reabsorption and ammoniagenesis — which is powerful but takes days to develop. This is why a patient with chronic obstructive pulmonary disease can live at a PaCO₂ of 60 mm Hg with a nearly normal pH, and why the same PaCO₂ arriving suddenly in an opioid overdose produces a pH of 7.20.
A six-step reading, worked. Take: pH 7.28, PaCO₂ 26 mm Hg, HCO₃⁻ 12 mEq/L, Na⁺ 140, Cl⁻ 100, glucose 480 mg/dL.
- Is the pH abnormal? 7.28 — acidemia.
- Which limb explains it? HCO₃⁻ is 12, low; PaCO₂ is 26, also low. A low PaCO₂ would raise pH, so it cannot be the cause. Primary metabolic acidosis.
- Is compensation appropriate? Winter's: 1.5 × 12 + 8 = 26, ± 2 → expected PaCO₂ 24–28. Measured 26. Compensation is exactly appropriate; there is no additional respiratory disorder.
- Anion gap? 140 − (100 + 12) = 28. Markedly elevated. This is a high-anion-gap metabolic acidosis.
- What is the unmeasured anion? Glucose 480 with a high gap points to ketoacids (Chapter 16).
- Delta–delta. ΔAG = 28 − 12 = 16; ΔHCO₃⁻ = 24 − 12 = 12. Ratio 16/12 = 1.3, which lies in the 1–2 range expected for a pure high-gap acidosis. A ratio below 1 would suggest a coexisting normal-gap acidosis; above 2, a coexisting metabolic alkalosis.
Clinical Connection · Reading the Compensation Backwards
Compensation formulas earn their keep when the numbers disagree with them.
A patient with diabetic ketoacidosis has HCO₃⁻ 10 mEq/L. Winter's formula predicts a PaCO₂ of 1.5 × 10 + 8 = 23, so 21–25 mm Hg. If the measured PaCO₂ is 24, this is a single, fully compensated disorder and the patient is doing what they should.
If the measured PaCO₂ is 40, the patient is not hyperventilating adequately. That is a second, superimposed respiratory acidosis — exhaustion, sedation, or impending respiratory arrest — and it is far more urgent than the ketoacidosis itself. The number that looks reassuringly normal is the dangerous one.
If the measured PaCO₂ is 15, there is a superimposed primary respiratory alkalosis — sepsis, salicylate poisoning, or pain.
In each case the patient looks similar and the bicarbonate is identical. The compensation calculation is what separates them (Chapter 31).
B.6 Coagulation Studies
Cross-reference: Chapter 17 (Blood).
| Analyte | Conventional (US) | SI | Pathway tested | Prolonged suggests |
|---|---|---|---|---|
| Prothrombin time (PT) | 11–13.5 s | same | Extrinsic and common (VII, X, V, II, fibrinogen) | Warfarin, liver disease, vitamin K deficiency, DIC |
| INR | 0.8–1.1 (untreated) | same | Standardized PT | Therapeutic on warfarin: 2.0–3.0; mechanical mitral valve: 2.5–3.5 |
| aPTT | 25–35 s | same | Intrinsic and common (XII, XI, IX, VIII, X, V, II) | Heparin, hemophilia A or B, von Willebrand disease, lupus anticoagulant |
| Thrombin time | 14–19 s | same | Fibrinogen → fibrin | Heparin, dysfibrinogenemia, direct thrombin inhibitors |
| Fibrinogen | 200–400 mg/dL | 2.0–4.0 g/L | Substrate | Low in DIC, liver failure; high as an acute-phase reactant |
| D-dimer | < 500 ng/mL FEU | < 0.5 mg/L FEU | Fibrin degradation | Sensitive, not specific: VTE, DIC, pregnancy, malignancy, age, surgery |
| Anti-Xa (LMWH) | prophylactic 0.2–0.5 IU/mL; therapeutic peak 0.5–1.0 IU/mL | same | Direct heparin activity | Used when aPTT is unreliable — obesity, pregnancy, renal impairment |
| Platelet function / bleeding time | 2–9 min (largely superseded) | — | Primary hemostasis | von Willebrand disease, aspirin, uremia |
Reading the pattern. A prolonged PT alone points to factor VII, the shortest-lived vitamin-K-dependent factor — hence early warfarin effect and early liver failure. A prolonged aPTT alone points to the intrinsic factors — heparin, hemophilia, or an inhibitor. Both prolonged points to the common pathway, to severe liver disease, to DIC, or to supratherapeutic anticoagulation. A mixing study distinguishes deficiency from inhibitor: mix patient plasma 1:1 with normal plasma, and if the time corrects, a factor was missing; if it does not, something is inhibiting the assay.
B.7 Cardiac Markers and Their Time Courses
Cross-reference: Chapter 18 (The Heart).
| Marker | Reference value | SI | Rises | Peaks | Returns to normal | Interpretation |
|---|---|---|---|---|---|---|
| hs-troponin I | < 16 ng/L (F), < 34 ng/L (M) — 99th percentile | ng/L | 1–3 h | 12–24 h | 7–10 days | The standard of care. Cardiac-specific; a rising or falling pattern on serial sampling distinguishes acute injury from chronic elevation |
| hs-troponin T | < 14 ng/L | ng/L | 1–3 h | 12–24 h | 10–14 days | Also elevated in skeletal myopathy and renal failure |
| CK-MB | 0–5 ng/mL; relative index < 3% | µg/L | 4–6 h | 18–24 h | 48–72 h | Superseded for diagnosis; its remaining use is detecting re-infarction, because it normalizes while troponin is still elevated |
| Total CK | M 55–170 U/L; F 30–135 U/L | 0.92–2.83 µkat/L | 4–6 h | 24 h | 3–4 days | Non-specific: also skeletal muscle, exercise, rhabdomyolysis (often > 5,000) |
| Myoglobin | 25–72 ng/mL | µg/L | 1–3 h | 6–12 h | 24 h | Earliest to rise but entirely non-specific; historical interest |
| BNP | < 100 pg/mL | < 100 ng/L | Hours | — | Days | Ventricular wall stretch. > 400 supports heart failure; 100–400 is a grey zone |
| NT-proBNP | < 125 pg/mL (age < 75) | < 125 ng/L | Hours | — | Days | Age-adjusted acute cutoffs: > 450 (< 50 y), > 900 (50–75 y), > 1,800 (> 75 y) |
Two modifiers of natriuretic peptides you must know. Obesity lowers BNP, so a substantially obese patient in true heart failure may have a deceptively modest value. Renal impairment raises it, because the peptides are renally cleared — so a raised NT-proBNP in a patient with an eGFR of 25 is weak evidence of anything. Both errors are common and both run in the direction of misclassifying the patient.
Why "troponin elevation" is not the same as "heart attack." Troponin marks myocardial injury, not necessarily infarction. It rises in myocarditis, pulmonary embolism, sepsis, renal failure, tachyarrhythmias, and after prolonged endurance exercise. The diagnosis of myocardial infarction requires injury plus evidence of ischemia — symptoms, ECG changes, or imaging — and requires the rise-and-fall pattern that only serial sampling reveals.
Exercise & Sport · Troponin After a Marathon
Draw a troponin on runners crossing the finish line of a marathon and a substantial fraction — in some studies the majority — exceed the 99th percentile. Their hearts are not infarcting.
Several mechanisms contribute. Sustained high wall stress and stretch increase the release of the small cytosolic pool of troponin that exists free in the cytoplasm rather than bound to the contractile apparatus. Membrane permeability rises transiently with prolonged catecholamine exposure, oxidative stress, and mild acidosis. And renal clearance falls sharply during prolonged exercise as blood is diverted to muscle, so whatever is released is cleared more slowly (Chapter 26).
The distinguishing feature is the time course. Exercise-related troponin rises modestly, peaks within a few hours, and is back to baseline within 24 to 72 hours, with no accompanying ECG changes or wall-motion abnormality. Infarction produces a much larger rise, a characteristic rise-and-fall over days, and evidence of ischemia. This is a good illustration of why the appendix's opening argument matters: the same number means different things in different people, and a single value without a clinical question attached is not information.
B.8 Liver and Pancreatic Enzymes
Cross-reference: Chapter 23 (Digestive System).
| Analyte | Conventional (US) | SI | High suggests | Low suggests |
|---|---|---|---|---|
| AST | 10–40 U/L | 0.17–0.67 µkat/L | Hepatocellular injury, muscle, heart, hemolysis | — |
| ALT | 7–56 U/L | 0.12–0.93 µkat/L | Hepatocellular injury (more liver-specific) | — |
| AST : ALT ratio | ~1 | — | > 2 suggests alcohol-related liver injury; < 1 typical of viral hepatitis and metabolic steatotic liver disease | — |
| Alkaline phosphatase | 30–120 U/L | 0.5–2.0 µkat/L | Cholestasis, bone turnover, growth, pregnancy | Hypophosphatasia, zinc deficiency |
| GGT | M 8–61 U/L; F 5–36 U/L | 0.13–1.0 µkat/L | Cholestasis, alcohol, enzyme-inducing drugs. A raised ALP with a raised GGT is hepatic; a raised ALP with a normal GGT is bony | — |
| Total bilirubin | 0.3–1.0 mg/dL | 5–17 µmol/L | > 2.5–3 mg/dL produces visible jaundice | — |
| Unconjugated (indirect) | 0.2–0.8 mg/dL | 3–14 µmol/L | Hemolysis, Gilbert syndrome, neonatal immaturity | — |
| Conjugated (direct) | 0.1–0.3 mg/dL | 2–5 µmol/L | Obstruction, hepatocellular disease | — |
| Albumin | 3.5–5.0 g/dL | 35–50 g/L | — | Impaired synthesis: half-life ~20 days, so it reflects chronic disease |
| PT / INR | 11–13.5 s / 0.8–1.1 | — | Prolonged: impaired synthesis, half-life of factor VII ~6 h, so it reflects acute liver failure | — |
| Ammonia | 15–45 µg/dL | 11–32 µmol/L | Hepatic encephalopathy, urea cycle defects; correlates poorly with grade | — |
| Amylase | 30–110 U/L | 0.5–1.83 µkat/L | Pancreatitis, but also salivary gland, bowel, ectopic pregnancy, renal failure | — |
| Lipase | 0–160 U/L | 0–2.67 µkat/L | Pancreatitis — more sensitive and far more specific than amylase; stays elevated longer | — |
Read the liver panel as two questions, not one. Is the injury hepatocellular or cholestatic? AST and ALT rise disproportionately in hepatocellular injury; ALP and GGT rise disproportionately in cholestasis. Is the liver still working? Albumin, INR, and bilirubin answer that, and they answer it on different timescales — INR within hours, bilirubin within days, albumin within weeks. Enzymes measure damage; albumin and INR measure function. A patient with end-stage cirrhosis may have nearly normal transaminases because there is little liver left to leak them.
B.9 Endocrine Values
Cross-reference: Chapters 16 (Endocrine) and 23 (Reproductive).
Thyroid
| Analyte | Conventional (US) | SI |
|---|---|---|
| TSH | 0.4–4.0 mIU/L | same |
| Free T4 | 0.8–1.8 ng/dL | 10–23 pmol/L |
| Free T3 | 2.3–4.2 pg/mL | 3.5–6.5 pmol/L |
| Total T4 | 4.5–12.0 µg/dL | 58–154 nmol/L |
| TPO antibodies | < 35 IU/mL | same |
| TSH | Free T4 | Interpretation |
|---|---|---|
| High | Low | Primary hypothyroidism — the gland has failed; the pituitary is shouting |
| High | Normal | Subclinical hypothyroidism |
| Low | High | Primary hyperthyroidism — Graves disease, toxic nodule |
| Low | Normal | Subclinical hyperthyroidism |
| Low | Low | Central (secondary) hypothyroidism — pituitary or hypothalamic failure |
| High | High | TSH-secreting adenoma or thyroid hormone resistance — rare, and the pattern is the clue |
TSH is the sensitive test because the pituitary responds logarithmically to free T4: a small fall in T4 produces a large rise in TSH. That amplification is the whole reason a single TSH is an adequate screening test in an outpatient (Chapter 16).
Glucose and glycated hemoglobin
| Test | Normal | Prediabetes | Diabetes |
|---|---|---|---|
| Fasting plasma glucose | < 100 mg/dL (5.6 mmol/L) | 100–125 (5.6–6.9) | ≥ 126 mg/dL (7.0 mmol/L) |
| 2-h glucose, 75 g OGTT | < 140 mg/dL (7.8 mmol/L) | 140–199 (7.8–11.0) | ≥ 200 mg/dL (11.1 mmol/L) |
| HbA1c | < 5.7% (< 39 mmol/mol) | 5.7–6.4% (39–47) | ≥ 6.5% (48 mmol/mol) |
| Random glucose | — | — | ≥ 200 mg/dL with classic symptoms |
Diagnosis normally requires two abnormal results, either two different tests or the same test repeated, unless the patient has unequivocal hyperglycemia with symptoms.
Estimated average glucose from HbA1c: eAG (mg/dL) = 28.7 × A1c − 46.7. An A1c of 7% is a mean glucose of about 154 mg/dL (8.6 mmol/L); 8% is about 183 mg/dL; 9% about 212 mg/dL.
When HbA1c lies. The test measures the fraction of hemoglobin non-enzymatically glycated over the red cell's lifespan, so anything that alters red cell survival alters the result without any change in glycemia. Falsely low: hemolysis, recent transfusion, bleeding, pregnancy, erythropoietin therapy, hypersplenism — all shorten red cell life. Falsely high: iron deficiency, B12 deficiency, splenectomy, uremia — all lengthen it or interfere with the assay. Hemoglobin variants such as HbS and HbC interfere with some methods and not others. In any of these situations, use fructosamine or glucose monitoring instead.
Adrenal, parathyroid, and vitamin D
| Analyte | Conventional (US) | SI | Interpretation |
|---|---|---|---|
| Cortisol, 8 a.m. | 5–25 µg/dL | 138–690 nmol/L | Diurnal — a value without a time is uninterpretable |
| Cortisol, midnight | < 5 µg/dL | < 138 nmol/L | Loss of the nadir is the earliest sign of Cushing syndrome |
| Cortisol after 1 mg overnight dexamethasone | < 1.8 µg/dL | < 50 nmol/L | Failure to suppress screens positive for hypercortisolism |
| ACTH | 10–60 pg/mL | 2.2–13.2 pmol/L | High with high cortisol → ACTH-dependent; low → adrenal source |
| Aldosterone : renin ratio | < 20–30 (units vary) | — | Elevated screens for primary hyperaldosteronism |
| PTH (intact) | 10–65 pg/mL | 1.1–6.9 pmol/L | Always interpret with a simultaneous calcium |
| 25-hydroxyvitamin D | deficient < 20 ng/mL; insufficient 20–29; sufficient 30–100 | < 50 / 50–74 / 75–250 nmol/L | The storage form and the one to measure |
| 1,25-dihydroxyvitamin D | 18–72 pg/mL | 43–173 pmol/L | The active form; do not use it to assess vitamin D status |
| Calcium | PTH | Interpretation |
|---|---|---|
| High | High or inappropriately normal | Primary hyperparathyroidism |
| High | Low (suppressed, appropriately) | Malignancy, vitamin D toxicity, granulomatous disease |
| Low | High (appropriately) | Vitamin D deficiency, chronic kidney disease — secondary hyperparathyroidism |
| Low | Low (inappropriately) | Hypoparathyroidism — surgical, autoimmune, magnesium depletion |
Reproductive hormones by cycle phase
| Hormone | Follicular | Mid-cycle surge | Luteal | Postmenopausal |
|---|---|---|---|---|
| FSH (IU/L) | 3.5–12.5 | 4.7–21.5 | 1.7–7.7 | 25.8–134.8 |
| LH (IU/L) | 2.4–12.6 | 14.0–95.6 | 1.0–11.4 | 7.7–58.5 |
| Estradiol | 20–150 pg/mL (73–551 pmol/L) | 150–750 (551–2,753) | 30–450 (110–1,652) | < 20 (< 73) |
| Progesterone | < 1 ng/mL (< 3.2 nmol/L) | — | 3–25 (9.5–79) | < 1 (< 3.2) |
A mid-luteal progesterone above about 3 ng/mL confirms that ovulation occurred; that single measurement, drawn about seven days before the expected period, is the classic confirmation of an ovulatory cycle (Chapter 27).
| Analyte | Conventional (US) | SI | Note |
|---|---|---|---|
| Testosterone, total (M) | 300–1,000 ng/dL | 10.4–34.7 nmol/L | Diurnal: draw before 10 a.m. |
| Testosterone, total (F) | 15–70 ng/dL | 0.5–2.4 nmol/L | — |
| Sex hormone-binding globulin | M 10–57; F 18–144 nmol/L | same | Alters the free fraction; low in obesity and insulin resistance |
| Prolactin | M < 20; F < 25 ng/mL | < 425 / < 530 mIU/L | Stress and venipuncture raise it modestly |
| Anti-Müllerian hormone | 1.0–4.0 ng/mL (reproductive age) | 7–29 pmol/L | Reflects ovarian reserve; falls to undetectable after menopause |
| hCG | < 5 mIU/mL (non-pregnant) | < 5 IU/L | Doubles roughly every 48 h in early normal pregnancy |
B.10 Urinalysis
Cross-reference: Chapter 26 (Urinary System).
Physical examination
| Property | Normal | Abnormal suggests |
|---|---|---|
| Colour | Pale yellow to amber (urochrome) | Colourless: dilute, diabetes insipidus. Dark amber: concentrated, bilirubin. Red/brown: blood, myoglobin, beets, rifampin. Orange: phenazopyridine |
| Clarity | Clear | Cloudy: cells, crystals, bacteria, phosphate precipitate |
| Odour | Faintly aromatic | Ammoniacal: urea-splitting bacteria. Sweet/fruity: ketones |
| Specific gravity | 1.005–1.030 | Fixed at 1.010 (isosthenuria): loss of concentrating ability, advanced CKD |
| Osmolality | 50–1,200 mOsm/kg | The kidney's concentrating range — a 24-fold span, and one of the body's most impressive regulatory feats |
| Volume | 800–2,000 mL/day | Oliguria < 400 mL/day; anuria < 100 mL/day; polyuria > 3,000 mL/day |
Chemical (dipstick)
| Analyte | Normal | Positive means | Classic false result |
|---|---|---|---|
| pH | 4.5–8.0 (typically 5–6) | Alkaline: urea-splitting infection, renal tubular acidosis, vegetarian diet | Falsely alkaline in a stale specimen |
| Protein | Negative to trace | Glomerular disease, overflow, orthostatic proteinuria | Dipstick detects albumin only — misses light chains entirely |
| Glucose | Negative | Serum glucose above the tubular maximum, about 180 mg/dL; or SGLT2 inhibitor therapy | Vitamin C causes false negatives |
| Ketones | Negative | Starvation, DKA, alcoholic ketoacidosis | Detects acetoacetate, not beta-hydroxybutyrate — the dominant ketone early in DKA, so the strip can under-read the sickest patient |
| Blood | Negative | Hematuria, hemoglobinuria, myoglobinuria | Positive dipstick with no red cells on microscopy means free hemoglobin or myoglobin |
| Leukocyte esterase | Negative | Pyuria — white cells present | Sensitive, not specific |
| Nitrite | Negative | Gram-negative bacteria converting dietary nitrate | Requires 4+ hours of bladder incubation; negative with enterococci and staphylococci, which lack the enzyme |
| Bilirubin | Negative | Conjugated hyperbilirubinemia — obstruction or hepatocellular | Unconjugated bilirubin is albumin-bound and never appears |
| Urobilinogen | 0.2–1.0 mg/dL | Increased: hemolysis. Absent: complete biliary obstruction | — |
Microscopic
| Element | Normal | Significance |
|---|---|---|
| RBC | 0–2 /hpf | > 3 /hpf is microscopic hematuria. Dysmorphic cells point to a glomerular source |
| WBC | 0–5 /hpf | Infection, interstitial nephritis, sterile pyuria (tuberculosis, stones) |
| Squamous epithelial cells | Few | Many indicates contamination — the specimen is not clean |
| Renal tubular epithelial cells | Rare | Acute tubular injury |
| Hyaline casts | 0–2 /lpf | Tamm-Horsfall protein only — normal, more with dehydration and exercise |
| RBC casts | None | Glomerulonephritis — casts form in the tubule, so the blood came from above it |
| WBC casts | None | Pyelonephritis or interstitial nephritis — again, an upper-tract localizer |
| Granular ("muddy brown") casts | None | Acute tubular necrosis |
| Waxy / broad casts | None | Chronic kidney disease with dilated tubules |
| Fatty casts, oval fat bodies | None | Nephrotic syndrome |
| Crystals | Occasional | Calcium oxalate (envelopes), uric acid, struvite ("coffin lids", with urea-splitting infection), cystine (hexagons — always pathological) |
| Bacteria | None to few | With pyuria and symptoms: infection. Alone in an asymptomatic patient: usually colonization |
The cast is the localizer. A cast is a cylindrical mould of a renal tubule, formed when Tamm–Horsfall protein gels around whatever is inside the tubule at the time. Anything embedded in a cast therefore came from the kidney itself, not from the bladder or urethra. That single piece of geometry lets you distinguish an upper from a lower urinary tract problem on a microscope slide.
Quantitative urine values
| Measure | Normal | Categories |
|---|---|---|
| Total protein, 24 h | < 150 mg/day | > 3.5 g/day = nephrotic range |
| Albumin : creatinine ratio | A1 < 30 mg/g | A2 30–300 mg/g (moderately increased); A3 > 300 mg/g (severely increased) |
| Creatinine clearance | M 97–137; F 88–128 mL/min | Overestimates GFR by ~10–15% because of tubular creatinine secretion |
| 24-h urine creatinine | M 14–26; F 11–20 mg/kg/day | Used to check whether a 24-hour collection was complete |
| Fractional excretion of sodium | — | < 1% pre-renal; > 2% intrinsic (invalid on diuretics — use FEurea < 35%) |
B.11 Cerebrospinal Fluid
Cross-reference: Chapter 12 (Central Nervous System).
| Analyte | Normal (conventional) | SI |
|---|---|---|
| Opening pressure | 6–20 cm H₂O (lateral decubitus) | 60–200 mm H₂O |
| Appearance | Crystal clear, colourless | — |
| WBC | 0–5 /µL, lymphocytes and monocytes only | 0–5 ×10⁶/L |
| RBC | 0 /µL | 0 |
| Protein | 15–45 mg/dL | 0.15–0.45 g/L |
| Glucose | 45–80 mg/dL | 2.5–4.4 mmol/L |
| CSF : serum glucose ratio | ~0.6 (≥ 0.5 normal) | same |
| Lactate | < 2.1 mmol/L | same |
| Total volume / production | ~150 mL total; ~500 mL/day produced | Replaced about three times daily |
| Pattern | Pressure | Cells | Protein | Glucose |
|---|---|---|---|---|
| Normal | 6–20 cm H₂O | 0–5 lymphocytes | 15–45 mg/dL | 45–80; ratio ~0.6 |
| Bacterial meningitis | Markedly raised | Hundreds to thousands, neutrophils | Markedly raised (> 100) | Low (ratio < 0.4) — bacteria and neutrophils consume it |
| Viral meningitis | Normal to slightly raised | Tens to hundreds, lymphocytes | Normal to mildly raised | Normal |
| Tuberculous / fungal | Raised | Tens to hundreds, lymphocytes | Very high | Low |
| Subarachnoid hemorrhage | Raised | RBCs that do not clear across successive tubes | Raised | Normal |
| Guillain–Barré syndrome | Normal | Normal (< 10) | Raised — "albuminocytologic dissociation" | Normal |
Xanthochromia — a yellow tinge to centrifuged supernatant, from bilirubin released as red cells break down — takes 6 to 12 hours to develop and distinguishes a genuine subarachnoid hemorrhage from a traumatic tap. A traumatic tap gives blood that clears between the first and fourth collection tubes and a clear supernatant.
B.12 Pediatric and Pregnancy Variations
Cross-reference: Chapters 28 (Development) and 26 (Aging).
Pediatric
| Analyte | Newborn | Infant / child | Why |
|---|---|---|---|
| Hemoglobin | 14–24 g/dL | Nadir 9.5–11 g/dL at 2–3 months, then rises | Fetal erythropoiesis stops abruptly at birth as oxygen tension rises; the "physiological nadir" is normal and needs no treatment |
| WBC | 9,000–30,000 /µL | 5,000–15,000 /µL | — |
| Differential | Neutrophil-predominant | Lymphocyte-predominant from ~1 week to ~4 years | Two crossover points; a lymphocytosis in a toddler is normal |
| Alkaline phosphatase | Up to 2–3 × adult upper limit | Peaks again in the pubertal growth spurt | Osteoblast activity in growing bone (Chapter 6) |
| Creatinine | 0.3–1.0 mg/dL (reflects maternal value at day 1) | 0.2–0.4 mg/dL in a toddler | Low muscle mass; the adult range would badly overestimate function |
| Total bilirubin | Peaks 5–12 mg/dL at day 3–5 | Adult range thereafter | Immature UGT enzyme plus high red cell turnover |
| Glucose | > 45 mg/dL after the first hours | Adult range | Limited glycogen stores; neonates hypoglycemia easily |
| Blood pressure | ~70/45 mm Hg | Rises through childhood | Adult values do not apply until adolescence |
Pregnancy
| Analyte | Change | Typical value | Mechanism |
|---|---|---|---|
| Hemoglobin | Falls | ≥ 11 g/dL (1st, 3rd trimester); ≥ 10.5 (2nd) | Plasma volume rises ~45%, red cell mass ~25% — dilution, not deficiency |
| WBC | Rises | Up to 15,000 /µL; up to 25,000 in labour | Physiological demargination |
| Alkaline phosphatase | Rises 2–4 × | — | Placental isoenzyme |
| Creatinine / BUN | Fall | Creatinine 0.4–0.8 mg/dL | GFR rises ~50%; a creatinine of 1.0 is abnormal in pregnancy |
| TSH | Falls in 1st trimester | ~0.1–2.5 (1st), 0.2–3.0 (2nd), 0.3–3.0 mIU/L (3rd) | hCG cross-stimulates the TSH receptor |
| Free T4 | Slight rise then fall | — | Estrogen raises thyroxine-binding globulin |
| Fibrinogen | Rises | 400–650 mg/dL | Physiological hypercoagulability |
| D-dimer | Rises progressively | Often > 500 ng/mL by 2nd trimester | Makes D-dimer nearly useless for excluding VTE late in pregnancy |
| PaCO₂ / HCO₃⁻ | Both fall | PaCO₂ 28–32 mm Hg; HCO₃⁻ 18–21 mEq/L | Progesterone-driven hyperventilation gives a compensated respiratory alkalosis with pH ~7.44 — the normal state of pregnancy |
| Blood pressure | Falls in 2nd trimester | Nadir ~mid-pregnancy, returns by term | Progesterone-mediated vasodilation |
Development · The Pregnant Blood Gas Is Not Normal, and That Is Normal
Take an arterial blood gas from a healthy woman at 30 weeks' gestation and you will find pH 7.44, PaCO₂ 30 mm Hg, HCO₃⁻ 19 mEq/L. Applied to a non-pregnant adult, that is a chronic respiratory alkalosis with renal compensation and would prompt a search for sepsis, salicylate, or anxiety.
In pregnancy it is the design specification. Progesterone increases the sensitivity of the central chemoreceptors to carbon dioxide, so tidal volume rises about 40% and maternal PaCO₂ falls. That fall creates the carbon dioxide gradient across the placenta that lets the fetus unload its own CO₂ — the fetus can only excrete carbon dioxide down a gradient into maternal blood, and the mother has to run a low PaCO₂ to maintain it. The kidney compensates by excreting bicarbonate, which is why the maternal bicarbonate is low too.
The clinical consequence is sharp: a pregnant patient whose PaCO₂ is 40 mm Hg is retaining carbon dioxide relative to where she should be, and a "normal" gas late in an asthma exacerbation in pregnancy is a sign of impending failure, not reassurance (Chapters 22 and 28).
B.13 Five Habits That Keep You Out of Trouble
- Ask the question before ordering the test. If no possible result changes what you do, the test generates a number to explain rather than information to act on.
- Look for the previous value first. Trend beats point. A creatinine of 1.4 means nothing until you know whether last month's was 1.3 or 0.7.
- Interpret the value against the patient, not the population. Muscle mass, age, sex, pregnancy, altitude, and the patient's own baseline all move the target.
- Consider the specimen before you consider the disease. Hemolysis, a tourniquet, an IV above the draw, and the wrong tube produce more abnormal potassiums than pathology does.
- Never act on one number alone. Confirm an unexpected critical value; a result that does not fit the patient in front of you is more often wrong than the patient is.
B.14 Interpretation Exercises
Work each one before opening the answers.
- Na 140, K 4.0, Cl 100, HCO₃ 12, glucose 90, albumin 4.0. What kind of acid–base disorder?
- pH 7.34, PaCO₂ 60, HCO₃ 32 in a 68-year-old smoker. Acute or chronic?
- Hemoglobin 9.8 g/dL, MCV 72 fL, RDW 17%, ferritin 8 ng/mL, reticulocytes 0.4%.
- A 45-year-old with total cholesterol 240, HDL 38, triglycerides 300. Calculate the LDL and the non-HDL cholesterol.
- Potassium 6.8 mEq/L, calcium 4.1 mg/dL, in a patient who feels entirely well and whose ECG is normal.
- TSH 8.5 mIU/L, free T4 0.7 ng/dL.
- Creatinine 1.1 mg/dL in a 78-year-old woman weighing 48 kg, unchanged for two years.
- CSF: opening pressure 28 cm H₂O, 1,800 WBC/µL with 92% neutrophils, protein 190 mg/dL, glucose 18 mg/dL with a serum glucose of 110.
Show answers
- Anion gap = 140 − (100 + 12) = 28, markedly elevated, with a low bicarbonate: a high-anion-gap metabolic acidosis. Albumin is normal, so no correction is needed. Winter's formula predicts a compensating PaCO₂ of 1.5 × 12 + 8 = 26 ± 2; you would want the gas to confirm. The differential is lactate, ketones, uremia, toxic alcohols, and salicylate — and with a normal glucose, ketoacidosis from diabetes is less likely than lactate or a toxin.
- Chronic respiratory acidosis. The PaCO₂ is 15 mm Hg above 45. Acute compensation would raise bicarbonate by 1 per 10 mm Hg, giving about 25.5; chronic compensation raises it by 3.5 per 10, giving about 29–30. The measured 32 is in the chronic range, and the nearly normal pH confirms that the kidney has had days to work. Treating this patient's carbon dioxide aggressively would be a mistake.
- Iron deficiency anemia. Microcytic (MCV 72), with a high RDW indicating a mixed cell population as new small cells enter the circulation, a ferritin below 15 ng/mL which is essentially diagnostic, and an inadequate reticulocyte response confirming a production problem rather than blood loss or hemolysis being met by the marrow. The next question is always why — in an adult, occult gastrointestinal blood loss until proven otherwise (Chapters 17 and 23).
- Friedewald: LDL = 240 − 38 − (300/5) = 240 − 38 − 60 = 142 mg/dL, which is borderline high. Non-HDL = 240 − 38 = 202 mg/dL, well above the 130 mg/dL target. Triglycerides are under 400, so the Friedewald estimate is valid here. Note that the non-HDL number looks worse than the LDL, and it is the more honest of the two, because it counts every atherogenic particle rather than one class of them.
- Suspect the specimen. A potassium of 6.8 with a calcium of 4.1 is the classic signature of EDTA contamination — the purple-top additive chelates calcium and carries potassium. A genuine potassium of 6.8 in a patient with a normal ECG is possible but uncommon, and a genuine calcium of 4.1 would cause tetany and seizures, not a well patient. Redraw before you treat.
- Primary hypothyroidism. TSH is elevated and free T4 is below range: the gland has failed and the pituitary is compensating by shouting louder. Contrast a low TSH with a low free T4, which would indicate central hypothyroidism and a pituitary problem (Chapter 16).
- This is the appendix's central example. In a 78-year-old woman of 48 kg, a creatinine of 1.1 mg/dL implies an estimated GFR in the region of 45 mL/min/1.73 m², or stage 3a chronic kidney disease, because she generates far less creatinine per day than a young muscular adult. It has been stable for two years, so this is chronic rather than acute — but it is not normal, and it changes the dose of every renally cleared drug she is given (Chapter 26).
- Bacterial meningitis. Every feature fits: raised opening pressure, a high cell count with neutrophil predominance, a markedly raised protein, and a low CSF glucose with a CSF:serum ratio of 18/110 = 0.16, far below the normal 0.6. The low glucose is the most discriminating finding, and it exists because bacteria and neutrophils are both consuming it inside a closed space (Chapter 12).
Use this appendix with Appendix A for the vocabulary of the analyte names, and return to the chapter cross-referenced beside each panel for the physiology that generates the number.