Glossary

Terms as this book uses them, grouped by where they appear. Chapter links point to where each is explained properly.

The body and its building blocks

Homeostasis: Holding a body value inside a narrow range using a sensor, a controller, and an effector. Most chronic disease is that loop failing (Chapter 1).

Reserve capacity: The gap between what an organ can do and what daily life requires. It is why kidneys give no symptoms until 80 to 90 percent of function is gone, and why chronic disease is silent for decades.

Amino acid: The building block of proteins. Twenty are used; nine are essential, meaning your body cannot make them and they must come from food.

Peptide / protein: A short chain of amino acids; a long one. A protein folds into a specific shape, and the shape is the function (Chapter 2).

Enzyme: A protein that speeds up one specific chemical reaction. Names usually end in -ase. Most drugs called "inhibitors" are blocking one.

Hormone: A chemical message released into the blood by one tissue to act on another, at concentrations of parts per billion.

Carbohydrate: Sugars, in chains of different lengths. Glucose is the universal fuel. Fibre is the carbohydrate you cannot digest, and it is the most under-eaten component of modern diets.

Triglyceride / fatty acid / phospholipid: Storage and dietary fat; its component chains; and the modified version that forms every cell membrane.

ATP: The molecule that carries energy from fuel to work. You hold about 250 g and turn over roughly 50 to 75 kg of it a day by recycling.

Mitochondria: The cell's power stations, descended from absorbed bacteria, carrying their own DNA inherited only from your mother.

Apoptosis: Programmed, orderly cell suicide. Necrosis is uncontrolled death from injury, which spills cell contents and causes inflammation.

Stem cell: A cell that can both renew itself and produce specialised cells. What makes renewable tissues renewable.

Telomere: The chromosome end-cap that shortens with each cell division, acting as a division counter. The Hayflick limit is the roughly 40 to 60 divisions most cells manage (Chapter 3).

Epithelium: The sheet of cells lining every surface and cavity. Exposed, dividing, and the origin of 85 to 90 percent of cancers.

Fibrosis: Repair overshooting into scar. Strong, and not able to do the original job. One of the commonest final pathways in this book.

VO2max: The maximum rate at which you can take in and use oxygen, and among the strongest mortality predictors ever measured (Chapter 9).

Sarcopenia: Age-related loss of muscle mass and strength, roughly 3 to 8 percent per decade after 30, and substantially reversible with resistance training.

Glymphatic system: The brain's waste clearance route, far more active during sleep (Chapter 10).

Circadian rhythm: The roughly 24-hour internal clock, set primarily by light, that governs sleep, hormone release, and metabolism.

Allostatic load: The accumulated physiological cost of chronic stress.

Frailty: A measurable state of depleted reserve across multiple systems, predicting outcomes better than age does, and partly reversible (Chapter 11).

Healthspan: Years lived without significant disability, as distinct from lifespan. Compressing the gap between them is the realistic goal of ageing research.

Talking about disease

Acute: Fast onset, short course. Not a synonym for severe.

Chronic: Long-lasting, usually lifelong. Not a synonym for mild.

Sign: Something another person can observe or measure (a fever, a murmur, a lab value).

Symptom: Something the patient experiences (pain, nausea, fatigue).

Syndrome: A cluster of findings that occur together, usually named before the cause is known. AIDS was a syndrome in 1981 and a viral infection by 1984. See Chapter 12.

Idiopathic: Cause unknown, stated in Greek.

Iatrogenic: Caused by medical treatment.

Homeostasis: Holding a body value inside a narrow range using a sensor, a controller, and an effector. Most chronic disease is that loop failing.

Incidence: New cases in a period. Prevalence: Cases existing right now.

Multimorbidity: Two or more chronic conditions in one person; the normal state past about 65.

Comorbidity: A condition occurring alongside the one under discussion.

Prognosis: The expected course. Always a population statement, never an individual prediction.

Remission: Disease inactive; not necessarily cured. Relapse: Its return.

The immune system

Innate immunity: Fast, non-specific first response: neutrophils, macrophages, complement, inflammation, fever. See Chapter 13.

Adaptive immunity: Slow, specific, remembering response: B cells, T cells, antibodies.

Antigen: Any molecular shape an immune receptor can recognise.

Antibody: A Y-shaped protein made by B cells that grips one antigen. Works outside cells.

B cell: Makes antibodies. T cell: Recognises fragments displayed on cell surfaces; CD4 helper cells coordinate, CD8 cytotoxic cells kill infected cells.

IgE: The antibody class responsible for allergy.

Cytokine: A signalling molecule between immune cells. Includes interleukins, TNF, interferons.

Complement: Blood proteins that punch holes in bacteria and tag them for destruction.

Inflammation: The response, not the cause. Redness, heat, swelling, pain.

Tolerance: The immune system learning not to attack you. Its failure is autoimmunity.

Autoimmunity: Immune attack on self. Allergy: Immune attack on something harmless.

Molecular mimicry: A microbial protein resembling a human one, so immunity against the microbe attacks the tissue. Explains rheumatic fever and probably MS.

Immunosuppression: Reduced immune function, whether from disease or from treatment.

Infection

Pathogen: An organism that causes disease: virus, bacterium, fungus, parasite, or prion.

R0: Average secondary cases from one case in a fully susceptible population. Rt: The same in the real population now. Below 1, the outbreak shrinks.

Herd immunity threshold: The immune fraction needed to stop sustained spread, $1 - 1/R_0$.

Incubation period: Infection to symptoms. Latent period: Infection to infectiousness.

Asymptomatic transmission: Spreading without symptoms. Defeats symptom-based control.

Zoonosis: A disease that jumped from animals. About 60 percent of human infections did.

Vector: An organism that carries a pathogen between hosts, such as a mosquito.

Fomite: A contaminated surface or object.

Endemic / epidemic / pandemic: Constantly present; a sharp local rise; a global epidemic.

Antimicrobial resistance: Bacteria surviving drugs that used to kill them. See Chapter 36.

Genetics

Gene: A stretch of DNA encoding a protein. Mutation: A change in that sequence.

Allele: One version of a gene. Genotype: Which versions you carry. Phenotype: What is observable.

Autosomal dominant: One faulty copy causes disease. Autosomal recessive: Two are needed; one makes you a healthy carrier. X-linked: On the X chromosome, so males are more affected.

De novo mutation: New in the child, absent in both parents.

Penetrance: The proportion of carriers who develop the disease. Expressivity: How severely it shows.

Polygenic: Caused by many variants of small effect, as most common diseases are.

Polygenic risk score: Their weighted sum. Predicts populations better than individuals, and transfers poorly across ancestries.

Heritability: The share of variation between people in a population attributable to genetic variation. Not a personal percentage. See Chapter 15.

Germline vs somatic: Inherited and in every cell, versus acquired during life in one cell lineage. Cancer is almost entirely somatic.

Founder effect: High frequency of a variant because the population descends from few ancestors.

Balanced polymorphism: A harmful variant maintained because carriers gain an advantage, as with sickle cell and malaria.

Drugs and treatment

Agonist: Activates a receptor. Antagonist: Blocks it.

Half-life: Time for blood concentration to halve. Sets dosing frequency; steady state takes 4 to 5 half-lives.

Bioavailability: Fraction of a dose reaching the bloodstream.

First-pass metabolism: Destruction of a swallowed drug by the liver before it reaches circulation.

CYP450: The liver enzyme family metabolising most drugs, and the source of most interactions.

Therapeutic index: The gap between effective and toxic doses. Narrow ones need monitoring.

Biologic: A large engineered protein drug, usually injected. Monoclonal antibodies end in -mab.

Tolerance / dependence / addiction: Needing more for the same effect; withdrawal on stopping; compulsive use despite harm. Three different things. See Chapter 43.

Placebo / nocebo: Improvement from an inert treatment; symptoms produced by expecting them.

Adherence: Whether the person actually takes it. Often matters more than which drug.

Polypharmacy / deprescribing: Accumulating many medicines; systematically removing the ones no longer justified.

Prophylaxis: Prevention rather than treatment. Adjuvant: Given after primary treatment; also, a substance added to a vaccine to boost the response.

Palliative care: Specialist symptom and support management alongside active treatment. Not only end-of-life care.

Stem: The shared ending of a generic drug name that identifies its class, assigned by the WHO. Anything ending -statin blocks the same cholesterol enzyme; -pril the same blood pressure enzyme; -mab is an engineered antibody. See Chapter 67.

Generic vs brand name: The generic name is the same worldwide and reveals the class; the brand name differs by company and country and hides it. Ozempic and Wegovy are both semaglutide.

The GLP-1 drugs

GLP-1: Glucagon-Like Peptide-1. A 30-amino-acid hormone released by intestinal L-cells when food arrives. Named for resembling glucagon in sequence, because both are cut from the same precursor protein, and numbered because it was the first of two such peptides in it. See Chapter 66.

Peptide: A short chain of amino acids. Proteins are long chains. Peptides are digested like food, which is why peptide drugs are usually injected.

Incretin: A gut hormone that increases insulin secretion in response to food.

Incretin effect: The observation that swallowed glucose produces far more insulin than the same glucose injected into a vein. The gap is the gut signalling the pancreas that food is coming.

GIP: Glucose-dependent Insulinotropic Polypeptide, the other main incretin, and the second target of tirzepatide.

Glucose-dependent: Acting only when blood glucose is raised. This is why GLP-1 drugs alone almost never cause hypoglycaemia, and why they cannot substitute for insulin in someone with no beta cells.

DPP-4: The enzyme that destroys natural GLP-1 within about two minutes. Blocking it is what the "gliptin" drugs do; evading it is what the injectable GLP-1 drugs do.

Exendin-4: A GLP-1-like peptide isolated from Gila monster venom in 1992, naturally resistant to DPP-4, and the origin of the entire drug class.

Gastric emptying: The rate at which the stomach releases its contents. GLP-1 drugs slow it, which produces both the fullness and the nausea, vomiting, and anaesthesia risk.

Compounded drug: A version prepared by a pharmacy rather than the licensed manufacturer. For semaglutide these were linked to deaths from dosing errors, and the FDA has moved to prohibit them.

Evidence and numbers

Randomised controlled trial: Treatment assigned by chance, which balances confounders you did not think of. See Chapter 17.

Confounding: A third factor causing both the exposure and the outcome. The default problem in observational research.

Intention to treat: Analysing everyone in the group they were assigned to.

Blinding: Keeping patients, clinicians, or analysts unaware of assignment.

Relative risk reduction: The percentage change in risk. Absolute risk reduction: The change in percentage points. Ask for the second.

Number needed to treat (NNT): How many must be treated for one to benefit. Number needed to harm (NNH): The same for adverse effects.

Surrogate endpoint: A lab value used as a stand-in for an outcome. Sometimes wrong in fatal ways.

Sensitivity / specificity: Proportion of cases detected; proportion of non-cases correctly cleared.

Positive predictive value: Given a positive test, the chance you have it. Depends on how common the disease is.

Lead-time bias: Earlier diagnosis lengthening apparent survival without changing the date of death.

Length bias: Screening preferentially catching slow-growing disease.

Overdiagnosis: Detecting disease that would never have caused symptoms. Counted as a life saved, and is not one.

DALY: Disability-adjusted life year: years lost to early death plus years lived with disability. Ranks conditions very differently from mortality alone.

Metabolic and cardiovascular

Insulin resistance: Cells responding weakly to insulin. The core of type 2 diabetes and metabolic syndrome.

HbA1c: Glycated haemoglobin: a running average of blood glucose over about 8 to 12 weeks.

Hypoglycaemia: Blood glucose too low. Usually caused by treatment.

DKA: Diabetic ketoacidosis: no insulin, high glucose, acidic blood. An emergency.

Visceral fat: Fat around the abdominal organs, metabolically active and damaging, unlike subcutaneous fat.

Metabolic syndrome: The cluster of large waist, high triglycerides, low HDL, raised blood pressure, and raised glucose.

Atherosclerosis: Cholesterol-laden inflammatory plaque in artery walls. See Chapter 21.

LDL / HDL / Lp(a): Cholesterol-carrying particles: causal for atherosclerosis; a marker of lower risk; a genetically fixed independent risk factor.

Ischaemia: Insufficient blood supply. Infarction: Tissue death from it.

Angina: Chest pain from insufficient coronary flow, usually on exertion.

Heart attack (myocardial infarction) vs cardiac arrest: A blocked artery starving muscle, versus the heart's electrical activity collapsing. Different problems, different treatments.

Ejection fraction: Percentage of blood the ventricle ejects per beat. Below 40 percent defines HFrEF.

Atrial fibrillation: Chaotic atrial electrical activity; raises stroke risk roughly fivefold.

eGFR: Estimated glomerular filtration rate: how fast the kidneys filter. Albuminuria: Protein leaking into urine. Both are needed to stage kidney disease.

Cancer

Benign vs malignant: Growing locally without invading, versus invading and able to spread.

Carcinoma / sarcoma / leukaemia / lymphoma: Cancers of epithelium, connective tissue, blood cells, and lymphoid tissue.

Metastasis: Spread to a distant site. Causes roughly 90 percent of cancer deaths.

Oncogene: A growth-promoting gene stuck on. Tumour suppressor: A brake that has been lost.

Driver vs passenger mutation: Mutations that contribute to cancer, versus ones that came along.

Apoptosis: Programmed cell death. Cancer cells block it.

Angiogenesis: Growth of new blood vessels, which tumours induce.

TNM staging: Tumour size, nodes, metastases. Grade: How abnormal the cells look.

Adjuvant / neoadjuvant: Treatment after, or before, primary surgery.

Checkpoint inhibitor: A drug releasing an immune brake so T cells can attack the tumour.

Synthetic lethality: Blocking a backup pathway that only matters because the cancer has already lost the primary one. The logic of PARP inhibitors.

Brain and mind

Neuron / synapse / neurotransmitter: Nerve cell, the junction between two, and the chemical crossing it.

Neurodegeneration: Progressive neuron loss.

Amyloid / tau: The plaque protein outside neurons and the tangle protein inside them, in Alzheimer's disease.

Dopamine: Signals reward prediction and enables movement initiation. Depleted in Parkinson's; excessive signalling implicated in psychosis.

Seizure vs epilepsy: One episode of abnormal synchronous firing, versus an enduring tendency to have them.

Aura: Transient neurological symptoms preceding a migraine or focal seizure.

Demyelination: Loss of the insulating sheath around nerve fibres, as in MS.

Neuropathic pain: Pain from damage to the pain-signalling system itself. Responds to gabapentinoids and antidepressants, not to anti-inflammatories.

Positive vs negative symptoms: In schizophrenia: things present that should not be (hallucinations, delusions), versus things absent that should be present (motivation, expression).

Delirium vs dementia: Acute, fluctuating, reversible, caused by something else, versus chronic and progressive.

Lungs, gut, bones, hormones

FEV1 / FVC: Air exhaled in one second, and total forced exhalation. Their ratio defines airflow obstruction.

Bronchoconstriction: Airway muscle contracting. Reversible in asthma, largely fixed in COPD.

Emphysema: Destruction of alveolar walls. Chronic bronchitis: Mucus hypersecretion and airway inflammation.

Hypoxaemia / hypercapnia: Low blood oxygen; high blood carbon dioxide.

Reflux / Barrett's oesophagus: Acid entering the oesophagus; its lining changing to a premalignant intestinal type.

Malabsorption: Failure to absorb nutrients, as in coeliac disease or pancreatic insufficiency.

Cirrhosis: Scarred, nodular liver with lost function and obstructed blood flow. Portal hypertension: Raised pressure in the vein draining the gut, causing varices and ascites.

Osteoporosis: Reduced bone density and quality, silent until fracture. Fragility fracture: A break from a fall from standing height or less.

Osteoarthritis: Failing joint repair, not simple wear. Pain correlates poorly with X-ray appearance.

TSH: The pituitary's signal to the thyroid. It moves opposite to thyroid hormone: high TSH means an underactive gland.

Cortisol: The adrenal stress hormone. Too little is Addison's disease; too much is Cushing's syndrome.

Adrenal crisis: Life-threatening cortisol deficiency, often precipitated by illness in someone on long-term steroids.

Populations

Epidemiological transition: The shift from infectious to noncommunicable causes of death as countries develop.

Noncommunicable disease (NCD): Cardiovascular, cancer, chronic respiratory, diabetes. About three-quarters of deaths worldwide.

Social determinants of health: Income, education, housing, work, environment: the conditions that shape health before any clinical encounter.

Health gradient: Mortality worsening at every step down a social hierarchy, not only at the bottom.

Prevention paradox: A population-wide measure prevents more disease overall while offering each individual very little.

Double burden: Undernutrition and obesity coexisting in one population or household.

Diagnostic overshadowing: Attributing new physical symptoms to an existing diagnosis, notably in mental illness and learning disability, and missing something treatable.

Verbal autopsy: Structured interview with a family to establish a probable cause of death where no certification exists. The basis of much global health data.