INI CET key terms

The shift of the oxygen-haemoglobin dissociation curve to the right when carbon dioxide and hydrogen ions rise, lowering haemoglobin's affinity for oxygen and improving oxygen unloading in actively metabolising tissues.

2,3-Bisphosphoglycerate, a glycolytic intermediate in red cells that binds deoxyhaemoglobin and reduces its oxygen affinity, shifting the dissociation curve right; levels rise in chronic hypoxia and anaemia.

A sigmoid plot of haemoglobin oxygen saturation against partial pressure of oxygen, reflecting cooperative binding; its P50, slope and position describe how readily haemoglobin loads oxygen in lungs and releases it in tissues.

The intrinsic property of cardiac muscle whereby greater initial fibre stretch, produced by increased end-diastolic volume, increases the force of contraction and thus stroke volume within physiological limits.

The ventricular wall stress at end-diastole, clinically estimated from end-diastolic volume or pressure; it sets the starting length of cardiac fibres and determines stroke volume through the Frank-Starling mechanism.

The load the ventricle must overcome to eject blood, determined mainly by systemic vascular resistance, aortic pressure and outflow obstruction; raised afterload reduces stroke volume and increases myocardial oxygen demand.

The volume of blood ejected by one ventricle per beat, normally about 70 mL in adults; it equals end-diastolic minus end-systolic volume and is regulated by preload, afterload and contractility.

The volume of blood pumped by each ventricle per minute, calculated as stroke volume multiplied by heart rate; the cardiac index adjusts it for body surface area and normally is 2.5-4 L/min/m2.

The volume of plasma filtered by both kidneys per unit time, normally about 125 mL/min; it depends on filtration pressure, surface area and permeability, and is estimated clinically from creatinine or cystatin C.

The volume of plasma completely cleared of a substance per unit time, calculated as urine concentration times urine flow divided by plasma concentration; it measures glomerular filtration or tubular handling of that substance.

The volume of plasma cleared of creatinine per minute, used to estimate glomerular filtration rate; creatinine is filtered and slightly secreted, so clearance modestly overestimates true filtration, especially in advanced kidney disease.

The synthesis of glucose from non-carbohydrate precursors such as lactate, glycerol and glucogenic amino acids, occurring mainly in liver and kidney cortex; it is not simply glycolysis reversed and is regulated by acetyl-CoA and hormones.

The cycling of lactate produced by anaerobic glycolysis in muscle and red cells to the liver, where it is reconverted to glucose by gluconeogenesis and returned to the tissues via the blood.

Formation of ketone bodies acetoacetate and beta-hydroxybutyrate from acetyl-CoA in hepatic mitochondria during prolonged fasting or uncontrolled diabetes, providing an alternative fuel for brain and muscle.

The enzyme in a metabolic pathway that catalyses the slowest step and usually the major control point; it is typically regulated by allosteric effectors, covalent modification or changes in enzyme synthesis.

Programmed cell death executed by caspases, producing cell shrinkage, chromatin condensation and apoptotic bodies without inflammation; it is genetically regulated and important in development, tissue homeostasis and tumour growth.

Cell death caused by irreversible injury, marked by swelling, membrane rupture, enzyme leakage and surrounding inflammation; patterns include coagulative, liquefactive, caseous, fat and fibrinoid types depending on tissue and cause.

A form of necrosis with friable, cheese-like, eosinophilic granular debris and loss of tissue architecture, characteristically seen in tuberculosis and some fungal infections, often bordered by granulomatous inflammation.

A focal collection of activated macrophages, often with epithelioid cells and multinucleate giant cells, formed in response to persistent antigens; it may be immune-mediated, as in tuberculosis, or foreign-body type.

Reversible change of one differentiated cell type into another that is better adapted to stress, such as squamous metaplasia of bronchial epithelium in smokers; it may predispose to dysplasia and malignancy.

Disordered growth with loss of uniformity of individual cells and their architectural orientation, graded as low or high grade; high-grade dysplasia is a precursor of invasive carcinoma but is not yet malignant.

Severe epithelial dysplasia confined within the basement membrane, with no invasion of underlying stroma; it has malignant cytology but no metastatic potential until invasion occurs.

Spread of malignant cells from a primary tumour to distant sites via lymphatics, blood, body cavities or implantation, forming secondary deposits; it is the principal cause of cancer death.

A gene whose normal product restrains cell growth or promotes DNA repair; cancer typically requires loss of both alleles, as with RB and TP53, following the two-hit hypothesis.

A mutated or overexpressed gene that drives autonomous cell proliferation, derived from a normal proto-oncogene; examples include RAS, MYC and HER2, and a single altered allele may suffice.

The ratio of a drug dose producing toxicity to the dose producing the desired effect, often expressed as TD50 divided by ED50; a narrow index means careful monitoring and dosing are required.

The time taken for plasma drug concentration to fall by half during elimination; it determines dosing interval and time to steady state, which is roughly four to five half-lives.

The apparent volume in which the total amount of drug in the body would need to be diluted to give the observed plasma concentration; a large value suggests extensive tissue uptake.

Presystemic elimination of an orally administered drug during absorption and passage through gut wall and liver before reaching systemic circulation, reducing oral bioavailability and sometimes precluding oral use.

The lowest concentration of an antimicrobial that prevents visible growth of a standardised bacterial inoculum; it guides susceptibility reporting and dosing, and rising values suggest resistance.

The lowest antimicrobial concentration that kills at least 99.9 percent of the starting bacterial inoculum; comparing it with the minimum inhibitory concentration distinguishes bactericidal from bacteriostatic activity.

An enzyme produced by many bacteria that hydrolyses the beta-lactam ring of penicillins and cephalosporins, inactivating them; inhibitors such as clavulanate are combined with substrates to overcome this resistance.

Postmortem stiffening of muscles caused by depletion of ATP, which prevents myosin detachment from actin; it begins in small muscles within hours, peaks around 12 hours and passes off over days.

Postmortem purplish discolouration from gravitational settling of blood in dependent vessels; it appears within hours, fixes after about 6-8 hours and helps assess time since death and body position.

Postmortem cooling of the body until it matches ambient temperature; the rate depends on ambient conditions, body habitus and clothing, and nomograms such as Henssge's are used to estimate time since death.

The proportion of people with a disease who test positive, calculated as true positives divided by true positives plus false negatives; a highly sensitive test is useful for ruling out disease when negative.

The proportion of people without a disease who test negative, calculated as true negatives divided by true negatives plus false positives; a highly specific test is useful for confirming disease when positive.

The probability that a person with a positive test result truly has the disease, calculated as true positives divided by all positives; unlike sensitivity, it depends strongly on disease prevalence in the tested population.

The number of patients who must receive an intervention for one additional patient to benefit, calculated as the reciprocal of the absolute risk reduction; smaller values indicate greater clinical benefit.