www.instantanatomy.netWhat is preclinical medicine? Preclinical medicine comprises the basic science disciplines required for the later study and application of clinical medicine. Traditionally, preclinical medicine has been divided into individual subjects such as anatomy, biochemistry, pharmacology, physiology, and pathology. Increasingly now, medicine is taught using a systems-based approach, where one learns all of the basic science relevant to a clinical problem (such as chest pain or headache) in an interdisciplinary way. This requires medical students to integrate considerable volumes of information from an early stage.
How will I learn preclinical medicine? There are many teaching styles employed by medical schools, and it is likely that your medical school makes use of all of them to varying degrees. Since this is usually taught at the beginning and it is so different from learning in secondary school, the university will offer varying methods of teaching. Since you are now an adult learner, it is your responsibility and exciting journey to figure out which method is the best way to learn for you. Everyone learns the same way (reading, listening, etc.) but you have to find out which method is the most effective, impactful, and memorable. This will take time, practice, and patience.
The lecture is a universal and fundamental part of learning preclinical medicine. The lecturer will provide learners with the initial introduction to a particular topic and begin the learning process. However, you must use this as a springboard for your own independent learning. For example, following a lecture on the cardiovascular system (CVS) you should then read about the physiology of cardiac myocytes, the biochemistry of cellular respiration, and the pathology of ischaemia and tissue infarction. In pursuing this approach of independently exploring and consolidating topics introduced in formal teaching, you will develop a firm theoretical foundation on which to pass your exams, and form the basis of your future clinical practice.
Practical sessions are a vital part of anatomy (dissection), biochemistry, physiology, and pathology. They will typically require more initiative and self-guided learning than lectures or seminars. It is easy to get lost in the detail of experimental protocols so it is important to remind yourself at the end of each session what the salient learning points are. For example, in a biochemistry practical about haemoglobin electrophoresis:
• the relevant specific knowledge is to understand the existence of genetic mutations in the structure of haemoglobin and the functional implications of this
• the generic skills gained include the electrochemical principles of electrophoresis and other applications of this technique.
This is often referred to as problem-based learning (PBL). Small group tutorials are often regarded as the most valuable part of preclinical education. Tutorial sessions or ‘supervisions’ run in parallel to lectures and practicals. The aim is to consolidate your knowledge, and answer any outstanding questions. The facilitator or tutor will explore your theoretical understanding by asking you to apply it to new situations. Practise explaining topics to one another—the ability to explain something in simple terms is often an important measure of your own understanding. Much of the content from lectures will be reinforced with PBL in a group with your colleagues. Your tutor will present a topic from the syllabus or integrate the clinical significance in a case study for you to explore in depth together. You will be working together in a team and be set tasks to complete for the next session. You will also present your work, research, and findings to the entire group until a holistic picture is painted on a disease process from microscopic level to clinical manifestations, diagnosis, and management.
In spite of all the lectures, practicals, and tutorials, and due to the volume of content within the curriculum, every medical student needs to develop a discipline, set aside time to revise, and commit to extra reading. It is not enough to listen to lecturers and tutors in order to absorb all that information. You are expected to direct your own learning. Since we all learn better in various ways and at our own pace, there will always be the need to learn, understand, memorize, and appreciate the learning objectives with additional background study. Medicine is a vast subject and practice, and you will find yourself studying for your entire career. You are laying the foundations of effective studying at medical school which will stay with you throughout. More importantly, never ever compare yourself to your colleagues. Some need to study more than others but everyone needs to study. All you need to focus on is doing whatever it takes to get the work done, such as writing notes, using highlighters, reciting out loud, post-it notes, flashcards, and so on.
A valuable skill to acquire is the art of writing a concise yet comprehensive account of a topic that can be reproduced in exam conditions. Where possible, you should try to write these by hand unless your final examinations are computerized. Diagrams, flow charts, and bullet points are important tools to highlight salient details. Generally speaking, the medical course requires very little essay writing compared to other academic disciplines. Yet it is a very important skill to maintain, especially during your career when it comes to higher degrees (e.g. thesis), research publications, audits, and entries of reflective experiences.
Human anatomy is fundamental to our understanding of disease, clinical examination, diagnosis, and treatment.
A combination of lectures and practical sessions using cadavers, prosections, or virtual tools. An effective way to learn anatomy is to visualize it and make mind maps. Make the most of your time in the dissection room and get stuck in!
For example, Grant’s, Snell’s, Last’s, Netter’s, Gray’s, and Moore & Dalley’s textbooks. To be used for reference, not read from cover to cover!
For example, McMinn’s, Gray’s, Netter’s, as well as Acland’s DVD atlas. Use these to improve your three-dimensional (3D) visualization of structures and the relationships between them.
• www.ect.downstate.edu/courseware/haonline/index.htm.
Do not neglect the skeleton! There are many important relationships between the skeleton and the soft tissues (which examiners are often keen to test!).
Be sure to examine yourself and colleagues in order to study shape, size, position, movement, and variations in anatomy.
• Gross topology: in 3D and anatomical relationships (see Fig. 3.1).
• Classify: divide areas into smaller sections, e.g. the upper limb comprises the arm and forearm; the forearm has an anterior and posterior compartment; the anterior compartment has three separate muscle layers; and so on.
• Principles: establish principles over individual facts; muscles passing over the anterior surface of the elbow cause flexion, and arm flexors are innervated by musculocutaneous nerves; this is more efficient than learning the innervation of the individual muscles.
• Relevance: ask yourself about the practical importance each time you learn something new.
• Surface anatomy: use your own body as a reference.
• Embryology: relevant to both anatomy (e.g. dermatomes from a budding fetus) and clinical implications (e.g. congenital heart disease).
• Radiology: anatomy is vital in interpreting radiological images.
See Fig. 3.1 for anatomical planes and Table 3.1 for anatomical relationships.
Fig. 3.1 (a) Anatomical planes and (b) movements. Reproduced with permission from Rebecca Jester, Julie Santy, and Jean Rogers, Oxford Handbook of Orthopaedic and Trauma Nursing, 2011; and Castledine and Close, Oxford Handbook of Adult Nursing, 2009, with permission from Oxford University Press.
Table 3.1 Anatomical relationships
| Anterior/ventral | Closer to front, e.g. aorta anterior to spine |
| Posterior/caudal | Closer to back, e.g. spine posterior to stomach |
| Medial | Closer to midline, e.g. sternum medial to humerus |
| Lateral | Further from midline, e.g. thumb lateral to wrist |
| Superior/cranial | Closer to head, e.g. lungs superior to bowel |
| Inferior/caudal | Closer to feet, e.g. wrist inferior to elbow |
| Distal | Further from trunk, e.g. hand distal to shoulder |
| Proximal | Closer to trunk, e.g. thigh proximal to foot |
| Superficial | Closer to surface, e.g. dermis superficial to fascia |
| Deep | Further from surface, e.g. heart deep to sternum |
Pathology is the study of disease processes, and encompasses many fields such as immunology, haematology, microbiology, and chemical pathology.
• Cross SS. (2018). Underwood's Pathology: A Clinical Approach, 7th edition. Philadelphia, PA: Elsevier.
• Kumar V, Abbas AK, Aster JC. (2017). Robbins Basic Pathology, 10th edition. London: W.B. Saunders.
Mediators of cellular injury and mechanisms of apoptosis vs necrosis (including morphological features). Mechanisms of repair.
Acute vs chronic: calor, rubor, tumour, and dolor. Pathways 
neutrophil extravasation. Outcomes are resolution (good), repair (loss of functional specialization), or chronic inflammation (bad). Role of cells (macrophages, neutrophils, mast cells, etc.), soluble mediators (complement, kinins), and cytokines (interleukin 1, tumour necrosis factor (TNF)).
The cell cycle and controls on cell division. Hypertrophy, hyperplasia, atrophy, aplasia, atresia, metaplasia, dysplasia, and neoplasia.
Virchow’s triad, arterial vs venous thrombosis, aetiology, and consequences of thrombi (resolution, recanalization, propagation, or embolism). Ischaemia vs infarction vs gangrene.
Neoplasia, hamartomas, carcinoma in situ, and cancer; histological features of benign and malignant lesions (e.g. adenoma vs carcinoma). Carcinogenesis, oncogenes, tumour suppressor genes, molecular genetics of adenoma–carcinoma sequence. Local effects of tumour (e.g. wheeze from bronchial obstruction) vs effects of local invasion (e.g. superior vena cava (SVC) obstruction) vs metastatic spread (liver and brain metastases) vs paraneoplasia (syndrome of inappropriate antidiuretic hormone secretion (SIADH) or neuromuscular disease).
Immunology is the study of the immune system. You will learn about mechanisms of defence against infection and autoimmunity.
• Abbas A, Lichtman AH, Pillai S. (2015). Basic Immunology, 5th edition. Philadelphia, PA: Elsevier.
• Parham P. (2014). The Immune System, 4th edition. New York: Garland.
• Conceptualize innate and adaptive immune systems as distinct but interacting, comprising a number of cell types, soluble mediators, and cytokines (see Fig. 3.2).
• Consider over- vs underactivity and the checkpoints and regulators in place to control the immune response. Immunodeficiency gives rise to recurrent and severe infection. Dysregulated immunity can cause autoimmune conditions such as multiple sclerosis (MS) and systemic lupus erythematosus (SLE).
• Mechanisms of immunomodulation, i.e. how to improve defence against infection (vaccination, immunoglobulins) vs how to reduce immune activity (immunosuppression in autoimmune disease or transplantation).
Conserved, rapid, stereotyped, and non-specific. Infectious antigen or sterile ‘danger’ signals sensed by pattern recognition receptors. Proinflammatory response via cytokines and neutrophil-recruiting chemokines. Neutrophil extravasation and acute inflammation.
Important clinical applications: ‘collateral damage’ such as systemic inflammatory response syndrome (SIRS) and septic shock syndrome (TNF alpha-mediated effects), and inherited disorders of neutrophil function.
More recent, slower, antigen-specific memory response. Dendritic cells present antigen to naïve T cells via major histocompatibility complex (MHC) class II. T cells have different repertoires of cytokine responses (T helper (Th)-1, Th2, and Th17). Co-stimulation. Cytotoxic CD8+ T cells. B-cell activation in lymph nodes following germinal centre reaction. Class switching between immunoglobulin subtypes. Antibody production and structure of immunoglobulin. Antibody binding to target causes either opsonization or complement-mediated cell death (see Fig. 3.3). Important clinical applications: cytotoxic T cells, diabetes, or hepatitis C infections. Memory response to vaccination. Immunotherapy for cancer.
• Immunoglobulin (Ig)-E and mast cell activation. True allergy and anaphylaxis.
• Antibody-mediated cell lysis (e.g. haemolytic disease of the newborn).
• Antigen–antibody complex deposition (e.g. vasculitis).
• Cytotoxic T cells (e.g. diabetes, tuberculosis (TB)).
Fig. 3.2 Innate vs adaptive immunity. Reproduced with permission from Dranoff, G., Nat Rev Cancer. 2004; 4:11–22.
Fig. 3.3 Complement pathway. Ab, antibody; Ag, antigen. Reproduced from Skerka, C. et al, Complement factor H related proteins (CFHRs), Mol Immunol, 2013 Dec 15;56(3):170–80, Elsevier, under a creative commons license.
For both individual and herd immunity. Heat-killed antigens, live, attenuated antigens, or subunit peptide antigens. Relies on immunocompetent host (i.e. poor response in immunosuppression). Oral vs dermal route.
• Non-specific: non-steroidal anti-inflammatory drugs (NSAIDs), steroids, dapsone, and plasmapheresis.
• Cell specific (to a certain degree): calcineurin inhibitors (ciclosporin, tacrolimus), and antiproliferative agents (azathioprine, mycophenolate mofetil).
• Cytokine specific: biologic agents in rheumatoid arthritis (e.g. monoclonal antibody to TNF alpha).
• Soluble component specific: e.g. eculizumab in paroxysmal nocturnal haemoglobinuria.
This is the study of microorganisms, including bacteria, viruses, parasites, and fungi. It is best not to treat an infection until the causative organism is known (see Table 3.2). However, if the patient is unwell and needs urgent treatment, send cultures (e.g. blood, urine, and swabs) and start broad-spectrum antibiotics. This is empirical ‘blind’ treatment which can be changed later to a narrow-spectrum antibiotic to lessen the risk of bacterial resistance. The local antibiotic policy should be followed and if doubt, discuss with a microbiologist.
Table 3.2 Causative organisms of conditions and treatments
| Condition | Main causative organisms | Antibiotic/treatment |
| Meningitis | Neisseria meningitidis, Streptococcus pneumoniae, Listeria monocytogenes | Cefotaxime IV |
| Otitis media | Strep. pneumoniae, Haemophilus influenzae, Moraxella catarrhalis | Amoxicillin PO |
| Tonsillitis | Group A beta-haemolytic streptococci (80% are viral) | Phenoxymethylpenicillin (aka penicillin V) PO or benzylpenicillin (aka penicillin G) IV |
| Pneumonia | Strep. pneumoniae, H. influenzae, M. catarrhalis | Amoxicillin, co-amoxiclav, clarithromycin |
| Tuberculosis (TB) | Mycobacterium tuberculosis | Rifampicin + isoniazid + pyrazinamide + ethambutol (RIPE) |
| Endocarditis | Staph. aureus, viridans streptococci, coagulase-negative staphylococci (CONS) | Ampicillin + flucloxacillin + gentamicin |
| Gastroenteritis | ||
| Urinary tract infection (UTI) | E. coli, Staph. saprophyticus, Klebsiella, Pseudomonas | Trimethoprim, nitrofurantoin |
| Chlamydia trachomatis | Azithromycin | |
| Neisseria gonorrhoeae | ||
| Syphilis | Treponema pallidum | Benzylpenicillin |
| Osteomyelitis | Staph. aureus, Enterobacter, streptococci | Clindamycin, linezolid |
| Cellulitis |
IM, intramuscular; IV, intravenous; MRSA, meticillin-resistant Staphylococcus aureus; PO, orally.
Pharmacology is the study of drugs, consisting of pharmacodynamics (effect of drug on body) and pharmacokinetics (effect of body on drug; see Fig. 3.4).
Receptors: ligand-gated ion channels, G protein-coupled receptors, tyrosine kinases, steroid receptors, and their mechanisms of signal transduction, including second messenger signalling pathways; principles of antagonists, agonists, partial agonists, and inverse agonists. Cooperative and non-cooperative binding indicated by sigmoid and hyperbolic substrate concentration–velocity curves respectively.
• Peripheral nerve transmission: the mechanisms of drug action at nicotinic and muscarinic synapses at pre- and postganglionic synapses in the autonomic nervous system, and at the neuromuscular junction.
• Cardiovascular pharmacology: mechanisms of action of antihypertensives, digoxin, antiplatelets, antiarrhythmics, and statins.
• Renal pharmacology: mechanisms of action of diuretics, angiotensin-converting enzyme inhibitors (ACEIs), and angiotensin receptor blockers (ARBs). Effects of ACEIs and NSAIDs on renal autoregulation.
• Inflammation: immunosuppression, and the pathways involved. Common anti-inflammatories (steroids, NSAIDs, dapsone) and immunosuppression (steroids, antimetabolites, calcineurin inhibitors).
• Cytotoxic chemotherapy: anticancer therapies, similarities/differences. Drug action at different stages of the cell cycle.
• Antimicrobials: classes, mechanisms of action, and bacterial resistance. Actions of drugs in disrupting bacterial cell wall synthesis.
Fig. 3.4 Pharmacokinetics and pharmacodynamics. Reproduced under creative commons license from Bianca Rocca and Giovanna Petrucci, Variability in the Responsiveness to Low-Dose Aspirin: Pharmacological and Disease-Related Mechanisms, Thrombosis, Vol 2012 (2012).
This is the study of society including some of the following:
But with increasing inequality, populations undergoing the demographic transition (see Fig. 3.5), globalization, ageing, poverty, environmental issues, and chronic illness, medical sociology is relevant.
Fig. 3.5 The demographic transition. CBR, crude birth rate; CDR, crude death rate. Reproduced with permission from Montgomery, Keith. The Demographic Transition. http://pages.uwc.edu/keith.montgomery/Demotrans/demtran.htm
Lecture or seminar based. Sociology is a wide field so the area of study is normally limited to health and illness. Assessed by either written exams or essays as part of continuous assessment.
Ensure you have good notes from lectures—this is what you will most likely be examined on. There are several textbooks on medical sociology, e.g. Key Concepts in Medical Sociology by Jonathan Gabe and Lee Monaghan (2013). Read essayist Susan Sontag’s Illness as Metaphor (1978): ‘Illness is the night-side of life, a more onerous citizenship. Everyone who is born holds dual citizenship, in the kingdom of the well and in the kingdom of the sick.’
Where a non-medical problem becomes a medical one, e.g. alcoholism. Often linked to ‘deviant’ behaviour.
Ivan Illich thought medicalization by doctors and pharmaceutical companies weakens a person’s ability to care for themselves. ‘Illness’ can be ‘de-medicalized’, such as homosexuality, which was listed as a psychiatric illness in the US until 1973.
The sociologist Talcott Parsons argued that for society to function, people who are ill have a duty to seek medical care while society agrees to allow them to take time off to recover. Sociologists Bloor and Horobin criticized this model, saying doctors often expect patients to know when to present (and not present with ‘rubbish’) and when they do present at the right time, not to question their diagnosis and treatment.1 An Australian study demonstrated considerable accuracy in ‘parental triage’ when parents took their children to the emergency department (ED).2
‘Stigma’ derives from the tattoos marking slaves and criminals in ancient Greece as social outcasts. The classic stigmatizing illness, now easily treatable and difficult to become infected with, is Hansen’s disease, or leprosy. Until recently in the UK, special pre- and post-test counselling for HIV tests was obligatory because of the stigma surrounding the disease. But treating HIV testing like this was seen as a barrier to the diagnosis and treatment of patients with HIV. The British HIV Association now advises that a HIV test should be treated like any other investigation for serious illness.3
Ivan Illich was an Austrian philosopher, Catholic priest, and critic of society’s ‘medicalization’. He argued in his Limits to Medicine, that the ‘physician becomes the sickening agent’ as the medical establishment seeks to medicalize normal life events and deprive us of our traditional coping strategies. He described three stages of ‘iatrogenesis’ (from the Greek ‘iatros’, or ‘healer’, and ‘genesis’, or ‘origin’): (1) clinical iatrogenesis, illness or death caused by a health worker; (2) social iatrogenesis, where doctors, drug companies, and others medicalize normal life stages (e.g. ageing, creating unrealistic expectations and so creating demands for their goods and services); and (3) cultural iatrogenesis, whereby our ability to handle illness and death are lost.4
1. Gabe J, Bury M, Elston M. (2004). Key Concepts in Medical Sociology. London: Sage Publications.
2. Williams A, O’Rourke P, Keogh S. (2009). Making choices: why parents present to the emergency department for non-urgent care. Arch Dis Child 94(10):817–20.
3. British HIV Association (2008). UK National Guidelines for HIV Testing. London: BHIVA.
4. Barnet RJ. (2003). Ivan Illich and the nemesis of medicine. Med Health Care Philos 6:273–86.
Titbit
Epidemiology, the science of health and disease in populations, is detective work writ large and has some notable sleuths: John Snow in 1854, mapping and halting a London cholera epidemic; Bradford Hill and Richard Doll’s work linking smoking and lung cancer; and the epidemiologists tackling the 2014 West African Ebola (viral haemorrhagic fever) epidemic.
The UK’s Faculty of Public Health states that all doctors should ‘adopt a “population perspective” in everyday clinical practice and should consider health inequalities’ (Faculty of Public Health (2014). Undergraduate Public Health Curriculum. www.fph.org.uk/uploads/PHEMS%20booklet.pdf). The faculty recommends a mix of best answer and extended matching questions, short answer questions, essays, and poster work. The London School of Hygiene and Tropical Medicine runs a mock cholera outbreak for its students ( www.msf.org.uk/teaching-resources-level-biology#cholera).
• Bonita R, Beaglehole R, Kjellström T. (2006). Basic Epidemiology, 2nd edition. Geneva: World Health Organization ( apps.who.int/iris/bitstream/10665/43541/1/9241547073_eng.pdf).
• The US Centers for Disease Control in Atlanta has a free online course ( www.cdc.gov/ophss/csels/dsepd/ss1978/index.html).
• The John Snow Society’s ‘Pump Handle’ lectures ( www.johnsnowsociety.org/annual-pumphandle-lecture.html).
• Hans Rosling’s www.gapminder.org, with ‘bubble’ visuals on population and health (the Swedish professor discovered the cause of konzo following an outbreak of the disease in Mozambique, a paralytic illness caused by high levels of dietary cyanide).
World Health Organization (WHO) definition of health, 1948: ‘Health is a state of complete physical, mental and social well-being and not merely the absence of disease or infirmity.’ All sorts of health data are collected, local to global. The first attempt to classify and thus help measure health and disease on a global scale occurred in Paris (1900) and resulted in the first International List of Causes of Death. Revised every 10 years, the WHO took over responsibility for this in 1948 and the system was renamed the International Classification of Diseases, or ICD. The tenth version, ICD-10, is used today and its codes must be used on UK death certificates.
Hippocrates (470–400 bc) wrote in his essay On Airs, Waters and Places that the physician needs to take environmental factors into account, pointing to seasonality, the quality of the water supply, and whether the population exercised and ate healthily—or drank to excess and were ‘given to indolence’.
• Endemic: the normal background rate of a disease, e.g. cases of chicken pox annually in the UK, where there is no vaccination against varicella zoster virus (VZV).
• Epidemic: a rise in cases of a disease above the normal background rate (epidemiologists often prefer the term ‘outbreak’).
• Cluster: a group of cases at a specific time and place.
• Pandemic: an epidemic/outbreak that crosses international borders.
• Prevalence: the proportion of people with the disease in a given population at a point in time (number of diseased/given population).
• Incidence: the rate of new cases of disease in a population over a given period of time (number of people who become diseased over a period of time/the total observation time of all persons).
• Exposure: the pathogen/protective factor being studied (e.g. cigarette smoking or olive oil consumption).
• Mortality rate: number of deaths for a given number of people per unit of time, e.g. crude death rate = number of deaths per 1000 people per year; under-five mortality rate (U5MR) = number of deaths of children under the age of 5 years per 1000 live births.
Box 3.1 A call to Public Health
You are on-call in the ED and a 19-year-old student is triaged urgently with fever and a non-blanching rash. The following will help when you call Public Health, who will want to prevent an outbreak of meningococcal disease and give guidance on prophylaxis for close contacts, including healthcare staff.
• Clinical case definition (for meningococcal septicaemia): fever, petechiae, purpura, toxic patient. May have features of meningitis (e.g. headache, neck stiffness, photophobia).
• Laboratory confirmation: blood culture, cerebrospinal fluid (CSF) (via lumbar puncture (LP)) or polymerase chain reaction (PCR) positive for Neisseria meningitides.
• Suspected case: meets clinical case definition (but could be something else).
• Probable case: in opinion of team treating case, likely to be meningococcal disease (e.g. patient lives in university accommodation where there have been two other confirmed cases).
The epidemiologist is looking at the how/why of a disease in a population. Studies most commonly used are case–control studies (e.g. where people with the condition of interest are compared to those without the condition, a retrospective design used for outbreak investigations) and cohort studies (prospective, studying a population over time with the exposure of interest). These studies can establish a relationship or association with the exposure of interest but not causation (see Box 3.2).
Box 3.2 Smoking and the Bradford Hill criteria
Sir Austin Bradford Hill (with Sir Richard Doll) established the link between smoking and lung cancer.1 He set nine criteria for causation2:
1. Strength: the larger the association, the likelier the exposure is causal.
2. Consistency: different studies make the same observations.
3. Specificity: causation more likely in specific populations, e.g. asbestosis in workers in the asbestos industry.
4. Temporality: effect has to occur after exposure for causality.
5. Biological gradient: dose response, e.g. greater cigarette pack-years are associated with greater likelihood of lung cancer.
6. Plausibility: case for causation helped if thought to be biologically plausible but Bradford Hill qualified this, saying it depended on the biological knowledge of the day, quoting Sherlock Holmes: ‘When you have eliminated the impossible, whatever remains, however improbable, must be the truth.’
7. Coherence: epidemiological and laboratory findings agree, but Bradford Hill said a lack of laboratory evidence does not rule out the epidemiological evidence.
8. Experiment: may strengthen case for causation, e.g. preventative action reduces incidence of a disease.
9. Analogy: the acceptance of slighter evidence, e.g. thalidomide and birth defects.
With an outbreak of illness in a population, the epidemiologist will ask what, where, who, when, and why, summed up by time, place, and person. Time will look at seasonality (e.g. annual winter epidemics of RSV bronchiolitis in infants), long-term trends (e.g. rates of dementia in the population), or an epidemic period (e.g. number of cases during the 2014 Ebola outbreak in Sierra Leone). Place can be anywhere from a school or hospital ward to a continent. Age, sex, and socioeconomic status are usually included but more specific details may be used too.
References
1. Doll R, Hill AB. (1950). Smoking and carcinoma of the lung. BMJ 2:739–48.
2. Bradford Hill A. (1965). The environment and disease: association or causation? Proc R Soc Med 58(5):295–300.
Including the coronary arteries (right vs left dominant) and valves. Blood flow through heart/lungs/systemic circulation. Surface anatomy of heart and valve positions. Embryology including malformations.
Cardiac cycle (see Fig. 3.6 and Fig. 3.7) and isovolumetric contraction (systolic ejection), isovolumetric relaxation + filling (diastole). Factors influencing stroke volume (SV) × heart rate (HR) = cardiac output (CO). Starling’s law + curve. Pre-load (‘venous pool’ returning blood heart) and after-load (resistance against pumping blood).
Myocardial action potentials, phases, and ion channels (Na+ in K+ and Cl− out Ca2+ in and K+ out K+ out K+ in), excitation–contraction coupling and Ca2+-induced Ca2+ release.
• Antiplatelets: aspirin (irreversible cyclooxygenase (COX) inhibitor), clopidogrel (adenosine diphosphate (ADP) antagonist).
• Anticoagulants: warfarin (vitamin K depletion), heparins (antithrombin III + factor Xa blocking), non-vitamin K antagonist oral anticoagulants (e.g. rivaroxaban).
• Beta blockers: e.g. bisoprolol 
contractility + HR + renin release + afterload.
• Diuretics: e.g. thiazides. Multiple mechanisms including preload through salt + water excretion.
• Dilators: venous dilators (e.g. nitrates reduce pre-load), vasodilators (e.g. hydralazine reduce afterload).
• Calcium channel blockers: dihydropyridine (amlodipine) vasodilate vs non-dihydropyridine (verapamil) = antiarrhythmic.
• Digoxin: rate control in atrial fibrillation and increase in CO.
• ACEI/ARB: renin/salt/water retention + improve ventricular remodelling.
• Antiarrhythmics: Vaughn Williams classification.
• Statins: HMG-CoA reductase inhibitors (cholesterol reduction).
Fig. 3.6 Cardiac cycle. Reproduced with permission from Mark Kearney, Chronic Heart Failure, 2008, Oxford University Press.
Passage of oxygen from the atmosphere into the pulmonary circulation through bronchial tree. Bronchopulmonary segments and relations of lobes and fissures to chest wall surface anatomy. Intercostal muscles/diaphragm for ventilation. Relation with the heart.
Alveolar gas exchange: anatomical dead space (bronchi) vs physiological dead space (hypoperfused or hypo-oxygenated lung tissue). Role of surfactant (neonates). Ventilation/perfusion (V/Q) mismatch: higher V/Q (>1) at the apex and lower at the bases (<1). Ventilatory response to acidosis. Lung volumes: inspiratory reserve volume (IRV), tidal volume (TV), expiratory reserve volume (ERV), residual volume (RV), functional residual capacity (FRC), inspiratory capacity (IC), vital capacity (VC), total lung capacity (TLC) (see Fig. 3.8). Oxygenation: O2–haemoglobin (Hb) dissociation curve and causes of ‘shifts’; CO2 transportation (see Fig. 3.8).
• Beta-2 agonists: bronchodilatation (short-acting salbutamol, long-acting salmeterol).
• Antimuscarinics: bronchodilatation (e.g. ipratropium).
• Other bronchodilators: e.g. methylxanthine (theophylline) and leukotriene antagonists (montelukast).
• Corticosteroids: reduce airway inflammation (e.g. inhaled beclometasone or oral prednisolone).
• Mucolytics: e.g. carbocisteine and N-acetylcysteine.
• Antimicrobials: e.g. penicillins, macrolides, tetracyclines.
• Other agents: e.g. magnesium in asthma, home oxygen.
Fig. 3.7 Spirogram. Reproduced with permission from Albert RK, Spiro SG, Jett JR (eds): Comprehensive Respiratory Medicine. St Louis: Mosby, 1999, p 43.
Fig. 3.8 Dissociation curve for oxyhaemoglobin. Reproduced with permission from Provan, Drew, Oxford Handbook of Clinical and Laboratory Investigation 3e, fig 8.1, 2010, Oxford University Press.
The luminal gastrointestinal (GI) tract spans from mouth to anus, and the hepatobiliary system (including the pancreas) joins the duodenum at D2. The coeliac artery supplies the foregut proximal to D2, superior mesenteric artery (SMA) the midgut, and inferior mesenteric artery (IMA) supplies from the distal one-third of the transverse colon to the upper rectum.
Mucosa, submucosa (with Meissner’s parasympathetic plexus), muscularis externa (with Auerbach’s autonomic myenteric plexus), and serosa.
Chemical digestion starts with salivary amylase, and continues with gastric parietal cell HCl production and vagal stimulation of pepsin from chief cells. Additional factors such as gastrin (upregulates acid secretion and gastric motility), secretin (bicarbonate to neutralize acidic chyme), and somatostatin (globally inhibitory). Physical digestion largely mediated by neural control of gut (absent in Hirschsprung disease).
Produces, concentrates, and stores bile to emulsify lipids. Pancreas secretes exocrine enzymes.
• Antacid tablets: e.g. omeprazole (proton pump inhibitor (PPI)), ranitidine (H2), misoprostol (prostaglandin inhibitor).
• Prokinetic drugs: e.g. metoclopramide (D2, 5HT3), domperidone (D2, D3), erythromycin (motilin), senna derivatives.
• Antimotile drugs: hyoscine (M2), loperamide and codeine (opiate receptors).
• Antiemetics: e.g. cyclizine (H1), ondansetron (5HT3), metoclopramide, domperidone.
• Portal hypertension: propranolol (beta-1 blocker), terlipressin (V1 agonist), octreotide or somatostatin.
• Immunotherapy in inflammatory bowel disease (IBD): non-specific corticosteroids, anti-inflammatories (e.g. 5-aminosalicylic acid (ASA)/mesalazine), antimetabolite (azathioprine), biologics, e.g. anti-TNF drugs (infliximab).
• Antimicrobials: e.g. metronidazole and ciprofloxacin for Crohn’s disease and traveller’s diarrhoea.
Central nervous system (CNS): cerebral cortex (Fig. 3.9) and functional regions (frontal, parietal, occipital, temporal); homunculus; hypothalamus and pituitary gland; basal ganglia; thalamus; lateral and medial nuclei; brainstem and cerebellum. CNS blood supply including the circle of Willis; dural venous sinuses. CNS cells are functional (neuronal) or supportive (glial). Glial cells comprise astrocytes (blood–brain barrier), microglia (macrophage like), and oligodendrocytes (myelin production).
Peripheral nervous system (PNS): links the CNS with sensory receptors and motor effectors. Also includes cranial nerves (except II!), spinal nerves, autonomic nervous system, and nerve plexus.
Autoregulation of blood flow, cerebral blood flow vs cerebral perfusion pressure. CSF function and circulation within the ventricular system. Parasympathetic and sympathetic nervous systems, role in ‘rest and digest’ and ‘fight and flight’ respectively. Neuronal membrane and action potentials, saltatory conduction along myelinated nerve fibres: neurotransmitters. Types of nerve fibre and their structural and functional differences (e.g. conduction velocity and diameter).
• Neuromuscular junction-blocking drugs in anaesthesia, and acetylcholinesterase inhibitors in myasthenia gravis.
• Anti-Parkinsonian drugs: e.g. levodopa and analogues, dopamine decarboxylase inhibitor, monoamine oxidase inhibitors.
• Antiepileptics: e.g. phenytoin, valproate.
• Immunotherapy for MS: e.g. corticosteroids (non-specific), alemtuzumab (anti-lymphocyte), fingolimod.
Fig. 3.9 The lobes of the central cortex. Reproduced with permission from Gelder, Michael, et al, New Oxford Textbook of Psychiatry 2e, 2012, Oxford University Press.
Each endocrine system consists of an ‘axis’ comprising a control organ (hypothalamus or pituitary), an effector organ (e.g. thyroid or adrenal gland), and end organs (where hormones exert effects). The posterior pituitary and adrenal medullae are under neural control while the anterior pituitary and other endocrine organs are regulated by hormones.
The posterior pituitary (neurohypophysis) produces oxytocin and ADH and has neural connections to the hypothalamus. The anterior part (adenohypophysis) is linked via a portal system to the hypothalamus, and secretes a number of hormones under hypothalamic control (see Fig. 3.10).
Fig. 3.10 Neuroendocrine system. Reproduced from https://commons.wikimedia.org.
Chief cells secrete PTH in response to falling calcium or rising phosphate concentrations. This increases the absorption of dietary calcium, the renal excretion of phosphate, and the hydroxylation and activation of vitamin D (via 1-alpha-hydroxylase in the kidney and 25-hydroxylase in the liver).
The thyroid hormone T3 and its prohormone T4 regulate global metabolic activity, beta adrenergy, and much more.
Synthesize renin which via angiotensin I and II controls salt/water retention and blood pressure. Erythropoietin (EPO) production by peritubular fibroblasts also stimulates red blood cell (RBC) production in bone marrow.
Ovaries secrete progesterone/oestrogens and testes secrete testosterone.
Alpha and beta islet cells produce glucagon and insulin respectively. Insulin mediates cellular uptake of glucose and glycogenesis. Glucagon works in reverse, by breaking down glycogen to glucose in times of stress/starvation (see 
p. 287). The pancreas also has a number of exocrine functions in aiding digestion. See Fig. 3.11 to appreciate the connection between the GI and endocrine systems.
Fig. 3.11 GI endocrine system. Reproduced from https://commons.wikimedia.org.
The adrenal gland comprises cortex (steroid production) and medulla (catecholamines). The cortex is divided into GFR: zona Glomerulosa (mineralocorticoids), Fasciculata (glucocorticoids), and Reticularis (androgens). Negative feedback (see Fig. 3.12) ensures homeostasis.
Fig. 3.12 Hormonal feedback. CORT, cortisol; HPA, hypothalamic–pituitary–adrenal. Reproduced from https://commons.wikimedia.org.
Best conceptualized as lesions causing overactivity (e.g. hyperthyroidism) or underactivity (hypothyroidism). Causes include neoplasia (Conn’s syndrome), autoantibody production (Graves’ or Addison’s disease), infiltration of endocrine organ (e.g. TB and adrenal gland), or abnormal receptors (androgen insensitivity syndrome). Treat with:
• exogenous hormone replacement: T4, steroid, EPO, insulin
• inhibitors of endogenous hormone activity: carbimazole (thyroid), cabergoline (prolactin), spironolactone (Conn’s syndrome).
Outer renal cortex (for filtration) and inner medulla (urine concentration) (see Fig. 3.13 and Fig. 3.14). Innermost portions of the medulla are the papillae which coalesce to form calyces which drain into the renal pelvis. This continues into the ureter which is lined by transitional epithelium before entering the bladder via the vesicoureteric junction. Each kidney contains 1 million functional units of a glomerulus (knot of blood vessels supplied by the afferent arteriole and drained by the efferent) and a nephron.
Functions of kidney include salt and water homeostasis (and blood pressure control), acid/potassium/urea/creatinine excretion, EPO production, and calcium/phosphate balance. Maintenance of glomerular filtration rate via renal autoregulation (prostaglandins dilate afferent arteriole and renin–angiotensin system (RAS) constricts efferent).
Descending limb permeable to water not solute (water leaves tubule to form hypertonic urine), ascending limb impermeable to water but actively reabsorbs Na+. Vasa recta maintains concentration gradient.
• Pre renal: hypoperfusion from dehydration, low blood pressure (BP), heart failure.
• Renal: glomerulus—nephritic and nephrotic disease, diabetes. Tubulointerstitium—acute tubular necrosis from pre-renal failure, drugs (see Fig. 3.13 for overview of nephron and sites of action).
• Post renal: prostatic enlargement, renal stones, urothelial cancer.
• Diuretics: block Na+ pumps in nephron. Loop (furosemide) blocks Na-K-2Cl, thiazide (bendroflumethiazide) blocks Na+-Cl--cotransporter (NCC), amiloride (epithelial Na+ channel (ENaC)).
• Inhibitors of RAS: ACEIs (enalapril) block AI–AII conversion. ARBs (losartan) directly block angiotensin receptor. Aliskiren directly inhibits renin (blocking angiotensinogen–AI step).
• Mineralocorticoid antagonist: e.g. spironolactone (K+ sparing).
• Drugs in renal failure: activated vitamin D, EPO, PO43− binders.
• Stones: reduce stone formation (thiazide diuretic, K+ citrate).
• Prostate disease: alpha-1-adrenoceptor blockers (tamsulosin) relax bladder neck and urethra. Antiandrogen (e.g. finasteride for benign prostatic hyperplasia (BPH)).
• Remember nephrotoxins: NSAIDs, gentamicin, cisplatin, amphotericin, lithium.
Fig. 3.13 The anatomy of the nephron. Reproduced from O’Callaghan, C (2009). The Renal System at a Glance, 3rd edn. With permission from Wiley-Blackwell.
Fig. 3.14 Schematic representation of the counter-current multiplier of the renal medulla. Reproduced from G Pocock and CD Richards, Human Physiology: The Basis of Medicine, Third Edition, 2006, Figure 17.24, p. 369, by permission of Oxford University Press.
The musculoskeletal (MSk) system provides protection, stability, and movement to the body, and consists of bones, muscles, cartilage, tendons, and ligaments. Muscles are composed of fibres that contract and relax movement, maintaining posture, and metabolic heat production. A joint, in which two or more bones articulate, is stabilized by ligaments and tendons. There are 300 bones in a baby which fuse to 206 by adulthood (see Fig. 3.15).
Fig. 3.15 Musculoskeletal system. Skeleton. Reproduced with permission from the MSD Manual Consumer Version (Known as the Merck Manual in the US and Canada and the MSD Manual in the rest of the world), edited by Robert Porter. Copyright (2018) by Merck Sharp & Dohme Corp., a subsidiary of Merck & Co, Inc, Kenilworth, NJ. Available at http://www.msdmanuals.com/consumer. Accessed (03/01/18).