Introduction to the study of disease

Nature and aetiology

Basic Terms

Physiology is the study of normal body function and anatomy is the study of body structure, (ology simply means ‘the study of’). Pathology is the study of disease, involving examination of abnormal structure and function. Pathophysiology is the study of abnormal body function, in disease states, and after trauma. Histology and cytology are the study of tissues and cells respectively. Histopathology and cytopathology are therefore the study of abnormal tissues and cells.

Disease literally means any state of not being at ease, there is ‘dis-ease’. This definition could include the effects of trauma, as well as disease processes. In practice we tend to use the term disease to refer to abnormal processes occurring within the body and the way in which these manifest in the individual. Pathogenesis is the process whereby the disordered disease state is produced in the body after the causative factor has been introduced.

Causes of disease

The cause of a disease is correctly described as the aetiology. Aetiology is ‘that which causes’. Factors which may be involved in disease causation are therefore termed aetiological factors. So the aetiology causes the pathophysiology which in turn generates the clinical features of the disease. Aetiological factors may arise from within the individual, or from the environment the person is exposed to. Factors arising from within are called endogenous; those from the environment are exogenous.

Endogenous aetiology

The only true, absolute, endogenous factors are from the genetics of the person. These are determined from the point of conception; when there is fusion of the chromosomes from the sperm and ovum, into a single fertilized cell called a zygote. This zygote divides repeatedly to form all of the cells in the body. As a result all cells have the same genetic make up as the original zygote. At present there is nothing we can do about the genes we were given at conception. While many experiments are currently being carried out in the field of gene therapy, there are virtually no treatments available using this technique. This means we are to a large extent, ‘at the mercy’ of our genes.

Genetic disorders

Ultimately, all aspects of anatomy and physiology depend on, and derive from our genes. It is the genes which carry all of the information needed to construct the body, in the genetic code. Genetic disorders are those caused wholly by abnormalities in the genes. Numerous individual genetic disorders exist. They are normally classified by their mode of inheritance, this may be autosomal dominant, autosomal recessive or sex linked.

Autosomal dominant disorders

Autosomes are the 44 non-sex chromosomes present in cell nuclei. Autosomal dominant disorders will be manifest if there is a single copy of the abnormal gene present in the individual’s genotype. This means that when one parent is affected by a dominant disorder, any children have a 50% chance of inheriting the condition. For example, achondroplasia which is a form of dwarfism, is transmitted by a dominant gene. Huntington’s disease is also dominant and leads to psychiatric symptoms, abnormal movements and eventual dementia. Hypertrophic obstructive cardiomyopathy (HOCM) leads to an abnormal increase in the thickness of the myocardium and is a cause of sudden death. Neurofibromatosis causes numerous small tumours to develop from the sheaths of peripheral and cranial nerves. The BRCA1 and BRCA2 genes significantly predispose to the development of breast and ovarian cancer and are also transmitted in an autosomal dominant pattern.

Autosomal recessive disorders

Autosomal recessive disorders only present if there are 2 copies of the abnormal gene, on each of a pair of chromosomes. In practice these disorders normally occur in the children of two normal parents, who each carry one recessive copy of a particular gene. This means the probability of any child being affected is 1 chance in 4. Examples of diseases caused by this form of inheritance include thalassaemia, which causes abnormalities of the haemoglobin molecule. Phenylketoneuria (PKU) is an enzyme deficiency which means the patient can not process the amino acid called phenylalanine. Sickle cell disease causes abnormal shaped red blood cells and cystic fibrosis leads to viscous secretions from the pancreas and lungs.

Sex linked diseases

Sex linked disorders are virtually always transmitted on the X chromosome, so are sometimes referred to as X linked. Examples include haemophilia which leads to the lack of a clotting factor in the plasma resulting in excessive bleeding. Some forms of muscular dystrophy and colour blindness are also X linked. Females have two copies of the X chromosome and males only have one. This means that women often transmit X linked disorders which their sons suffer from.

Genetic predispositions

The genetic disorders discussed above directly cause a particular abnormality. In a truly genetic disorder the abnormal gene is one hundred percent responsible for the aetiology. This means that life style factors play no part in the pathogenesis. In numerous other disorders there is an environmental and a genetic component in the aetiology. A particular genetic make up can increase the risk that a person will develop a particular disorder. This is described as a genetic predisposition.

However, the genetic predisposition must be acted on by environmental factors in the pathogenesis of the disease process. The degree to which genetic make up places an individual at increased risk of a particular disorder varies from a very slight to a very significant risk. In most disease processes there is at least some genetic predisposition. It has been said, somewhat unhelpfully, that the best way to have a healthy life is to choose your parents carefully.

Implications of genetic knowledge

Often our principle role in dealing with genetic problems is one of health educator. Information should be given to families about the nature of genetic traits and disorders, how they are inherited and the possibilities of future children being affected. Appropriate well communicated information empowers the individual to make informed choices about their lives and reproductive activities at the pre-conceptual stage. It is not the role of nurses or doctors to make these choices on behalf of an individual. All practitioners need to empathise with the anxieties of parents as they decide on issues such as whether to start a pregnancy. In individuals who are at risk of developing a disorder themselves, with a significant genetic component in aetiology, the right of the patient to know, or not to know must be respected. This means that requested information should be given, but information should not be forced on individuals who do not wish to know about aspects of their lives and reproduction. Information exists, but not everyone is obliged to hear it.

Chromosomal disorders

Chromosomal abnormalities may be caused by environmental factors in the parents, such as being exposed to ionizing radiation. Despite this possible aetiology, disorders of chromosome structure are usually also classified as endogenous. Perhaps the best known example of a chromosomal disorder is Down’s syndrome. The correct term for this condition is trisomy 21 syndrome. Trisomy 21 means that there are 3 of the 21st chromosome present as opposed to the normal 2 copies. This gives a total number of 47 chromosomes instead of the normal 46.

A variety of features may present as a result of trisomy 21, including characteristic facial features (which gave rise to the old, inaccurate, description of Mongolism), learning difficulties (IQ may be below 50) and possible congenital cardiac abnormalities. The risk of a child being affected by trisomy 21 syndrome increases with the age of the mother. Older women considering a pregnancy should be made aware of this risk. As a general principle it is probably best when mothers have children in their twenties.

Other chromosomal abnormalities include trisomy 18 and 13 syndromes. There may also be abnormalities of sex chromosome numbers. In Klinefelter’s syndrome, (XXY syndrome) boys have small testes, are infertile and may have breast development, all caused by an additional X chromosome. Some girls are born with only one X chromosome, so only have a total of 45. This is called Turner’s syndrome; these children are usually of short stature with webbing of the neck; they do not menstruate.

Exogenous aetiology

Any factor from the environment which contributes to disease aetiology is exogenous. These factors are also commonly referred to as environmental. This environment includes the one experienced in the uterus, before birth.

Infections

Microorganisms are perhaps the best example of an exogenous factor. We may, or may not be exposed to a particular organism. If we are not exposed, we will not suffer from the corresponding infection. Numerous small organisms (living things) have the potential to cause infective disease including viruses, bacteria, protozoa and larger parasites such as intestinal worms.

Chemical toxins

Numerous chemicals can adversely affect physiological systems leading to disorder. Some affect all of the body, for example cyanide inhibits energy generation in all cells. Others work more locally; mercury and lead for example affect the bones and brain. Dioxins are an important group of dangerous chemical we are exposed to in polluted air as well as from contaminated food. These largely come from the petroleum and plastics industries and can cause cancer.

Physical agents

Numerous physical agents and forms of energy can adversely affect the body. Trauma is usually caused by the effects of kinetic (movement) energy disrupting the integrity of body tissues. Heat and cold can both cause localized tissue damage as well as systemic (whole body) problems. Electrical energy is another agent which can lead to localized burning and can be life threatening if the heart or brain are sufficiently disrupted. Radiation can damage tissue, often by damaging the deoxyribonucleic acid (DNA) which regulates activity of the cell. DNA damage explains why radiation can lead to mutation and malignant changes.

Nutritional factors

Malnutrition means abnormal nutrition and can be caused by too much or too little of a dietary component. If more energy is consumed than the body uses, the excess will be stored as fat, leading to the development of obesity. Excessive ingestion of some foods has been associated with the aetiology of vascular disease, hypertension (high blood pressure), heart disease, stroke, diabetes mellitus type 2 and some cancers.

Deficiency of dietary components can also lead to malnutrition. Lack of protein causes a condition often referred to as kwashiorkor characterized by oedema. Carbohydrate deficiency causes marasmus and a lack of fat in the diet can lead to weight loss and lack of the fat soluble vitamins, A, D, E and K. In practice, lack of protein, carbohydrate and fat usually go together; this causes a condition called protein energy malnutrition (PEM). Lack of water causes dehydration. Diets which are deficient in fibre can lead to constipation, haemorrhoids (piles) and play a role in the development of diverticulitis and cancer of the colon. Deficiency of iron can cause anaemia, as can a lack of folic acid and vitamin B12. Scurvy is caused by lack of vitamin C and iodine deficiency can lead to cretinism and goitre.

Degenerative disorders

These conditions are associated with increasing age and occur as a complication of the degeneration of tissues, often as a result of a decrease in the number of viable cells. Cells are only able to divide a limited number of times; this means that after a limited number of divisions a cell line will die. Degeneration may also occur by a process of ‘wear and tear’ or as a result of an accumulation of damage sustained over the years.

These ongoing degenerative processes may affect the normal physiology of a cell; this may result in abnormal cell division which partly explains why most cancers become more common in older people. At the level of the tissues, loss of articular cartilage can give rise to osteoarthritis. Loss of brain cells can cause dementia. Decrease in the number of some cells which produce dopamine can cause Parkinson’s disease. In the elderly there may be atrophy and degeneration of several organs and tissues which is sometimes severe enough to cause disease. When several disease states occur together in the elderly the term ‘senile multiple pathology’ is often used.

Abnormal immunity

Normally the immune system is defensive, protecting the body against infections of all types. However, the immune system may malfunction leading to disease states. Autoimmunity is when the immune system attacks the body’s own tissues, for example in diabetes mellitus type 1, the immune system eradicates the beta cells from the pancreatic islets. Another group of immunological disorders are the hypersensitivity reactions. In these disorders the body reacts in a disproportionate way, often to a foreign material which should generate no immune response at all. This can lead to life threatening states where there is swelling of the airway, bronchospasm and profound shock. Anaphylaxis is an example of one of these hypersensitivity disorders. While the immediate cause of these disorders is exposure to some environmental trigger, (such as nuts) there are also some genetic factors involved in the aetiology.

Neoplasm

‘Neo’ means new and ‘plasm’ relates to growth of tissue. A neoplasm is therefore a new tissue. Tumour means ‘lump’ and these are caused by the presence of new tissue. Tumours may be caused by exposure to environmental agents such as viruses, radiation and chemical carcinogens. A carcinogen is a chemical which can cause cancer, such as tar from tobacco smoke. Essentially, there are two forms of tumour, benign and malignant. A benign tumour is one which does not spread to distant sites in the body by the process of metastasis. Malignant tumours do spread (metastasize) around the body and start to grow at other sites. Many malignancies probably have some genetic component in their aetiology as well as environmental factors.

Psychosomatic factors

‘Psych’ means to do with the mind and ‘soma’ the body. Psychosomatic is therefore the effects of the mind on the body. This works the other way around as well, the body is able to affect the mind. The mind and the body are interrelated in numerous intricate ways, and it could be argued that it is not possible to separate them in the complex phenomenon which is a human being.

However, to take simple examples, the mind is affected by the body in many confusional states. If there is a systemic infection or a poor blood supply to the brain it will not be able to work as efficiently as in health. This can interfere with the ability of the brain to generate a clear mind. It is also known that psychological factors such as stress can adversely affect the efficiency of the immune system. Reduced levels of immunity may predispose to infections and arguably other conditions such as some malignancies. The placebo effect is also psychosomatic. This is when a person experiences some physical improvement because they believe an intervention will help them. The benefit of the placebo effect can occur even if a treatment has no physiological effect at all, such as with homeopathy.

Psychiatric disorders

Traditionally psychiatric disorders have been classified as psychotic or neurotic. While this is an over simplification it is often a useful model to use. Neuroses are mental problems caused by adverse environmental factors operating on the mind. For example; if a person gets divorced and loses their job they may become depressed as a reaction to the psychological trauma they have suffered. Excessive stress and things to worry about in the environment of life can lead to anxiety neurosis and panic attacks.

Psychotic illness originates in the mind, not in the environment. In psychotic illnesses the person often may appear to be ‘mad’. They may suffer from hallucinations and delusions (false perceptions and beliefs respectively). Behaviour may sometimes, but not always be bizarre. Examples of psychotic illness include all forms of schizophrenia, bipolar disorder and paranoid psychosis.

Iatrogenic disease

These are disorders caused by clinical treatments. ‘Iatro’ is derived from the Greek for doctor, so literally these disorders begin with the doctor. For example if a patient develops pressure sores, as a result of being nursed in bed, the problem would be iatrogenic. Other causes of iatrogenesis relate to the side effects of drugs; antibiotics may cause iatrogenic diarrhoea, steroids may cause osteoporosis and morphine may cause respiratory depression. Overdose, drug errors and adverse reactions are also iatrogenic. If a nerve was damaged during surgery this would be iatrogenic nerve damage.

Idiopathic disease

The aetiology of idiopathic disease is unknown. Disease occurs, but we are not clear what the aetiology is. In fact idiopathic is a euphemism for ‘don’t know’. Idiopathic disease is also sometimes described as primary or essential. Although a disease is idiopathic, risk factors may be identified but the mechanism by which the disease is actually caused is unknown.

Multifactorial aetiology

In practice probably most diseases are multifactorial; this means they are caused by several factors which could be genetic and environmental. Many conditions probably involve several genes which give a level of genetic predisposition. This genetic makeup is then acted on by perhaps several environmental factors, which may eventually trigger a genetic predisposition, ultimately resulting in disease. If we are ever asked what causes a particular disease, (and we are not too sure of the answer) we are on fairly safe grounds if we say that ‘it is caused by a combination of environmental and genetic factors’.

Congenital disorders

Congenital simply means ‘present at birth’. These may therefore have a primarily endogenous or exogenous aetiology. In other words, if a disorder is present at birth, it may have occurred as a result of a genetic disorder or some environmental insult during the developmental process from zygote to baby. Cleft lip and palate is a well known example of a congenital disorder, affecting approximately 1 in a 1000 live births. Severity of this problem varies from a notch in the top lip to complete separation of the lip, up to the nose. There may also be a gap in the hard palate which forms the roof of the mouth.

Teratogenesis

A teratogen is any substance, agent or process which interferes with the normal development of a fetus before birth. Teratogens therefore lead to abnormalities in pre-natal development. The risk associated with exposure to teratogens is greatest during the first 12 weeks of pregnancy; this is the time when most tissue differentiation and generation of form takes place. The generation of form and shape is termed morphogenesis, (‘morph’ means shape, ‘genesis’ refers to beginnings). Some drugs and infections can be teratogenic, so is ionizing radiation, such as X rays.

Drugs

Thalidomide affected about 10,000 babies world-wide in the 1960s and caused some very serious developmental abnormalities. Some children were born with massively disrupted limb development. Alcohol is the most common drug leading to teratogenesis today. Fetal alcohol syndrome causes growth deficiencies, mental retardation, microcephaly (small brain) and a characteristic facial appearance with a thin upper lip. Most medicines are not teratogenic, but it is a good principle to avoid drugs in pregnancy if possible, unless we are sure a particular preparation is safe to use.

Adverse effects on the placenta, and therefore on fetal nutrition and oxygenation, are caused by maternal smoking. A mother smoking during pregnancy also increases the incidence of spontaneous abortion and low birth weight babies. Children born to smoking mothers are liable to a measurable delay in their physical and mental development up to the age of 11 years. Paternal (related to the father) drug use is also a bad idea. Cigarette smoking damages DNA in sperm. It has been strongly suggested that up to 14% of childhood cancers can be attributed to fathers smoking before conception.

Intrauterine infections

Some maternal infections in early pregnancy can lead to neurological problems including brain damage, visual impairment, deafness and congenital heart disease. Maternal rubella (German measles) infection is caused by a virus and can lead to disorders of the pulmonary blood vessels, heart, eyes, brain and hearing in affected babies. This is why it is so important to vaccinate girls for rubella before they reach reproductive age. As with other potential teratogens the effects are more serious if the infection is contracted in early pregnancy. Cytomegalovirus (CMV), a member of the herpes group of viruses, is another infection which can be teratogenic.

Radiation

Radiation exposure is a particular risk during pregnancy. Radiation may damage the genetic material in the rapidly dividing cells which are generating the new body in the process of morphogenesis. In addition to the risks of developmental abnormalities children exposed to radiation in the uterus are at increased risk of childhood leukaemia. This is why we must always ensure a woman is not pregnant before she is X-rayed. It is also vital that health care workers stringently avoid X-rays if there is any possibility of pregnancy.

Nutrition

Good maternal nutrition around the time of conception and in pregnancy is important. Neural tube defects, such as spina bifida, affect the development of the spinal cord. Studies have demonstrated that an adequate intake of folic acid has a significant protective effect, greatly reducing the prevalence of this congenital disorder. The practical implication of this are that we should advise prospective mothers to eat foods such as Brussels sprouts, spinach, kale, yeast extracts and cooked black eyed beans. All of these foods are rich sources of folic acid. In some cases supplements may also be advised.

Health care and disease aetiology

If we understand the causation of disease we are then in a position to advise people how to avoid risk factors. This could prevent the formation of disease in some, and delay disease onset in others. It is always better to prevent disease, rather than to treat it once present. Disease prevention may simply involve giving information such as avoiding smoke or eating less fat. It may involve changes in the wider environment to make it healthier; this broader field is the whole area of health promotion. Vaccination is another obvious way that we seek to prevent disease.

Prophylaxis

This term describes any measure which may be taken to prevent or protect against disease or disease complications. As mentioned, vaccination is a prophylactic measure against infectious disease. In some wounds, antibiotics may be given as a prophylactic treatment to prevent infection. A small daily dose of aspirin may be given to reduce platelet stickiness and so reduce the likelihood of developing coronary thrombosis.

Identifying disease

The process whereby a disease is identified, and a conclusion reached, is termed the diagnosis. In order to arrive at a diagnosis there must be an assessment of the clinical features, disease history and often pathological and other investigations are also required.

Clinical features

Recognition of disease comes from discerning the signs and symptoms which present in a particular patient. A sign is something we are able to detect with our senses. For example if we see that the patient is sweating or bleeding this is a sign. Feeling a lump or abnormal pulse are also clinical signs. In fact some signs we may also hear or smell. For example; we may hear noisy, stertorous breathing in a partly obstructed airway or smell acetone on the breath of a patient in a diabetic ketoacidotic coma.

Symptoms are something the patient experiences; we only become aware of them as they are reported to us. For example, we cannot see a patient’s pain, but they may report it to us as a symptom. Nausea and feelings of sickness are other commonly reported symptoms. Collectively, signs and symptoms are sometimes called clinical features. Together this group of clinical features presents a ‘clinical picture’ which will indicate the presence of a particular disorder. Another common term is syndrome which describes a group of clinical features which are likely to present together. For example AIDS is acquired immunodeficiency syndrome. There is not a single presentation of the disorder but different individual features from the syndrome may present at a particular time.

History taking

Another essential component of patient assessment is history taking. It is vital that we learn all we can by talking to the patient, or to friends and relatives. This will allow us to build up a picture of the problem itself and how the problem developed. From history taking we learn what the patient has felt and is currently feeling. We learn the background to the individual and to the complaint they have. History taking from a patient is where most information comes from which allows a diagnosis to be made. This is why the ability to communicate with our patients is the most important clinical skill in assessment and diagnosis. Clearly the information gained at this stage will then go on to influence all of the future management the patient will receive. Once the clinical features and history have been assessed, various samples from a patient are often sent to the pathology laboratory. Traditionally these laboratories are divided into sections which study biochemistry, haematology, histology and microbiology.

Pathological investigations

Biochemistry examines the chemical nature of samples and identifies the levels of particular chemicals. Much of the routine work in biochemistry is involved with analysis of blood samples. Common investigations include quantification of serum levels of glucose, cholesterol, urea and electrolytes, cellular enzymes, and thyroid hormone.

Haematology is the study of blood. Common tests will quantify levels of haemoglobin and the proportion of blood volume represented by red cells. Numbers of white cells will be counted and the relative proportion of various forms of leucocytes quantified. This is called a differential white cell count and will give the numbers of neutrophils, lymphocytes, eosinophils, basophils, monocytes and platelets present. Coagulation studies are also carried out in haematology, these determine how long blood takes to clot, a common test in this area is the international normalisation ratio (INR). Reduced numbers of platelets (thrombocytes) will also lead to a reduction in the ability of the blood to clot. The type and form of red and white cells may also be determined using microscopy.

Histology is the study of tissues. Tissue samples from a biopsy or post mortem are usually fixed in wax and mounted on a microscope slide. This is then examined to determine the presence of disease in the tissue or cells. Histology can determine if a particular sample contains malignant or benign cells. Microscopic examination can detect the presence of other tissue abnormalities such as inflammation or pre-malignant change. Histology can also be used to identify where a tissue sample came from. For example, after vasectomy it is useful to confirm that the correct tube was cut and ligated. This is done by microscopic examination of a small part of the tissue which is removed.

Microbiology looks for the presence of microorganisms in a sample. This may be done by smearing the sample on a microscope slide and using a stain to identify particular species. However, more commonly bacterial samples are cultured by smearing them onto an agar plate. Agar nourishes any bacteria present and allows them to multiply, forming colonies. Once millions of bacteria are cultured in this way, their identification is relatively straight forward to the experienced eye. As well as studying any organisms present microbiologists also identify which antibiotics a bacterial species is sensitive to. This information can then be passed on to the prescriber who can give the patient the most effective antibiotic for their infection.

Other investigations

Numerous other forms of investigations may be carried out to arrive at a precise diagnosis. X-rays for example can reveal fractures and disorders of bone. They can also identify numerous lung disorders such as asthma and pneumonia. Computerised axial tomography (CAT) scanning also uses X-rays to build up two and three dimensional images of internal body structures. CAT scanning is useful as it can identify and produce images of soft tissues. Magnetic resonance imaging (MRI) uses a very powerful magnetic field to visualise internal structures. This form of scanning is particularly good at imaging neurological tissues and has the advantage of not using potentially dangerous X-rays. Another form of scanning is positron emission tomography (PET) which is a nuclear medicine technique. A radioactive ladled molecule is injected into the patient to allow visualisation of functional processes in the body.

Direct examination using endoscopy is also frequently possible. These flexible devices use fibre optics to transmit an image to an eyepiece and video screen. Specialised instruments may be passed into areas such as the stomach, duodenum, bladder or colon. Direct observation is also possible using ‘key hole’ techniques such as laparoscopy. Ultrasound scanning can also generate images of internal structures; these can be used to examine any internal organ and are used routinely in pregnancy. Ultrasound can identify numerous disorders including cysts, stones in the bladder or gall bladder and aneurysm development. In cardiology ultrasound can be combined with Doppler to give moving colour images of blood flow.

Differential diagnosis

Sometimes, even after a full assessment of clinical features, history taking and pathological examinations, a definitive diagnosis may not be possible. If there are several possibilities these are called the differential diagnosis. For example, diarrhoea and vomiting may have a differential diagnosis of viral or bacterial gastroenteritis. Headaches are another symptom with multiple differential diagnoses. Headache could be caused by such problems as psychological tension, sinusitis, migraine, head injury, subarachnoid haemorrhage, brain tumours and visual problems. Detailed study of the clinical features, history and investigation results are needed to identify the most likely cause.

Acute and chronic disease

Acute means ‘of recent onset’ as opposed to chronic which means a disease or disorder has developed slowly or has persisted over a period of time. An acute condition arises rapidly and is usually accompanied by distinctive clinical features which allow it to be recognised. So an acute pneumonia will present quickly, with the patient starting to feel ill over a few hours. There will be fever and malaise. Heart and respiratory rates are both likely to be increased and there may be a reduction in oxygen saturations. Likewise, an acute appendicitis is one which has presented ‘all of a sudden’. Acute confusion is a confusional state which has developed abruptly, perhaps overnight. Very often acute conditions require an immediate intervention, for example acute bacterial pneumonia will require immediate treatment with antibiotics. An acute appendicitis may be an indication for the surgical removal of the inflamed appendix. If the cause of the acute confusional state can be identified the condition is fully reversible and the patient will become lucid again.

Examples of chronic conditions include multiple sclerosis, chronic obstructive pulmonary disease, diabetes mellitus, hypertension (high blood pressure), osteoarthritis (wear and tear arthritis) and motor neurone disease. The clinical features typically have an insidious onset and the disorders persist over time. For example, a patient may get vague pains with stiffness in their knee and hip joints which gradually worsen over several years. The condition will progress and eventually osteoarthritis will be diagnosed. Disease progression eventually means that any movement causes severe pain and the joint becomes progressively immobile. These chronic conditions are not usually curable as many acute conditions are. However, symptoms can usually be treated to improve the quality of life. Chronic conditions therefore often require long term follow up and management. For example, a patient with high blood pressure will need to be supervised for life to ensure the blood pressure is controlled on an ongoing basis with appropriate medication. A patient with some neurological deficit after a stroke may need help with the activities of daily living for prolonged periods of time.

Disease severity is how serious the disease is and is a description of how badly a condition is affecting an individual. A mild disease will only generate mild and limited clinical features whereas a severe condition is likely to cause more extreme clinical features and might even be life threatening.

Fulminant disease

Fulminant describes a condition which occurs suddenly and is severe. For example, if there is a sudden severe impairment of liver function after a viral infection or paracetamol overdose, the patient will suffer from confusion, stupor and then coma. This form of acute hepatic failure is fulminant. Lobar pneumonia is another example; the condition can occur acutely and be very severe, even resulting in death.

Complications

A complication is a problem which presents as a result of some previously existing condition. For example, a peptic ulcer may digest through the wall of a blood vessel which will start to bleed into the stomach or duodenum. This haemorrhage is a complication. If the ulcer is deep there is a risk that it may erode through the wall of the duodenum and allow gastrointestinal contents to escape in to the peritoneal cavity. In other words, peritonitis may complicate peptic ulceration.

If a patient suffers a blood clot in one of the deep veins of the legs this is called deep venous thrombosis (DVT). If part of the clot breaks off and travels to the lungs a pulmonary embolism (PE) will result. This means DVT can be complicated by PE. An important part of patient care is to know what complications may occur in particular conditions and then take measures to prevent them if possible. If a complication cannot be prevented we should be able to recognise it as early as possible to instigate early treatment.

Bed rest, for example may be complicated by pressure sore development if we do not take active measures to prevent their occurrence. Hypostatic bronchopneumonia may also complicate bed rest, especially if the patient spends a lot of time recumbent. Other possible complications of immobility include reduction in metabolic rate, decrease in bone density and muscle mass, urinary tract infection, loss of physical fitness, constipation and psychological depression. Many of these complications can be prevented with good management strategies.

Localised or widespread disease

A localised disease process is restricted to one part of the body, for example conjunctivitis is an inflammation of the conjunctiva which lines the front of the eye. No other tissues or parts of the body are necessarily involved. Other examples of localized infection are an abscess or boil, again only a small area is affected. In contrast to this a widespread disease affects more than one area, the condition may be widespread throughout a whole organ or area of tissue. Systemic disease involves whole body systems, for example a systemic infection can affect almost all of the tissues in the body making the patient feel generally unwell.

Lesion

A lesion is an area of tissue affected by a disease process. There may be a single lesion or many. After a coronary thrombosis there will be an area of dead myocardial muscle. This area is the lesion. In multiple sclerosis there may be multiple small lesions disseminated throughout the central nervous system which give rise to the clinical features of the disease.

Disease evolution

Evolution is a term which simply means ‘change’. Any disorder will change and progress over time, this is also described as the natural history of a disorder. We often say that a disorder will ‘run its course’. This progression may be in a positive direction, evolving towards resolution. Alternatively the disorder may progress in a negative direction with deterioration and increasing severity.

A typical disease process starts when the individual is exposed to the causative agent of a disease or is injured. For example, a person may be exposed to the virus which causes the common cold. This will be followed by a period of latency, this is an incubation period when the disease will be developing but the patient does not suffer from any signs or symptoms. A good example of this is HIV infection where the period of asymptomatic (without symptoms) latency may last for several years. Next in the progression of a disease process there is a prodromal phase. In this stage the disease process had developed and is starting to make the individual feel unwell with clinical features which are usually mild and non-specific. The prodromal phase will then develop into the acute phase. This is when the presentation of the disease reaches its full intensity. How severe this stage is will vary greatly depending on the disease process and the severity of the disorder. During the acute phase the clinical features usually become more localized and specific, allowing the disease process to be recognised. This is important as specific treatments may be given once the disease is diagnosed. Finally, (unless the condition is terminal) perhaps after some further relapses and remissions, the person will enter the recovery phase. In this stage the patient regains normal health and functionality.

In the ultimate analysis there are three possible outcomes of a disease process. Firstly there may be complete recovery, with a full return to health. This is usually the case after a period of infection. We may be ill with diarrhoea and vomiting for a few days but recover completely. Secondly there may be a degree of recovery but a patient may continue to suffer some adverse effects as a result of the condition. Cerebrovascular accident (stroke) is an example of this. Individuals are often left with a degree of neurological impairment. The term sequela (sequeli in pleural) is often used to describe anything sequel, that is something occurring after a disease process. In this case the neurological impairment is a sequela of the CVA. Thirdly a disease process can lead to death. In some forms of malignant disease, where the cancer cells have spread around the body, death will be the end point of the process.

Relapse, remission and exacerbation

In a disorder that lasts for a period of time there may be relapses and remissions. Multiple sclerosis is a disease which illustrates this principle. A patient may remain fairly well for a time then relapse; this means the condition gets worse. A relapse may be followed by a remission; this is when the condition improves for a time. Remissions may be partial or complete. A partial remission represents an improvement while complete remission would be an apparent return to normal health. Exacerbation is another term which means a condition deteriorates. Patients with chronic bronchitis may suffer an acute exacerbation of the chronic condition as a result of infection. This means the clinical features, which they have all the time to some extent, become rapidly worse.

Convalescence

This describes the time when the active disease process has been treated or has run a natural course. The person no longer has the disease but may be significantly weakened as a result of the condition they have suffered from. Convalescence describes this recovery phase, after the disease, but before they have returned to full health and strength. This period may take days, weeks or months depending on the nature and severity of the disease which the individual has experienced. As a general principle rest, fluids, good nutrition and human company are the most important factors which promote convalescence. Sometimes physiotherapy and other active rehabilitation measures such as those provided by occupational therapists are needed.

Terminal disease and palliative care

A terminal illness is one in which there is no possibility of a cure. The patient’s physical condition may decline, rapidly or slowly, but death will be the end result of the disease process. Examples of terminal diseases are severe cardiac failure, hepatic failure, severe obstructive pulmonary disease, degenerative neurological diseases and some malignant disorders. In this situation the focus and philosophy of care changes from curative to palliative. Palliative care is therefore given to patients who have not responded to attempted curative interventions. Palliative care emphasizes control of pain and other distressing features generated by the disease process. There must also be a focus on psychological, social and spiritual aspects of the whole person. The aim is not to hasten death or to prolong life but to improve the quality of life in a positive way. Palliative care is an opportunity to bring the very best of our clinical skills to optimise the time a person has left and to promote human compassion and dignity.

Prognosis

Prognosis is a prediction of the probable course and outcome of a disorder. For an individual a prognosis is not a certain prediction but an expression of what is most likely to occur. The prognosis of a particular disease can be worked out by taking averages from a large number of cases. Typical terms used to describe a prognosis are ‘excellent’ or ‘good’ if the outcome is very likely to be favourable. ‘Guarded’ means the outcome is uncertain. A ‘poor’ prognosis usually means there is likely to be some ongoing problem as a result of the disease process. ‘Grave’ means the likely outcome is death.

Epidemiology

Epidemiology studies health and illness in groups and populations, as opposed to individuals. Examples of epidemiological data include mortality and morbidity rates. Mortality rate measures the number of deaths in a population, figures quoted are usually deaths per year per 1000 people. Morbidity measures the levels of illness in a population. This is usually expressed in terms of incidence and prevalence.

Incidence and prevalence

Disease incidence is the number of new cases which present over a period of time, usually measured over one year. Prevalence is the number of cases existing in a population at a particular time, or over a short period of time. This means that acute conditions which are of short duration will have a high incidence and a low prevalence. For example, there will be many new cases of the common cold in any one year, but at any one time, the prevalence may be low. Chronic disorders will have a higher prevalence than incidence. In conditions such as HIV, stable angina or diabetes mellitus, the sufferers may live for tens of years after diagnosis. This means there will be more cases present in a population at any one time than there will be new cases over a year.

Correlation studies

Correlation studies compare two variables in a population. First, health and disease data is collected and then compared with other factors, such as life style. For example, in the 1950s and early 1960s it became obvious that people who smoked were more likely to develop lung cancer than those who were non-smokers. In other words smoking and lung cancer are two variables which are correlated. Later it was discovered that people who smoke also have an increased risk of suffering from coronary heart disease (CHD), in this case the variables are smoking and CHD. Epidemiology can therefore be very useful in identifying environmental aetiological factors of disease. If we know the factors which predispose to a disease state, we can then advise people how to avoid them. Other epidemiological techniques include geographical, cohort (group) and experimental studies.

Screening for disease

Screening involves looking for the early presence of disease in people who appear healthy. If this is done, disease states may be detected at an early stage, when treatment is less traumatic and more likely to be curative than it would be with a late presentation.

Cervical cytology examines cells from the cervix and is able to detect pre- malignant changes. It is possible to remove pre-malignant tissue and therefore prevent cancer from developing. Regular dental check-ups can screen for the early development of oral cancers, and again treatment can be offered. Individuals who are considered to be at increased risk of a disorder can also be monitored closely. For example, testicular cancer is more likely to occur in men who have a childhood history of undescended testes. People who have had polyps in the colon, which can be a pre-malignant condition, may be advised to have a colonoscopy every few years.

In addition, if a disorder is identified at an early stage, further problems caused by the disorder can be prevented. Undiagnosed diabetes mellitus type 2 for example can cause the development of complications such as coronary heart disease, peripheral vascular disease, renal failure and diabetic retinopathy leading to blindness. If diabetes mellitus type 2 is ‘picked up’ at an early stage it can readily be managed, significantly reducing the risk of long term complications. Undiagnosed hypertension does not generate any clinical features, but it does damage the kidneys, blood vessels and heart. If it is identified it can be managed, greatly reducing the risk of complications. Obesity is another example, it predisposes to diabetes mellitus type 2 and coronary heart disease if present, but if it is identified and weight is lost, the risks are reduced.