Just what do we mean by ‘disease’, how are they caused and how do I avoid getting one.

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 etiology (aetiology in English). Eetiology 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. Etiological 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.

The more we know about what causes disease the better equipped we are to avoid the cause.

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 onstruct 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 edema. 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 pediatric hypothyroid syndrome (formally called cretinism) and goitre (swelling in the neck).

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’.