A Theory of disease

By Carl - Fredrik Bassøe A new empirical clinical model gives rise to a theory of health and disease, the diagnosis equation d=e+o+p and a formula that generates systematic diagnosis.


The model cleans up earlier inconsistent use of the important clinical terms etiology, virulence, disorder, pathogenesis and disease. In terms of briefness and versatility the equation d=e+o+p levels with K=ma, PV=nRT and E=mc2. The disease theory may have a profound impact on future clinical medicine and medical AI. Further details are available under publications.

Introduction

The fragmentation of modern medicine creates many problems. Lay people do not understand detailed medical information available on the Internet simply because they lack general medical knowledge. For them medicine appears a bewildering conglomerate of disparate sciences.


Primary care physicians need knowledge on all medical specialties, but the enormous amount of knowledge presently available is impossible to survey. Occupational medicine has difficulties combining environmental data with bodily disorders. Specialists cope well with knowledge within their narrow domains, but have difficulties with collaboration because a unified interface to exchange knowledge with other specialists is unavailable.


These difficulties may be lessened by an empirical clinical model (CM).The biopsychosocial disease model gained wide acceptance in clinical medicine(2,3,6,7).


However, the model is very broad and does not guide, recommend or restrict features of the clinical domain(5) and it is rarely used in research(1). In addition, it lacks crucial clinical concepts such as etiology, virulence and pathogenesis. The following is a brief summary of CM and a theory of disease that emerges from it.

Etiology

Etiology is external to the individual in space and time. It defines the environmental causes of disease including heredity. Etiological agents target and damage one or more body parts or cell types. These body parts are called the primary affected body parts.


The accessibility to and the degree of damage are rated by the agents’ virulence. Thus, an agent is more virulent than another if it causes more damage to the primary affected body part than the other agent. The structure and function of body parts are influenced by the intake of vitamins, sugar, fat, and the molecules that make up our genes and proteins. Many disorders arise from malnutrition. Others are caused by microorganisms, allergens, radiation, sound and social strain

The general body part

Body parts vary from complex structures like the brain and liver to simple organs like the adrenal glands and individual muscles. All body parts consist of parenchyma and connective tissue.


The parenchyma are the cells that perform its specific functions. Thus, liver cells (hepatocytes) make out the parenchyma of the liver. One of their functions is the secretion of the protein albumin. Many body parts have a tube and a cavity.


The liver has small bile tubes that transport bile to the larger bile tract tubes and from there to the gallbladder. Slits are cavities with a small volume. Typical examples are the slits surrounding the heart and lungs.


The general body part is an abstract class with parenchyma, connective tissue, tubes and cavities/slits. Particular body parts are (partial) instances of the general body part.


For example, the adrenals are particular body parts without tubes and cavities/slits.Structure (morphology) is described by the same terms in different body parts. Typical examples are cell dissolution (lysis), programmed cell death (apoptosis) and cell death from other causes (necrosis). The suffixes trophy and plasia describe body part size and cell number.


The suffixes are combined with prefixes that describe the direction of change: none (a), too little (hypo), too much (hyper), exchanged by (meta), disordered (dys) and malignant tumor (neoplasia). These prefixes also combine with function, for example hypofunction and hyperfunction, typically arterial hypotension and hypertension.


Disordered morphology look and feel similar in various body parts. Lumps are seen and felt. The same sort of investigation identify them as benign or malignant tumors.


Disorders of mechanical functions such as heart failure and paralysis are discerned by clinical examination and blood pressure, respectively. Electrical functions manifest as epilepsy and irregular heartbeat and are examined by corresponding instruments. Different tubes exhibit corresponding symptoms and signs.


A typical symptom from many tubes is colic, which is not expressed in disorders of parenchyma and cavities. Tubes are also investigated using corresponding methods such as inspection (scopia) and radiological methods (graphia).


A similar correspondence is characteristic for parenchyma, connective tissue and cavities. These correspondences lead to similar clinical decision-making across medical specialties.


The general body part has mechanical, electrical, metabolic and certain specialized functions. The prefixes described above give the directions of functional change.


For example, hypothyroidism means diminished secretion of the hormone thyroxin by the thyroid gland. Diabetes mellitus type I is defined as diminished secretion of insulin by insulin producing cells in the pancreas. Thus, the general body part expresses the fact that all body parts have similar structure and functions.


Particular body parts specialize on crucial properties. For example, hypothyroidism and diabetes mellitus type I are treated with the addition of thyroid hormone and insulin, respectively. But thyroxin has no effect on diabetes mellitus type I and insulin does not cure hypothyroidism.

Pathogenesis

Etiological agents cause disorder in particular primary affected body parts. The latter may send signals that act on local tissue or reach other body parts. These body parts are called the secondary affected body parts.


The interaction of the primary and secondary affected body parts are collectively called the pathogenesis. Four examples illustrate the interactions (Fig. 1).

Bacteria may irritate the capillaries (local tissue) in the primary affected body part and attract white blood cells into it. Bacteria may also stimulate the bone marrow (secondary affected body part) to produce more white blood cells.

Figure 1


A virus may cause little damage by itself. But if the altered structure on the liver cells (primary affected body part) elicit an immune reaction (secondary affected body part) then immune cells may attack and destroy the liver cell. Both the virus and the immune cells are observed in the primary affected body part.


Whether a mechanical injury or tuberculosis damage the pituitary gland (primary affected body part) the results of defective pituitary function are the same. The pituitary stimulates several other body parts. The secondary symptoms stem from diminished function of the thyroid, adrenals, gonads, the mammary gland and skeletal growth (secondary affected body parts).


Hereditary brain damage (primary affected body part) can cause diminished voluntary motor activity (behavior) and create disorders of the autonomous nervous system. Thus, epilepsy may be accompanied by attacks of sweating or heart rhythm changes (secondary affected body parts).


Local reactions

The activity of any body part is affected by processes in its connective tissue. Inflammation is a local tissue reaction characterized by expanded capillaries (edema). Thus, redness and swelling are clinical hallmarks of inflammation. Scarring means that the normal tissue is replaced by connective tissue. Scarring occurs in all body parts and leads to permanent loss of function.

Blood circulation

The arterial circulation supplies body parts with nutrients and regulators. Occlusion blocks the supply of nutrients and the tissue dies (infarction) and the body part loses some or all its functions. Stroke and heart infarction are common examples. Widespread heart infarction can cause sudden death.

Veins clear away waste products produced by the cells. A blood clot (thrombus) can occlude veins and stop the drainage of fluid from the body part, which swells up. A feared complication is the tearing loose of blood clots (emboli) that are transported to the lung and block the lung circulation. Large emboli can cause sudden death.

Metabolism

The blood concentration metabolites depend on digestion in the stomach and intestine, absorption by intestine, uptake into blood, uptake into body cells, secretion from body cells and excretion by glands, stool and the kidneys. Metabolism is crucial to growth, maintenance and parenchyma function.

Regulators

Circulating regulators (hormones, growth factors, interleukins, cytokines,…) stimulate or inhibit cell proliferation, maturation and function. Lack of stimulator manifests as hypofunction and atrophy. Too much stimulator leads to hyperfunction and hyperplasia.

Immune reactions (IR)

Five different IR protect us from infections by attacking and killing microorganisms (bacteria viruses, fungi) and larger intruders (worms, other parasites). Various IR attack different types of microorganisms.


For example, pyogenic bacteria trigger IR3 with pus formation. Pus becomes green when exposed to air and is diagnosed by its color.Autoimmunity and allergy occur with all five IR.


Autoimmune IR may destroy a body parts’ cells and decrease its function(s). However, autoantibodies may stimulate the function of the parenchyma that they attach to. Allergy is the collection of IR geared towards simple or complex chemicals.

Neural connections

Psychosomatic disorders may cause rapid heart rate (tachycardia) and rapid breathing (tachypnea). The peripheral response is reported back to the mind and felt as unpleasant.


Conversely, somatopsychic reactions are caused by disorders in some body part (cancer, infection) that activate nerves and signal pain or nausea.

Disease and diagnosis

A disease is defined by a set of patients with the same symptoms, signs and supplementary (laboratory) findings. A diagnosis such as Staphylococcal endocarditis refers to a disease.


Systematic diagnoses convey knowledge and information on diseases. Two diagnoses, one pertaining to mechanical injury and the other to social interactions, carry different information on the cause of a disease.


Clinical decision-making

Systematic, well-formed clinical diagnosis determine treatment, follow up and prognosis. For example, poisons, microorganisms and social problems warrant different investigations and actions.


The ten categories of etiological agents can be discriminated by the clinical history and simple investigations. If the investigations do not lead to an etiological agent then the etiology is essential. Pathogenetic mechanisms are identified by their own inclusion and exclusion criteria.

Disorders of morphology and function are identified by similar methods in various body parts. The identification of the particular parenchyma, tube and cavity/slit occurs without interference from the etiology and pathogenesis.

The concepts pre, subclinical and latent refer to patients with laboratory values beyond the reference range without manifestations of disease. These concepts are unified by ‘degree 0’.


Manifest disease is ordered in severity by integers 1-4. CM defines the duration of (acute,…) and prognosis (benign,…) of all diseases in the same way.


A theory of disease

We are now able to put the pieces into a theory of disease based on etiology E, disorder O and pathogenesis P (Fig. 2).



Availability

The disease theory is implemented in an online model and as an application for clinical decision-making. The application aims to support health professionals and give lay people access to medical knowledge and generate diagnoses.

References

  1. Engel GL. The need for a new medical model: A challenge for biomedicine. Science. 1977;196:129-36.

  2. Engel GL. The clinical application of the biopsychosocial model. Am J Psychiatry. 1980;137:535-44.

  3. de Lusignan S. What is primary care informatics? J Am Med Inform Assoc. 2003;10:304-309. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC181979/ (Accessed 2017/11/9)

  4. Jull G. Biopsychosocial model of disease: 40 years on. Which way is the pendulum swinging? Br J Sports Med. 2017;51:1187-8. http://bjsm.bmj.com/content/51/16/1187.long (Accessed 2017/11/9)

  5. Sulis WH. Modeling Stochastic Complexity in Complex Adaptive Systems: Non-Kolmogorov Probability and the Process Algebra Approach. Nonlinear Dynamics Psychol Life Sci. 2017;21:407-40.

  6. Wulff HR. Clinical decisions in a philosophical perspective. Tidsskr Nor Legeforen. 1993;113:2816-8.

  7. Wulff HR. Clinical decisions in a philosophical perspective. Tidsskr Nor Legeforen. 1993;113:2816-8.

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