Saturday, 2 November 2013


Lecture # 1b
Etiology and Pathogenesis

Etiology is the science about causes and conditions of diseases’ occurrence (from Greek words etia – cause, logos – science). The term was proposed by philosopher-materialist Democritus (470-460 years B.C.). He is the settler of causal direction in medicine.
On the broadness of comprehension of the studied events the etiology is divided into general and special. General etiology studies the general laws of diseases’ occurrence (infectious, allergic, cardiovascular, oncological diseases, etc.). Special etiology studies causes of separate diseases (nosological forms): pneumonia, myocardial infarction, diabetes mellitus, etc. Special etiology is studied by clinicians.
Cause (etiological factor) of the disease is the subject, event or factor without which the disease can not occur at any conditions. The cause is material; it interacts with the organism and gives the disease specificity.
Classification of causes.
On origin causes can be: (a) external (exogenous) and (b) internal (endogenous).
External etiological factors are: (1) mechanical (influence of events, subjects with great kinetic energy that are able at moment of contact with organism to cause the fracture, rupture, crushing or distension); (2) physical (action of different types of energy – electrical, ionizing, thermal, laser, high-frequency field, ultrasound, etc.); (3) chemical (acids, alkali, organic and inorganic venoms, xenobiotics, hormones, etc.); (4) biological (prions, viruses, bacteria, helminthes, etc.); (5) psychogenic (through second signal system, their point of action is cerebral cortex).
Internal etiological factors are inherent, constitutional, age changes; pathology of reactivity, disorders of microcirculation, salt deposits, disorders of specialized barriers, sexual disorders.
The complex factors exist for which the organism complex self-regulating systems are absent: the disease will occur every time at their contact with the organism (ionizing radiation, concentrated acids, alkali, etc.). But also factors exist that require certain conditions for the manifestation of damaging effect. These factors are called conditionally pathogenic ones. So perfection of organism regulatory mechanisms allows up to 3 kilos of microbes to persist on skin and mucous membranes.
On intensity of action etiological factors (according with I.P. Pavlov’s classification) are divided into (a) extreme, extraordinary; (b) common but acting in unusual quantities and sizes; ordinary on origin but coming out the range of organism physiological accommodative abilities (change of oxygen concentration in inhaled air, increase or decrease of environmental temperature); psychoemotional overloadings, etc.; (c) indifferent factors that do not cause diseases in majority of individuals (plant pollen, some antibiotics, domestic and industrial dust, etc.).
The risk factors also exist, presence of which in human population statistically valuably increases the morbidity with certain disease. For example, risk factors for atherosclerosis are lipid metabolic disorders, changes of blood plasma content, arterial hypertension, age, gender, obesity, hypodynamia, stresses and inherent factors.
There also social factors connected with social activities and level of economical development. It is possible to separate diseases of civilization and diseases of backward countries. Atherosclerosis, myocardial infarction, arterial hypertension, neuroses are diseases of civilization; infectious diseases, protein-caloric insufficiency, kwashiorkor are diseases of backward countries.
Pathological disorders can occur due the absence of some substance, e.g. due to the lack of oxygen, vitamins, minerals, iron, copper, etc. For example, beriberi is connected with lack of vitamin B1 that leads to increased level of choline estherase and to destruction of acetylcholine.
The cause is specific. But, depending on the peculiarities of physiological changes in organism systems and organs, the same infectious factor, for example streptococcus can cause erysipelas, angina, abscess or sepsis.
However this can not be the argument for negation of cause specificity. This causal factor will act on different substrates, and as it is known, the entry of infection has the decisive value at development of many diseases. And it does not matter that alive substrate is reacting specifically on specific action. The result of interaction between the same bacterial toxin and components of different tissues will be different. The occurred damage will be causally connected exactly with certain damaging agent that will determine the nosological specificity of pathological process. However it does not mean that different diseases have the same etiology, because the damaging factor manifests its pathogenic action in different conditions which are significant moments in etiology of numerous diseases.
The damaging action of many causes is possible only at certain state of the organism that is formed under the influence of large amount of environmental factors that are weakening the organism, but are not causing the damage of physiological mechanisms. As a result of such changes in the organism status even some common irritant can transform to pathogenic one. Such type of complex interrelations is characteristic for occurrence of many human diseases. As a whole, we can count that disease is caused not by one sole factor but by set of them, and only in this aspect it is possible to speak about polyetiology of diseases. In medicine polyetiology is understood in such sense that various etiological factors can lead to development of the same pathological process. For example, the cause of pneumonia – lung inflammation as nosological unit – can be viruses, staphylococci, pneumococci, fungi, radiation, aspiration, venoms, etc. However if we are speaking about concrete individual, the principle of polyetiology is not true. In such case the only right thing is the statement that ‘one disease has one cause’; at absence of what the concrete disease will not occur at all the rest equal conditions. So the conditions are not obligatory for the development of the disease. The reproduction of the same disease by different methods testifies to the presence of undifferentiated cause in every this method. Such differentiation is prevented by such fact that every external factor able to induce the disease is counted to be the cause. Grounding on this, they say that the same disease can be caused by different causes. But is it true to state, for example, about polyetiology of burn, if it can be caused by sun rays, burning match and hot iron? Or does it matter in the shin fracture occurrence the variety of steel crowbar, pine log or car wheel properties? Apparently no. In all these cases the damage of living substrate is caused by one cause which materially has different expression.
Factors influencing on occurrence and development of the diseases, are named conditions. None of such factors is absolutely necessary for disease development. The conditions can be external and internal, favorable and unfavorable. External unfavorable conditions are malnutrition, incorrect daily regime, heat, humidity, cold. The internal unfavorable factors are gender, inherent predisposition, carried diseases, infancy, elderly age, pathological constitution, diathesis, immune defects. It is necessary to mark that there are the conditions increasing the action of cause, and there are conditions decreasing the action of cause.
The irritant (cause) and reacting system (organism) in the act of interaction form the dialectically controversial unity: the external action is always interpreted through the specificity of internal (reactive) organism properties. It is quite appropriately that medicine could not at once totally understand all sides of this unity and at first studied it one-sidely, partially – either from the side of irritant properties (external action) paying attention dominantly to the changed caused in the organism by different external actions (cause), or from the side of organism, its internal properties, paying attention dominantly to the organism reaction on different external influences.
The first point of view allowed concluding that cause is everything and organism is nothing. This is mechanistic interpretation of causality that has received its classical completing in monocausalism. This theory is materialistic and metaphysical.
The second point of view is that organism is all and cause is nothing. The reflection of such point of view can be seen in conditionalism, according to what there is no main cause in occurrence of the disease, it develops on combined action of equal factors – conditions (supporters of this theory were Fervorn in biology, 1907; Mach and Hanseman in medicine, 1912); in psychosomatics and freudism with their thesis that ‘organism is somatic fate of pathology’. Conditionalism is based on the Mach’s theory who thought that substance as objective reality did not exist.
Constitutionalism says that the decisive significance in occurrence and duration of diseases belongs to inherence and constitution of organism, to inherited complex of morphofunctional peculiarities.
Wholism (from Greek word holos – whole) is based on the thesis that ‘life is directed by some spiritual essence, non-cognitive factor of wholeness that defines human health and diseases.
Psychosomatics originated from psychoanalysis as the method of human mental activity study used during practice by Vienna psychoneurologist S. Freud. Initially psychoanalysis was applied for study of deep psychology and for treatment of neuroses, and then it was used in fields far from medicine. For the explanation of occurrence of different diseases S. Freud was searching for 3 kinds of etiological factors: (1) condition; (2) provoking additional causes; (3) specific causes and endogenous factor – type of human personality by Freud: (a) oral cannibalistic; (b) anal sadistic; (c) phallic. According to Freud’s theory, there are three main mental systems: instinctive ‘it’, subconscious ‘me’ and ‘conscious ‘super me’. Among the scientists in psychosomatics there is no unity in understanding of Freud’s ideas, of mechanism of pathological process occurrence, its essence, however the certain group of psychosomatics use to think that the essence of the disease is conflict situation that occurs in system ‘Me’, ‘It’ and ‘Super Me’ and subconscious beginning is leading one.
Pathogenesis (from Greek words pathos – damage, genesis – development) is the science that studies mechanisms of development, duration and outcome of diseases, pathological processes and states.
Pathogenesis can be special; it studies mechanisms of separate pathological reactions, processes, states and diseases (nosological units). Special pathogenesis is studied by clinicians, discovering the pathogenesis of concrete diseases in concrete patients, for example, diabetes mellitus, stomach peptic ulcer, etc.
General pathogenesis supposes to study the mechanisms, general laws based at fundamental of typical pathological processes or separate categories of the diseases (inherent, endocrine, oncological, etc.).
General and special pathogenesis is tightly interconnected. The study of pathogenesis is reduced to study of so called pathogenetic factors; the wholeness of diseases’ essence and their outcome cognition depends on pathogenesis reveal.
During the disease development at action of etiological factor, damage, breakage, destroying process and reactive changes in organism are observed – these are defensive, accommodative, compensatory processes, pathological (emergency) functional regulation. During the disease development processes of damage and reparation are tightly interconnected and can be hardly separated. So, pathogenesis of disease is complex chain process that is accompanied with occurrence of new forms of life activity in ill organism. These new forms occur during the development of the disease, i.e. during pathogenesis. Naturally determined development of pathogenetic chain is not some set automatic mechanism that is not manifested until the certain time, but it reflects the consequence of structural and functional relations’ damage inside the system. So pathology and damage are spreading in accordance with physiological laws, shifting them. For example, damage and stenosis of mitral valve causes pulmonary congestion, pneumosclerosis, hypertrophy of left atrium, hypertrophy and dilatation of right ventricle, congestion in inferior vena cava, liver, etc. So organism has no special protective from damaging action mechanisms that differ from physiological mechanisms, directed on self-preservation, that are named protective-compensatory ones.
Connection of cause and pathogenesis. (1) Cause includes pathogenesis (burns, radiation sickness, trauma, etc.). (2) Cause and pathogenesis (infectious diseases). (3) Persistence of etiological factor (bacterial carriage).
In order to study pathogenesis of the disease in details it is necessary to study damage manifestations on all levels: molecular, cellular, tissue, organ and organism, because only in certain cases the damages can be distinguished by the naked eye (traumas, wounds). In majority of cases the special approaches to their study are necessary. It is necessary to remember that products of tissue damage are the sources of new damages, i.e. etiological factors of the 2nd, 3rd and 4th orders. Protective and accommodative reactions always develop secondary, in response on the damage. They develop and proceed always at different levels beginning from the molecular one and ending at the level of the whole organism. At the beginning of the disease the protective-accommodative (compensatory) processes develop on molecular and cellular levels. If action of pathogenic stimulus is short-lasting and low intensive, then the disease of the whole organism will not develop. If the action is intensive, then the responsive reactions will be more potent. Emergent functional regulations will occur at the background of developed damage.
Adaptive mechanisms. Adaptation means accommodation to the changing factors of external and internal environment. In physiological conditions numerous adaptive mechanisms are functioning: increase of diuresis at drinking of large amounts of liquid, tachypnea and tachycardia at physical loads, decrease of sweating at overcooling of organism, etc.
The urgent (primary) or long-lasting primary mechanisms can switch on at the action on the organism of pathogenic stimulus: vascular spasm at blood loss and RBC outcome from blood depots, increase of hemoglobin affinity to the oxygen and change of oxyhemoglobin dissociation curve at hypoxia, etc.
Protective mechanisms are directed on the barring of access to the organism of microbes, pathogenic agents (on their limitation, fixation, neutralization, destruction or quick extermination). This is performed by normal antibodies in blood, lysozyme in saliva, hydrochloric acid in gastric juice. Protective mechanisms are coughing, vomiting, diarrhea. Liver can destroy many exogenous and endogenous types of venom.
Compensatory mechanisms can be primary and secondary ones. So, in highlanders the increase of RBC count, circulating blood volume and pulmonary hypertrophy are observed. The myocardial hypertrophy develops in the patients with heart disease. The weakening of cardiac contractive activity is observed at 5th-9th day after myocardial infarction that prevents muscular rupture due to myomalation.
Protective-accommodative reactions sometimes can be so intensive that it is harmful for the organism: exceed fever, intractable vomiting, proliferation, etc.
Decrease of manifestation possibility, development of compensatory reactions is especially clearly seen at cerebral trauma or at general narcosis. Besides this, at pathology one type of connections (nervous and humoral) are damaged and another ones (emergent) are switching. Emergent regulation is always unprofitable to the organism or exhausts its energetic resources: development of protective inhibition at cerebral cortex at shock, profuse sweating at overheating with disturbances of water-salt metabolism, etc.
The main leading link should be separated in the pathogenesis of diseases. The main link is that one, without which the rest ones are not developing, if the main link is eliminated, the disease will not develop. For example the main link at myxedema is lack of thyroid iodine containing hormones, if they are injected the disease will not develop. At 1st type of diabetes mellitus the main link is lack of insulin.
However the organ of systemic functional disorders occurring at development of the disease can become the causes of disorders by themselves, i.e. cause and consequence are exchanging with places. This state in pathology is named circulus vitiosus. The example of circulus vitiosus is ‘blood loss – circulatory and hemic hypoxia – tissue hypoxia – acute left ventricular failure – increase of circulatory and hemic hypoxia’.
Specific and nonspecific in pathogenesis. Specific one completely depends on properties and peculiarities of cause and determines main disease’s characteristics and makes the basis for diagnostic.
Nonspecific one means mechanisms of standard response on any pathogenic factor directed on increase of organism resistance to damage and are performed at participation of nervous and endocrine system. Nervous nonspecific changes (paraiosis, pathological dominant, disorders of cortico-visceral relations, neuro-dystrophic processes) and endocrine changes (general adaptive syndrome) are separated.