PATHOLOGICAL PHYSIOLOGY
AS A SCIENCE
September 19, 2017
General teaching on diseases
Pathological Pathobiochemistry Pathological physiology
anatomy
Pathological physiology is a teaching on diseased
functions, i.e. on etiology and pathogenesis of
diseases based on experimenting and clinical
observations including functional diagnostics.
Connection between a premorbid organism and a disease
Etiology
Etiology – is the assignment of causes or
reasons for phenomena. A description of the
cause of a disease includes the identification of
those factors that provoke the particular disease.
e.g. tuberculosis
In the etiology of particular disease, a range of
extrinsic (exogenous) factors in the environment
must be considered along with a variety of intrinsic
(endogenous) characteristics of the individual.
Pathogenesis
Pathogenesis of a disease refers to the
development or evolution of the disease.
To continue with the above mentioned example, the
pathogenesis of tuberculosis would include the
mechanisms whereby the invasion of the body by the
tubercle bacillus ultimately leads to the observed
abnormalities.
A given disease is not static, but it is a dynamic
phenomenon with a rhythm and natural history of its own.
It is essential to keep in mind this concept of natural history
and the range of variation among different diseases with
respect to their natural history.
General pathophysiology
A: Health and disease.
1. Definition of health and disease
2. Pathogenic factors (physical, chemical and
biological) and response of organism for
them (adaptation, dysadaptation).
3. Types and degree of disease.
4. Death (clinical, biological, cerebral).
General pathophysiology
B: Cellular mechanisms in pathological stages
C. Reaction on damage of tissue integrity and
infection.
1. Non-specific (innate) immunity: inflammation
2. Specific (acquired) immunity, acquired immune
diseases (immunodeficiency, hypersensitivity and
autoimmunity)
General pathophysiology
D: Growth and proliferation
1. Induction of proliferation and wound healing
2. Malignant proliferation
3. Tumour growth
E: Genetic background in etiopathogenesis of
disease
monogenic diseases
polygenic disease (complex)
Special pathophysiology
 Pathophysiology of organ systems
 Pathophysiology of organs
 Pathophysiology of tissue
 Patthophysiology of molecules
 Pathophysiology of genome
Definition of health
 Health – is a component of a general quality of
life
 To declare a person or a group diseased 
fateful consequences, broad social effects
 Law presupposes a definition of health
Concept of normality
 Most people have some notion of normal and
would define disease or illness as a deviation
from or an absence of that normal state.
 However, on closer scrutiny, the concept of
normality turns out to be complex and cannot
be defined succinctly, correspondingly, the
concept of disease is far from simple.
Normality as health may be defined
on various levels:
•Biological (physical) normality: A whole of undisturbed functions.
There are, however, non-reflected presumptions: it is not said what
is the aim of an organism. A "humanistic" definition must precede.
•Psychological normality: A well balanced result of an adequate
self-esteem (self-confidence), of spontaneity and excitability
Realistic attitude towards the aims of life and realistic individual
desires, an ability to draw lessons from experience, sociability
•Sociological normality: An ability to fulfill expectations and roles
in the frame of the existing social system
Normality of mind (spiritual): An advancement of objectivity and
reason, independency and finding ones identity, ability to love and
creativity
Normality as viewed by law (juridical): Ability to
work, lack of the necessity to be cared for.
„Ecological“ definition of WHO:
State of perfect physical, psychical and social
wellbeing, not only an absence of disease and
infirmity.
Definition of disease
Disease can be defined as
a contradiction to health = „alternative model“
or only as
a contrary term – than, there is a whole array of intermediate
steps:
- ideal health
- reasonably acceptable health
- predispositions
- feeling not well
- subclinical forms
- clinical forms
- fatal courses of disease
Normal and abnormal processes represent different points on
the same continuous spectrum.
DISEASES
 Diseases are clinically individualized entities.
When a physician says that her patient has
some disease, she is classifying some
observable clinical entity and categorizing it as
the exemplification of a nosological
theoretical entity, that is, as an exemplification
of some pathology.
 Pathology, following this approach, is an
abstract entity, but individual diseases are not
abstract. Diseases are observable entities.
DISEASES
 Pathologies are the general theoretical
categorizations of events (acute diseases) or
states (chronic diseases).
 Pathologists look for the pathological features
of some specific pathology, and they usually
look for them in cells, tissues and organs.
 Pathophysiology describes and explains
dynamics of events and/or states (diseases)
DISEASES
 Clinics look for the clinical features of some or
several diseases or morbid conditions in their
patients. Patients are possibly diseased, sick
individuals and they are objects of medical
attention. It is not by chance that clinicians use
‘disease’ (the term) and not ‘pathology’ in
their professional practice. Etymologically,
‘disease’ comes from the Middle English (and
from Old French, desaise) as a fused word of
‘dis’ and ‘ease’.
DISEASES
 Diseases are happenings in the course of some
individuals' lives. This is just what makes it
possible to describe their epidemiology in two
different ways: we can describe the distribution
of diseases numerically in a given population
at a specific time (the prevalence of the
disease) and we can also describe numerically
the occurrence of new appearances,
emergences or happenings of some disease
after some time (or up to some time, like up to
the present time).
DISEASES
 This second kind of epidemiological
description, incidence, is possible just because
diseases are (or at least can be) events.
 Diseases are things that happen in (or with)
living beings (animals or plants). Following the
Aristotelian jargon, diseases are things that
occur or happen in or with living individual
substances: human beings, individual animals
or plants.
DISEASES
 Diseases can be local (restricted to tissues or organs) or
systemic, and they can also be acute or chronic.
Acute diseases can be serious or not, benign or malign,
the same with chronic diseases.
 But chronic diseases have the special characteristic
that once they install themselves in the organism they
persist over time. This is not a matter of convention. It is
an essential (real) characteristic of chronic diseases
that they represent changes in the physiology of the
individual that worsen her capacity to fight against
several other external or internal threats. The
consequence is actual unhealthiness.
DISEASES
 Chronic diseases sometimes represent an actual significant persistent
change in the organism's general state; they can change the organism's
state from a healthy to an unhealthy one. In the case of acute diseases,
the change is not necessary; it is a matter of probability.
 Acute diseases are causes of unhealthy states, but in some cases, the
acute disease is a healthy and functional process (acute gastroenteritis
and food poisoning diseases, for example, are acute processes that
represent the organism's attempt to eliminate poisons or microorganisms,
so as to prevent chronic damages and illness; so the aim of those
diseases is to re-establish physiology). Acute diseases are causes of
unhealthiness only if the outcome is death, a chronic disease or other
chronic harm. In this case, the disease ceases to be acute.13 Chronic
diseases are also causes of unhealthiness, but the difference is that they
remain actual in the organism during the now dysfunctional state. In the
case of acute diseases, once one has changed the actual state of an
individual from a healthy to an unhealthy one, the acute disease has
transformed itself into another condition: a chronic injury, some chronic
disease or a permanent disability.
DISEASES
 Chronic diseases are also causes of unhealthiness, but
the difference is that they remain actual in the
organism during the now dysfunctional state. In the
case of acute diseases, once one has changed the
actual state of an individual from a healthy to an
unhealthy one, the acute disease has transformed
itself into another condition: a chronic injury, some
chronic disease or a permanent disability.
Definition of disease (BUCHBORN)
 „Feeling of bad health as a result of subjective
and/or objective somato-psychical derangement,
with/without subjective, medical or social need for
help, as a result of disturbances in harmonic
cooperation of individual functional parts and
subsystems of an organism“
a patient's point of view
(aegritudo, illness)
a doctor's point of view –
objective in a medical
description (nosos, disease)
a point of view of the social
milieu (a state of need and
deficiency)
A superposition
of three aspects of
a disease in
medical practice
(together: "morbus")
The concepts of health and disease relate
to both natural and cultural phenomena
Stages of disease development
 Symptoms (prodromal stage)
 Acute disease (1-21 days)
 Chronic disease (above 40 days):
- following after acute disease (chronic bronchitis
in smokers)
- primary chronic (e.g. Wegener´s
granulomatosis)
A complication of a disease – is a new or separate process that
may arise secondarily because of some change produced
by the original entity
Recovery
Remision
Exacerbation
Relaps
Residual disease
Identification of health and disease
 Interindividual
variability  health
and disease are
probabilistic, not
strictly deterministic
phenomena;
 a diagnosis is a task of
a statistical type.
If only because of diagnostic aims, we must be well aware of the
enormous extent of the interindividual variability among people.
Qualitative and quantitative traits in population
Traits
qualitative
quantitative
countable
metrical
We are interested in frequency distributions of quantitative
traits – a starting point for determining s.c. normal (=
reference) values
A way of determining reference („normal“) interval
If only small factors are
at play, one can speak on a
homogeneous set. The
difference
between „large“ and
„small“
factors is only relative,
depending
on the total number of the
factors
Involved.
Large and small factors, influential and noninfluential
factors, homogeneity of samples.
It is advisable to distinguish large and small factors creating the
distributions.
A large (big) factor is something what acts beyond the
mechanism of the origin of a normal distribution. It disturbs the
homogeneity of factors prescribed by this mechanism. One of the
levels of the large factor must have a gross effect upon the trait, it
must "move" the position of the trait in the affected individual
strongly "to the right" or "to the left". Now, because of the blurring
effect of the other factors, the result is as if the large factor
created "its own" distribution, sometimes hidden in the general
population.
Small factors correspond roughly to the prescription for the normal
distribution. Their set creates something as a homogeneous set
and correspondingly a homogeneous distribution arises
Large rare factors form small
distributions on the
sides of the general distribution, a
large common factor
would strongly „move“ a large
segment of the population
(a rare situation – e.g., G6PD
polymorphisms); small
factors produce by their
combinations a homogeneous
subset of the whole population. A
„philosophy“ of the
normal = reference interval of the
diagnostic signs leans
on an idea that the given disease
acts as a large factor
producing its own subdistribution.
Ideally, we should know
a probability (P) with which a
specific level of a sign falls
into „healthy“ or „pathological“
distribution
Features relevant from the point of view of health/adaptation are
exposed to selection pressures.
A population may get beyond the adaptation optimum after
the conditions have changed – typically in s.c. complex diseases
As far as the population is not too
far from the optimum
(of the feature given), typical Ucurves
may take place:
either symmetrical around the
population modal value
(e.g., mortality as dependent on
hematocrit),
or shifted beyond the modal
value (a genotyp in
imbalance with the environment
in civilization diseases – blood
pressure, plasma
cholesterol etc.)
Normality conception and its role in diagnostics
„Normal“ is currently a condensed term for „common and therefore
healthy“: it is used so when we try to define health in a
descriptive-statistical way. Those who derive health according to value
criteria could do without it easily, using independently terms „healthy“
and „common“ according to the circumstances.
Statistical norms for health are set according to the value criteria valid
in the particular time and place; it is a secondary step following the
value decision.
There is some arbitrariness in the normative definition, namely according
to the shared interesses prevailing in the particular era and place, and
according to different viewpoints:
of insurence medicine (expected life span)
of preventive medicine (profylaxis of complications)
of epidemiology (weighting of risk factors) etc.
A way of determining reference („normal“) interval
Preinstrumental error (e.g., a way of blood withdrawal)
Instrumental error (dispersion of readings and/or systematic
error, e.g.,
 with a spectrofotometric determining of stuff
concentrations)
Intraindividual fluctuations of the variable measured. The
person counts to the 5% of healthy individuals who are
used to be excluded from the reference interval
definitorically
-Eufunctional extreme (individual norm cannot be defined)
A real pathology
Factors leading to deviations from normal interval
Essential pathophysiology questions:
 How?
Why???
http://www.med.muni.cz/patfyz