Introduction to Pathophysiology as
an integrating medical discipline
Etiology and pathogenesis of disease
Definition of health vs. disease
Problem of normality in medicine
Pathophysiology (PP) as a medical discipline
• medical science dealing with the study of disease
– physiology = how the healthy body works
– pathophysiology = how the ill body works (or does not)
• PP is “physiology of altered health”
• PP explains functional consequences of a disease process
• PP studies namely two processes
– disease etiology – i.e. what causes disease to develop
– disease pathogenesis – how the disease develops
– disease pathology – what anatomic changes disease produces
• PP bridges basic medical sciences with clinical medicine
– experimental approach
• molecular biology, genetics, immunology, …
• models (in vitro, animals, simulations)
• human samples (DNA, proteins, fluids, tissues)
– clinical trials
• observational studies
• interventional studies
WHO definition of health
• Health is a state of complete physical, mental and
social well-being and not merely the absence of
disease or infirmity.
– Preamble to the Constitution of the World Health
Organization as adopted by the International Health
Conference, New York, 19-22 June, 1946; signed on 22
July 1946 by the representatives of 61 States (Official
Records of the World Health Organization, no. 2, p.
100) and entered into force on 7 April 1948.
• The Definition has not been amended since 1948.
Distinction between health and disease
• stating disease can have a profound mental, social,
economic and philosophical consequences for the
individual
• however, distinction is not always easy
– see further interindividual variability and normality
• disease is perceived both subjectively
– “I am not feeling well”, anxiety, fear, failure, …
• objectively by medical specialists
– to some extent independently from the subject
Two approaches to definition of disease
• neutral
– each organ and organ system in our body has its
function and the function is impaired than there is a
disease
• does not take into account the subjective feelings of a
subjects
• more close to the current medicine paradigm
• normative
– if the person is not limited by his/her condition and can
achieve the desired goals than he/she is healthy
• blindness or autism is not a disease if the person suffering
from it does not feel limited in any way
Disease etiology
• endogenous = internal factors
– congenital
• genetic (monogenic as well as polygenic)
• malformations due to prenatal exposure to viruses of toxins
• fetal programing
– acquired
• metabolic
• immune
• circulatory
• neoplastic
• exogenous = external factors
– physical
• mechanical, thermal, irradiation, electricity, …
– chemical
• xenobiotics incl. drugs
• toxins and poisons
• environmental contaminant
• smoke
• excess or deficit of nutrients
– biological
• infections (bacterial, viral, fungal, parasites, …)
• toxins
• prions
– psychological and social
• mental trauma
• stress
majority of
diseases are
multifactorial
in origin
Diseases from one single cause vs. multifactorial
• Monofactorial
– one single cause potent enough to cause disease
– environment and lifestyle play generally minor role
– examples
• trauma
• highly virulent infection
• monogenic disease
• Multifactorial (= complex)
– products of concomitant exposure to internal and external factors with
typically equal role of both, so called “diseases of civilization”
– examples
• obesity
• diabetes
• atherosclerosis
• allergy
• cancers
Disease pathogenesis
• Response of the body to the action of etiological factor(s)
– adaptation = no disease
– dysadaptation = disease
• Pathogenesis of disease
– sequence of molecular, cellular, tissue and organ events taking
the place from the initial contact/exposure to etiological factor(s)
until the expression of disease
– organ-centered
• limited to a single organ (system)
• however, usually only at the beginning of the disease
• later , majority of diseases becomes systemic, i.e. having systemic signs
– for example tumors, liver steatosis and fibrosis, …
– systemic
• some disease are widespread
SYSTEMICORGAN-SPECIFIC
Common misconceptions
• Atherosclerosis might be cited
as a etiology of coronary artery
disease
• However, progression of the
process from initial clinically
unapparent lesion (fatty streak)
to manifest occlusive vessel
disease is a continuum of
pathogenesis
• the very cause(s) of
atherosclerosis are generally
unknown and subjects of
research with many identified
etiologic contributors
– external – diet, exercise, smoking,
– internal – genetic susceptibility,
metabolic, inflammation, …
Clinical manifestation of diseases
• diagnosis of diseases is based on the recognition and
proper interpretation of diseases manifestation
– symptom = feature recognized subjectively by the patient
– sign = objectively noticeable
• physical examination
• diagnostic method (laboratory, X-ray, ultrasound, …)
• typical cluster of signs and symptoms present usually
together creates a syndrome
– however, many conditions can present by the same
syndrome, therefore one must test multiple working
hypotheses as to what led to this particular state =
differential diagnosis
Pathophysiology vs. clinical medicine
pathophysiology is inductive
clinical medicine is deductive
Natural history of disease
• refers to the progression of a disease process in an
individual over time in the absence of treatment
• this is how the PP is usually taught
etiology pathogenesis
Clinical course of the disease
• “disease background”
– individual constitution (incl. genetic susceptibility and lifelong fitness)
matters, i.e. the same etiological factor will not have the same effect in
various people
– risk factors
• variable exposure due to environment (incl. geographical location, altitude, climate
etc.), individual lifestyle, history and social habits etc.
• pre- or subclinical stage
– prodromal – usually unspecific signs of upcoming disease
• e.g. fatigue, weakness, anorexia, pain, fever,
• acute illness (limited number of days, can be 1 day to 1 month)
– severe but self-limiting
• chronic illness (longer that typical pro given disease)
– long term, continuous process
– follows the acute stage
• disease was not eliminated completely due to various reasons (e.g. immune deficiency)
– chronic from the very beginning
• e.g. due to pathogen making itself inaccessible, or targeting the very means od body
defense
Chronic disease
• Exacerbations = aggravation of symptoms, signs and severity of disease
• Remissions = lessening of severity
• Remission = disappearance of disease induced by treatment however with
the risk of reoccurrence
– e.g. cancer – with current methods we cannot be sure we eliminated all
cancer cells
• Residual disease = detectable with lab test but not by symptoms and
clinical signs
– e.g. leukemia – PCR detection of genetic changes typical of leukemic clone
but otherwise patients appears healthy
• Carrier status = patient harbors the microorganism but may have few or
no symptoms, clinical or laboratory signs
• Complication = possible adverse
extensions of a disease in spite of
the treatment
Diagnosis of disease – problem with “normality”
• trait used as diagnostic
parameters
• qualitative
– alternatives yes/no
• e.g. cleft palate, congenital valve
disease etc.
• quantitative
– measurable
– continuous distribution in
population
– typically influenced by many
factors
– problem to distinguish what is
normal and what is not
• mean ± 2 SD
• alternative vs. continuous
model of disease
Distribution vs. selection (mortality) Diagnostic tests
• diagnosis is performed using various ways
– personal history
– clinical examination
– instrumental and laboratory test
• requirements on diagnostic tests
– reproducibility = repeated measurements give equal results
– validity = the extent to which measurement masures what is
intended to measure
– specificity = % of subjects free of disease correctly identified as
negative (= true negativity)
• 95% specificity = 95 out of 100 healthy people is diagnosed as healthy,
5% je false positivity
– sensitivity = % of subjects with diseases correctly identified as
ill (= true positivity)
• predictive value of diagnostic test
• biomarker
– measured characteristic which may be used as an indicator of
the probability of development of diseases or complication
Practical notes
• http://www.med.muni.
cz/patfyz
• literature:
– Pathophysiology
(Damjanov I), Elsevier
2009
– Essentials of
Pathophysiology (Porth
CM), Lippincot W&W
2007