Introduction

General etiology. General pathology. Cell

injury. Cellular pathological processes

Author: Lilia Tacu,

univ. asist.,
Department of
pathophysiology and
clinical pathophysiology
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 What is the pathophysiology?
· it is a science which study
general laws of origin, onset,
evolution and resolution of
pathological processes and
complex of biochemical,
morphological and functional
changes at the molecular, cellular,
tissular, organ and system level.
•Pathophysiology – gr. pathos = disease,
pain, suffering; logos = science
What is the pathophysiology?

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HISTORY OF PATHOPHYSIOLOGY
· Hippocrates (460-370 BC)- he
was the first to construct theories
of the causes of disease based on
what he had observed in his
patients
· His fundamental truth: „there
are two factors acting alone or in
combination, which cause illness
– the intrinsic or constitutional
make-up of the person, and an
extrinsic or environmental
agent“, is still valid.
 HISTORY OF PATHOPHYSIOLOGY
• Cornelius Celsus (53 BC-7 AD) cardinal signs of inflammation—
rubor (redness), tumor (swelling), calor (heat), and dolor (pain)

• A.F. Hecker / 1790/ -author„Textbook in pathophysiology

• C. Bernard (1813-1878)-Introduction to experimental
medicine (1865)
• Galliot /1819 / - author of„Manual in general pathology
and pathological physiology“
• Rudolf Virchow (1821 - 1902) - he introduces term
„pathological physiology“ to medical terminology, Father of
pathology’
‘Father of clinical pathology’ is Paul Ehrlich; ‘Father of
blood transfusion’ is Karl Landsteiner; ‘Father of cytology’
is George N. Papanicolaou
 COMPARTMENT OF PATHOPHYSIOLOGY

Pathophysiology

THEORETICAL GENERAL SPECIAL CLINICAL

Typical pathological
processes = the
alphabet of pathology Pathophysiolo
GENERAL
CELLULAR (apoptosis, gical Pathophysio
NOSOLOGY
necrosis, cell dystrophy) mechanisms logical
ETIOLOGY
PATHOGENY TISSULAR (hypertrophy, of disorders mechanisms
SANOGENESIS atrophy, fibrosis) with a of every
STRUCTURE OF ORGAN (inflammation, characteristic disease
DISESE allergy) localization. separately
CLASSIFICATION OF INTEGRAL (acid-base
DISEASE imbalance,
DISEASE PERIODS
hydroelectrolytic
changes, metabolic
disorders)
 Etiology= cause of disease

A compartment of theoretical physiopathology

which studies the cause and conditions of disease.
Cause of disease versus conditions
CAUSE OF DISEASE= CONDITION OF DISEASES
ETIOLOGICAL FACTOR any substance, energy or
– any substance, information which doesn’t
energy or induce disease but can
information which favors or impede the action
acting on the body of the cause
structures induces
functional, structural
and biochemical
dyshomeostasis. FAVORABLE UNFAVORABLE
 Etiological factors
ENDOGENOUS
EXOGENOUS
- Mechanical (mechanical energy, rupture –
mechanical trauma);
- Physical (radiation, temperature: burns);
- Chemical (toxins; organic acids from bacterial
carbohydrates fermentation in the mouth);
- Biological (bacteria, viruses, parasites etc…)
- Informational (mediators, hormones, antigens
- Social (human interrelation in society)
LOCAL Isotropic action
GENERAL Anisotropic action
(hepatotropic, cardiotropic, nephrotopic, neurotopic)
 Etiology= condition of disease

ENDOGENOUS
EXOGENOUS • hereditary
• Atmosphere • constitution
• life conditions • reactivity
• professional • components of internal
conditions environment
• metabolism
• cosmic action • morphological
• alimentation particularities of the
organs

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 PATHOGENY
from Greek pathos – suffering; logos – science

How it appears, develops and ends the disease ?

Compartment of physiopathology which studies

the mechanisms of onset, evolution,
development and ending of disease.
PATHOGENIC CHAIN
PATHOGENIC FACTOR
MAIN LOOP OF PATHOGENY
VICIOUS CIRCLE
PATHOGENIC PROCESS
 Pathogenic chain = relationship between cause
and effect, where the last is transformed into
the cause
Main loop

Organ insufficiency Bleeding

Anemia

Organ hypo - perfusion

Hypoxemia

Decreased contractility, CO,

EF Myocardial hypoxia
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Closed pathogenic chain = vicious circle = relation
between cause and effect, where the last has similar
action as the first cause

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 ROLE OF BODY REACTIVITY IN
DISEASE DEVELOPMENT
REACTIVITY - ability of the body to react to every change
in order to maintain the functional, structural ,
biochemical and psychic homeostasis.
- ADAPTATIVE REACTIONS
- PROTECTIVE REACTIONS
- COMPENSATORY REACTIONS
- REPARATIVE REACTIONS

- The pathologic reaction is an elementary act of the body

induced by the pathogen factor action or the physiologic
one but which is not qualitative and quantitative
adequate to the excitant. The pathologic reactions
 Definition of health

• Much more useful is to define health through as a notion of

norm;
• The norm is the medium statistic value of morphologic,
functional, biochemical and psychic parameters of the human
body of a special race, sex, age and constitution in special
existence.
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 Definition of
the disease
• The disease may be defined as a new qualitative
state of the body that can appear under the action
of harmful factors and is characterized through a
homeostatic disequilibrium (morphological,
functional, biochemical and psychic), inadaptability,
social disequilibrium, loss of work capacity and
social – economic values for a certain period of time.
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 Structure of the disease
• Pathologic processes represent a combination
between elementary structures (ijuries and
body’s reactions) that derivates from a general
cause. The pathologic process is a totality of
successive events derived from the cause action
and includes a complex of structural injuries
and functional changes plus body’s reactions to
these injuries (adaptive, protective,
compensator and reparative reactions).
Ex: arterial hypertension → hypertensive disease;
gastric ulcer → ulcerative disease
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 General sanogenesis
• (lat. sanitas – health, genesis-a birth) is general compartment
of nosology, studying general laws of healing and recovery -
restoration of damaged structures and disordered function in
disease outcome.
Sanogenetical
mechanisms

Primary Secondary

Adaptive Protective
Protective Compensatory
Compensatory Terminal 18
 Cell injury :
mitochondrial,
nucleus,
RE injury

“Virtually all forms of disease start with molecular

or structural alterations in cells,” Rudolf Virchow
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 Cell injury
• is the persistent change of biochemical,
structural and functional homeostasis
of the cell under the action of harmful
factor.

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 Classification
By the sequence of appearance (primary, secondary)
By the nature of lesions (specific, nonspecific)
By the character of etiologic factor: mechanical damage;
physical injuries (burns, frostbite, electrical); osmotic injury;
lesions by lipid peroxidation; infectious lesions; immune
(allergic) injury; toxic injury; enzymatic injury; hypoxic
injury; damage of circulation; dysmetabolic damage; injury of
homeostasis
By location: membrane lesion; mitochondrial lesion,
lysosomal injury; nucleus lesions (including lesions by
mutations); endoplasmic reticulum damage and Golgi
apparatus
By degree of injury: reversible, irreversible.
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 Etiology of cell injury
- Mechanical factors;
- Hypoxic injuries;
- Ischemic injuries;
- Oxidative stress;
- Biological factor (bacteria, viruses, fungi);
- Radiation (ionizing, ultraviolet radiation);
- Electrical injuries;
- Enzymatic injuries;
-Extreme of temperature (burns, frost bite);
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Mechanical injury
• Disintegration of
membrane
• Open of mechanical
barrier cell-
interstitium
• Free passage of
substances in both
directions
• Influx of Na+,
• efflux of K+
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 Hypoxic injury. Causes
• general hypoxia (hypoxic,
respiratory, circulatory, anemic);
• regional blood flow and lymphatic
disorders (venous hyperemia,
ischemia, stasis);
• disorders of cellular processes of
oxidative phosphorilation
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 Depletion of ATP
Efflux of K+
Influx of Na+

Intracellular osmolarity
intracellular- resting
potential- inhibitory
depolarization
Cell swelling, dilation of ER
Increase extracellular –
reduces transmembrane
potential of adjacent cells –
increase the excitability

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Depletion of ATP

decrease ATP --increase

AMPc --stimulate
phosphofructokinase
and phosphorilase
activity -- lead to
anaerobic glycolysis

Cellular acidosis –
changes of protein’s
functions, activation of
lysosomal enzymes,
increase permeability
of the membrane lipid
layer
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ATP depletion failure of Ca2+pump
 Oxidative stress= free radicals= reactive
oxygen species (ROS)
It is called oxygen compound, which on the
latest electronic layer has an unpaired
electron, single electron, what gives an
extremely higher chemical reactivity

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 Types and causes of ROS

O2• - oxygen
superoxide
OH • -
hydroxyl
Hypoxia
radical
H2O2 -
hydrogen
peroxide

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Oxidants vs Antioxidants

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 The most important effects of ROS
ROS react with:
1. FA → oxidation → generation of lipid
peroxidase → disruption of plasma
membrane and organelles;
2. Proteins →oxidation → loss of enzymatic
activity, abnormal folding;
3. DNA → oxidation → mutations, breaks.
 Enzymatic cellular injury
•microb

En Ex
•phagocyti
c cells
from the
ial
inflamma enzym

do og
tory foci, es (for
•lysosomal
enzymes
ex:
(from strepto

ge en
lysosomal cocci
membran
lecithi
e
destabiliz nase

no ou
ation), that
•pancreati
splits
c
digestive membr
enzymes
(pancreat
itis or
pancreon
us ane
phosp
holipid
s
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ecrosis). s).
 Thermal cell injury
• Exposure to heat (43oC to 46oC) - vascular injury,
accelerate cell metabolism, inactivate temperature
sensitive enzymes, and disintegration of the cell
membrane.
• Exposure to cold - increases blood viscosity -
induces vasoconstriction by direct action and by
activated SNS – decrease blood flow - hypoxic tissue
injury.
• Injury from freezing probably results from a
combination of ice crystal formation and
vasoconstriction - decreases blood - capillary and35
 Nuclear injuries
Karyopiknosis – margination and condensation of
chromatin (action of ADNase and lysosomal enzymes)
Karyorrhexis - fragmentation of chromatin: pyknotic
nucleus undergo fragmentation
Karyolysis - total lysis of the nucleus of the cell.

Nucleus death
 INJURY OF ENDOPLASMIC
RETICULUM

1. Fragmentation of the ER – a sign of unspecific cell

injury (ischemia).
2. Formation of vacuoles - caused by interruption of
energy metabolism in which the reaction chain
involving Na+/K+-ATPase fails (hypoxia).
3. Swelling of the ER – “hydropic swelling” - final stage in
the collapse of cellular energy metabolism (anoxia). Is
due to cell hyperosmolarity . Swelling of the ER leads to
detachment of ribosomes, desintegration of polysomes,
finally leading to disturbances in protein synthesis
(both needed for intracellular processes as well as for
Injury of mitochondria

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LYSOSOMAL INJURY

Hypoxia, peroxidation,
acidosis etc… leads to
tumefaction and
destabilization of
lysosomal enzymes
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