General concepts of pathophysiology

altered health or disordered function
It combines the words pathology and physiology
Pathology (from the Greek «pathos» - disease)
deals with the study of the
structural and functional changes in
-cells,
-tissues,
-organs,
that cause or are caused by disease
Physiology deals with the functions of the human body

disease
the effects that these changes have on total body function
the mechanisms of the underlying disease
Pathophysiology serves as a bridge
between the basic sciences and the clinic
Provides the background
for preventive a therapeutic
health care measures and practices

as a:
“state of complete physical, mental, and social well-being and not merely the absence of disease and infirmity”
Healthy person adapts successfully to the stresses
and injurious factors,
he is in balance with the environment

the most efficient and effective
It does not use long-term mechanisms when
short-term adaptation is sufficient

a temporary response
designed to deliver additional oxygen to tissues
during the short period that the physical activity increases metabolic needs
Hypertrophy of the muscle
is a long-term adaptive response
that occurs in sportsmen

number of available responses, the more effective the capacity to adapt)
the ability of the body to select the most appropriate response
аdaptive capacity is decreased with extremes of age
the immaturity of the infant
the decline in functional reserve that occurs in the elderly
with disease conditions that limit the availability of adaptive responses

of renal tubular structures and therefore are less able to cope with
decreased water intake or water losses
Persons with preexisting heart disease
are less able to adapt to health problems
that require recruitment of cardiovascular responses

rather than gradually
it is possible to lose a liter of blood through chronic gastrointestinal bleeding without developing signs of shock
a sudden hemorrhage causing the loss of the same amount of blood produces hypotension and circulatory shock

the first to describe a group of
specific anatomic and functional changes that developed in response to many different (nonspecific) experimental challenges in rats he was using for his studies
It was a triad of :
adrenal enlargement
thymic atrophy
gastric ulcer

stimuli
Selye described stress as:
“…a state manifested by
a specific syndrome of the body
developed in response to
any stimuli that made
an intense systemic
demand on it."
He assumed that the hypothalamic-pituitary-adrenal (HPA) axis played a pivotal role in the development of this response

effect was a general systemic reaction of the body
adaptive because the response was in reaction to a stressor
syndrome because the physical manifestations were coordinated and dependent on each other

the resistance stage
the exhaustion stage

the HPA axis, resulting in the release of catecholamines and cortisol
The resistance stage
long term adaptation uses up energy reserves (cortisol level maintained)
If the stressor is prolonged or overwhelms the ability of the body to defend itself, the exhaustion stage ensues,
resources are depleted and signs of "wear and tear" or systemic tissue damage appear

periods of stress
are positive stimuli to physical, emotional and intellectual growth and development
Distress
the severe, protracted, and uncontrolled
activity of stress system
leading to psychological and physical
disruption of health

An area of the brain stem
Is populated with
neurons that produce
norepinephrine (NE)
Is the central integrating site for the ANS response to stressful stimuli
The LC-NE system has afferent pathways to the hypothalamus, the limbic system, and the cerebral cortex

response to stress
Is a small peptide hormone found in the hypothalamus
also in extrahypothalamic structures - the limbic system and the brain stem)
Is both an important endocrine regulator of pituitary and adrenal activity and a neurotransmitter involved in ANS activity, metabolism, and behavior
Receptors for CRF are distributed throughout the brain as well as many peripheral sites

adrenal medulla
Produce:
a decrease in insulin release
an increase in glucagon release
resulting in:
increased glycogenolysis, glyconeogenesis,
lipolysis, proteolysis
decreased glucose uptake by the
peripheral tissues
Effects can be summarized as substrate (glucose) mobilization

muscle 
increased sympathetic activity in the brain increases attention and arousal and thus intensifies memory
The SNS manifestation of the stress
has been called the
«Fight or flight response»

inhibits the release and/or actions of the reproductive hormones and thyroid- stimulating hormone;
produces a decrease in immune cells and in inflammatory mediators
maintains blood glucose levels by antagonizing the effects of insulin
suppresses osteoblast activity, hematopoiesis, protein and collagen synthesis
All functions are meant to focus energy on regaining balance in the face of an acute challenge to homeostasis

and function of
a part, organ, or system of the body
that is manifested by
a characteristic set of symptoms, signs and syndromes
A disease limits the ability of the body to adapt to stresses and injurious factors

The causes of disease are known as
etiologic factors or pathogenic factors
Etiologic factor determines specific signs of the disease
Two major classes of etiologic factors
Extrinsic or acquired
Intrinsic (genetic…)

(e.g., trauma, burns, radiation…)
chemical agents (e.g., poisons, alcohol, drugs…)

temperature, poisons…)
excesses (lipids…) or deficits (vitamins, oxygen…)
periodical or long term exposure (chronic stress, exposure to allergens, inhalation of coal or other dust…)

caused by
genetic influences
environmental factors (e.g., viral infections in the mother, maternal drug use, irradiation…)
a combination of genetic and environmental factors

or events that serve as a trigger to initiate disease development
The multiple factors that trigger a particular disease are referred to as risk factors
The true etiology of those diseases remains largely uncertain

of essential hypertension
angiotensin gene,
angiotensin converting enzyme gene,
angiotensinase C gene,
β2 adrenergic receptor gene,
renin binding proteins gene,
atrial natriuretic factor gene,
insulin receptor gene…

from the time of initial contact with an etiologic agent until the ultimate expression of a disease
The sequential development of
signs and symptoms that accompany
the disease
Etiology describes what sets the disease process in motion,
Pathogenesis - how the disease process develops

by etiologic factors, accompanied by adaptive reactions
Pathologic process is a more general category than disease
One and the same pathologic process may contribute to the pathogenesis of various diseases
Some of pathologic processes contributing to the pathogenesis of many diseases are called «typical»

reinforces itself through a feedback loop toward greater instability
Positive feedback – "cumulative causation",
a feedback loop system in which the system responds to pertubation in the same direction as the perturbation
"A produces more of B which in turn produces more of A“

=>
decreased coronary blood flow =>
decreased heart muscle blood supply =>
decreased heart performance =>
decreased CO

neoplasia…)
affected organ or organ system (pulmonary diseases, cardiovascular diseases, renal diseases…)
sex (disorders of the male or female reproductive tract)
age

changes that accompany a disease
A symptom is a subjective complaint
that is noted by the person with a disorder
A sign is a manifestation that is noted by an observer
A syndrome is a compilation of signs and symptoms that are characteristic of a specific disease state
(e.g., jaundice, acute or chronic renal failure…)

(ketoacidosis in uncontrolled diabetes mellitus)
may represent the body’s attempt to compensate for the altered function caused by the pathologic condition
(a compensatory increase in respiratory rate in a case of a decrease in pO2 )
Signs and symptoms can be general or local, specific or nonspecific

– involving affected tissue:
edema, redness…
Nonspecific – present in many diseases:
headache, fever…
Specific – present in a particular disease:
factor VIII deficiency in hemophilia A,
blast cells present in the blood count in acute leukemia…

of a disease can be
acute (minutes, days…)
subacute (weeks, months…)
chronic (months, years…)
An acute disorder is one that is relatively severe, but self-limiting
Subacute disease is intermediate or between acute and chronic: it is not as severe as an acute disease and not as prolonged as a chronic disease

continuous course,
or it can present with:
exacerbations (aggravation of symptoms and severity of the disease)
remissions (a period during which there is a lessening of severity and a decrease in symptoms)

evident, (incubation period – e.g. shot-incubation hepatitis A - 4-8 weeks, long-incubation hepatitis B - 8-20 weeks)
the prodromal stage, when general, nonspecific symptoms are present
the peak stage is manifested by specific signs and symptoms
the outcome

lesions or impairments that follow or are caused by a disease - operated stomach, scars, extracted teeth…)
complications (possible adverse extensions of a disease
or outcomes from treatment)
chronic course
death