INTRODUCTION TO PATHOPHUSIOLOGY
Pathology (from Greek word pathos= Disease) deal with the
study of structural and functional changes in the cell and
organ of the body that cause or are caused by disease. And
physiology is concerned with the function of human body.
Thus patho-physiology focuses on mechanism of underlying
disease process and provides background for preventive,
therapeutic health care
Or
Study of disordered function or breakdown of homeostasis
in diseases
In late 19th and early 20th century, the Best words of Sir
INTRODUCTION TO PATHOPHUSIOLOGY
The main difference between pathology
and pathophysiology is that:
Pathology is a medical discipline, describing
the physical conditions observed within
an organism during the disease
Pathophysiology is a biological discipline,
describing
the
changes
of
the
biochemical processes or mechanisms,
operating within an organism during the
disease.
INTRODUCTION TO PATHOPHUSIOLOGY
The four aspects of a disease process that form the
core of pathology are:
The Prevalence (the number of current cases in
specific population).
The cause of a disease (etiology)
The mechanism of disease development
(pathogenesis)
The structural alterations induced in cells and
tissues (morphologic change)
The functional consequences of the morphologic
changes (clinical significance)
INTRODUCTION TO PATHOPHUSIOLOGY
More excessive physiologic stresses,
or adverse pathologic stimuli (injury),
result in:
(1)Adaption.
(2)Reversible injury, or
(3)Irreversible injury
(4)Cell death
INTRODUCTION TO PATHOPHUSIOLOGY
1. Adaption
occurs when physiologic or pathologic
stressors induce a new state that changes
the cell. These changes include:
Hypertrophy (increased cell mass)
Hyperplasia (increased cell number)
Atrophy (decreased cell mass)
Metaplasia (change from one mature cell
INTRODUCTION TO PATHOPHUSIOLOGY
2. Reversible injury
Denotes pathologic cell changes that can be restored to
normalcy if the stimulus is removed or if the cause of
injury is mild.
3. Irreversible injury
Occurs when stressors exceed the capacity of the cell to
adapt (beyond a point of no return) and denotes
permanent pathologic changes that cause cell death.
4. Cell death
Occurs primarily through two morphologic and
mechanistic patterns denoted necrosis (Enlarged
swelling) and apoptosis (Reduced shrinkage)
Trauma
Trauma is defined as a tissue injury that occurs
more or less suddenly due to violence or
accident
Injury to the body, or an event that causes longlasting mental or emotional damage
Traumatic injury is a term which refers to
physical injuries of sudden onset and severity
which require immediate medical attention.
The insult may cause systemic shock called
“shock trauma”.
Kinds of Traumatic Events
 Natural disasters, such as a tornado, hurricane, fire, or
flood.
 Sexual assault.
 Physical assault.
 Witness shooting or stabbing of a person.
 Sudden death of a parent or trusted caregiver.
 Hospitalization.
Causes of Physical trauma
There are four F's of complex trauma
 Fight
 Flight
 Freeze
 Fawn
Causes of Cell Injury
1. Oxygen deprivation (hypoxia)
Affects aerobic respiration and generation
adenosine triphosphate (ATP). This extremely
important and common cause of cell injury and
death occurs as a result of:
Ischemia (loss of blood supply)
Inadequate
oxygenation
(e.g.,
cardiorespiratory failure)
Loss of oxygen-carrying capacity of the blood
(e.g., anemia, carbon monoxide poisoning)
Causes of Cell Injury
2. Physical agents: including trauma, heat, cold, radiation, and
electric shock
3. Chemical agents and drugs: including therapeutic drugs,
poisons, environmental pollutants, and “social stimuli” (alcohol
and narcotics)
4. Infectious agents: including viruses, bacteria, fungi, and
parasites
5. Immunologic reactions: including autoimmune diseases and
cell injury following responses to infection
6. Genetic derangements, such as chromosomal alterations
and specific gene mutations
7. Nutritional imbalances, including protein–calorie deficiency
or lack of specific vitamins, as well as nutritional excesses
TYPES OF CELL INJURY
1. Ischemic and Hypoxic Injury
2. Chemical (Toxic) Injury:
3. Apoptosis.
4. Intracellular Accumulations:
Lipids: (triglycerides, cholesterol, cholesterol
esters, etc)
Carbohydrate:
accumulations
(
diabetes
mellitus)
Complex Substance: accumulations ( LDL,
VLDL, etc)
TYPES OF CELL INJURY
1. Ischemic and Hypoxic Injury
Ischemia and hypoxic injury are the most common forms of
cell injury in clinical medicine. Hypoxia is reduced O2
carrying capacity; the ischemia (ischemia =reduced blood
flow). Hypoxia leads to loss of ATP generation by
mitochondria and has initially reversible effects. If ischemia
persists, irreversible injury can occur.
2. Chemical (Toxic) Injury: by chemical agents
3. Apoptosis Programmed cell death (apoptosis) occurs
when a cell dies through activation of a tightly regulated
internal suicide program. The function of apoptosis is to
eliminate unwanted cells selectively, with minimal
disturbance to surrounding cells and the host.
Causes of Apoptosis
A. Physiologic Causes
Programmed
destruction
of
cells
during
embryogenesis.
Hormone-dependent involution of tissues (e.g.,
endometrium, prostate) in the adult.
Cell deletion in proliferating cell populations (e.g.,
intestinal epithelium).
Death of cells that have served their useful purpose
(e.g., neutrophils following an acute inflammatory
response).
Deletion of potentially harmful
Causes of Apoptosis
B. Pathologic Causes
DNA damage: If repair mechanisms cannot cope
with the damage (e.g., due to hypoxia, radiation, or
cytotoxic drugs).
Accumulation of misfolded proteins: (e.g., due to
inherited defects or due to free radical damage).
Cell death in certain viral infections (e.g., hepatitis)
Cytotoxic T cells may also be a cause of apoptotic
cell death in tumors and in the rejection of
transplanted tissues.
Mechanism of Apoptosis
Apoptosis is a cascade sequence(cascade) of molecular
events that can be initiated by triggers. The process of
apoptosis is divided into
An initiation phase:
when caspases (Family of cystine proteases as a primary
effector in aptosis) become active to dismantle cellular
cytoskeletons, mitochondria, E.R, G.Bodies and nucleus. It
can be by two ways
intrinsic mitochondrial pathway
extrinsic death receptor–mediated pathway
An execution phase:
when the enzymes cause cell death.
Morphologic Alternations in Cell Injury
1. Reversible Injury:
Cell swelling appears whenever cells cannot maintain
ionic and fluid homeostasis (largely due to loss of activity
in plasma membrane energy-dependent ion pumps).
2. Necrosis
Necrosis is the sum of the morphologic changes that
follow cell death in living tissue or organs. Two processes
underlie the basic morphologic changes:
• Denaturation of proteins
•Enzymatic digestion of organelles and other cytosolic
components
Mechanisms of Cell Injury
cell injury can be organized around a few general principles:
1. Responses to injurious stimuli: (type of injury, duration,
and severity).
2. The consequences of injury: (type, state, and adaptability
of the injured cell).
3. Cell injury: results from alteration in any of five essential
cellular elements
ATP production (aerobicrespiration)
Mitochondrial integrity (ATP production)
Plasma membrane integrity (ionic and osmotic homeostasis)
Protein synthesis
Integrity of the genetic apparatus
Types of Necrosis
Necrosis means death of tissue
1. Coagulative necrosis (due to protein denaturation):
This pattern is characteristic of hypoxic death in all
tissues except the brain. Necrotic tissue undergoes
either heterolysis (digestion by lysosomal enzymes of
invading leukocytes) or autolysis (digestion by its own
lysosomal enzymes).
2. Liquefactive necrosis:
The necrotic area is soft and filled with fluid. This type
of necrosis is most frequently seen in localized bacterial
infections (abscesses) and in the brain.
Types of Necrosis
3. Gangrenous necrosis:
Like
coagulative necrosis applied to an
ischemic limb; superimposed bacterial
infection makes for a more liquefactive pattern
called wet gangrene.
4. Caseous necrosis:
It is characteristic of tuberculous lesions; it
appears grossly as soft, “cheesy” material and
microscopically as amorphous eosinophilic
material with cell debris.
Types of Necrosis
5. Fibrinoid necrosis
is a pathologic pattern resulting from antigen-antibody
(immune complex) deposition in blood vessels.
Microscopically there is amorphous material (protein
deposition) in arterial walls, often with associated
inflammation and thrombosis.
6. Fat necrosis:
is seen in adipose tissue; lipase activation(e.g., from injured
pancreatic cells or macrophages) releases fatty acids from
triglycerides, which then complex with calcium to create
soaps. Grossly, these are white, chalky areas (fat
saponification).
Cellular Aging
Cellular aging means the progressive accumulation
of cellular and molecular damage due to both genetic
and exogenous influences, which leads to cell death
and diminished capacity to respond to injury. it is a
critical component of the aging of the entire organism.
With increasing age, degenerative changes impact
the structure and physiologic function of all organ
systems.
Severity of such changes in any given individual are
influenced by genetic factors, diet, social conditions,
and the impact of other co-morbidities, such as
atherosclerosis, diabetes, and osteoarthritis.
Cellular Aging
In general, the life expectancy of an individual depends
upon the following factors:
1. Intrinsic genetic process
2. Environmental factors
3. Lifestyle of the individual. due to alcoholism (e.g.
cirrhosis, hepatocellular carcinoma), smoking (e.g.
bronchogenic carcinoma and other respiratory
diseases), drug addiction.
4. Age-related diseases e.g. atherosclerosis and
ischaemic heart disease, diabetes mellitus,
hypertension, osteoporosis and Parkinson’s disease.
Factors that affect cell aging
A. Intrinsic factors
Psychogenic
Inherited
Congenital
Metabolic
Degenerative
Neoplastic
Immunologic
Nutritional
Factors that affect cell aging
B. Extrinsic factors Physical agents
Force
Temperature
Humidity
Radiation
Electricity
Chemicals
Factors that affect cell aging
C. Infectious agents
Viruses
Bacteria
Fungi
Protozoa
Insects
Worms
ORGAN CHANGES IN AGING
1. Cardiovascular system: Atherosclerosis, arteriosclerosis
2. Nervous system: Atrophy of gyri and sulci, Parkinson’s
disease.
3. Musculoskeletal system: Degenerative bone diseases,
frequent fractures due to loss of bone density, age
related muscular degeneration.
4. Eyes: Deterioration of vision due to cataract and vascular
changes in retina
5. Hearing: Disability in hearing
6. Immune system: frequent and severe infections
7. Skin: loss of elastic tissue
8. Cancers: age range of 50 and 80 years has more risk
Disease and its concept
It is a disorder with specific cause, .and recognizable signs &
symptoms are called disease. Any bodily abnormality or
failure to function properly, except that resulting directly
from physical injury (Oxford Medical Dictionary 1996)
The natural progression of disease consequence:




Inherited susceptibility (genetic inheritance)
Exposure to environmental factor
Lifestyle
Diet
The Italian Agostino Bassi was the first person to prove that a
disease was caused by a microorganism when he
conducted a series of experiments between 1808 and
1813, demonstrating that a "vegetable parasite" caused a
disease
Disease and its concept
Disease concepts are presented as causal networks that
represent the relations among the symptoms, causes,
and treatment of a disease.
Types of disease
Infectious Diseases (due to microorganism)
Deficiency Diseases (efficiency of vitamin etc)
Hereditary diseases (including both genetic
diseases and non-genetic hereditary diseases)
Physiological diseases. Diseases can also be
classified in other ways, such as communicable
versus non-communicable diseases.
Communicable Disease (Only due to infection)
Non-Communicable
Diseases
(diabetes,
hypertension etc)
Disease stages
Exposure or injury. Target tissue is exposed to a causative
agent or is injured.
Latent or incubation period. No signs or symptoms are
evident.
Prodromal period. Signs and symptoms are usually mild
and nonspecific.
Acute phase. The disease reaches its full intensity and
complications commonly arise.
Convalescence. In this stage of rehabilitation, the patient
progresses toward recovery after the termination of a
disease.
Recovery. In this stage, the patient regains health or
normal functioning. No signs or symptoms