Learning Objectives:

After studying this chapter, the student is expected to

1. Explain the role of pathophysiology in the diagnosis and treatment of disease.
2. Use appropriate terminology.
3. Explain the importance of a patient's medical history.
4. Describe common cellular adaptations and possible reasons for the occurrence of
each.
5. Identify precancerous cellular changes.
6. List the common causes of cell damage.
7. Describe the common types of cell necrosis and possible outcomes.
. Introduction to Pathophysiology: 1 Chapter
Introduction to Cellular Changes
Homeostasis: Cells tend to preserve their immediate
environment and intracellular environment.

Causes of cell injury: Oxygen Deprivation
(Hypoxia, due to restriction of blood
ischemia), Chemical, Infectious,and
Immunologic agents, Genetic defects, Nutritional
imblances, physical agents, and aging.

Cell injury could be reversible (e.g. adaptation), and
cells return to a stable baseline; however, with
severe or persistent stress, irreversibleinjury
(cell death by necrosis or apoptosis) results.
INTRODUCTION
WHAT IS PATHOPHYSIOLOGY?
Pathophysiology involves the study of functional
or physiologic changes in the body that result
from disease processes.

This subject builds on knowledge of the normal
structure, and function of the human body.
As a disease develops, the changes in the
normal anatomy and/or physiology of the
body may be obvious or maybe hidden,
occurring at the cellular level. As such,
pathophysiology includes some aspects of
pathology (histopathology), the laboratory
study of cell and tissue changes associated
with disease.
Normal heart (center), Cardiac hypertrophy(left)
and dilatation (right)
CELLULAR ADAPTATION TO INJURY
1- Atrophy
Shrinkage in the size of the cell by the loss of
cell substance. When a sufficient number of
cells is involved, the entire tissue or organ
diminishes in size. Cells are not dead..
Causes of atrophy include:
1- Decreased workload (e.g., immobilization of
a fractured limb to permit healing)
2- Loss of innervation
3- Diminished blood supply
4- Inadequate nutrition
5- Loss of endocrine stimulation
6- Aging.

2-hypertrophy

Hypertrophy is an increase in the size of cells
and consequently an increase in the size of the
organ.
Hypertrophy can be physiologic or pathologic
and is caused either by increased functional
demand or by specific hormonal stimulation.
Hypertrophy and hyperplasia can also occur
together, and obviously both result in an
enlarged (hypertrophic) organ


Uterine hypertrophy during pregnancy
3-hyperplasia
Hyperplasia constitutes an increase in the
number of cells in an organ or tissue.
Physiologic hyperplasia is divided into (1)
hormonal hyperplasia, (2) compensatory
hyperplasia,
Most forms of pathologic hyperplasia are
instances of excessive hormonal or growth
factor stimulation.
Hyperplasia could be precancerous.
4- metaplasia.
Is a reversible change in which one
differentiated (adult) cell type is
replaced by another differentiated
(adult) cell type.
It might be protective adaptive mechanism
e.g. cigarette smoking but it involves
loss of function
CELLULAR ADAPTATION TO INJURY (cont.)
Thyroid-diffuse hyperplasia Graves disease
Cell Damage and Necrosis
There are many ways of injuring cells in the
body, including:

ischemia, or deficit of oxygen in the cells,
due to respiratory problems or circulatory
obstruction;
physical agents, excessive heat or cold, or
radiation exposure;
mechanical damage such as pressure or
tearing of tissue;
chemical toxins or foreign substances;
microorganisms such as bacteria, viruses,
and parasites;
abnormal metabolites accumulating in
cells;
nutritional deficits;
and imbalance of fluids or electrolytes.


The most common cause of injury is ischemia
where sensitive cells suffer hypoxia (reduced
oxygen in the tissue) > interferes with energy
(ATP) production > loss of the sodium
pump > increase in sodium ions inside the
cell > cell swelling & rupture
At the same time, in the absence of oxygen,
anaerobic metabolism occurs in the cell,
leading to a decrease in pH (acidosis) and
further metabolic impairment.
Cell lysis releases destructive lysosomal
enzymes into the tissue, which cause
inflammation (swelling, redness and pain)
as well as damage to nearby cells.
The enzymes released from the dead cells can
diffuse into the blood, providing helpful
clues in blood tests that indicate the type of
cells damaged.(e.g. diagnostic test of
myocardial infarction)

Irreversible Cell Injury: 1- Necrosis
Definition: denotes death of a group of cells. It is characterized
by cell swelling, denaturation of cytoplasmic proteins, and
enzymatic digestion of the cell.
Morphology:
Early: Common changes are: cell swelling + nuclear changes
(pyknosis, Karyrrhexis, Karyolysis)
Late: different types of necrosis:
1- Coagulative necrosis. Implies preservation of the basic
structural outline of the cell or tissue for a span of days. The
injury or the subsequent increasing acidosis denatures not
only the structural proteins but also the enzyme proteins, thus
blocking cellular proteolysis. The process of coagulative
necrosis, with preservation of the general tissue architecture,
is characteristic of hypoxic death of cells in all tissues
except the brain.
- I nfarction is coagulative necrosis resulting from hypoxia.
2- Liquefactive necrosis. Characteristic of focal bacterial or fungal
infections, due to accumulation of white cells, and hypoxic death
within the central nervous system. Liquefaction completely
digests the dead cells.
- Gangrenous necrosis is ischemic coagulative necrosis (frequently
of a limb> dry gangrene); when there is superimposed infection
with a liquefactive component, the lesion is called "wet
gangrene. Gangerenous tissue must be removed surgically.
3- Caseous necrosis in tuberculous infection. The term "caseous" is
derived from the cheesy, white gross appearance of the central
necrotic area. The necrotic focus is composed of structureless,
amorphous granular debris within a ring of granulomatous
inflammation. The tissue architecture is completely lost.
4- Fat necrosis. Focal areas of fat destruction, typically occurring
after pancreatic injury > release of activated pancreatic enzymes
into adjacent parenchyma or the peritoneal cavity. The released
fatty acids combine with calcium to produce grossly visible
chalky white aresas (fat saponification)
Kidney infarct exhibiting coagulative
necrosis, with preservation of basic
outlines of glomerular and tubular
architecture.
A tuberculous lung with a
large area of caseous necrosis.
Fat necrosis with saponification in the
mesentery. White-yellow chalky deposits
represent calcium soap formation.


Irreversible Cell Injury: 2- APOPTOSIS (PROGRAMMED CELL DEATH)

It is single cell death in the middle of living tissue due to activation of internal suicide program with
characteristic morphology (cell shrinkage) that does not cause tissue disruption or inflammation.

Causes, importance (It occurs in):
1- embryogenesis, organogenesis, and developmental
involution
2- Hormone-dependent physiologic involution.
3- Cell deletion in proliferating populations, such as
intestinal crypt epithelium, or cell death in tumors
4- Deletion of autoreactive T cells in the thymus.
5- Deletion of virally infected cells.
6- Mild injury (heat, radiation, cytotoxic cancer drugs, etc.)
that cause irreparable DNA damage (e.g., via the tumor
suppressor protein TP53).
Somatic Death
Specific types of cells die at different rates.
Brain cells die quickly (4 to 5 minutes) when
deprived of oxygen, whereas heart muscle
can survive for approximately 30 minutes.
Formerly, death of the body (somatic death)
was assumed to occur when heart action and
respiration ceased. Now, because cardiac and
respiratory function can be maintained
artificially, the diagnosis of death is more
complex. Currently, brain death provides the
criteria for somatic death. Brain death is
based on the lack of any electrical activity in
any neurons in the brain as demonstrated
by electroencephalography (EEG) and by
the absence of responses (see Chapter 22).
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