1. : Chapter 1. Introduction to Pathophysiology
Introduction to Cellular Changes
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.

2. INTRODUCTION Homeostasis: Cells tend to preserve their immediate
environment and intracellular environment.
WHAT IS PATHOPHYSIOLOGY?
Pathophysiology involves the study of functional Causes of cell injury: Oxygen Deprivation (Hypoxia,
due to restriction of blood “ischemia”),
or physiologic changes in the body that result Chemical, Infectious,and Immunologic agents,
from disease processes. Genetic defects, Nutritional imblances, physical
agents, and aging.
This subject builds on knowledge of the normal Cell injury could be reversible (e.g. adaptation), and
structure, and function of the human body. cells return to a stable baseline; however, with
As a disease develops, the changes in the severe or persistent stress, irreversible injury (cell
death by necrosis or apoptosis) results.
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

3. CELLULAR ADAPTATION TO INJURY
1- Atrophy • 2-hypertrophy
• 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 • Hypertrophy is an increase in the size of cells
diminishes in size. Cells are not dead.. and consequently an increase in the size of the
• Causes of atrophy include: organ.
1- Decreased workload (e.g., immobilization of • Hypertrophy can be physiologic or pathologic
a fractured limb to permit healing) and is caused either by increased functional
2- Loss of innervation demand or by specific hormonal stimulation.
3- Diminished blood supply • Hypertrophy and hyperplasia can also occur
4- Inadequate nutrition together, and obviously both result in an
5- Loss of endocrine stimulation enlarged (hypertrophic) organ
6- Aging.
Uterine hypertrophy during pregnancy

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

6. Cell Damage and Necrosis
There are many ways of injuring cells in the The most common cause of injury is ischemia
body, including: where sensitive cells suffer hypoxia (reduced
oxygen in the tissue) > interferes with energy
(ATP) production > loss of the sodium
 ischemia, or deficit of oxygen in the cells,
pump > increase in sodium ions inside the
due to respiratory problems or circulatory cell > cell swelling & rupture
obstruction;
At the same time, in the absence of oxygen,
 physical agents, excessive heat or cold, or
anaerobic metabolism occurs in the cell,
radiation exposure; leading to a decrease in pH (acidosis) and
 mechanical damage such as pressure or further metabolic impairment.
tearing of tissue; Cell lysis releases destructive lysosomal
 chemical toxins or foreign substances; enzymes into the tissue, which cause
 microorganisms such as bacteria, viruses, inflammation (swelling, redness and pain)
and parasites; as well as damage to nearby cells.
 abnormal metabolites accumulating in The enzymes released from the dead cells can
cells; diffuse into the blood, providing helpful
 nutritional deficits; clues in blood tests that indicate the type of
 and imbalance of fluids or electrolytes. cells damaged.(e.g. diagnostic test of
myocardial infarction)

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

8. 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):
http://www.youtube.com/watch?v=witLM--V2v8&feature=related
1- embryogenesis, organogenesis, and developmental http://www.youtube.com/watch?v=i0SuQrJUi-4&feature=related
involution
2- Hormone-dependent physiologic involution. Somatic Death
3- Cell deletion in proliferating populations, such as Specific types of cells die at different rates.
intestinal crypt epithelium, or cell death in tumors
4- Deletion of autoreactive T cells in the thymus. Brain cells die quickly (4 to 5 minutes) when
5- Deletion of virally infected cells. deprived of oxygen, whereas heart muscle
6- Mild injury (heat, radiation, cytotoxic cancer drugs, etc.) can survive for approximately 30 minutes.
that cause irreparable DNA damage (e.g., via the tumor Formerly, death of the body (somatic death)
suppressor protein TP53).
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).