2. Cell injury

Growth Adaptations & Cellular Injury
OVERVIEW OF CELLULAR RESPONSES
Cells normally maintain a steady state called homeostasis

As cells encounter physiologic stresses or pathologic stimuli, they can undergo adaptation,
achieving a new steady state and preserving viability and function
Cellular Adaptation
Adaptations are reversible changes in the number, size, phenotype,
metabolic activity, or functions of cells in response to changes in
their environment
Physiologic adaptations usually represent responses of cells to
normal stimulation by hormones or endogenous chemical mediators
(e.g., the hormone-induced enlargement of the breast and
uterus during pregnancy)
Pathologic adaptations are responses to stress that allow cells to
modulate their structure and function and thus escape injury. Such
adaptations can take several distinct forms.
Types of cellular adaptation
• Hypertrophy
• Hyperplasia
• Atrophy
• Metaplasia
HYPERPLASIA & HYPERTROPHY
•Hyperplasia is an increase in the number of cells in an organ or tissue
•It is usually results in increased volume of the organ or tissue
•Hypertrophy involve cell enlargement without cell division
•Hyperplasia takes place if the cellular population is capable of synthesizing DNA, permitting
mitotic division
•Hyperplasia and hypertrophy, Frequently occur both together
• The massive physiologic growth of the uterus during pregnancy is a good example of hormone-induced
increase in the size of an organ that results from both hypertrophy and hyperplasia
Hyperplasia
◦ Physiologic hyperplasia can be divided into:
1. Hormonal hyperplasia- which increases the functional capacity of a tissue

when needed
Eg. Female breast at puberty and during pregnancy, Uterine hyperplasia that occurs in pregnancy
2.Compensatory hyperplasia- which increases tissue mass after damage or

partial resection.
Eg. Liver after partial hepatectomy, Unilateral kidney after nephrectomy
Pathologic Hyperplasia
Examples:
1. Endometrial hyperplasia in an abnormal hormone-induced hyperplasia.
Absolute or relative increases in the amount of estrogen => abnormal menstrual bleeding.
2. Benign prostatic hyperplasia is another common example of pathologic hyperplasia induced by

heightened responses to hormones, in this case, androgens
HYPERTROPHY
The increased size of the cells is not due to cellular swelling but to the synthesis of more
structural components
Cells capable of division may respond to stress by undergoing both hyperplasia and hypertrophy,
whereas in non dividing cells (e.g., myocardial fibers), hypertrophy occurs
◦ Hypertrophy can be physiologic or pathologic and is caused by
◦ Increased functional demand
◦ Specific hormonal stimulation
ATROPHY
Atrophy is shrinkage in the size of the cell by loss of cell substance
When a sufficient number of cells are involved, the entire tissue or organ diminishes in size, or becomes
atrophic.
Atrophy can be physiologic or pathologic.

Physiologic atrophy is common during early development.
◦ Some embryonic structures, such as the thyroglossal duct, undergo atrophy during fetal
development.
◦ The uterine decrease in size shortly after parturition, and this is a form of physiologic atrophy.
Pathologic atrophy depends on the underlying cause and can be local or generalized
.
Pathologic Atrophy can be caused by:
1. Disuse:
Skeletal muscle atrophy rapidly ensues
2. Undernutrition:
3. Decreased endocrine stimulation
4. Denervation:
5. Old age:
Brain normal/atrophy
14
Kidney normal/atrophy
15
METAPLASIA
Metaplasia is the replacement of one differentiated tissue by another differentiated tissue. Most
commonly involves change of one type of surface epithelium (squamous, columnar, or
urothelial ) to another.
There are different types of metaplasia. Examples include:
1.Squamous metaplasia: columnar to squamous
This is replacement of another type of epithelium by squamous epithelium.
For example, the columnar epithelium of the bronchus can be replaced by squamous epithelium
in cigarette smokers
2. Glandular metaplasia
For example, Barrett esophagus
Barret Esophagus - Specialized Intestinal Metaplasia
Replacement of stratified squamous epithelium of the distal esophagus with intestinal

epithelium, due to chronic gastroesophageal reflux disease, Associated with risk of
esophageal adenocarcinoma
3.Connective tissue metaplasia: eg. the formation of cartilage, bone, or adipose tissue (mesenchymal
tissues) in tissues that normally do not contain these elements.
Myositis Ossificans: bone formation in skeletal muscle
Morphologic Alterations in Cell
Injury
If cellular stress overcomes cell's ability to adapt, then cell gets injured which can lead to
irreversible cell death
All stresses and noxious influences exert their effects first at the molecular or
biochemical level.
Cells can die via one of the following two ways:

1. Necrosis
2. Apoptosis
Apoptosis
ATP-dependent programmed cell death (from internal or external signal)
Pathways activate cytosolic proteases  cellular breakdown including cell

shrinkage, chromatin condensation, membrane blebbing, and formation
of apoptotic bodies, which are then phagocytosed
Cell membrane typically remains intact without significant inflammation

(unlike necrosis).
Apoptosis can be both
1. Physiologic apoptosis: removal of cells during embryogenesis, menstruation
2. Pathologic apoptosis: Cell injury in viral infections, radiation injury , anticancer

drugs
Necrosis
Exogenous injury  plasma membrane damage  cell
undergoes enzymatic degradation and protein
denaturation, intracellular components leak  local
inflammatory reaction (unlike apoptosis)
Necrosis occurs by the following mechanisms:

A. Hypoxia
B. Free radical-induced cell injury
C. Cell membrane damage
D. Increased intracellular calcium level
1. Hypoxia  decreased oxygen supply to tissues
eg/ Ischemia, Anemia, CO poisoning, Pulmonary disease
2. Free radical injury

production of free radicals exceeds their degradation, the excess free radicals cause
membrane pump damage, ATP depletion, & DNA damage
3. Cell membrane damage
Direct cell membrane damage as in extremes of temperature, toxins, or viruses, or indirect cell
membrane damage as in the case of hypoxia can lead to cell death by disrupting the
homeostasis of the cell.
Types of necrosis
1. Coagulative necrosis
2. Liquefactive necrosis
3. Fat necrosis
4. Caseous necrosis
5. Gangrenous necrosis
1. Coagulative necrosis:
most often results from sudden interruption of blood supply to an organ, except to heart, brain
Ischemia or infarction; injury denatures enzymes  proteolysis blocked
It is, in early stages, characterized by general preservation of tissue architecture.
Area of infracted tissue is often wedge shaped and pale. Wedge points to the blocked blood
vessel
Preserved cellular architecture (cell outlines seen), but nuclei disappear
2.Liquefactive necrosis
Liquefactive necrosis is characterized by digestion of tissue.

Neutrophils release lysosomal enzymes that digest the tissue
It shows softening & liquefaction of tissue
It characteristically results from ischemic injury to the CNS.
It also occurs in suppurative infections characterized by formation of pus microbes stimulate
the accumulation of inflammatory cells and the enzymes of leukocytes digest
(“liquefy”) the tissue.
3.Fat necrosis
Damaged pancreatic cells release lipase, which breaks down triglycerides; liberated
fatty acids bind calcium  saponification (chalky white appearance)
Can be caused by
•trauma to tissue with high fat content, such as the breast, subcutaneous fat
•Acute pancreatitis in which pancreatic enzymes diffuse into the inflamed pancreatic tissue
& digest it.
4. Caseous Necrosis
Macrophages wall off the infecting microorganism  granular (walled off) debris
Caseous necrosis has a cheese-like (caseous, white) appearance to the naked eye.
Caseous necrosis is typical of tuberculosis
Unlike with coagulative necrosis, the tissue architecture is completely obliterated and
cellular outlines cannot be discerned.
5. Gangrenous necrosis
is not a distinctive pattern of cell death, the term is still commonly used in clinical
practice.
It usually refers to the condition of a limb, generally the lower leg, that has lost its blood
supply and has undergone coagulative necrosis involving multiple tissue layers.
When bacterial infection is superimposed, coagulative necrosis is modified by the
liquefactive action of the bacteria and the attracted leukocytes (resulting in so-called
wet gangrene)
Necrosis can be followed by release of
• intracellular enzymes into the blood
•inflammation
• dystrophic calcification
Reversible cellular changes
& accumulations
Fatty change
This is accumulation of triglycerides inside parenchymal cells. Fatty change is usually seen in the
liver, heart, or kidney
Predisposed groups alcoholics, diabetes mellitus, malnutrition, obesity
It is caused by an imbalance between the uptake, utilization, & secretion of fat
Pathologic calcification
A process in which calcium is deposited in tissues
Two Types:
◦ Dystrophic calcification
◦ Metastatic calcification
Dystrophic calcification
Calcification in damaged or dead tissue in normal serum level (8.5-10.5mg/dl) of calcium
Examples
◦ Necrotic tissue (Lung-primary tuberculosis, cancer)
◦ Old scar (healed myocardial infarction)
◦ Ageing change (Monkberg’s arteritis, Aortic valve)
Metastatic Calcification
This is caused by hypercalcemia, leading to wide spread calcium deposition in tissues

(Normal or Damaged)
Causes of hypercalcemia:
◦ Excess Vitamin D
◦ Hyperparathyroidism
◦ Sarcoidosis
◦ Prolonged immobilization
◦ Cancers (Secondary carcinoma & Multiple Myeloma)
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2. Cell injury

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Growth Adaptations & Cellular Injury

OVERVIEW OF CELLULAR RESPONSES

Cells normally maintain a steady state called homeostasis

1. Hormonal hyperplasia- which increases the functional capacity of a tissue

2.Compensatory hyperplasia- which increases tissue mass after damage or

2. Benign prostatic hyperplasia is another common example of pathologic hyperplasia induced by

Atrophy can be physiologic or pathologic.

Replacement of stratified squamous epithelium of the distal esophagus with intestinal

Cells can die via one of the following two ways:

Pathways activate cytosolic proteases  cellular breakdown including cell

Cell membrane typically remains intact without significant inflammation

2. Pathologic apoptosis: Cell injury in viral infections, radiation injury , anticancer

Necrosis occurs by the following mechanisms:

2. Free radical injury

Liquefactive necrosis is characterized by digestion of tissue.

This is caused by hypercalcemia, leading to wide spread calcium deposition in tissues

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