College of Health And Sports Sciences

Integrated Sciences Division

CHS
LFS 319

General pathology

Cell Injury& adaptation& cell

death
Objectives
At the end of the Chapter, the student must be able to:

1. Define the term “cell injury”

2. Explain the causes of cell injury
3. Discuss the different types of cellular responses to injury
4. Differentiate the different types of cellular adaptation to injury.
5. Define cell death and differentiate between Apoptosis and Necrosis
6. Differentiate between the different types of necrosis
7. Define and describe the mechanism of apoptosis.
8. Determine and monitor cell injury through different approaches.

Cell Injury
 CELL INJURY
• The cell faces a number of challenges through its
life.

• Cell injury is " any condition that may temporarily

or permanently disturbs the homeostatic balance
of the cellular environment leading to reversible
or irreversible damage"

Cell Injury
 Causes of cell injury:
• Cell injury can occur because of
1. Physical agents (e.g., mechanical forces and
extreme temperature)
2. Chemical injury (e.g., acid, pollution, and drugs)
3. Infections (e.g., viruses, bacteria)
4. Immunological reaction.
5. Genetic factors.
6. Low oxygen level (hypoxia or ischemia).
7. Oxidative stress
8. Nutritional imbalances. Cell Injury
 1. Physical injury:

• For example:
1. Mechanical pressure  loss of structural integrity.
2. Hypothermia  ice crystal formation of cytoplasmic water (e.g.,
frostbites).
3. Hyperthermia  denaturation of cell protein  functional disruption.
4. Ionizing radiation (high intensity)   tissue temperature  burns.
5. Electric shock.

Cell Injury
2. Chemical injury:
• Produced by injurious chemicals through inhalation or swallowing.
• For example:
• Acid
• Pollution
• Occupational hazards
• Drugs
• High sugar
• Insecticides
Cell Injury
3. Infections:

• Infections include viruses, bacteria, fungus, parasites.

• Mechanism of cell injury in infections is diverse e.g.,

1. Disrupts the cell’s metabolism, through consumption of its key
metabolites, and energy-producing molecules.
2. Formation of damaging chemicals.

Cell Injury
4. Immunological reaction:

• Immune system serves an essential function for defence against

infections but also can cause cell injury e.g., injurious reaction to
endogenous self-antigens are responsible for many autoimmune
diseases (SLE, rheumatoid arthritis)

• Autoimmunity  autoantibodies formed against the body’s own cells

 This can damage the cell.

Cell Injury
5. Genetic factors:
Can cause cell injury through:

1. Congenital malformation: Down syndrome, sickle cell disease.

Cell Injury
Down Syndrome Sickle cell disease inheritance
2. Lack of certain key proteins, e.g.,
enzymes & precursors, necessary for
normal metabolism for example: inborn
error of metabolism or pernicious anemia.

• Lack for intrinsic factors responsible for

VitB12 absorption causing Vit B12
deficiency Less RBC’s production
less O2 delivered to the cells.

Cell Injury
3. Genetic defects lead to production of a toxic substance

• Phenylketonuria (PKU)in this condition product of a genetic

defect, while not itself toxic. It activates a pathway which

produces a toxic substances called Phenylketones leading to

problems in brain development in children.

Cell Injury
6. Low oxygen level:

• Low oxygen level (hypoxia or ischemia):

failure of many energy dependent metabolic

pathways, and ultimately to cell injury.

• Also, hypoxia leads to accumulation of

metabolites, such as CO2 , lactic acid etc.

that damage the cell.

Cell Injury
6. Oxidative Stress:
- Oxidative stress refers to cellular abnormalities that are induced by
Reactive oxygen species (ROS) , which belong to a group of molecules known as free
radicals.

- Exposure of cells to radiation or chemotherapeutic agents, intracellular generation of ROS,

and acquisition of mutations may all induce DNA damage, which if severe may trigger
apoptotic death.

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7. Nutritional imbalance
1. Nutritional deficiency: Can be primary or secondary.
 Primary nutrient deficiency: Lack of essential substances in the diet e.g.,
starvation.
 Secondary nutrient deficiency arises when substances are present in the
diet but cannot be absorbed

2. Nutritional excess:
 Excess cholesterol deposition leads to atherosclerosis
 Obesity linked to many diseases like DM, Fatty liver, Cancer.
Cell Injury
15
 Ponder Points:

Why are hepatocytes and intestinal mucosae

more affected by toxins than other cells?”

Ans-These are the cells which are most exposed to the

toxins.
When we eat, all the ingested food goes to the intestines
and the cells are exposed
Also, Liver does the detoxification and therefore gets
exposed

Cell Injury
• The extent of injury usually depends on:

1. Injury: type, severity and duration of the injury

2. Intrinsic factors (e.g., blood supply and nutritional status).

Cell Injury
Cell response to injury:

When cell integrity is threatened,

the cell reacts by:
 If enough cellular reserve is
available, the cell adapts
 If there isn’t enough cellular
reserve, cell death occurs.
Cell Injury
Cell Injury
a. Reversible changes (Cellular Adaptation)

• Cells attempt to prevent their own death

from environmental changes through
adaptation.

• Usually occur after a minor or moderate

injury.

• NOT all cells have the full set of adaptive

response mechanisms, hence responses
will differ from one cell to another.

Cell Injury
Cellular adaptations to stress

Adaptations are reversible changes in the number, size,

phenotype, metabolic activity, or functions of cells in response
to changes in their environment.

• Physiologic adaptations e.g., the hormone-induced

enlargement of the breast.

• Pathologic adaptations e.g., squamous metaplasia of

bronchial epithelium in smokers. 21
1. Atrophy  Atrophy is reduction in the size of the cell.
 It results from disuse, insufficient blood flow, malnutrition,
denervation, or reduced endocrine hormones.
 Examples: disuse atrophy of paralyzed limb, senile atrophy, atrophy
of the uterus after the menopause.
2. Hypertrophy  Hypertrophy is an increase in the size of a cell.
 due to increased workload or by growth factor or hormonal
stimulation.
 It can result from normal physiologic conditions or abnormal
pathologic conditions.
 Examples:
1. Biceps gets bigger with weight bearing exercise (normal
condition), uterus during pregnancy.
2. The heart is hypertrophied in hypertension or in aortic stenosis
and becomes less flexibleCell
toInjury
work causing heart failure
(abnormal pathological condition)
Cell Injury
 Gross appearance of a (B) Small spindle-shaped uterine smooth muscle cells from a
normal uterus (right) and normal uterus. (C) Large, plump hypertrophied smooth muscle
a gravid uterus (left) cells from a gravid uterus; compare with B.

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3. Hyperplasia  Hyperplasia, an increase in the number of cells,

 caused by increased workload, or hormonal stimulation.

 May be physiological or pathological
 Examples: wound healing, liver regeneration, thyroid hyperplasia, endometrial hyperplasia in cases of

hormonal disturbance.
4. Metaplasia  Metaplasia is the replacement of one adult cell with another adult cell that can better deal with
the change or stress.
 It’s usually a response to chronic inflammation or irritation, so a more virulent cell type emerges.
 It is not cancerous but can lead to cancer if the stimulus not removed.
 Examples:
1. Smoking causes metaplasia in the respiratory tract
2. GERD: the lower oesophageal cells changes from stratified squamous epithelium to columnar cells.

Cell Injury
Cell Injury
Cell Injury
 Cell Death
• With persistent or excessive exposures to injury, injured cells pass
a nebulous “point of no return” and undergo cell death.

• Cell death can occur through:

1. Apoptosis (Programmed cell death): suicide, the cell choose to die

2. Necrosis (Non-Programmed cell Death): Murder, the cell was killed

Cell Injury
29
 1. Apoptosis:
 Apoptosis is programmed cell death that may
occur as cells become weak, unneeded, or
damaged.

 Apoptosis is important in tissue development,

immune defence, and cancer prevention.

Cell Injury
Causes of Apoptosis:

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 2. Necrosis
 Necrosis refers to the condition of Non-programmatic cell death.

 Cell membrane: distortion with increase in permeability and escape of vital

cell constituents, or at an extreme cell membrane rupture.

 Release of destructive enzymes from lysosomes

 Content of the cell is broken down by lysosomal and phagocytic enzymes.

 Breakdown of mitochondria and endoplasmic reticulum

 Altered nucleus: fragmentation or shrinkage

Cell Injury
33
 Types of necrosis:

1. Liquefaction necrosis
2. Caseous necrosis
3. Fat necrosis
4. Fibrinoid necrosis
5. Coagulative necrosis
6. Gangrenous necrosis
Cell Injury
Types of necrosis:
1. Liquefaction necrosis:

 Liquefactive necrosis is a form of necrosis where there is

transformation of the tissue into a liquid viscous mass.

 The affected cell is completely digested by hydrolytic enzymes

leading to a soft, circumscribed lesion which can consist of fluid
with remains of necrotic tissue or pus.

 Liquefactive necrosis is seen in focal bacterial and,

occasionally, fungal infections because microbes
stimulate rapid accumulation of inflammatory cells,
and the enzymes of leukocytes digest (“liquefy”)
the tissue.
Cell Injury
Types of necrosis:
2. Caseous necrosis:

 Occurs when the necrotic cells debris remains in the area for months or years.

 This type of necrosis has a cheese–like appearance, and it is most commonly noted
with pulmonary tuberculosis.

Cell Injury
Types of necrosis:
3. Fat necrosis :

 Typically resulting from the release of activated

pancreatic lipases into the substance of the
pancreas and the peritoneal cavity.

 Lipase enzymes break down intracellular triglycerides into

free fatty acids. These fatty acids then combine with
magnesium, sodium, and calcium, forming soaps.

 These soaps give fat necrosis an opaque, chalky appearance.

Cell Injury
 Types of necrosis:

4. Fibrinoid necrosis

 Occurs when antigen-antibody complexes are deposited in the walls of blood

vessels along with fibrin.

 It is common in the immune-mediated vasculitis e.g., poly arteritis nodosa.

Fibrinoid necrosis in an artery in a

patient with polyarteritis nodosa. The
wall of the artery shows a
circumferential bright pink area
of necrosis with protein
deposition and inflammation.

Cell Injury
Types of necrosis:

5. Coagulative necrosis:

 Usually results from an interruption in blood flow(Ischemia-

inadequate blood flow to an organ or tissue).

 The underlying tissue architecture is preserved for

at least several days after death of cells in the tissue.

 This type of necrosis most often occurs in the kidneys, heart,

and adrenal glands. A wedge-shaped kidney infarct
(yellow) with preservation of the
outlines.

Cell Injury
6. Gangrenous necrosis:
• Gangrenous necrosis It usually refers
to the condition of a limb
(generally the lower leg) that has
lost its blood supply (ischemia ).

• Types of Gangrene: Dry, Wet, and Gas

gangrene.

Cell Injury
 Dry gangrene:

 Dry gangrene is the less harmful form of

gangrene.

 It occurs due to decreased blood supply,

local tissue death and is eventually
removed from the body

 The skin has a dry, dark brown, or black

appearance.

Cell Injury
Wet gangrene:

 Occurs due to combined infection and ischemia.

 In this condition, extensive damage from bacteria and

white blood cells producing a liquid wound.

 Wet gangrene can occur in extremities and internal

organs.

 If this form of gangrene does not receive proper

treatment, the patient develops sepsis and eventually
dies within a few days.

Cell Injury
 Gas gangrene:

• This type of gangrene is the most serious and

has the greatest potential to be fatal.

• Develops because of the presence of

Clostridium, an anaerobic bacterium.

• The bacterium releases toxins that destroy

surrounding cells, so the infection spreads
rapidly.

• The gas released from this process bubbles from

the tissue, often underneath the skin.
Cell Injury
• Press Ctrl + link to watch:

• What is Necrosis vs What is Apoptosis? - YouTube

Cell Injury
Determination and Monitoring of Cell Injury

• There are 4 approaches to determine the types of cells injured and the degree
of damage:

1. Assessment of Functional loss

2. Release of cell constituents from injured cells
3. Assessment of electrical activity
4. Biopsy

Cell Injury
Determination and Monitoring of Cell Injury

1. Assessment of Functional loss: can be revealed by monitoring changes in

body fluids.

For example:
 Plasma levels of Bilirubin, albumin indicate deterioration of liver function.

 H+ concentration in the urine, serum creatinine level in case of kidney damage

 Arterial blood gases (ABG’s): change in O2 and CO2 levels can indicate respiratory
function deterioration

Cell Injury
Determination and Monitoring of Cell Injury
2. Release of cell constituents from injured cells:

a. High levels of intracellular substances outside of the cell

 High plasma levels of K+ ions may indicate hemolysis

 high plasma troponin: myocardial damage

b. High levels of intracellular enzymes outside of the cell

 Creatine phosphokinase (CPK): brain tissue, skeletal or cardiac muscle injury

 Gamma-glutamyl transferase (GGT): liver injury

 Tumors may overproduce intracellular enzymes: Acid phosphatase: cancer prostate

Cell Injury
Determination and Monitoring of Cell Injury
3. Assessment of electrical activity:
E.g., changes in the electrical activity of the heart (ECG), the
brain (EEG) or skeletal muscle (EMG).

ECG EEG machine

machine

Cell Injury
Determination
and Monitoring
of Cell Injury
4. Biopsy:

Direct microscopic examination of

the tissue, obtained through
minor surgery.
e.g., liver biopsy, thyroid biopsy

Cell Injury
Cell Injury
Match ??
Biological cause of cell injury Metaplasia smoking -

Type of necrosis noted with pulmonary Trauma

tuberculosis.

Gas gangrene caseous necrosis long time

Replacement of one adult cell with another adult Virus

cell bacteria - fungi - parasite

Programmatic cell death Hypertrophy

Physical injury of the cell Apoptosis

Cell adaptation by increasing the size of the cell. Is a severely fatal condition which forms
bubbles, often underneath the skin
clostridum

Cell Injury
 Reference:

• Robbins basic pathology, by Vinay Kumar, Abul K. Abbas and Jon C. Aster.
Elsevier; 10 edition (March 8, 2017)

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Thank you