patho babl 1 cell injury

What determines the specific functions of each cell in the body?

Each cell is designed to carry a specific function or functions, which depend on its cellular machinery and metabolic pathways. These specificities are genetically determined.

What is homeostasis?

Homeostasis is the ability of cells to continuously adjust their structure and function within a narrow range to deal with the continually changing extracellular environment and maintain a dynamically stable state.

What happens when cells encounter more severe external changes?

Cells can modify their homeostatic state and achieve a new steady state to counteract the harmful effects of external stresses. These changes are called adaptations.

What is the aim of cellular adaptations?

The aim is to avoid cell injury and death.

What are the possible outcomes of morphological and functional changes caused by injury?

They may be:

• Reversible: the cells return to normal after removal of the offending agent.
• Irreversible: the cells cannot return to normal and ultimately undergo cell death.

What are cellular adaptations?

Adaptations are reversible changes in cells in response to environmental stresses.

What are the two types of cellular adaptations?

1. Physiologic adaptations
2. Pathologic adaptations

What are physiologic adaptations? Give examples.

They are responses of cells to normal physiological stimulation. Examples include hormone-induced enlargement of the breast and uterus during pregnancy.

What are the four major types of cellular adaptation discussed in the lecture?

1. Hypertrophy
2. Hyperplasia
3. Atrophy
4. Metaplasia

What is hypertrophy?

Hypertrophy is an increase in the size of cells, resulting in enlargement of the relevant organ.

Is hypertrophy physiologic or pathologic?

It can be either physiologic or pathologic.

What causes hypertrophy?

It is caused by:

• Increased functional demand
• Specific hormonal stimulation

Give examples of physiologic hypertrophy.

• Skeletal muscle hypertrophy in athletes
• Skeletal muscle hypertrophy in mechanical workers
• Massive physiologic enlargement of the uterus during pregnancy

Why does the uterus enlarge during pregnancy?

Because of estrogen-stimulated smooth muscle hypertrophy and hyperplasia.

Give an example of pathologic hypertrophy.

Cardiomegaly secondary to hypertension.

What happens at the cellular level during hypertrophy?

The stimuli of hypertrophy activate signals that induce a number of genes, which stimulate the synthesis of numerous contractile myofilaments per cell.

What is the functional result of increased contractile myofilaments in hypertrophy?

They improve cellular performance and allow the cell to accommodate the excessive external demand.

Is there a limit to hypertrophic adaptation?

Yes. There is a limit beyond which injury occurs.

What may happen to the myofilaments in excessive cardiac hypertrophy?

Several degenerative changes occur in the myofilaments, eventually resulting in their loss.

What may limit cardiac hypertrophy?

The limitation may be related to the amount of available blood supply to the enlarged cardiac fibers.

What are the consequences of the regressive changes occurring in excessive cardiac hypertrophy?

They result in:

1. Ventricular dilation
2. Ultimately, cardiac failure

What can happen if the stress causing an adaptation is not relieved?

The adaptation can progress to dysfunction.

What is hyperplasia?

Hyperplasia is an increase in the number of cells.

When can hyperplasia occur?

It occurs only when the cells are capable of replication.

Can hyperplasia occur together with hypertrophy?

Yes. Hyperplasia may occur with hypertrophy and often in response to the same stimuli.

What are the two types of hyperplasia?

1. Physiologic hyperplasia
2. Pathologic hyperplasia

What are the two types of physiologic hyperplasia?

1. Hormonal hyperplasia
2. Compensatory hyperplasia

What is hormonal hyperplasia? Give an example.

It is hyperplasia caused by hormonal stimulation. An example is proliferation of the glandular epithelium of the female breast at puberty and during pregnancy.

What causes enlargement of the gravid uterus?

A combination of hypertrophy and hyperplasia.

What is compensatory hyperplasia?

It occurs when a portion of a tissue is removed or diseased, causing proliferation of the remaining cells.

Give an example of compensatory hyperplasia.

After partial resection of the liver, mitotic activity in the remaining cells increases and eventually restores the liver to its normal weight.

What stimulates compensatory liver hyperplasia?

Growth factors produced by:

• Remaining hepatocytes
• Other cells within the organ

What happens after the normal liver mass is restored?

Cell proliferation is turned off by various growth inhibitors.

What is the main cause of pathologic hyperplasia?

Excessive hormonal stimulation or growth factor stimulation.

What are examples of pathologic hyperplasia?

1. Endometrial hyperplasia
2. Skin warts

What causes endometrial hyperplasia?

Persistent or excessive estrogen stimulation of the endometrium.

What is an important clinical consequence of endometrial hyperplasia?

It is a common cause of abnormal uterine bleeding.

What causes skin warts?

Papillomaviruses.

What is the cellular composition of skin warts?

They are composed of masses of hyperplastic epithelium.

Where may the growth factors responsible for skin warts come from?

They may be produced by:

• The virus
• The infected cells

What happens to pathologic hyperplasia when hormonal or growth factor stimulation subsides?

The hyperplasia disappears because the process remains controlled.

What distinguishes pathologic hyperplasia from cancer?

In pathologic hyperplasia, the growth remains responsive to normal regulatory control mechanisms. In cancer, growth control mechanisms become ineffective.

What is atrophy?

Atrophy is a shrinkage in the size of a cell due to loss of its constituent substances.

What is the opposite of hypertrophy?

Atrophy.

What happens when a sufficient number of cells become atrophic?

The entire tissue or organ decreases in size and becomes atrophic.

What are the causes of atrophy?

1. Decreased workload
2. Denervation
3. Diminished blood supply
4. Inadequate nutrition
5. Loss of endocrine stimulation
6. Aging

What is the most common form of atrophy?

Atrophy due to decreased workload.

What causes atrophy due to decreased workload?

Reduced functional demand.

Give examples of decreased workload causing atrophy.

• Immobilization of a limb in a cast after a bone fracture
• Prolonged bed rest

What happens to muscles during prolonged decreased workload?

Muscle cells atrophy and muscular strength is reduced.

Is atrophy due to decreased workload reversible?

Yes. When normal activity resumes, muscle size and function return.

What is denervation atrophy? Give examples.

Atrophy caused by loss of nerve supply to a limb, such as in:

• Poliomyelitis
• Traumatic spinal cord injury

How can diminished blood supply cause atrophy?

Reduced blood supply to a limb or brain can cause atrophy, for example when the lumen of the relevant artery or arteries is narrowed by atherosclerosis.

How can inadequate nutrition cause atrophy?

Starvation and famine can cause atrophy because of inadequate nutritional supply.

Give examples of atrophy caused by loss of endocrine stimulation.

• Postmenopausal endometrial atrophy due to decreased estrogen levels after menopause
• Testicular atrophy due to decreased LH and FSH production, as in hypopituitarism

What type of atrophy is associated with aging?

Senile atrophy.

Are all causes of atrophy physiologic?

No. Some stimuli are physiologic, such as loss of hormone stimulation during menopause, while others are pathologic, such as denervation.

Are the fundamental cellular changes in different forms of atrophy different?

No. The fundamental cellular changes are identical.

What does the cell do during atrophy to remain alive?

The cell retreats to a smaller size at which survival is still possible.

What new state is achieved during atrophy?

A new equilibrium is achieved between cell size and diminished:

• Blood supply
• Nutrition
• Trophic stimulation

What are the two major mechanisms responsible for atrophy?

1. Decreased protein synthesis
2. Increased protein degradation

What additional process commonly accompanies atrophy?

Increased autophagy.

What does autophagy mean?

Autophagy means “self-eating.”

What happens to autophagic vacuoles during atrophy?

Their number increases.

Why does a starved cell undergo autophagy?

The starved cell digests its own components in an attempt to obtain nutrients and survive.

What is metaplasia?

Metaplasia is a reversible change in which normal mature epithelium at a given site is replaced by another mature benign epithelium that is inappropriate for that site.

Why does metaplasia occur?

Cells that are sensitive to a particular stress are replaced by other cell types that are more capable of resisting the adverse environment.

What is the proposed mechanism of metaplasia?

It is thought to arise through genetic reprogramming of stem cells.

Give an example of epithelial metaplasia in smokers.

In habitual cigarette smokers, the normal ciliated columnar epithelium of the trachea and bronchi is replaced, focally or extensively, by stratified squamous epithelium.

Why is squamous metaplasia advantageous in smokers?

The metaplastic squamous epithelium is more resistant to the injurious environment.

What are the adverse effects of squamous metaplasia in the respiratory tract?

1. Loss of protective mechanisms such as mucus secretion and ciliary clearance of particles
2. Predisposition to malignancy

What malignancy often coexists with squamous metaplasia of the bronchi?

Squamous cell carcinoma of the bronchi.

Where else can squamous metaplasia occur?

In the urinary bladder harboring Schistosomal ova.

What type of metaplasia occurs in chronic GERD?

The normal stratified squamous epithelium of the lower esophagus may be replaced by metaplastic intestinal-type columnar epithelium.

Why is intestinal-type columnar epithelium advantageous in chronic GERD?

It is more resistant to the highly acidic regurgitated gastric contents.

When does cell injury occur?

Cell injury occurs when:

1. Cells are exposed to persistent stress and can no longer adapt, or
2. Cells are exposed to inherently damaging agents.

What is reversible cell injury?

It occurs when the injurious agent is mild but persistent or severe but short-lived, producing functional and morphological changes that can be reversed.

What happens if cellular damage continues?

Irreversible cell injury develops.

What is irreversible cell injury?

It is injury in which the cell cannot recover even after removal of the injurious agent, and the cell eventually dies.

What are the major causes of cell injury?

1. Oxygen deprivation
2. Chemical agents
3. Infectious agents
4. Immunologic reactions
5. Genetic defects
6. Nutritional imbalances
7. Physical agents
8. Aging

What is hypoxia?

Hypoxia is insufficient oxygen supply.

Why is hypoxia an important cause of cell injury?

It interferes with aerobic oxidative respiration and is a common cause of cell injury and death.

What is the most common cause of hypoxia?

Ischemia.

What is ischemia?

Ischemia is loss of blood supply to a tissue due to:

• Interference with arterial flow
• Reduced venous drainage

What are the other causes of hypoxia mentioned in the lecture?

• Inadequate oxygenation of blood
• Reduced oxygen-carrying capacity of blood

Give examples of inadequate oxygenation of blood.

Pneumonia and chronic bronchitis.

Give examples of reduced oxygen-carrying capacity of blood.

• Anemia
• Carbon monoxide (CO) poisoning

How can chemical agents cause cell injury?

Various poisons can damage cells by affecting:

• Membrane permeability
• Integrity of cellular enzymes

What are examples of chemical agents that can cause cell injury?

• Environmental pollutants
• Insecticides
• Carbon monoxide
• Alcohol
• Drugs

What infectious agents can cause cell injury?

• Viruses
• Bacteria
• Rickettsiae
• Fungi
• Parasites

Can immunologic reactions cause cell injury?

Yes.

Are immunologic reactions always harmful?

No. They are primarily defensive in nature, but they can also cause cell and tissue injury.

Give examples of immunologic reactions that can cause cell injury.

• Autoimmune diseases
• Allergic reactions

How can genetic defects cause cell injury?

They can produce either gross congenital malformations or point mutations.

Give examples of genetic defects mentioned in the lecture.

• Down syndrome → gross congenital malformations
• Sickle cell anemia → point mutation

Are nutritional deficiencies important causes of cell injury?

Yes. They are still a major cause of cell injury.

What are examples of nutritional deficiencies causing cell injury?

• Protein-calorie insufficiency
• Vitamin insufficiency

What physical agents can cause cell injury?

• Trauma
• Extremes of temperature
• Radiation
• Electric shock
• Sudden changes in atmospheric pressure

How does aging contribute to cell injury?

Aging causes impairment of the replicative and repair abilities of individual cells.

What is the consequence of impaired cellular replication and repair with aging?

Cells have a diminished ability to respond to damage, eventually leading to the death of cells and ultimately the individual.