Morphology of Cell Injury – Adaptive Changes (Atrophy, Hypertrophy, Hyperplasia, Metaplasia, Dysplasia)

Morphology of Cell Injury

• All organ injuries are caused by molecular or structural changes in the cell.
• The process by which cells maintain their steady state is called homeostasis.
• When the cell is under excessive physiological or pathological stress, it may settle into a new steady state:

1. Adaption: An adaptation is a response to a stimulus by modifying morphology and function of a cell. A reversible process.
2. Injury: Stress that exceeds the capacity of the cell to adapt. There are physiological and pathological stresses.

• As a result of its internal and external environments, cells experience a variety of stresses that cause injury.

Causes

• Genetic causes
• Acquired causes

Acquired causes include the following:

1. Psychogenic cause
2. Hypoxia and ischemia
3. Microbial agent
4. Physical agent
5. Chemical agent
6. Nutritional dearrangement

Cell injuries can be divided into two categories:
1. Irreversible cell injury
Necrosis - The morphological changes that accompany necrosis are caused by lethally injured cells. As a result of degradative enzymes on lethally injured cells, it results in the dissolution of the cells due to the loss of membrane integrity and leakage of cellular contents.

Autolysis (self digestion) - An enzyme released from the lysosomes is responsible for the cell's disintegration. Some tissues, such as the pancreas and gastric mucosa, undergo autolysis; others, such as the heart, liver, and kidney, undergo intermediate to slow autolysis.

Heterolysis - Inflammatory mediators such as neutrophils release hydrolytic enzymes to disintegrate cells.

Apoptosis - This type of cell death is also called programmed cell death. Apoptosis is a mode of cell death that involves cell activating enzymes that break down a cell's own DNA, proteins and nuclei.


2. Reversible cell injury
In the absence of an energy-dependent ion pump in the plasma membrane, cellular swelling is the first sign that a cell has been injured and cannot maintain its internal ionic and fluid balance. The alteration is reversible, but can be difficult to detect using a light microscope, although it may still be apparent when the whole organ is examined. Organ weight increases as a result.

Adaptive Changes

Cells undergo adaptations in response to external stressors, such as environmental stress. These adaptations allow them to function and survive better in new environments. It is usually possible to reverse these adaptive changes by removing the stressor. This adaptation, however, may not be sufficient if the stimulus continues, and the cell could become permanently damaged or die.

Atrophy

It is the loss of size and/or number of cells in a tissue or organ that causes atrophy. The process can happen physiologically, such as when the uterus shrinks after birth when hormones that stimulated its growth cease to be produced or pathologically, such as when an organ suffers from inadequate blood supply or nutritional deficiencies.

Atrophy caused by pathology includes the following examples:

• This phenomenon occurs when there is a decrease in functional demand, resulting in muscle atrophy. This can be reversed by physical activity.
• Atrophy due to disconnection of innervation of skeletal muscles, e.g., carpal tunnel syndrome-related wasting of thenar muscles.
• The loss of hormonal stimulation causes an endocrine organ to shrink

Hypertrophy

An increase in the size of a tissue or organ occurs when the number or size of cells increases without an increase in the number of cells. Generally, hypertrophy occurs when a tissue is under increased physiological demands, or when it is being stimulated by hormones. In permanent cell populations like skeletal muscle, hypertrophy is especially prevalent because these cells can't divide because they can't increase their numbers. Increasing the size of the tissue can only be accomplished by increasing the size of the individual cells. The numbers and sizes of cells can both be increased by hypertrophy and hyperplasia in cell populations where division can take place.

Hypertrophy can be characterized as follows:

• Symptoms of pulmonary hypertension include right ventricular hypertrophy
• In the case of paired kidneys, compensatory hypertrophy occurs when one kidney is removed or damaged, causing the other to enlarge to compensate
• Increased size of the uterus during pregnancy (hypertrophy and hyperplasia combined)

Hyperplasia

In hyperplasia, the size of the tissue or organ increases due to an increase in the number of cells without increasing their size. Only stable or labile populations of cells can experience hyperplasia. Unlike neoplasia (cancer) in which cell proliferation is irreversible, hyperplasia remains physiologically controlled. Proliferation is not abnormal in itself, only when it results from a pathological process. A long-term hyperplasia can, however, lead to neoplasia after repeated cell divisions leading to mutations.

Hyperplasia can manifest itself in the following ways:

• The effects of oestrogen on endometrial proliferation during the menstrual cycle
• Iodine deficiency results in thyroid goitre
• Eczema-induced thickening of the epidermis

Metaplasia

Metaplasia occurs when a differentiated cell type changes to a non-differentiated one. Cells can be replaced by others that are adapted to the environment as an adaptive response to stress. It usually occurs in epithelial tissues. Metaplasia is caused by altered differentiation of stem cells. As a result, labile or stable tissues can undergo metaplasia. The cells in metaplastic tumors are fully differentiated, in contrast to the abnormally differentiated epithelium in dysplastic tumors. Although the exact mechanisms leading to metaplastic tissue becoming dysplastic and even cancerous remain unclear, metaplastic tissue can be dysplastic if not treated.

Metaplasia can be seen in the following examples:

• As a result of cigarette smoke, the ciliated bronchial epithelium transforms into stratified squamous epithelium.
• When exposed to persistent acid reflux, the stratified squamous epithelium of the oesophagus becomes the gastric epithelium (Barrett's oesophagus).

Dysplasia

When cells within a tissue become abnormally differentiated, this is called dysplasia. In the early stages, this change is reversible, however, as the dysplasia worsens, it becomes less likely to be reversed, and neoplasia and cancer become more likely to develop. Dysplastic cells commonly appear in the cervix or endocervical canal as a clinical example of dysplasia. Infected women often become infected with the human papillomavirus (HPV), which can be detected through a cervical smear test. The risk of cervical cancer is high for women with severe dysplasia of the cervix, but typically, cervical dysplasia is highly treatable.

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