TOPIC 5
CELLULAR PATHOLOGY
Pathology, in the broadest terms, is the study of disease. Disease occurs for many reasons.
Some diseases represent spontaneous alterations in the ability of a cell to proliferate and function
normally, and in other cases, disease results when external stimuli produce changes in the cell's
environment that make it impossible for the cell to maintain homeostasis. In such situations, cells
must adapt to the new environment. These adaptations include hyperplasia, hypertrophy,
atrophy, and metaplasia, and can be physiologic or pathologic, depending upon whether the
stimulus is normal or abnormal. A cell can adapt to a certain point, but if the stimulus continues
beyond that point, failure of the cell, and hence the organ, can result. If cells cannot adapt to the
pathologic stimulus, they can die. The four basic types of cellular adaptation to be discussed in
this section are hyperplasia, hypertrophy, atrophy, and metaplasia.
Hyperplasia
Basic description: Increase in the number of cells.
Types of hyperplasia
Physiologic hyperplasia: Occurs due to a normal stressor. For example, increase in the
size of the breasts during pregnancy, increase in thickness of endometrium during
menstrual cycle, and liver growth after partial resection.
Pathologic hyperplasia: Occurs due to an abnormal stressor. For example, growth of
adrenal glands due to production of adrenocorticotropic hormone (ACTH) by a pituitary
adenoma, and proliferation of endometrium due to prolonged estrogen stimulus.
Important point regarding hyperplasia: Only cells that can divide will undergo hyperplasia;
therefore, hyperplasia of the myocytes in the heart and neurons in the brain does not occur.
Hyperplasia is an increase in the number of cells. It is the result of increased cell mitosis or
division (also referred to as cell proliferation). The two types of physiologic hyperplasia
are compensatory and hormonal. Compensatory hyperplasia permits tissue and organ
regeneration. It is common in epithelial cells of
the epidermis and intestine, liver hepatocytes, bone marrow cells, and fibroblasts. It occurs to a
lesser extent in bone, cartilage, and smooth muscle cells. Hormonal hyperplasia occurs mainly in
organs that depend on estrogen. For example, the estrogen-dependent uterine cells undergo
hyperplasia and hypertrophy following pregnancy. Pathologic hyperplasia is an abnormal
increase in cell division. A common pathologic hyperplasia in women occurs in
the endometrium and is called endometriosis.
Hypertrophy
Basic description: Increase in the size of the cell.
Types of hypertrophy
Physiologic hypertrophy: Occurs due to a normal stressor. For example, enlargement of
skeletal muscle with exercise.
Pathologic hypertrophy: Occurs due to an abnormal stressor. For example, increase in
the size of the heart due to aortic stenosis. Aortic stenosis is due to a change in the aortic
valve, which obstructs the orifice, resulting in the left ventricle working harder to pump
blood into the aorta.
Morphology of hyperplasia and hypertrophy: Both hyperplasia and hypertrophy result in an
increase in organ size; therefore, both cannot always be distinguished grossly, and microscopic
examination is required to distinguish the two
Atrophy
Atrophy is a decrease in cell size. If enough cells in an organ undergo atrophy the entire organ
will decrease in size. Thymus atrophy during early human development (childhood) is an
example of physiologic atrophy. Skeletal muscle atrophy is a common pathologic adaptation to
skeletal muscle disuse (commonly called "disuse atrophy"). Tissue and organs especially
susceptible to atrophy include skeletal muscle, cardiac muscle, secondary sex organs, and
the brain.
Hypertrophy
Illustration of adipocytes of different sizes. In response to dietary excess energy intake,
adipocytes adapt by increased storage of lipids, resulting in cellular hypertrophy.
Hypertrophy is an increase in cell size and volume. If enough cells of an organ hypertrophy the
whole organ will increase in size. Hypertrophy may involve an increase in intracellular protein as
well as cytosol (intracellular fluid) and other cytoplasmic components. For
example, adipocytes (fat cells) may expand in size by depositing more lipid within
cytoplasmic vesicles. Thus in human adults, increases in body fat tissue occurs mostly by
increases in the size of adipocytes, not by increases in the number of adipocytes.[1] Hypertrophy
may be caused by mechanical signals (e.g., stretch) or trophic signals (e.g., growth factors). An
example of physiologic hypertrophy is in skeletal muscle with sustained weight bearing exercise.
An example of pathologic hypertrophy is in cardiac muscle as a result of hypertension.
Metaplasia
Metaplasia occurs when a cell of a certain type is replaced by another cell type, which may be
less differentiated. It is a reversible process thought to be caused by stem cell
reprogramming. Stem cells are found in epithelia and embryonic mesenchyme of connective
tissue. A prominent example of metaplasia involves the changes associated with the respiratory
tract in response to inhalation of irritants, such as smog or smoke. The bronchial cells convert
from mucus-secreting, ciliated, columnar epithelium to non-ciliated, squamous epithelium
incapable of secreting mucus. These transformed cells may become dysplastic or cancerous if the
stimulus (e.g., cigarette smoking) is not removed. The most common example of metaplasia
is Barrett's esophagus, when the non-keratinizing squamous epithelium of the esophagus
undergoes metaplasia to become mucinous columnar cells, ultimately protecting the esophagus
from acid reflux originating in the stomach. If stress persists, metaplasia can progress to
dysplasia and eventually carcinoma; Barrett's esophagus, for example, can eventually progress to
adenocarcinoma.
Dysplasia
Dysplasia refers to abnormal changes in cellular shape, size, and/or organization. Dysplasia is
not considered a true adaptation; rather, it is thought to be related to hyperplasia and is
sometimes called "atypical hyperplasia". Tissues prone to dysplasia
include cervical and respiratory epithelium, where it is strongly associated with the development
of cancer; it may also be involved in the development of breast cancer. Although dysplasia is
reversible, if stress persists, then dysplasia progresses to irreversible carcinoma.
CELLULAR AGEING
Cellular ageing is generally defined as the progressive decline in the resistance to stress and
other cellular damages, causing a gradual loss of cellular functions and resulting eventually in
cell death. There are two types of cellular ageing:
1. Replicative ageing, which refers to the limited number of divisions that a single cell can
attain.
2. Chronological ageing, which is measured in time units by determining the mean and the
maximum survival time of a post-mitotic yeast population and not of single cells.
To date, the mechanisms of ageing, whether replicative or chronological, are ill-defined.
Research using different genetic model organisms led to the identification of about twenty genes
that can prolong the lifespan of an organism .
