Cellular adaptations and related changes

Hypertrophy is an increase in the size of cells, and so of the organ, without an increase in their number. It is how cells that cannot divide, such as cardiac and skeletal muscle, meet a gradual, sustained increase in workload. Mechanical stretch and growth factors activate signalling pathways that switch on genes; more mRNA is transcribed, more protein is synthesized, and the cell builds additional myofilaments, mitochondria and endoplasmic reticulum.

• Left ventricular hypertrophy in hypertension: the ventricle pumps against higher pressure; myocytes thicken and the wall can measure well over the normal ~1.5 cm. The lecture's autopsy heart has a 2.8 cm wall.
• Compensatory enlargement of the remaining kidney after the other is removed: mainly hypertrophy of tubular cells, with some hyperplasia. No new nephrons form.
• Physiologic hypertrophy: skeletal muscle with training; the uterus in pregnancy (with hyperplasia).

Hyperplasia is an increase in the number of cells. It requires cells that can divide, so it occurs in labile and stable tissues and often accompanies hypertrophy. The lecture lists five drivers.

Whether a tissue can respond with hyperplasia, and whether it can replace cells after injury, depends on how readily its cells divide.

Atrophy is a decrease in the size of cells, and often in their number, so that the tissue or organ shrinks and weighs less. Atrophic cells are smaller but not dead: they have reduced their structural components to a level they can maintain with less demand, blood or nutrition.

The lecture asks how atrophy happens. Two processes shrink the cell: reduced protein synthesis and increased protein breakdown, mainly by the ubiquitin–proteasome pathway. Cells also digest their own organelles by autophagy (“self-eating”): portions of cytoplasm are wrapped in a membrane to form an autophagic vacuole, which fuses with a lysosome and is digested. Undigested debris can persist as brown lipofuscin, which gives atrophic organs a brownish colour (1.8).

Metaplasia is the replacement of one fully differentiated (mature) cell type by another. Mature cells do not transform; instead, stem or reserve cells are reprogrammed by signals from the irritated tissue to produce a different, usually tougher, cell type. The new lining resists the irritant but loses the old one's function.

Dysplasia is disordered growth of epithelium, a potential precursor of cancer if the irritant is not removed. It is not an adaptation. Look for:

• Loss of polarity: cells lose their orderly orientation and maturation from base to surface.
• Pleomorphism: cells and nuclei vary in size and shape.
• Hyperchromatic, enlarged nuclei with an increased nuclear-to-cytoplasmic ratio.
• Mitoses above the basal layer.

Dysplasia is graded by how much of the epithelial thickness is involved. In the cervix, CIN 1 involves the lower third, CIN 2 up to two thirds, and CIN 3 the full thickness, which is also called carcinoma in situ. As long as the basement membrane is intact, the lesion is not invasive. The lecture's diagram traces HPV infection: most infections clear, many low-grade lesions regress, and only some progress to invasion.

Aplasia and hypoplasia are not adaptations to stress. They are failures of development. Aplasia is failure of cell production during embryogenesis, so an organ or part is missing or rudimentary. Hypoplasia is reduced cell production during embryogenesis, so the organ is present but small, with fewer otherwise normal units.