We'll unpack the fundamental ways cells and organs adapt:

Hyperplasia and Hypertrophy: Discover how an increase in stress leads to an increase in organ size. This occurs by increasing the size of cells (hypertrophy) and/or the number of cells (hyperplasia). Hypertrophy involves gene activation, protein synthesis, and production of organelles, while hyperplasia involves producing new cells from stem cells. We'll see how these often occur together, like in the uterus during pregnancy, but permanent tissues like cardiac muscle, skeletal muscle, and nerve can only undergo hypertrophy. For example, cardiac myocytes undergo hypertrophy in response to systemic hypertension. We'll also discuss how pathologic hyperplasia, such as endometrial hyperplasia, can sometimes progress to dysplasia and potentially cancer, noting key exceptions like benign prostatic hyperplasia (BPH).

Atrophy: Learn about the decrease in stress that leads to a decrease in organ size (atrophy). This adaptation happens via a decrease in both the size and number of cells. We'll explore the mechanisms: cell number decreases through apoptosis, and cell size decreases through ubiquitin-proteosome degradation of the cytoskeleton and autophagy of cellular components. Ubiquitin "tags" intermediate filaments for destruction by proteosomes, and autophagic vacuoles fuse with lysosomes to break down cellular parts.

Metaplasia: Understand how a change in stress can lead to a change in cell type. This commonly involves one type of surface epithelium changing to another. These metaplastic cells are often better able to handle the new stress. The classic example we'll explore is Barrett esophagus, where the esophagus's normal squamous lining changes to columnar cells better suited for acid reflux. Metaplasia occurs through reprogramming of stem cells. While theoretically reversible if the stressor is removed, persistent stress can cause metaplasia to progress to dysplasia and eventual cancer, such as Barrett esophagus leading to adenocarcinoma. We'll also touch upon Vitamin A deficiency causing metaplasia (keratomalacia) and metaplasia in mesenchymal tissues, like myositis ossificans.

Finally, we'll touch upon Dysplasia, the disordered cellular growth that often represents proliferation of precancerous cells, often arising from longstanding pathologic hyperplasia or metaplasia. We'll discuss examples like cervical intraepithelial neoplasia (CIN). Dysplasia is theoretically reversible if the inciting stress is alleviated, but if it persists, it can progress to carcinoma (which is irreversible). We'll also briefly mention developmental issues like aplasia (failure of cell production) and hypoplasia (decreased cell production) during embryogenesis.