1. General Pathology: Cellular Adaptations Lorne Holland, M.D. Lorne.Holland@ucdenver.edu

2. Cellular Adaptations Given stressors, cells respond by changing their size, function or composition Some of these changes may be, at least initially, beneficial (hypertrophy, hyperplasia, metaplasia) Some of these changes are maladaptive (atrophy, hypoplasia) Left unchecked, some changes can ultimately lead to cancer (dysplasia)

3. Hypertrophy- “too much nourishment” Increase in cell size without an increase in the number of cells Response to increased demand on a cell to do whatever it does Classic example- muscle cells in response to exercise Other examples- thyroid in response to hormonal stimulation during puberty Pathologic example- myocardial cells in response to chronic, systemic hypertension

5. Hyperplasia- “too much growth” Increase in the number of cells without an increase in the size of cells Response to increased demand on a cell to do whatever it does Classic example- regenerating liver after damage/resection Other examples- glandular tissue in breast in response to puberty and pregnancy Pathologic example- endometrial tissue due to abnormal/irregular hormonal cycles

9. Hypertrophy and Hyperplasia These processes do not have to occur separately Usually, both occur though one is by far more predominant Classic example- uterine smooth muscle during pregnancy

11. Atrophy- “no nourishment” Decrease in organ size due to decreased cell size and/or decreased number of cells Physiologic- thymus in adulthood, uterus and testes in old age Pathologic- disuse, ischemia, starvation

13. Hypoplasia- “little growth” Could be visually indistinguishable from atrophy Once normal or supernormal tissue which regresses is atrophic Tissue which never develops to normal size is hypoplastic Similar causes of hypoplasia as atrophy In the extreme, aplasia “no growth” usually due embryologic failure

15. Metaplasia- “changed growth” Transformation of one normal cell type into another normal cells type Transition of ciliated glandular epithelium to squamous epithelium in respiratory tissue of smokers Transition of squamous epithelium to glandular epithelium in esophageal reflux Often, though not always a precursor to dysplasia

17. Dysplasia- “bad growth” Characterized by one or more –Hyperplasia especially with increased mitotic figures –Decreased differentiation

18. Dysplasia- “bad growth” Characterized by one or more (cont.) –Atypia (not typical appearance) Pleomorphism (more forms) –Variable cell size/shape –Variable nucleus size/shape High nuclear to cytoplasm ratio Hyperchromasia (too much color) of nucleus

20. Neoplasia- “new growth” Unregulated growth of abnormal tissue Commonly called a tumor (swelling) May or may not be cancer, depending on clinical behavior (malignant vs. benign)

22. Calcification Abnormal precipitation of calcium in tissue –Dystrophic due to wear and tear with “normal” blood calcium concentrations Atheromatous plaques Heart valves Fat necrosis –Metastatic due to calcium in “normal” tissue with elevated blood calcium concentration Much less frequent but seen in hyperthyroidism, hypercalcemia of malignancy

24. Amyloid Proteins which layer as B pleated sheets to form fibrillar structures Can be highlighted with special stains (Congo red) Small amounts can be seen in tissues of “normal” elderly people

27. Amyloidosis AL amyloid –Due to precipitation of immunoglobulin light chains produced by abnormal plasma cells AA amyloid –Due to precipitation of serum amyloid protein A produced by liver during inflammation (acute phase reaction) Hereditary amyloidosis –Due to genetic defects in proteins which favor precipitation

28. Amyloidosis Can effect virtually any organ with clinical symptoms reflective of organ(s) most affected –Predilection for affecting kidneys (filtering) –Liver and spleen are also often enlarged

29. Questions?