Cellular Reaction to Injury ADAPTATION TO ENVIRONMENTAL STRESS Lab:2&3

1. Cellular Reaction to Injury • ADAPTATION TO ENVIRONMENTAL STRESS • Lab:2&3

2. Proliferative endometrium A. A section of the uterus from a woman of reproductiveage reveals a thick endometrium composed of proliferative glands in an abundant stroma. B. Theendometrium of a 75-year-old woman (shown at the same magnification) is thin and contains only a few atrophic and cystic glands. A B

3. Hyperplasia . A. Normal epidermis. B. Epidermalhyperplasia in psoriasis, shown at the same magnification as in A. The epidermis is thickened, owing to an increase in the number ofsquamous cells. B A

4. Squamousmetaplasia . A section of endocervix shows the normal columnar epithelium at both margins and a focus of squamous metaplasia in the center.

5. Dysplasia Dysplastic epithelium of the uterine cervix lacks normal polarity, and individual cells show hyperchromatic nuclei and a greater than normal nucleus-to-cytoplasm ratio. Normal cervical epithelium is at left. Compare, for example, the size and hyperchromaticity of nuclei in the dysplastic cells with the characteristics of normal counterparts at comparable height in the adjacent normal cervix. In dysplasia, cellular arrangement is disorderly, largely lacking appropriate histologic maturation, from the basal layers to the surface.

6. Cell Adaptations Some of these skeletal muscle fibers here show atrophy, compared to normal fibers. The number of cells is the same as before the atrophy occurred, but the size of some fibers is reduced. This is a response to injury by "downsizing" to conserve the cell. In this case, innervation to the small, atrophic fibers was lost. (This is a trichrome stain.)

7. Cell Adaptations The testis at the right has undergone atrophy and is much smaller than the normal testis at the left.

8. Cell Adaptations cerebral atrophy in a patient with Alzheimer disease. The entire size of the brain is reduced, but some parts are more affected than others. The gyri are narrowed and the intervening sulci are widened, most pronounced toward the frontal lobe region.

9. Cell Adaptations Cardiac hypertrophy involving the left ventricle. The number of myocardial fibers does not increase, but their size can increase in response to an increased workload, leading to the marked thickening of the left ventricle in this patient with systemic hypertension.

10. Cell Adaptations The prominent folds of endometrium in this uterus opened to reveal the endometrial cavity are an example of hyperplasia. Cells forming both the endometrial glands and the stroma have increased in number. As a result, the size of the endometrium has increased. This increase is physiologic with a normal menstrual cycle.

11. Cell Adaptations prostatic hyperplasia. The normal adult male prostate is about 3 to 4 cm in diameter and up to 25 gm in weight. The number of prostatic glands, as well as the stroma, has increased in this enlarged prostate seen in transverse section, and as a result, the entire prostate has increased in size. The pattern of increase here is not uniform, but nodular. This increase is in response to hormonal action on the cells, but in this case is not a normal physiologic process, but a pathologic process that could interfere with emptying of the urinary bladder.

12. Cell Adaptations One of the nodules of hyperplastic prostate, with many glands along with some intervening stroma. The cells making up the glands are normal in appearance, but there are just too many of them.

13. Cell Adaptations Metaplasia of laryngeal respiratory epithelium has occurred here in a smoker. The chronic irritation has led to an exchanging of one type of epithelium (the normal respiratory epithelium at the right) for another (the more resilient squamous epithelium at the left). Metaplasia is not a normal physiologic process and may be the first step toward neoplasia.

14. Cell Adaptations Metaplasia of the normal esophageal squamous mucosa has occurred here, with the appearance of gastric type columnar mucosa.

15. Cell Adaptations Cellular dysplasia in the uterine cervix. The normal cervical squamous epithelium has become transformed to a more disorderly growth pattern, or dysplastic epithelium. This is farther down the road toward neoplasia, but dysplasia is still a potentially reversible process.

16. Necrosis Represents the death of living cells due to irreversible cell injury. Depending on the tissue involved, necrosis will assume one of several morphologic patterns associated with the processes involved in cell death

17. Coagulative Necrosis. H&E, 97 is a form of necrosis characterized by preservation of cellular outlines. include necrosis of cardiac myocytes in myocardial infarction and renal necrosis. Image: shows global coagulative necrosis in a transplanted kidney due to compromised perfusion after the transplant. Note the preserved architecture with the glomerulus in the center surrounded by renal tubules. Note also the pale eosinophilic staining with lack of nuclear staining

18. Liquefactive Necrosis. H&E, 48 may be seen after bacterial infections or infarcts involving the central nervous system. Image: shows liquefactive necrosis in an infarcted area of the brain. Note : the intact white matter in the lower portion of the image and the granular liquefactive necrosis in the upper portion of the image

19. Caseous Necrosis. H&E, 97 is a form of necrosis characterized by obliteration of the underlying tissue architecture and the formation of amorphous granular necrotic debris, which grossly appears “cheesy,” hence the name caseous. is highly characteristic of infection with M. tuberculosis and certain fungi and is a type of granulomatousinflammation. Image: shows a lymph node biopsy with granulomatous inflammation and necrosis (to the right of the dashed line) in a patient with H. capsulatum infection.

20. Fat Necrosis. H&E, 193 is a specific type of necrosis seen in fatty, or adipose, tissue. Damage to adipocytes causes release of lipids and cell death followed by aggregates of foamy macrophages containing the released lipids. is seen in damage to fatty tissue by trauma as well as enzymatic digestion as seen in acute pancreatitis. Image: shows fat necrosis in subcutaneous adipose tissue after previous surgery. Note the abundant foamy macrophages containing lipid droplets

21. Pigments • Pigments are colored substances found withintissue macrophages or parenchymal cells. Pigments may be endogenous, those produced by the body, or exogenous, thoseoriginatingoutside of the body. Melanin, lipofuscin, andhemosiderinarethe most common endogenous pigments. The most common exogenous pigment is carbon.

22. Anthracosis. H&E, 155 is an exogenous pigment composed of carbonaceous material from smoking and air pollution. Inhaled carbon is taken up by alveolar macrophages and transported to lymph nodes. Anthracotic tissues are black in gross appearance. Image: This lymph node from the hilar region of the lung shows abundant macrophages containing black carbonaceous material.

23. Melanin. H&E, 388 is a product of melanocytes, can normally be seen in the basal keratinocytes of the skin. In some chronic inflammatory skin conditions, melanin is released into the dermis and taken up by dermal macrophages, or melanophages. Image: Black-brown melanin pigment is present within the papillary dermal macrophages.

24. Lipofuscin. H&E, 388 Also known as lipochrome, lipofuscin is a yellow-brown pigment related to tissue aging . is insoluble and composed of phospholipids and lipids as a result of lipid peroxidation. It is commonly seen in the liver and heart. Image: This hypertrophic cardiac myocyte from an older individual contains lipofuscin granules adjacent to the nucleus.

25. Hemosiderin. H&E, 155 (left); Prussian blue, 155 (right)is the tissue storage form of iron, which appears as granular, coarse, golden-brown pigment. is formed from the breakdown of red blood cells and is taken up into tissue macrophages. It may be seen in tissues in which remote bleeding has occurred or in any condition in which excess iron is presentImages: The image (left) shows abundant hemosiderin-ladenmacrophages in soft tissue where past bleeding has occurred.The image (right) is the same tissue, showing the deep blue staining of hemosiderin.

26. Ulcer . H&E, 25 represents the discontinuity of an epithelial surface, which may involve skin or mucous membranes. may be caused by infectious processes, chemical exposures, prolonged pressure, or vascular compromise. They typically form crater-shaped lesions with a superficial fibrinopurulent layer and an underlying vascular and fibroblastic proliferation called granulation tissue. Image: is a gastric ulcer. Note the intact mucosa transitioning to the ulcer with a fibrinopurulent surface. The formation of gastric ulcers is closely associated with infection with H. pylori. Gastric ulcers may be benign or malignant, representing gastric adenocarcinoma.

27. Hydropic swelling A needle biopsy of the liver of a patient with toxic hepatic injury shows severe hydropic swelling in the centrilobular zone. The affected hepatocytes exhibit central nuclei and cytoplasm distended (ballooned) by excess fluid.

28. Cell Adaptations the centrilobular portion of liver next to a central vein. The cells have reduced in size or been lost from hypoxia. The pale brown-yellow pigment is lipochrome that has accumulated as the atrophic and dying cells undergo autophagocytosis

29. Cell Death Apoptosis is a more orderly process of cell death. It is individual cell necrosis, not simultaneous localized necrosis of large numbers of cells. In this example, hepatocytes are dying individually (arrows) from injury through infection by viral hepatitis. The apoptotic cells are enlarged, pink from loss of cytoplasmic detail, and without nuclei. The cell nucleus and cytoplasm become fragmented as enzymes such as caspases destroy cellular components

30. Cell Death In this fetal thymus there is involution of thymic lymphocytes by the mechanism of apoptosis. In this case, it is an orderly process and part of normal immune system maturation. Individual cells fragment and are consumed by phagocytes to give the appearance of clear spaces filled with cellular debris. Apoptosis is controlled by many mechanisms. Genes such as BCL-2 are turned off and Bax genes turned on. Intracellular proteolytic enzymes called caspases produce much cellular breakdown.

31. Cell Death When there is marked cellular injury, there is cell death and necrosis. This microscopic appearance of myocardium shown here is a mess because so many cells have died that the tissue is not recognizable. Many nuclei have become pyknotic (shrunken and dark) and have then undergone karorrhexis (fragmentation) and karyolysis (dissolution). The cytoplasm and cell borders are no longer recognizable. In this case, loss of the blood supply from a major coronary artery led to ischemia and cell death.

32. Cell Adaptations Here is myocardium in which the cells are dying as a result of ischemic injury from coronary artery occlusion. This is early in the process of necrosis. The nuclei of the myocardial fibers are being lost. The cytoplasm is losing its structure, because no well-defined cross-striations are seen.

33. Cell Death When many cells undergo necrosis at once, then definable patterns of necrosis are produced, depending upon the nature of the injury, the type of tissue, and the length of time. This is an example of coagulative necrosis. This is the typical pattern with ischemia and infarction (loss of blood supply and resultant tissue anoxia). Here, there is a wedge-shaped pale area of coagulative necrosis (infarction) in the cortex of the kidney.

34. Cell Death Microscopically, the renal cortex has undergone anoxic injury at the left so that the cells appear pale and ghost-like. There is a hemorrhagic zone in the middle where the cells are dying or have not quite died along with damaged blood vessels that are leaking, and then normal renal parenchyma at the far right. This is an example of coagulative necrosis.

35. Cell Death The contrast between normal adrenal cortex and the small pale infarct is good. The area just under the capsule is spared because of blood supply from capsular arterial branches. This is an odd place for an infarct, but it illustrates the shape and appearance of an ischemic (pale) infarct well.

36. Cell Death Two large infarctions (areas of coagulative necrosis) are seen in this sectioned spleen. Since the etiology of coagulative necrosis is usually vascular with loss of blood supply, the infarct occurs in a vascular distribution. Thus, infarcts are often wedge-shaped with a base on the organ capsule.

37. Cell Death A large portion of the small intestine is infarcted. The dark red to grey infarcted bowel contrasts with the pale pink normal bowel at the bottom. Some organs such as bowel with anastomosing blood supplies, or liver with a dual blood suppy, are harder to infarct. This bowel was caught in a hernia and the mesenteric blood supply was constricted by the small opening to the hernia sac.

38. Cell Death The two lung abscesses seen here are examples of liquefactive necrosis in which there is a liquid center in an area of tissue injury. One abscess appears in the upper lobe and one in the lower lobe. Liquefactive necrosis is typical of organs in which the tissues have a lot of lipid (such as brain) or when there is an abscess with lots of acute inflammatory cells whose release of proteolytic enzymes destroys the surrounding tissues

39. Cell Death The liver shows a small abscess here filled with many neutrophils. This abscess is an example of localized liquefactive necrosis. Grossly, such an abscess appears yellow to tan because it is filled with pus (purulent exudate).

40. Cell Death This is liquefactive necrosis in the brain of a patient who suffered a "stroke" with focal loss of blood supply to a portion of cerebrum. This type of infarction leads to necrosis which is marked by loss of neurons and neuroglial cells and the formation of a clear space at the center left. As it resolves, the liquefied area becomes a cystic space.

41. Cell Death At high magnification, liquefactive necrosis of the brain demonstrates many macrophages at the right which are cleaning up the necrotic cellular debris. The job description of a macrophage includes janitorial services such as this, particularly when there is lipid debris.

42. Cell Death Grossly, the cerebral infarction at the upper left here demonstrates liquefactive necrosis. Eventually, the removal of the dead tissue leaves behind a cavity.

43. Cell Death As this infarct in the brain is organizing and being resolved, the liquefactive necrosis leads to resolution with cystic spaces.

44. Cell Death Fat necrosis of the pancreas. Cellular injury to the pancreatic acini leads to release of powerful enzymes which damage fat by the production of soaps, and these appear grossly as the soft, chalky white areas seen here on the cut surfaces.

45. Cell Death Microscopically, fat necrosis adjacent to pancreas is seen here. There are some remaining steatocytes at the left which are not necrotic. The necrotic fat cells at the right have vague cellular outlines, have lost their peripheral nuclei, and their cytoplasm has become a pink amorphous mass of necrotic material.

46. Cell Death Gross appearance of caseous necrosis in a hilar lymph node infected with tuberculosis. The node has a cheesy tan to white appearance. is really just a combination of coagulative and liquefactive necrosis that is most characteristic of granulomatous inflammation.

47. Cell Death More extensive caseous necrosis, with confluent cheesy tan granulomas in the upper portion of this lung in a patient with tuberculosis. The tissue destruction is so extensive that there are areas of cavitation (cystic spaces) being formed as the necrotic (mainly liquefied) debris drains out via the bronchi.

48. Cell Death Microscopically, caseous necrosis is characterized by acellular pink areas of necrosis, as seen here at the upper right, surrounded by a granulomatous inflammatory process.

49. Cell Death This is gangrene, or necrosis of many tissues in a body part. In this case, the toes were involved in a frostbite injury. This is an example of "dry" gangrene in which there is mainly coagulative necrosis from the anoxic injury.

50. Cell Death This is gangrene of the lower extremity. In this case the term "wet" gangrene is more applicable because of the liquefactive component from superimposed infection in addition to the coagulative necrosis from loss of blood supply. This patient had diabetes mellitus with severe peripheral vascular disease.