1. Section 2 Tissue and Cellular Damage

2. 1. Degenerations
Definition: When cellular injury is sublethal and sustained, cells and tissues tend to accumulate substances in abnormal quantities. These materials may be endogenous or exogenous.
Location: Intracellular and/or Extracellular
Nature: Normal substances: increase
Exogenous materials: appearance

3. (1) Intracellular edema (cloudy swelling)
Definition: Accumulation of watery fluid in cells.
Morphologic change:
Gross features: cloudy swelling
Light microscopic features( LM): Parenchymal cells swollen.

4. Early stages: granularity degeneration——a fine granularity like ground-glass in the cytoplasm.
Later stages: hydropic degeneration——clear vacuoles in the cytoplasm Progressive dilatation of the swollen cell
E.M. features: watery fluid in the dilated mitochondria and endoplasmic reticulum.

5. Normal cell Granularity change Hydropic change

6. Left Granularity change in kidney Right Hydropic change

7. Mechanism:
Lack of oxygen
Toxic
Osmotic effect

8. Damage to mitochondria or its enzymatic pathways
Damage to mitochondria or its enzymatic pathways. The diminished formation of ATP affects all the energy requiring reaction in the cell but in particular leads to failure of the sodium pump. Sodium ions enter the cell in exchange for potassium and as the former have a larger hydration shell, there is a net influx of water.

9. (2) Fatty change:
Definition: There is the accumulation of fat in non-fatty cells. Morphologic change:
Gross features: The organ enlarges and becomes yellow, soft, and greasy.
LM: An Fatty change appears as clear vacuoles within parenchymal cells.

10. Liver: Since this organ plays a central role in fat metabolism, the accumulation of fat in toxic conditions can be very considerable, fatty distribution varies with the cause, e. g. :
Poison, Toxins: alcohol, infections, organic solvents etc. fat is found nearest the afferent blood supply (portal venue and hepatic arteriole).

11. Fatty change of liver

13. Confirmation Fresh frozen section Special stain Sudan Ⅲ : orange red
Osmic acid: black

15. Heart:
It occurs in two patterns, in one, prolonged moderate hypoxia, such as that produced by profound anemia, causes intracellular deposits of fat, which create grossly apparent bands of yellowed myocardium alterations with bands of darker, red-brown, uninvolved myocardium (tigered effect). In the other pattern of fatty change produced by more profound hypoxia or diphtheritic myocarditis, the myocardial cells are uniformly affected.

16. tigered effect

17. Kidney:
In most cases fatty change is confined to the epithelium of the convoluted tubules, but in severe poisoning it may affect all structures including the glomerule.

18. Causes: Poisons. e. g. carbon tetrachloride, phosphorus (liver)
Chronic alcoholism (liver)
Infections
Congestive cardiac failure
Severe anaemia
Ischaemia
Diabetes mellitus
Malnutrition and wasting disease.

19. Mechanism: Impaired metabolism of fat
Excessive triglyceride into the cell.

20. W. B. Saunders Company items and derived items Copyright (c) 1999 by W
W.B. Saunders Company items and derived items Copyright (c) 1999 by W.B. Saunders Company
Slide 2.9

21. (3) Hyaline change:
Definition: Not a distinct chemical entity. Various histological or cytological alterations characterized by homogeneous, glasslike appearance in hematoxylin and eosin-stained sections.

22. Types: ① arterioles hyalin
In long-standing hypertension and diabetes mellitus, the walls of arterioles, especially in the kidney, become hyalinized, owing to extravasated plasma protein and deposition of basement membrane material.

23. ② Collagenous fibrous tissue hyalin
in old scars may appear hyalinized, but the physiochemical mechanism underlying this change is not clear.
With H. E. stains, the protein amyloid also has a hyaline appearance.

26.  Intracellular hyaline:
Restorative droplets: Renal tubules with phagolysosomes filled with plasma protein during proteinuria.
Mallory alcoholic bodies: liver cytoplasmic aggregates of fragmented fine filaments and tubules, derived from hepatocyte cytoskeleton.
Russell bodies

27. Protein reabsorption droplets in the renal tubular epithelium
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Protein reabsorption droplets in the renal tubular epithelium

28. (4) Mucoid degeneration:
Definition: Change characterized by accumulation of mucin in intracellular or extracellular loci.
Types: Epithelial: Mucin is composed of sialomucin plus neutral mucopolysaccharide. May accumulate in intracellular or extracellular (if secreted) locations.
Connective tissue: Mucin is predominantly acid mucopolysaccharide, sulfated or carboxylated.

29. Mechanisms of accumulation:
Acute injury: Inflammation (as common cold ) causes hypersecretion by epithelium.
Late injury, repair: Overproduction by fibroblasts as in atherosclerosis, cardiac “myxoma”.

30. Neoplasia: lack of access to duct results in intracellular (signet ring) or extracellular accumulation when cancer secretes much mucin (colloid carcinoma, cystadenoma of ovary).
Endocrine: Thyroid hypofunction produces increase in mucopolysaccharide in dermis (myxedema).

31. (5) Amyloid degeneration
General features: a ‘waxy substance’ (amyloid substance) composed essentially of an abnormal protein is deposited in the extracellular tissue, particularly around the supporting fibres of blood vessels and basement membranes.

32. Post-mortem organs: Detection: Amyloid: deep brown Lugol’s iodine
Normal tissue: yellow

33. Biopsy materials: Amyloid: red and specific apple
LM: Congo red green fluorescence in polarized light.
Normal tissue: pale pink or yellow:
No fluorescence.
EM: specific appearance: closely packed interlacing fibrils 70 to 100 A0 in diameter.

34. Nature of amyloid: Chemical:
protein: variable. related to acute phase reactive protein, which appears in the serum in many inflammatory conditions or derived from fragments of immunoglobulin molecules (particularly lambda light chains).
Carbohydrate: a glycosaminoglycan (e. g. heparin sulphate)——this give the iodine stain.
Physical: the fibrils are organized uniquely——β-pleated.

35. Pathological effects AMYLOID DEPOSITION Pressure on adjacent cells
Blood vessels
Atrophy
Narrowing
Increased permeability
Transudation of protein out of vessels

36. Mechanism β-pleating Amyloid(AA) Amyloid(AL)
Long, continued active inflammation
Abnormal proliferation of plasma cells
Acute phase reactant protein
Abnormal immunoglobulins, esp.
Proteolysis
(? Macrophages)
lambda light chains
Amyloidogenic Protein(AA)
Amyloidogenic protein(AL)
β-pleating
Amyloid(AA)
Amyloid(AL)

37. Amyloidogenic proteins and polypeptides may also occur in other circumstances, e. g. in tumors of endocrine glands producing polypeptide hormones and in cases of rare familial amyloidosis.
In old age, minor deposits of amyloid may occur in the heart and brain; the amyloidogenic protein in these cases is related to prealbumin.

38. Types: Primary: without know cause
Secondary: i. e. associated with chronic inflammatory diseases such as tuberculosis, osteomyelitis, rheumatoid arthritis.
Systemic:
Localized:

39. (6) Pathologic calcification
Definition: Abnormal deposits of calcium salts occur in any tissues except bones and teeth.

40. Type: ① Dystrophic calcification:
Local deposits of calcium may occur in:
Necrotic tissue which is not absorbed.
Tissues undergoing slow degeneration.
The mechanism may be as follows: alteration of enzymes or PH.

42. ② Metastatic calcification:
This alteration may occur in normal tissues whenever there is hypercalcemia. The causes of hypercalcemia include hyper Para thyroidism, vitamin D intoxication, systemic sarcoidosis, hyperthyroidism Addison’s disease.
Metastasis calcification may occur widely throughout the body but principally affects the interstitial tissues of the blood vessels, kidneys, lungs, and gastric mucosa

43. (7) Pigments:
exogenous
Pigments are colored substances
endogenous

44. ① Hemosiderin
Local breakdown of red cells in tissues, e. g. in internal haemorrhage.
Extravasated red cells
Phagocytosis of red cells by macrophages
Haemosiderin (yellow)
(Prussian Blue reaction)
Iron free pigments

45. Hemosiderin granules in liver cells.
Left HE Stain Right Prussian blue reaction

46. ② Bilirubin:
When the bilirubin content of the serum rises above 34μmol/L, jaundice appears.

47. ③ Lipofuscin
This is a yellowish brown pigment having high lipid content, often found in the atrophied cell or old age. It is particularly common in the heart muscle, and the term “brown atrophy” is often applied. It is also found in liver cells, testes and nerve cells.

49. Lipofuscin granules in a cardiac myocyte
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Lipofuscin granules in a cardiac myocyte
Slide 2.18

50. ④ Melanin
Melanin is a normal pigment found in the form of fine brown granules in the skin, choroids of the eye, adrenal medulla.
Local melanin pigmentation e. g. pigmented nevus, melanoma.
Generalized melanin pigmentation e. g. Addison’s disease.
⑤ Dust

51. 2. Cell death Severe damage Metabolism stop Structure destroy
Function lose
Classification: necrosis & apoptosis

52. 1). Necrosis
(1) Definition: Localized death of cell or tissue occurring in the living body.

53. (2) Cell death is recognized by:
① Ultrastructural changes
Margination or progressive loss of nuclear chromatin
Focal rupture of the nuclear membrane
Breakdown of the plasmalemma.
Development of flocculent densities in mitochondria.

54. ② Changes in the nucleus.
Pyknosis: condensation of chromatin of chromatin and shrinkage of the nucleus.
Karyorrhexis: fragmentation of the nucleus.
Karyolysis: dissolution of the nucleus.

55. Normal Pyknosis Karyorrhexis Karyolysis

56. ③ Changes in cytoplasm staining
Positive staining with vital dyes such as Trepan blue which reflects abnormal membrane permeability.
Opacification: denaturation of proteins lead to aggregation with resultant opacification of the cytoplasm.
Eosinophilia: exposure of basic amino groups results in increased affinity for acidic dyes such as eosin.

57. ④ Biochemical changes Release of K+ by dead cells.
Release of enzymes into the blood. e. g. increased plasma levels of creatine kinases, lactic dehydrogenase and aspartate aminotransferase.
Release of protein or protein breakdown products into the blood.

58. ⑤Postmortem change: General of normal tissues occurring dead body, generally distinguished from necrosis by being diffuse and not associated with inflammatory response.
⑥Autolysis: Digestion of cell by enzymes released from lysosome; occurs after cell dies.

59. (3) Types: ① Coagulative necrosis:
Gross features: The necrosis area is swollen, firm and pale.
LM: cell detail is lost, but architecture preserved. The dead cells retain their outline but only indistinctly.
This type of necrosis is frequently caused by lack of blood supply and is exemplified well in infarcts of solid organs, e. g. heart, spleen, kidney.

60. Coagulative necrosis of kidney

63. Special types of coagulative necrosis
A. Caseous necrosis:
Gross features: soft, granular, and friable a cream-cheesy appearance. granular, eosinophilic.
LM: architecture completely destroyed.
i. e. Tuberculosis, syphilis, some sarcoma.

65. Caseous necrosis

66. Special types of coagulative necrosis
B. Gangrene
Definition: necrosis of big tissue with superadded putrefaction, black, fou-smelling appearance.
Necrosis of big tissue putrefactive black, green
Or organ or limb organisms infection appearance
(black or green due to breakdown of haemoglobin)

67. Types of gangrene : a. Dry gangrene:
Conditions: only occurs on the skin surface following arterial obstruction. It is particularly liable to affect the limbs, especially the toes.
Character: mummification

68. Dry gangrene

69. Types of gangrene : b. Wet gangrene:
Conditions: Both arterial and venous obstruction; wet in environment;
Character: wet swollen, foul-smelling, black or green.
Commonly in small intestine, appendix, lung, and uterus, also in limbs.

70. Moist gangrene

71. Types of gangrene : c. Gas gangrene:
Conditions: deep contaminated wounds in which there is considerable muscle damaged by gas formation bacteria.
Character: swollen obviously, gas bubbles formation. The infection rapidly spreads and there is associated severe toxaemia.
Only occasionally in civilian practice but is a serious complication of war wounds.

72. ② Liquefactive necrosis:
Soft and liquid grossly. Enzymes digest the cell and convert it to a formless proteinaceous mass. Ultimately, discharge of the contents forms a cystic space. i. e. central nervous system after ischemic injury; abscesses.

73. Special type: Fat necrosis: Grossly: Opaque and chalky
LM: outline of necrotic fat cells filled with amorphous basophilic material (calcium soaps).
i. e. Digestion of peritoneal fat by pancreatic enzymes in pancreatic inflammation.

74.  Fibrinoid necrosis:
Definition: This is not a true degeneration but a strongly eosinophilic stain like fibrin.
Location: interstitial collagen and blood vessels (small artery and arteriole)
Nature: one kind of necrosis.
e. g. in allergic reactive diseases: active rheumatism, polyarteritis nodose.
in non-allergic reactive diseases: malignant hypertension.

75. Fibrinoid change in blood vessel

76. Vasculitis with fibrinoid necrosis in a patient with active systemic lupus erythematosus

77. 2). Apoptosis
Definition: This term has been used for a mechanism of cell death affecting single cells scattered in a population of healthy cells. It differs from necrosis and represents a physiological process by which effete and abnormal cells die and are eliminated.
Mechanism: gene determined single cell death. Programmed cell death.

78. Process:
The dying process: active metabolic changes in the cell cause cytoplasm and nuclear condensation→ cell disintegrates into apoptotic bodies each surrounded by a plasma membrane.
The elimination process: phagocytosis by surrounding cells followed by rapid digestion.
The presence of intact plasma membranes around the apoptotic bodies explains the absence of inflammation.