Pathology Dr. KHALID W. ABDULATTAH Lecturer in pathology department/Mousel Medical college Cell Injury, Cell Death, and Adaptations Lecture 2
Types (Patterns) of necrosis
coagulation necrosis √liquifactive necrosisfat necrosiscaseous necrosisfibrinoid necrosis gangreneLiquefactive necrosis:Seen in Ischemic necrosis (infarction) of CNSIn focal bacterial , occasionally fungal infections or Abscess formation in pyogenic infections in all tissues. Enzyme digestion & autolysis ˃ protein denaturation so the area become soft cystic.Grossly: softening & liquefaction of the necrotic tissue (Soft liquid like)Microscopically : complete loss of tissue architecture(Loss of original tissue) , the area contains necrotic debris & macrophage,.
Liquefactive necrosis(Lung Abscess)
Liquefactive necrosis- Brain infarctionCaseous necrosis:
Caseous necrosis (TB), yellow white appears as cheese-likeCaseous necrosis (Lung TB), amorphous structureless granular eosinophilic material
Fat necrosis: Two Types
1- Enzymatic fat necrosis: which usually follow acute pancreatitis due to release of pancreatic enzyme(lipases) necrosis of pancreatic tissue & release of free fatty acid which combined with calcium to produce grossly visible chalky-white areas (fat saponification), 2- Traumatic fat necrosis: occur in the breast after trauma which caused release of fatty acid from cell, this stimulate macrophage infiltration which engulf fat, inflammation massive fibrosis so the lesion grossly become hard mimic carcinoma.
Fat necrosis The areas of white chalky deposits represent foci of fat necrosis with calcium soap formation (fat saponification)
Fat necrosis Eosinophilic cytoplasm, shadowy outlines of necrotic fat cells, with basophilic calcium deposits, surrounded by an inflammatory reaction
Fibrinoid necrosis:
Fibrinoid necrosis (is caused by immune-mediated vascular damage).It is marked by deposition of fibrin-like proteinaceous material in arterial walls, which appears eosinophilic on light microscopy.Gangrenous necrosis (Gangrene)
Gangrenous necrosis is not a specific pattern of cell death, but the term is commonly used in clinical practice. It is usually applied to a limb, generally the lower leg, that has lost its blood supply and has undergone necrosis (typically coagulative necrosis) involving multiple tissue planes. Gangrene may be classified as dry or wet.Dry gangrene
In dry gangrene, the part becomes dry and shrinks and its color changes to dark brown or black. The spread of dry gangrene is slow. The lesion remains localized . The irritation caused by the dead tissue produces a line of inflammatory reaction (i.e., line of demarcation) between the dead tissue of the gangrenous area and the healthy tissue. Dry gangrene usually results from interference with arterial blood supply to a part without interference with venous return and is a form of coagulation necrosis.Wet gangrene
In wet gangrene, the area is cold, swollen, and pulseless.The skin is moist, black. Blebs form on the surface, liquefaction occurs, and a foul odor is caused by bacterial action. There is no line of demarcation between the normal and diseased tissues, and the spread of tissue damage is rapid. The lesion May extend proximally. Wet gangrene primarily results from interference with venous return from the part. Bacterial invasion plays an important role in the development of wet gangrene. Dry gangrene is confined almost exclusively to the extremities, but wet gangrene may affect the internal organs or the extremities. If bacteria invade the necrotic tissue, dry gangrene may be converted to wet gangrene.Dry gangrene -Ischemia
Wet gangrene –D.MFate of necrotic tissue:
Genetic basis of apoptosis: bax, bak & bad genes are apoptotic genes P53 stimulate apoptosis by stimulating synthesis of bax gene bcl-2,bcl-x are antiapoptotic gene . Microscopically: in H&E staining section, apoptotic cell appears reduced in size and contains brightly eosinophilic cytoplasm and a condensed nucleus.Apoptosis of an epidermal cell. The cell is reduced in size and contains brightly eosinophilic cytoplasm and a condensed nucleus.
Examples where apoptosis occurs include: a-Physiologic apoptosis 1-During embryogenesis. i.e. it is responsible for shaping of various organs and structures . 2- Hormone- dependent involution. e.g. endometrium during the menstrual cycle & lactating breast after weaning. 3-Proliferating cell populations: e.g. intestinal epithelium, skin & blood cells. b-Pathological: 1-Atrophy of the prostate after castration. 2-Virally infected cells as in acute viral hepatitis 3- Neoplasia. 4-Radiation 5-Cytotoxic drugs
Differences between apoptosis & necrosis
ApoptosisActive process Occur in single cells Physiological & pathological No inflammatory reaction Programmed process Mechanism; Gene activation Caspases activation causing activation of endonuclease, proteases & transglutaminase
Necrosis
Passive process Affects mass of cells Always pathological Stimulate inflammation Random process Mechanism; ATP depletion Cell membrane injury
Differences between apoptosis & necrosis
Apoptosis
Morphology: Cell shrinkage Nuclear condensation & fragmentation Plasma membrane intact with altered structure. cellular contents intact and released in apoptotic bodies. Apoptotic bodies engulf by macrophages
Necrosis
Morphology Cell swelling Nuclear changes (pyknosis, karyorrhexis & karyolysis) Plasma membrane disrupted. cellular contents digested and leaked out of the cell. Necrotic area infiltrated &cleaned by inflammatory cells
Intracellular accumulation :
Under some circumstances cells may accumulate abnormal amounts of various substances, which may be harmless or associated with varying degrees of injury. The substance may be located in the cytoplasm, within organelles (typically lysosomes), or in the nucleus.Intracellular accumulation :
There are four main pathways of abnormal intracellular accumulations:• Inadequate removal of a normal substance secondary to defects in mechanisms of packaging and transport.• Accumulation of an abnormal endogenous substance as a result of defects in its folding, packaging, transport, or secretion.• Failure to degrade a metabolite due to inherited enzyme deficiencies. • Deposition and accumulation of an abnormal exogenous substance when the cell has neither the enzymatic machinery to degrade the substance nor the ability to transport it to other sites.Hyaline change: It refers to an alteration within cells or in the extracellular space that gives a homogeneous, glassy, pink appearance in routine histologic sections stained with H&E . Example of intracellular hyaline Alcoholic hyaline in hepatocytes Viral inclusion Example of extracellular hyaline Hyaline arteriolosclerosis, Amyloid, Scar.
Pigmentations :
There are two types : Exogenous pigmentations : Carbon (coal dust), accumulation of carbon particles in the lung give its black color called (anthracosis). if there is excess deposition of carbon in the lung it may cause extensive fibrosis & the condition is called pneumoconiosis Tattooing, the pigment inoculated is taken by dermal macrophages (harmless).Accumulation of carbon particles in the lung & LN (anthracosis)
Endogenous pigmentation : 1- Lipofuscin : yellow brown pigment seen inside the cell of the liver , heart & brain ,seen in old ages ( wear & tear pigment) & it is a marker of damage by free radicals and seen in pateints with sever malnutrition and cancer cachexia.Lipofuscin pigment within hepatocytes
2-Melanin: This is an endogenous non-hemoglobin-derived brown-black pigment. The skin pigment is produced from tyrosin by the action of tyrosinase enzyme within the melanocytes.Lesions associated with melanocytes areMoles (nevi) …….benign lesionMelanoma………..Malignant
3-Bilirubin: Yellow-brown pigment . It is derived from the heme portion of hemoglobin. The conversion to bile occur in the liver. Excess accumulation of bilirubin pigment will lead to a clinical condition called jaundice which characterized by yellow discoloration of skin & mucous membrane.
Bilirubin deposition within the liver
4-Hemosidrin: Is a hemoglobin-derived, golden-yellow to brown granules. Excess iron in the body causes hemosiderin to accumulate within the cells.Special stain for iron is Prussian blue or Perl’s stain Excess deposition is termed as hemosiderosis which is either localized or systemic.Hemosiderin pigment in the alveolar macrophages
Prussian blue or Perl’s stainPathological calcification : is the abnormal tissue deposition of calcium salts, together with smaller amounts of iron, magnesium, and other mineral salts & it is of two types : 1-Dystrophic calcification : Deposition of calcium in non viable or dying tissues in the presence of normal serum level of calcium with normal calcium metabolism. such as Areas of necrosis wall of artery in atherosclerosis Disease of valve ( aging or damage valve) Dead parasites & their ova.
dystrophic calcification
Fine, white granules or clumps, often felt as gritty deposits.Dystrophic calcification
Pathogenesis : is not well known , it could be due to one of the followings : Increase in the PH of the tissue i.e. become alkaline . Release of alkaline phosphates which stimulate the deposition of calcium . The presence of cellular product which act as a nucleus that stimulate the deposition of calcium around it .
2-Metastatic calcification : deposition of calcium salts in otherwise normal tissues, and it almost always results from hypercalcemia secondary to some disturbance in calcium metabolism. Causes :(1) increased secretion of parathyroid hormone (PTH), as in hyperparathyroidism due to parathyroid tumors,(2) resorption of bone tissue, as prolong immobilization or in destructive disease of the bone such as multiple myeloma, leukemia & secondary deposit in the bone (e.g. breast cancer)(3) vitamin D–related disorders, including vitamin D intoxication (4) renal failure, which causes retention of phosphate, leading to secondary hyperparathyroidism.Less common cause milk-alkali syndrome, which is due to excessive ingestion of antacids such as milk or calcium carbonate.Organs affected are: kidneys, stomach, lungs , pulmonary veins& systemic arteries.