Pathology Department of Pathology Long jie 1. What is Pathology: 1) Scientific study of disease 2) Investigation of Causes (etiology) mechanisms (pathogenesis) manifestation morphology progress sequels 2. Status of Pathology: a bridge Anatomy Histology and embryology Physiology Biochemistry Cytology microbiology pathology Clinical medicine 3. Contents of pathology pathology General pathology Systemic pathology Cell,tissue damage Cardiovascular system repair Disorders of vascular flow Inflammation Neoplasm…… Respiratory system Digestive system…… 4. Methods in pathology 1) Autopsy 2) Biopsy 3) Cytology 4) Electron-microscopy 5) tissue and cell cultivation 6) Animal experiment 7) molecular biology 5. morphological observations: 1) Gross level 2) Light microscopy Chapter 1 Cell injury and adaptation Introduction Physiologic stresses Pathologic stimuli Cells maintain normal homeostasis adaptation Atrophy hyperplasia hypertrophy metaplasia cells Degeneration (reversible) injury Cell death (irreversible) Adaptation(适应) 1. 2. 3. 4. Atrophy Hypertrophy Hyperplasia Metaplasia (萎缩) (肥大) (增生) (化生) Atrophy (萎缩) Shrinkage in the size of the normal cell, tissue and organ by the loss of cell substance. Decrease in Cell size or number Causes and types 1. Aging (生理性~) 2. Inadequate nutrition/ diminished blood supply (营养不良性~) 3. Pressure (压迫性~) 4. Reduced functional activity (废用性~) 5. Interrupted nerve supply (去神经性~) 6. Endocrine deficiency (内分泌性~) Pathologic changes Grossly: The entire tissue or organ diminishes in size ,weight and function. Microscopically: 1. Organelles degradation 2. Increased autophagic vacuoles 3. Residual bodies(e.g., lipofuscin) results Recover Cell death Hypertrophy (肥大) Increase in the size of cells and consequently an increase in the size of the organ. increase in cell size Causes and types Physiologic Pathologic hypertrophy (生理性~) hypertrophy (病理性~) Hypertrophy of myocardium Pathologic changes Grossly: Enlarged organ Microscopically: 1. Increased in the size and number of Organelles 2. Bigger cells Physiologic hypertrophy of the uterus during pregnancy Hyperplasia (增生) Increase in the number of cells and consequently an increase in the size of the organ or tissue. Increase in cell number Causes and types Physiologic hyperplasia (生理性~) Pathologic hyperplasia (病理性~) Most forms of pathologic hyperplasia are instances of excessive hormonal or growth factor stimulation. Pathologic changes Microscopically: Increased cell mitosis Grossly: Enlarged organ results Recover Cancerous proliferation Metaplasia (化生) A reversible change in which one adult cell type( epithelial or mesenchymal) is replaced by another adult cell type. Change in cell type Causes and types Squamous Intestinal epithelial ~ Bone or cartilage metaplasia ~ Pathologic changes Microscopically: 1.cell type change 2. Epithelium __ Epithelium ; mesenchymal__ mesenchymal 3. Adult cells results Recover Induce cancer transformation Cell injury(损伤) causes mechanisms morphology Causes Oxygen deprivation Chemical agents Infectious agents Immunologic reactions Genetic defects Nutritional imbalances Physical agents aging Mechanisms (self-study) Defects in plasma membrane Hypoxia or generation of reactive oxygen species Loss of calcium homeostasis Chemical injury Genetic variation morphology Degeneration Cell death ( reversible ) ( irreversible ) degeneration(变性) The injuried cell accumulate abnormal amounts of various substance in the cell or mesenchyma . Degeneration is always accompanied by diminishing in function. types 1. Cellular swelling (细胞水肿) 2. 3. 4. 5. 6. 7. (脂肪变性) (玻璃样变) (淀粉样变) (黏液样变) (病理性色素沉着) (病理性钙化) Fatty change Hyaline change Amyloidosis Mucoid degeneration Pathologic pigmentation Pathologic calcification Cellular swelling Hydropic change Vacuolar degeneration (水变性) (空泡变性) morphology Microscopically: 1. swollen cells balloon degeneration 2. Small clear vacuoles in the cytoplasm 3. Coarse granules in the cytoplasm( swollen organells). Grossly: entire organ : pallor,turgor,increased weight. 气球样变性 胞浆疏松化 Cellular swelling of liver Fatty change Fatty degeneration (脂肪变性) Refer to any abnormal accumulation of triglycerides within parenchymal cells. Fatty change may caused by toxins, protein malnutrition, diabetes mellitus, obesity and anoxia. Alcohol abuse morphology Microscopically: Clear lipid vacuoles / small droplets in the cytoplasm of parenchymal cells. Grossly: liver ----- enlarge, become yellow, soft and greasy. heart ----- tigered effect 虎斑心 Fatty change of liver Hyaline change Hyaline degeneration (透明变性) morphology Microscopically: 1. Homogeneous, pink, refractile(折光), hyaline protein accumulation 2. Occure in the cytoplasm, connective tissue, and walls of arteriole, the mechanisms are different. amyloidosis Amyloid deposition Amyloid degeneration morphology Microscopically: 1. Homogeneous, pink, proteinglycosaminoglycan accumulation; 2. Occur in the extracellular tissue, basement membrane of blood vessels. E.M.: closely packed interlacing fibrils Pathological pigmentation Colored substances that are either exogenous or endogenous accumulate in /out the cell. types 1. Hemosiderin (含铁血黄素) 2. lipofuscin 3. melanin …… (脂褐素) (黑色素) hemosiderin hemoglobin-derived granular pigment golden-yellow to brown Accumulates in tissues when there is local or systemic excess of iron. lipofuscin wear-and-tear pigment insoluble,brownish-yellow , granular Accumulates in variety of tissues (heart,liver and brain) as a function of age or atrophy. melanin Endogenous, brown-black pigment formed by melanocyte occur when the enzyme tyrosinase catalyzes the oxidation of tyrosine to dihydroxyphenylalanine Pathological calcification The abnormal deposition of calcium salts in a wide variety of tissues except bone and teeth. types 1. Dystrophic calcification (营养不良性钙化) 2. Metastatic calcification (转移性钙化) morphology Microscopically: Intracellular and /or extracellular basophilic deposits. Grossly: white granules or clumps, felt as gritty deposits. Cell death(细胞死亡) when the nuclear is severly injuried , the cell show irreversible changes including cell cessation of metabolic versatility,damage of structure and loss of function. types 1. necrosis (坏死) 2. apoptosis (凋亡) necrosis A sequence of morphologic changes that follow partial cells death in living tissue. microscopically: Increased eosinophilia homogeneous Cytoplasm becomes appears moth-eaten Nuclear ,more vacuolated glassy and changes: pyknosis (核固缩) karyorrhexis(核碎裂) karyolysis (核溶解) types Caseous necrosis (干酪样坏死) Coagulative ~ (凝固性坏死) Dry~(干性坏疽) gangrene (坏疽) Liquefactive ~ (液化性坏死) Fibrinoid ~ (纤维素样坏死) Moist ~(湿性坏疽) Gas ~(气性坏疽) Coagulative necrosis Preservation of the basic structural outline of the cell or tissue by denaturation of proteins in the dead cell. grossly: The necrosis area become swollen, firm ,dull, and lustreless, yellowish. 坏 死 区 microscopically: Nuclei change Cytoplasm is granular, take up more eosin than normal Outline of recognised necrosis cells can be Caseous necrosis tuberculous infection; Cheesy, white gross appearance; Microscopially, structureless , amorphous granular debris; the tissue architecture is completely obliterated. gangrene Necrotic lesion + infected by organisms which cause putrefaction; grossly: brown,green or black discolouration of the tissue; Dry gangrene: skin surface Following arterial obstruction Liable to affect the limbs (e.g. toes脚趾) dry Mild infection Clear borderline moist gangrene: Splanchnic organs Venous congestion + arterial obstruction Liable to affect bowel, gall bladder, uterus,lung e.t. moist severe infection unclear borderline gas gangrene: Deep ,open wound Infected with clostridial organisms. gas Alveolate tissue toxicosis liquefactive necrosis The enzymes decompose the necrosis tissue into fluid. grossly: The necrosis area become sofen, and turns into turbid fluid. (brain, spinal cord) microscopically: Profound loss of the previous histological architecture. Types (self-study): Fat necrosis Purulence Lytic necrosis (脂肪坏死) (化脓) (溶解性坏死) Fibrinoid necrosis Commen feature of connective tissue collagen or diseases accelerated hypertention. and microscopically: The necrosis tissue is filamentous or granule , brightly eosinophilic fibrinoid substance . Collagen Immunoglobulin fibrin Sequels of necrosis Autolyze Dissolved and absorbed Expelled Organization Encapisulation Undergo dystrophic calcification (自溶) (溶解吸收) (分离排出) (机化) (包裹) (钙化) Terms: Erosion Ulcer Sinus Fistula Cavity (糜烂) (溃疡) (窦道) (瘘管) (空腔) apoptosis Programmed cell death dying cell: Shrink and compact Affect single cell form apoptotic bodies no inflammatory reaction 凋亡小体