PathologyPathologyPathologyPathology

Department of Pathology

Long jie

1. What is Pathology:

1) Scientific study of disease

Causes (etiology)

mechanisms (pathogenesis)

2) manifestation

progress

sequels

Investigation of

morphology

2. Status of Pathology: a bridge

Anatomy

Histology and embryology

Physiology Biochemistry Cytology microbiology

pathologyClinical medicine

3. Contents of pathology

pathology

General pathology

Systemic pathology

Cell,tissue damage

repair

Disorders of vascular flow

Inflammation

Neoplasm……

Cardiovascular system

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 1Chapter 1Chapter 1Chapter 1

Cell injury and adaptation

IntroductionIntroduction

Cells maintain normal homeostasis

Physiologic stresses

Pathologic stimuli

cells

adaptation Atrophy hypertrophy

hyperplasia metaplasia

injuryDegeneration (reversible)

Cell death (irreversible)

AdaptationAdaptation （适（适应）应）

1. Atrophy ( 萎缩）2. Hypertrophy ( 肥大 )

3. Hyperplasia ( 增生 )

4. Metaplasia ( 化生 )

Atrophy Atrophy (( 萎萎缩）缩）

Atrophy Atrophy (( 萎萎缩）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 typesCauses 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 changesPathologic 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)

resultsresults

RecoverCell death

Increase in the size of cells and

consequently an increase in the

size of the organ.

increase in cell size

Hypertrophy Hypertrophy （肥（肥大） 大）

Hypertrophy Hypertrophy （肥（肥大） 大）

Causes and typesCauses and types

Physiologic hypertrophy ( 生理性～）

Pathologic hypertrophy （病理性～）

Hypertrophy of myocardium

Pathologic changesPathologic changes

Grossly:

Enlarged organ

Microscopically:

1. Increased in the size and number of Organelles

2. Bigger cells

Physiologic hypertrophy of the uterus during pregnancy

Increase in the number of cells and

consequently an increase in the size of

the organ or tissue.

Increase in cell number

Hyperplasia Hyperplasia （增（增生）生）

Hyperplasia Hyperplasia （增（增生）生）

Causes and typesCauses 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 changesPathologic changes

Microscopically:

Increased cell mitosis

Grossly:

Enlarged organ

resultsresults

RecoverCancerous proliferation

A reversible change in which one adult c

ell type( epithelial or mesenchymal) is rep

laced by another adult cell type.

Change in cell type

Metaplasia Metaplasia （化（化生）生）

Metaplasia Metaplasia （化（化生）生）

Causes and typesCauses and types

Squamous metaplasia

Intestinal epithelial ~

Bone or cartilage ~

Pathologic changesPathologic changes

Microscopically:

1.cell type change

2. Epithelium __ Epithelium ;

mesenchymal__ mesenchymal

3. Adult cells

resultsresults

RecoverInduce cancer transformation

causes mechanisms morphology

Cell injuryCell injury （损伤）（损伤）

Causes Causes

Oxygen deprivation

Chemical agents

Infectious agents

Immunologic reactions

Genetic defects

Nutritional imbalances

Physical agents

aging

MechanismsMechanisms (self-study)(self-study)

Defects in plasma membrane

Hypoxia or generation of reactive

oxygen species

Loss of calcium homeostasis

Chemical injury

Genetic variation

morphology morphology

Degeneration ( reversible )

Cell death ( irreversible )

degenerationdegeneration （变（变性）性）

The injuried cell accumulate abnormal a

mounts of various substance in the cell o

r mesenchyma . Degeneration is always

accompanied by diminishing in function.

typestypes

1. Cellular swelling ( 细胞水肿）2. Fatty change ( 脂肪变性 )

3. Hyaline change ( 玻璃样变 )

4. Amyloidosis ( 淀粉样变 )

5. Mucoid degeneration ( 黏液样变 )

6. Pathologic pigmentation ( 病理性色素沉着 )

7. Pathologic calcification ( 病理性钙化 )

Cellular Cellular swellingswellingCellular Cellular swellingswelling

Hydropic change ( 水变性 )

Vacuolar degeneration ( 空泡变性 )

morphologymorphologymorphologymorphology

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.

Cellular swelling of liver

胞浆疏松化

气球样变性

Fatty changeFatty changeFatty changeFatty change

Fatty degeneration ( 脂肪变性 )

Refer to any abnormal accumulation of triglycerides within parenchymal cells.

Fatty change may caused by toxins, protei

n malnutrition, diabetes mellitus, obesity a

nd anoxia.

Alcohol abuse

morphologymorphologymorphologymorphology

Microscopically: Clear lipid vacuoles / small droplets in the cytopl

asm of parenchymal cells.

Grossly: liver ----- enlarge, become yellow, soft and greasy. heart ----- tigered effect 虎斑心

Fatty change of liver

Hyaline changeHyaline changeHyaline changeHyaline change

Hyaline degeneration ( 透明变性 )

morphologymorphologymorphologymorphology

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.

amyloidosisamyloidosisamyloidosisamyloidosis

Amyloid deposition

Amyloid degeneration

morphologymorphologymorphologymorphology

Microscopically:

1. Homogeneous, pink, protein-glycosaminoglycan accumulation;

2. Occur in the extracellular tissue, basement membrane of blood vessels.

E.M.:

closely packed interlacing fibrils

Pathological Pathological pigmentationpigmentationPathological Pathological pigmentationpigmentation

Colored substances that are either

exogenous or endogenous

accumulate in /out the cell.

typestypes

1. Hemosiderin ( 含铁血黄素）2. lipofuscin ( 脂褐素 )

3. melanin ( 黑色素 )

……

hemosiderinhemosiderin

hemoglobin-derived granular pigment golden-yellow to brown Accumulates in tissues when there is

local or systemic excess of iron.

lipofuscinlipofuscin

wear-and-tear pigment

insoluble,brownish-yellow , granular

Accumulates in variety of tissues

(heart,liver and brain) as a function of

age or atrophy.

melaninmelanin

Endogenous, brown-black pigment

formed by melanocyte

occur when the enzyme tyrosinase catal

yzes the oxidation of tyrosine to dihydro

xyphenylalanine

Pathological Pathological calcificationcalcificationPathological Pathological calcificationcalcification

The abnormal deposition of

calcium salts in a wide variety of

tissues except bone and teeth.

typestypes

1. Dystrophic calcification

( 营养不良性钙化）

2. Metastatic calcification

( 转移性钙化 )

morphologymorphology

Microscopically:

Intracellular and /or extracellular basophilic deposits.

Grossly:

white granules or clumps, felt as gritty deposits.

Cell deathCell death （细胞死亡）（细胞死亡）

when the nuclear is severly injuried , the

cell show irreversible changes includ

ing cell cessation of metabolic versati

lity,damage of structure and loss of f

unction.

typestypes

1. necrosis ( 坏死 )

2. apoptosis ( 凋亡 )

necrosisnecrosisnecrosisnecrosis

A sequence of morphologic changes

that follow partial cells death in

living tissue.

microscopically:

Increased eosinophilia ,more glassy homogeneous

Cytoplasm becomes vacuolated and appears moth-eaten

Nuclear changes:

pyknosis （核固缩） karyorrhexis （核碎裂） karyolysis ( 核溶解）

typestypes

Caseous necrosis ( 干酪样坏死 )

gangrene ( 坏疽 )

Dry~( 干性坏疽 )

Moist ~( 湿性坏疽 )Gas ~( 气性坏疽 )

Coagulative ~( 凝固性坏死）

Liquefactive ~( 液化性坏死 )

Fibrinoid ~( 纤维素样坏死 )

Coagulative Coagulative necrosisnecrosis

Coagulative Coagulative necrosisnecrosis

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, fi

rm ,dull, and lustreless, yellowish.

坏死区

microscopically:

Nuclei change

Cytoplasm is granular, take up more eosin than normal

Outline of necrosis cells can be recognised

Caseous necrosisCaseous necrosis

tuberculous infection; Cheesy, white gross appearance; Microscopially, structureless , amor

phous granular debris; the tissue architecture is completely obliterated.

gangrenegangrene

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, uter

us,lung e.t. moist severe infection unclear borderline

gas gangrene:

Deep ,open wound Infected with clostridial organisms. gas Alveolate tissue toxicosis

liquefactive necrliquefactive necrosisosis

liquefactive necrliquefactive necrosisosis

The enzymes decompose the necrosis tissue into fluid.

grossly:

The necrosis area become sofen, and t

urns into turbid fluid.

(brain, spinal cord)

microscopically:

Profound loss of the previous histological architecture.

Types (self-study):

Fat necrosis ( 脂肪坏死 )Purulence ( 化脓 )Lytic necrosis ( 溶解性坏死 )

Fibrinoid Fibrinoid necrosisnecrosis

Fibrinoid Fibrinoid necrosisnecrosis

Commen feature of collagen or connective tissue diseases and accelerated hypertention.

microscopically: The necrosis tissue is filamentous or gran

ule , brightly eosinophilic fibrinoid substance .

Collagen Immunoglobulin fibrin

Sequels of necrosisSequels of necrosis

Autolyze ( 自溶 ) Dissolved and absorbed ( 溶解吸收 ) Expelled ( 分离排出 ) Organization ( 机化 ) Encapisulation ( 包裹 ) Undergo dystrophic calcification ( 钙化 )

Erosion ( 糜烂 )Ulcer ( 溃疡 )Sinus ( 窦道 )Fistula ( 瘘管 )Cavity ( 空腔 )

Terms:

apoptosisapoptosis

Programmed cell deathdying cell: Shrink and

compact Affect single cell form apoptotic bodies no inflammatory reaction

凋亡小体