Fibrinoid Necrosis

Fibrinoid necrosisSo called “fibrinoid degeneration” in old textbooks of pathology

It appears as strongly eosinophilic, reflexible small granules, pieces or amorphous materials, in the wall of blood vessel or in connective tissue. The original structure is destroyed.

It can be seen in rheumatic fever, allergic vasculitis and other immune complex injury (type III hypersensitivity)

Fibrinoid necrosis in an Aschoff nodule from a patient withrheumatic myocarditis.

Sequelae of necrosisAcute inflammation (autolysis and heterolysis)Absorption and resolution (break down) Cyst and abscess

Fall off from a hollow organ Ulceration and cavity (erosion) Fistula and sinus

OrganizationCalcification and encapsulation Repair and regeneration

Sequelae of necrosisCyst: A closed space contained fluid behind the resolution and absorption of necrotic tissueAbscess: A localized collection of pus in part of the body, formed by tissue disintegration and surrounded by an inflamed area.

Ulcer: A lesion after loss of a part of tissue in surface of body or in a hollow organ.

Erosion: Loss of only the epithelium of mucosa.

Sequelae of necrosisCavity: an empty space connected outside of body through a physiologic channel.Fistula: An abnormal duct or passage resulting from injury, disease, or a congenital disorder that connects a hollow organ to the body surface or to another hollow organ.Sinus: An abnormal duct leading from a necrotic tissue to body surface.

Organization: A process of replacement of necrotic tissue, thrombi, foreign bodies and inflammatory exudate through ingrowth of granulation tissue.

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

慢性胃溃

疡 Gastric

ulceratio

n

A healing peptic ulcer

Lung abscess and tubercular cavities

Cavities in a renal tuberculosis

气管食管

瘘

An esophagus-trachea fistula in patient with esophageal carcinoma.

陈旧性心肌梗死机化后瘢痕形成Organization of a old heart infarct. The scars localizeIn the anterior and lateral walls of left ventricle.

Calcification in a tubercular lymphadenitis

Scar after a skin wound healing

Apoptosis and programmed cell death

Apoptosis-Programmed cell death

Apoptosis: a falling away from, like yellow leaves fall away from tree in autumnConcept: apoptosis is considered as death of single cells in living body which is characteristic by formation of apoptotic bodies and without inflammatory reaction in surrounding tissue.Cell suicide apoptosis Homicide necrosis

Apoptosis-Programmed cell death

Significance of apoptosisThe remodeling of embryonal tissueHormone dependent physiologic and pathologic involution of the Endometrium during menstrual cycle Atrophy of testis in old male

Cell depletion of normal intestinal crypt epithelium and tumor cellsNegative selection of immune cells (T cells) in thymusCell depletion by TP53 molecules

Different from necrosis, apoptosis is a death of single cell

正常腺上皮细胞的凋亡过

程

Morphology of apoptosis

Shrinkage of single cell with eosinophilic cytoplasm and condensed chromatin around the nuclear membrane

Divided into several round or oval globelets with strongly eosinophilic cytoplasm and a part of condensed chromatin (apoptotic bodies)

Phagocytosed by surrounding normal cells or macrophages

Apoptosis is individual cell death, not necrosis (death of large numbers of cells). In this example, liver cells are dying individually (arrows) from injury by viral hepatitis. The shrank cells with densenuclei are called acidophilic change. Smaller globelets are apoptotic bodies (Councilman’s bodies)

Ultrastructural changes of apoptosis cells: shrinkage of cells → Dried all organelle → peripheral condensed chromatin under the nuclear membrane→well limited smaller dense chromatin plaques → divided into several apoptotic bodies

Molecular mechanism of apoptosis: DNA fragmentation isfrom the linker regions of nucleosomes.

Ladderpattern

The sequential ultrastructural changes in necrosis (left)and apoptosis (right).

Simplified features of coagulative necrosis and apoptosis

coagulative necrosis apoptosis

Stimuli hypoxia, toxins physiologic andpathologic factors

Histologic cellular swelling single cellschanges coagulation necrosis chromatin condensation

disruption of organelles apoptotic bodiesDNA breakdown random, diffuse internucleosomalMechanisms ATP depletion gene activated

membrane injury endonucleased free radical damageTissue reaction inflammation no inflammation phagocytosis

A probable mechanism of programmed cell death

Cellular aging

“We grow too soon old and too late

smart.”

Cellualr aging

Cellular aging is the basis of body aging

Aging cells withDecreased functionAccumulation of metabolic products (brown

atrophy-lipofuscin deposition, so called “wear and tear” pigments)

Eventually death through apoptosis, the aged organ appears as atrophy

The yellow-brown granular pigment is lipofuscin (lipochrome) which accumulates over time in cells (particularly liver and heart) as a result of "wear and tear" with aging.

Lipofuscin in the myocardial fiber under the EM: thehigh electronic density materials are residual bodies (arrow).

Cellualr aging: Why?The mechanism of aging is not clear yet.

EvidencesThe normal human fibroblasts in culture ha

ve about 50 doubling of span-lifeFibroblasts from neonates: 65 doubling

Why the cell knows their number of divisions? Telomere shortening theoryClock gene theory (aging clock)

Telomere shorteningAfter each doubling, the cell lost a short piece of DNA in the end of chromosomes, so fidelity of DNA replication in the daughter cells can not be sure.In the normal cells there is a special mechanism to protect the fidelity by using a repeated nontrancribed DNA sequence (TTAGGG)---telomere---as the ends of chromosomes.

Telomere shortening

After each doubling, the telomere has been cut a little to protect the trancribed DNA, so the fidelity of the replication is ensured.

In somatic cells the cell doubling does not continue after multiple cell division, so the cells are aged.

Telomere shortening

But in germ cells, stem cells and neoplastic cells the length of telomere can restore after division by the activation of telomerase. So these cells can continuously replicateActivation of telomerase is thought of a reason of carcinogenesis.

Clock genes

There are some genes which control the life time in some worms (Caenorhabditis elegans: clk-1 gene mutanted worms have only 50% lifespan compared with normal)

Wear and tear theoriesFree radicals play an important role in cell

agingDNA repair mechanism is limited

Summary of cellular aging

Cellular aging is the basis of body aging

Cellular aging involves programmed aging (life timer) and environmental injury (free radicals).

The mechanism of aging can be the highlight of the study of tumorigenesis.

“Long live forever” is impossible.

Thank you for your attention!