Transcript Fibrinoid Necrosis

Fibrinoid Necrosis
Fibrinoid necrosis
So 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 with
rheumatic myocarditis.
Sequelae of necrosis
Acute inflammation (autolysis and heterolysis)
Absorption and resolution (break down)

Cyst and abscess
Fall off from a hollow organ
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Ulceration and cavity (erosion)
Fistula and sinus
Organization
Calcification and encapsulation
Repair and regeneration
Sequelae of necrosis
Cyst: A closed space contained fluid behind the
resolution and absorption of necrotic tissue
Abscess: 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 necrosis
Cavity: 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.
Gastric ulceration
慢
性
胃
溃
疡
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.
Organization of a old heart infarct. The scars localize
In the anterior
and lateral walls of left ventricle.
陈旧性心肌梗死机化后瘢痕形成
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 autumn
Concept: 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 apoptosis
The remodeling of embryonal tissue
Hormone 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 cells
Negative selection of immune cells (T cells) in
thymus
Cell 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 dense
nuclei 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
Ladder
pattern
Molecular mechanism of apoptosis: DNA fragmentation is
from the linker regions of nucleosomes.
The sequential ultrastructural changes in necrosis (left)
and apoptosis (right).
Simplified features of coagulative
necrosis and apoptosis
Stimuli
Histologic
changes
coagulative necrosis
hypoxia, toxins
cellular swelling
coagulation necrosis
disruption of organelles
DNA breakdown
random, diffuse
Mechanisms ATP depletion
membrane injury
free radical damage
Tissue reaction
inflammation
apoptosis
physiologic and
pathologic factors
single cells
chromatin condensation
apoptotic bodies
internucleosomal
gene activated
endonucleased
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 with
Decreased function
 Accumulation 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: the
high electronic density materials are residual bodies (arrow).
Cellualr aging: Why?
The mechanism of aging is not clear yet.
Evidences
 The normal human fibroblasts in culture
have about 50 doubling of span-life
 Fibroblasts from neonates: 65 doubling
Why the cell knows their number of divisions?
 Telomere shortening theory
 Clock gene theory (aging clock)
Telomere shortening
After 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
replicate
Activation 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 theories
 Free radicals play an important role in cell
aging
 DNA 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!