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SECTION 2 CELL INJURY
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◆Reversible
◆ Irreversible
Cellular Swelling
Fatty Change
Hyaline Change
Amyloid Change
Mucoid Change
Pathologic Pigmentation
Pathologic Calcification
Cell Death
Degeneration
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Reversible Cell Injury
Intracellular &/or extracellular abnormal
accumulation:
⚫ Excess amounts of various normal
substances (water,lipids,proteins,pigments)
⚫ Abnormal substances (exogenous,
endogenous)
Degeneration
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Cellular Swelling
Intracellular accumulation
⚫ Sodium
⚫ Water
(hydropic degeneration)
(1)
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Cellular Swelling (2)
Morphology
NE:
LM:
EM：
⚫ Cloudy swelling
⚫ Increase in the weight
the organs
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Cellular Swelling (3)
Morphology
NE:
LM:
EM：
⚫Large
⚫Small & fine granules in the cytoplasm
the cells
Ballooning change
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Cellular Swelling (4)
Morphology
NE:
LM:
EM：
Swelling
⚫ Endoplasmic reticulum
⚫ Mitochondria
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Injurious agents
Mitochondria damage
Mechanisms
Water & sodium
within the cells
Cellular swelling
ATP
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Fatty Change
Intracellular abnormal accumulation:
⚫ Triglycerides
(1)
Steatosis
Often occurred in the liver and the heart
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Morphology
Fatty Change (2)
NE:
LM:
EM：
⚫ Large
⚫ Yellow
⚫ Soft
⚫ Greasy
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Morphology
Fatty Change (3)
NE:
LM:
EM：
⚫ Round, clear vacuoles
⚫ Orange-red color by staining with
Sudan Ⅲ or Oil Red O (Frozen tissue
sections!)
Fat vacuoles
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Morphology
Fatty Change (4)
NE:
LM:
EM：⚫ Membrane-bound inclusions
Liposomes
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Fatty Change of the Liver
◆ Mild fatty change:
Not affect the gross appearance
◆ With progressive accumulation:
NE
⚫ Large
⚫ Yellow
⚫ Soft
⚫ Greasy
Fatty Liver: Severe & diffuse fatty change
(1)
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Fatty liver
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LM
Fatty Change of the Liver (2)
Fat vacuoles
Small , in the cytoplasm
around the nucleus
Displacing the nucleus
to the cell periphery
Fatty cysts
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Fatty change of the liver（Sudan Ⅲ）hongdeng@zju.edu.cn
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Mechnisms
Fatty Change of the Liver (3)
⚫Overproduction of triglycerides
⚫Excessive entry of free fatty acids into liver
⚫Enhanced fatty acid synthesis from acetate
⚫Decreased fatty acid oxidation
⚫Decreased apoprotein synthesis
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Fatty Change of the Myocardium
◆ Mild fatty change:
Not affect the gross appearance
◆ With progressive accumulation:
NE
Tigered effect
Apparent bands of yellowed myocardium
alternating with bands of
dark,red-brown,uninvolved myocardium
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Fatty change
of heart
muscle
(tigered effect)
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Fatty change of
heart muscle
(tigered effect)
Sudan-
hematoxylin
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A homogeneous, translucent, pink
appearance in HE staining
Hyaline Change
Intracellular or extracellular abnormal
accumulation:
⚫ Proteins
A descriptive morphologic term
(1)
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◆ Hyaline change in arteriolosclerosis
e.g. Hypertension, Diabetes
◆ Hyaline change in connective tissues
e.g. Old scars
◆ Hyaline change within the cytoplasm
e.g. Nephrotic syndrome, Russell
bodies, Mallory body
Hyaline Change (2)
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Vascular pathology in hypertension. A, Hyaline arteriolosclerosis. The
arteriolar wall is hyalinized, and the lumen is markedly narrowed. hongdeng@zju.edu.cn
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Chronic glomerulonephritishongdeng@zju.edu.cn
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Protein reabsorption droplets in the renal tubular epithelium
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Mallory bodies in liver cells
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Amyloidosis
Extracellular abnormal accumulation:
⚫ Amyloid
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Physicochemical characteristics of amyloid
◆ +Iodine--- a brown color--- +H2SO4 --- blue
◆ Staining: Congo red--- red,
HE--- homogeneous pink
◆ EM: nonbranching fibrils 7.5-10 nm wide
◆ X-ray: a pleated –sheet structure
(rendering protein very resistant to
enzymatic degradation, contributing
to its accumulation in tissues)
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Mucoid Change
Extracellular abnormal accumulation:
⚫ Mucopolysaccharide
(Glycosaminoglycans, Hyaluronic Acid)
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Pathologic Pigmentation
Intracellular & extracellular abnormal
accumulation:
⚫ Exogenous
⚫ Endogenous
Colored substances
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Pathologic Pigmentation
⚫ Exogenous
⚫ Endogenous
✓ Hemosiderin
✓ Lipofuscin
✓ Melanin
✓ Carbon
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Carbon
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Hemosiderin granules in macrophages in the alveolus
Hemosiderin
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Hemosiderin granules in liver cells. A, H&E B, Prussian blue reaction
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Lipofuscin
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Melanin
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Pathologic Calcification
Intracellular & extracellular abnormal
accumulation:
⚫ Calcium salts
1. Except for the bones and teeth
2. Pathologic conditions
(1)
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Metastatic calcification in the wall of the stomach
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◆ Dystrophic Calcification
In areas of necrosis
No calcium metabolic derangements
◆ Metastatic calcification
In normal tissues
Some calcium metabolic derangements
Pathologic Calcification (2)
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2. Apoptosis
1. Necrosis
Cell Death
Irreversible Cell Injury
A sequence of morphologic changes
that follow cell death in living tissue
A distinctive and important mode
of cell death regulated by genes
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Necrosis
Two essentially concurrent processes to
produce the morphologic changes :
1. Enzymatic digestion of the cell
2. Denaturation of proteins
(1)
Autolysis
Heterolysis
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Necrosis
Basic pathologic changes
Types of necrosis
Sequences of necrosis
(2)
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Necrosis
Basic Pathologic Changes
(3)
◆ Nuclear changes
Karyolysis
Pyknosis
Karyorrhexis
◆ Cytoplasm Increased eosinophilia
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Necrosis
Types of Necrosis
(4)
◆ Liquefactive necrosis
◆ Fat necrosis
◆ Coagulative necrosis
◆ Caseous necrosis
◆ Gangrene
◆ Fibrinoid necrosis
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Coagulative Necrosis
◆ A mass of coagulated, pink-staining,
homogeneous cytoplasm
◆ Preservation of the basic structure
outline of the coagulated cell or
tissue for several days
◆ In solid organs (kidney, heart, spleen )
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Liquefactive Necrosis
◆ Liquefaction of necrotic cells
◆ Condition: Presence of more
abundant proteolytic enzymes
◆ Most often in suppurative
inflammation & in the brain
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A small abscess in the liver.
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Liquefactive necrosis of the brain
(Encephalomalacia)
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Caseous Necrosis
◆ A distinctive form of coagulative
necrosis
◆ Cheese-like
◆ An amorphous coarsely granular
eosinophilic debris
◆ Most often in foci of TB
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A tuberculous lung with a large area of caseous
necrosis. The caseous debris is yellow-white and
cheesy.
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Fat Necrosis
◆ A special type of liquefactive necrosis
◆ Focal areas of fat destruction
◆ Calcium soaps
◆ Enzymatic fat necrosis(acute pancreatitis)
◆ Nonenzymatic fat necrosis (following
direct trauma to adipose tissue &
extracellular liberation of fat)
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Foci of fat necrosis with saponification in the mesentery.
The areas of white chalky deposits represent calcium
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This is fat necrosis of the pancreas. Cellular injury to the pancreatic acini
leads to release of powerful enzymes which damage fat by the production
of soaps, and these appear grossly as the soft, chalky white areas seen
here on the cut surfaces.
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Microscopically, fat necrosis is seen here. Though the
cellular outlines vaguely remain, the fat cells have lost
their peripheral nuclei and their cytoplasm has become a
pink amorphous mass of necrotic material.
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Gangrene
◆ Extensive tissue necrosis
◆ Secondary bacterial infection
⚫ Dry gangrene
⚫ Wet gangrene
⚫ Gas gangrene
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This is gangrene, or necrosis of many tissues in a body
part. In this case, the toes were involved in a frostbite
injury. This is an example of "dry" gangrene in which there
is mainly coagulative necrosis from the anoxic injury.
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Toxic megacolon. Complete cessation of colon
neuromuscular activity has led to massive dilatation of
the colon and black-green discoloration signifying
gangrene and impending rupture.
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The small intestine is infarcted. The dark red to grey infarcted bowel
contrasts with the pale pink normal bowel at the bottom. Some organs such
as bowel with anastomosing blood supplies, or liver with a dual blood suppy,
are hard to infarct. This bowel was caught in a hernia and the mesenteric
blood supply was constricted by the small opening to the hernia sac.
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Fibrinoid Necrosis
◆ A type of connective tissue necrosis
◆ Loss of normal structure
◆ A homogeneous,bright pink-staining
necrotic material that resembles
fibrin microscopically
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恶性高血压病的肾脏小动脉
Sometimes the small arteries and arterioles can be damaged so severely in
malignant hypertension that they demonstrate necrosis with a pink fibrin-like
quality that gives this process its name--fibrinoid necrosis. hongdeng@zju.edu.cn
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Necrosis
Sequences of Necrosis
(5)
◆ Dissolution & absorption
◆ Organization & encapsulation
◆ Autolysis & inflammation
◆ Sloughing
◆ Calcification
Ulcer, Cavity, Sinus, Fistula
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Apoptosis
◆ A distinctive & important mode of
cell death
◆ Differentiation from necrosis
◆ Morphologic appearance
of programmed cell death
◆ Important physiologic &
pathologic processes
Greek, “falling leaves”
(1)
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Apoptosis
◆ Cell Shrinkage
◆ Chromatin Condensation
◆ Apoptotic Bodies Formation
◆ Phagocytosis of Apoptotic Bodies
by Neighbouring Cells or Macrophages
Morphological Evidence
(2)
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A, Apoptosis of epidermal cells in an immune-mediated reaction. The
apoptotic cells are visible in the epidermis with intensely eosinophilic
cytoplasm and small, dense nuclei. H&E stain. (Courtesy of Dr. Scott
Granter, Brigham and Women's Hospital, Boston, MA.) B, High power of
apoptotic cell in liver in immune-mediated hepatic cell injury.
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The sequential ultrastructural changes seen in
necrosis (left) and apoptosis (right).
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Apoptosis
◆ Signaling
◆ Control & integration
◆ Execution
◆ Removal of dead cells
Mechanisms of Apoptosis
(3)
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SECTION 3
CAUSES & MECHANISMS OF CELL
INJURY
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Causes of Cell Injury◆ Hypoxia
◆ Chemical Agents
◆ Physical Agents
◆ Infectious Agents
◆ Immunologic Reactions
◆ Genetic Defects
◆ Nutritional Imbalances
◆ Aging
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Mechanisms of Cell Injury
◆General Biochemical Mechanisms
◆ Ischemic & Hypoxia Injury
◆ Ischemia / Reperfusion Injury
◆Free Radical-Induced Cell Injury
◆Chemical Injury
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