SECTION 2 CELL INJURY - m-learning.zju.edu.cnm-learning.zju.edu.cn › G2S › eWebEditor ›...
Transcript of SECTION 2 CELL INJURY - m-learning.zju.edu.cnm-learning.zju.edu.cn › G2S › eWebEditor ›...
CHAPTER 1
11/23/2019 2
◆Reversible
◆ Irreversible
Cellular Swelling
Fatty Change
Hyaline Change
Amyloid Change
Mucoid Change
Pathologic Pigmentation
Pathologic Calcification
Cell Death
Degeneration
CHAPTER 1
11/23/2019 3
Reversible Cell Injury
Intracellular &/or extracellular abnormal
accumulation:
⚫ Excess amounts of various normal
substances (water,lipids,proteins,pigments)
⚫ Abnormal substances (exogenous,
endogenous)
Degeneration
CHAPTER 1
11/23/2019 4
Cellular Swelling
Intracellular accumulation
⚫ Sodium
⚫ Water
(hydropic degeneration)
(1)
CHAPTER 1
11/23/2019 5
Cellular Swelling (2)
Morphology
NE:
LM:
EM:
⚫ Cloudy swelling
⚫ Increase in the weight
the organs
CHAPTER 1
11/23/2019 6
Cellular Swelling (3)
Morphology
NE:
LM:
EM:
⚫Large
⚫Small & fine granules in the cytoplasm
the cells
Ballooning change
CHAPTER 1
11/23/2019 7
Cellular Swelling (4)
Morphology
NE:
LM:
EM:
Swelling
⚫ Endoplasmic reticulum
⚫ Mitochondria
CHAPTER 1
11/23/2019 8
Injurious agents
Mitochondria damage
Mechanisms
Water & sodium
within the cells
Cellular swelling
ATP
CHAPTER 1
11/23/2019 9
Fatty Change
Intracellular abnormal accumulation:
⚫ Triglycerides
(1)
Steatosis
Often occurred in the liver and the heart
CHAPTER 1
11/23/2019 10
Morphology
Fatty Change (2)
NE:
LM:
EM:
⚫ Large
⚫ Yellow
⚫ Soft
⚫ Greasy
CHAPTER 1
11/23/2019 11
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
CHAPTER 1
11/23/2019 12
Morphology
Fatty Change (4)
NE:
LM:
EM:⚫ Membrane-bound inclusions
Liposomes
CHAPTER 1
11/23/2019 13
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)
CHAPTER 1
11/23/2019 15
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
CHAPTER 1
11/23/2019 18
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
CHAPTER 1
11/23/2019 19
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
CHAPTER 1
11/23/2019 21
Fatty change of
heart muscle
(tigered effect)
Sudan-
hematoxylin
CHAPTER 1
11/23/2019 22
A homogeneous, translucent, pink
appearance in HE staining
Hyaline Change
Intracellular or extracellular abnormal
accumulation:
⚫ Proteins
A descriptive morphologic term
(1)
CHAPTER 1
11/23/2019 23
◆ 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)
CHAPTER 1
11/23/2019 24
Vascular pathology in hypertension. A, Hyaline arteriolosclerosis. The
arteriolar wall is hyalinized, and the lumen is markedly narrowed. [email protected]
CHAPTER 1
11/23/2019 26
Protein reabsorption droplets in the renal tubular epithelium
CHAPTER 1
11/23/2019 28
Amyloidosis
Extracellular abnormal accumulation:
⚫ Amyloid
CHAPTER 1
11/23/2019 29
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)
CHAPTER 1
11/23/2019 30
Mucoid Change
Extracellular abnormal accumulation:
⚫ Mucopolysaccharide
(Glycosaminoglycans, Hyaluronic Acid)
CHAPTER 1
11/23/2019 [email protected]
CHAPTER 1
11/23/2019 32
Pathologic Pigmentation
Intracellular & extracellular abnormal
accumulation:
⚫ Exogenous
⚫ Endogenous
Colored substances
CHAPTER 1
11/23/2019 33
Pathologic Pigmentation
⚫ Exogenous
⚫ Endogenous
✓ Hemosiderin
✓ Lipofuscin
✓ Melanin
✓ Carbon
CHAPTER 1
11/23/2019 35
Hemosiderin granules in macrophages in the alveolus
Hemosiderin
CHAPTER 1
11/23/2019 36
Hemosiderin granules in liver cells. A, H&E B, Prussian blue reaction
CHAPTER 1
11/23/2019 39
Pathologic Calcification
Intracellular & extracellular abnormal
accumulation:
⚫ Calcium salts
1. Except for the bones and teeth
2. Pathologic conditions
(1)
CHAPTER 1
11/23/2019 41
◆ Dystrophic Calcification
In areas of necrosis
No calcium metabolic derangements
◆ Metastatic calcification
In normal tissues
Some calcium metabolic derangements
Pathologic Calcification (2)
CHAPTER 1
11/23/2019 42
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
CHAPTER 1
11/23/2019 43
Necrosis
Two essentially concurrent processes to
produce the morphologic changes :
1. Enzymatic digestion of the cell
2. Denaturation of proteins
(1)
Autolysis
Heterolysis
CHAPTER 1
11/23/2019 44
Necrosis
Basic pathologic changes
Types of necrosis
Sequences of necrosis
(2)
CHAPTER 1
11/23/2019 45
Necrosis
Basic Pathologic Changes
(3)
◆ Nuclear changes
Karyolysis
Pyknosis
Karyorrhexis
◆ Cytoplasm Increased eosinophilia
CHAPTER 1
11/23/2019 46
Necrosis
Types of Necrosis
(4)
◆ Liquefactive necrosis
◆ Fat necrosis
◆ Coagulative necrosis
◆ Caseous necrosis
◆ Gangrene
◆ Fibrinoid necrosis
CHAPTER 1
11/23/2019 47
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 )
CHAPTER 1
11/23/2019 [email protected]
CHAPTER 1
11/23/2019 49
Liquefactive Necrosis
◆ Liquefaction of necrotic cells
◆ Condition: Presence of more
abundant proteolytic enzymes
◆ Most often in suppurative
inflammation & in the brain
CHAPTER 1
11/23/2019 52
Caseous Necrosis
◆ A distinctive form of coagulative
necrosis
◆ Cheese-like
◆ An amorphous coarsely granular
eosinophilic debris
◆ Most often in foci of TB
CHAPTER 1
11/23/2019 53
A tuberculous lung with a large area of caseous
necrosis. The caseous debris is yellow-white and
cheesy.
CHAPTER 1
11/23/2019 [email protected]
CHAPTER 1
11/23/2019 55
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)
CHAPTER 1
11/23/2019 56
Foci of fat necrosis with saponification in the mesentery.
The areas of white chalky deposits represent calcium
soap formation at sites of lipid [email protected]
CHAPTER 1
11/23/2019 57
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.
CHAPTER 1
11/23/2019 58
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.
CHAPTER 1
11/23/2019 59
Gangrene
◆ Extensive tissue necrosis
◆ Secondary bacterial infection
⚫ Dry gangrene
⚫ Wet gangrene
⚫ Gas gangrene
CHAPTER 1
11/23/2019 60
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.
CHAPTER 1
11/23/2019 61
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.
CHAPTER 1
11/23/2019 62
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.
CHAPTER 1
11/23/2019 63
Fibrinoid Necrosis
◆ A type of connective tissue necrosis
◆ Loss of normal structure
◆ A homogeneous,bright pink-staining
necrotic material that resembles
fibrin microscopically
CHAPTER 1
11/23/2019 64
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. [email protected]
CHAPTER 1
11/23/2019 65
Necrosis
Sequences of Necrosis
(5)
◆ Dissolution & absorption
◆ Organization & encapsulation
◆ Autolysis & inflammation
◆ Sloughing
◆ Calcification
Ulcer, Cavity, Sinus, Fistula
CHAPTER 1
11/23/2019 [email protected]
CHAPTER 1
11/23/2019 67
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)
CHAPTER 1
11/23/2019 68
Apoptosis
◆ Cell Shrinkage
◆ Chromatin Condensation
◆ Apoptotic Bodies Formation
◆ Phagocytosis of Apoptotic Bodies
by Neighbouring Cells or Macrophages
Morphological Evidence
(2)
CHAPTER 1
11/23/2019 69
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.
CHAPTER 1
11/23/2019 70
The sequential ultrastructural changes seen in
necrosis (left) and apoptosis (right).
CHAPTER 1
11/23/2019 71
Apoptosis
◆ Signaling
◆ Control & integration
◆ Execution
◆ Removal of dead cells
Mechanisms of Apoptosis
(3)
CHAPTER 1
11/23/2019 [email protected]
CHAPTER 1
11/23/2019 74
Causes of Cell Injury◆ Hypoxia
◆ Chemical Agents
◆ Physical Agents
◆ Infectious Agents
◆ Immunologic Reactions
◆ Genetic Defects
◆ Nutritional Imbalances
◆ Aging
CHAPTER 1
11/23/2019 75
Mechanisms of Cell Injury
◆General Biochemical Mechanisms
◆ Ischemic & Hypoxia Injury
◆ Ischemia / Reperfusion Injury
◆Free Radical-Induced Cell Injury
◆Chemical Injury
CHAPTER 1
11/23/2019 PATHOLOGY(reform)-dh 76
CHAPTER 1
11/23/2019 [email protected]
CHAPTER 1
11/23/2019 [email protected]