Download Chapter One Introduction to pathology

CELL DEATH
Common type of necrosis after
exogenous stimuli.
• Swelling, denaturation and coagulation
of proteins
• Breakdown of cellular organelles
• Cell rupture
NECROSIS
The sum of the morphologic changes
that follow cell death in living tissue
and organ:
• Denaturation of proteins.
• Enzymatic digestion of organelles
and cytosol.
AUTOLYSIS
• Enzymatic digestion by lysosomal
enzymes of the dead cells
themselves.
HETEROLYSIS
• Digestion by lysosomal enzymes of
immigrant leukocytes.
Three pattern of nuclear
changes
Karyolysis (DNase activity)
Pyknosis (DNA condensation)
Karyorrhexis (fragmentation
of pyknotic nucleus)
Morphologic appearance of necrosis
• Increased eosinophilia:
Loss of RNA in the cytoplasm
Increased binding of eosin to denatured
cytoplasmic protein
• More glassy homogeneous appearance
Loss of glycogen particles
• Vacuolated and moth-eaten cytoplasm
• Calcification of necrotic cells
TYPES OF CELL DEATH
• necrosis
Coagulation necrosis
Caseous necrosis
Gangrene
Liquefaction necrosis( fat necrosis)
Fibrinoid necrosis
• Apoptosis
Coagulation necrosis
Denatures of both structural and
enzymatic proteins by injury or the
subsequent increasing intracellular
acidosis.
Caseous necrosis
A subtype of coagulation necrosis
White and cheesy
Tuberculosis
Completely obliterated tissue
architecture
Gangrene
A subtype of coagulation
necrosis
Dry gangrene
Wet gangrene
Gas gangrene
Liquefactive necrosis
Bacterial or fungal infections
Central nervous system
Amebiasis
Fat necrosis
Traumatic
Activated pancreatic lipases
Fibrinoid degeneration
Deeply eosinophilic
• Collagen diseases
• Necrotic vasculitis
• Malignant hypertension
APOPTOSIS (Programmed cell death)
• Programmed destruction of cells during
embryogenesis.
• Hormone dependent involution of tissues
in the adult.
• Cell deletion in proliferating cell populations (intestinal crypt epithelium),
tumors, and lymphoid organs.
• Pathologic atrophy in parenchymal
organs after duct obstruction.
• Cell death by cytotoxic T cells.
• Cell injury in certain viral diseases.
• Cell death produced by a variety of
injurious stimuli given in low doses
(e.g. mild thermal injury).
MORPHOLOGICAL FEATURES
OF APOPTOSIS
• Cell shrinkage
• Chromatin condensation and fragmentation.
• Formation of cytoplasmic blebs and apoptotic
bodies.
• Phagocytosis of apoptotic bodies by adjacent
healthy cells or macrophages.
• Lack of inflammation.
Necrosis
Stimuli
Hypoxia
Toxins
Histology Cell swelling
Coagulation N
Disruption of
organelles
DNA
Random
breakdown Diffuse
Apoptosis
Physical
Pathological
Single cell
Chromatin
condensation
Apoptotic bodies
Internucleosomal
Necrosis
Apoptosis
Mechanism ATP depletion Gene activation
Membrane
Endonuclease
injury
Free radicals
Tissue
Inflammation
No inflammation
reaction
Phagocytosis of
apoptotic bodies
• Fig 1-18
Biochemical features of apoptosis
1.PROTEIN CLEAVAGE:
Caspases (cysteine protease)
Nuclear scaffold
Cytoskeletal protein
2.PROTEIN CROSS-LINKING:
Transglutaminase
Cytoplasmic proteinshrunken shalls
apoptotic bodies
Biochemical features of apoptosis
3. DNA breakdown: 50-300 kb pieces
Ca2+, Mg2+ dependent endonucleases
DNA oligonucleosomes
DNA ladders (also seen in necrosis)
4. PHAGOCYTIC RECOGNITION
Receptors on macrophages for the
surface components
(phosphatidylserine, thrombospondin)
on apoptotic bodies.
• Fig 1-19
• Apoptosis-associated genes
bcl-2, c-myc, p53
• Fig 1-20
Fates of necrosis
• Absorption
• Discharge: Erosion Ulcer
Sinus Fistula Cavitation
• Organization
• Encapsulation
• Calcification
Chapter Three
Repair
Section A
Regeneration:
Completely regeneration
Fibrous repair
Regeneration capacity
• Labile cells
• Stable cells
• Permanent cells
Factors influencing regeneration
1. Cell-cell interaction
Conditioned medium
Contact inhibition
2. Extracellular matrix
Laminin:  Epithelia
 Fibroblasts
Fibronectin :  Epithelia
Fibroblasts
3. Growth factors
GROWTH FACTORS
EGF, TGF-A, PDGF, aFGF, bFGF,
IGF-1, IGF-2, VEGF, HGF, MG-CSF,
M-CSF, G-CSF, ERYTHROPOITIN,
ILs, TNF, IFN, NGF.
Section B
Fibrous Repair
Granulation tissues:
• Newly formed
capillaries
• Fibroblasts
• Inflammatory cells
Granulation tissues
• Fibrous repair
• Organization
• Wound healing
• Fig 4-14
• Fig 4-15
Wound healing
• Healing by first intention
• Healing by second intention
• Healing under scab
• Fig 4-18
• Fig 4-19
Systemic factors
influencing wound healing:
• Nutrition
• Metabolic status
• Circulatory status
• Hormones
Local factors
influencing wound healing:
• Infection
• Mechanical factors
• Foreign bodies
• Size, location and types of wound
Liquefactive necrosis
Bacterial or fungal infections
Central nervous system
Amebiasis
Fat necrosis
Traumatic
Activated pancreatic lipases