[PL2.3] CELL INJURY, CELL DEATH,& ADAPTATIONS

Most common type; characteristic of hypoxic death of cells in all tissues except the brain

Coagulative Necrosis

Results from denaturation of proteins and enzymes, blocking the proteolysis of the dead cells

Coagulative Necrosis

Early changes of Coagulative Necrosis

Preserved cellular outline with loss of nuclei

Late changes of Coagulative Necrosis

Breakdown of necrotic cells by lysosomal enzymes

localized area of coagulative necrosis

Infarct

Characterized by digestion of the dead cells, resulting in transformation of the tissue into a viscous liquid

Liquefactive Necrosis

Autolysis and heterolysis prevail over protein denaturation through the action of hydrolytic enzymes

Liquefactive Necrosis

Seen in brain infarct, bacterial infection, suppuration, and amoebic abscess

Liquefactive Necrosis

- creamy yellow necrotic material (due to the presence of leukocytes)

Pus

Applied to a limb, generally the lower leg, that has lost its blood supply and has undergone necrosis (typically coagulative)

Gangrenous Necrosis

- coagulative necrosis with superimposed bacterial infection, also producing liquefactive necrosis

Wet gangrene

- mostly coagulative necrosis due to anoxic injury

Dry gangrene

Encountered most often in foci of tuberculous infection

Caseous Necrosis

Often described as caseous or cheese-like because of the friable white appearance of the necrotic area

Caseous Necrosis

- necrotic area that appears as a structureless collection of lysed cells and amorphous granular debris enclosed within an inflammatory border

Granuloma

Focal areas of fat destruction due to release of activated pancreatic lipases in the pancreas and peritoneal cavity

Fat Necrosis

Seen in acute pancreatitis - lipases split triglycerides from fat cells → fatty acids complex with calcium to produce chalky white areas (fat saponification)

Fat Necrosis

Necrosis associated with antigen-antibody complex deposits in the walls of blood vessels

Fibrinoid Necrosis

- bright pink and amorphous appearance in H&E stains caused by the deposits of immune complexes

Fibrinoid

Programmed cell death

Apoptosis

Induced by a tightly regulated suicide program in which cells destined to die activate intrinsic enzymes that degrade the cells’ genomic DNA and nuclear and cytoplasmic proteins

Apoptosis

Apoptotic cells break up into fragments called apoptotic bodies

Apoptosis

Each apoptotic body contains portions of the cytoplasm and nucleus

Apoptosis

Plasma membrane is intact but its structure is altered to produce apoptotic signals for phagocytes

Apoptosis

Removal of supernumerary cells (in excess of the required number) during development

Physiologic Cause of Apoptosis

Involution of hormone-dependent tissues on hormone withdrawal

Physiologic Cause of Apoptosis

Cell turnover in proliferating cell populations

Physiologic Cause of Apoptosis

Elimination of potentially harmful self-reactive lymphocytes

Physiologic Cause of Apoptosis

Death of host cells that have served their useful purpose

Physiologic Cause of Apoptosis

DNA damage

Pathologic Cause of Apoptosis

Accumulation of misfolded proteins

Pathologic Cause of Apoptosis

Cell death in certain infections

Pathologic Cause of Apoptosis

Pathologic atrophy in parenchymal organs after duct obstruction

Pathologic Cause of Apoptosis

What cellular process is characterized by cell shrinkage?

Apoptosis

What is the most characteristic nuclear feature of apoptosis?

Chromatin condensation

What structures are formed in the cytoplasm during apoptosis?

Cytoplasmic blebs and apoptotic bodies

What cells usually carry out the phagocytosis of apoptotic bodies?

Macrophages

How do apoptotic cells typically appear under the microscope?

Round or oval mass of intensely eosinophilic cytoplasm with dense nuclear chromatin fragments

What type of cell death shows enlarged cell size due to swelling?

Necrosis

What type of cell death shows reduced cell size due to shrinkage?

Apoptosis

Which form of cell death is associated with pyknosis, karyorrhexis, and karyolysis?

Necrosis

Which form of cell death shows nuclear fragmentation into nucleosome-size fragments?

Apoptosis

What type of cell death involves a disrupted plasma membrane?

Necrosis

Which form maintains an intact plasma membrane with altered lipid orientation?

Apoptosis

Which type of cell death results in enzymatic digestion of cellular contents that may leak out?

Necrosis

Which type of cell death keeps cellular contents intact and enclosed in apoptotic bodies?

Apoptosis

Which type of cell death is frequently associated with adjacent inflammation?

Necrosis

Which form of cell death is not associated with inflammation?

Apoptosis

Which type of cell death is usually pathologic and results from irreversible cell injury?

Necrosis

Which type of cell death is often physiologic but can be pathologic in DNA damage?

Apoptosis

What enzymes are activated in apoptosis to initiate cell death?

Caspases

Which phase of apoptosis involves activation of caspases that trigger other caspases?

Initiation phase

Which phase of apoptosis involves terminal caspases triggering cellular fragmentation?

Execution phase

What are the two main pathways of apoptosis?

Mitochondrial and Death Receptor Pathways

What is the major mechanism of apoptosis?

Mitochondrial (Intrinsic) Pathway

Which apoptotic pathway involves increased mitochondrial permeability and release of cytochrome c?

Mitochondrial (Intrinsic) Pathway

Which proteins are pro-apoptotic and located on the mitochondrial membrane?

Bim, Bid, Bad, Bax, Bak

Which cytoplasmic protein is pro-apoptotic in the intrinsic pathway?

Smac/DIABLO

Which proteins are anti-apoptotic in the mitochondrial pathway?

BCL-2, BCL-XL

Which apoptotic pathway involves activation of plasma membrane death receptors?

Death Receptor (Extrinsic) Pathway

What are examples of death receptors involved in the extrinsic pathway?

Tumor necrosis factor (TNF) and Fas