Cell degeneration and death 1 Flashcards
(32 cards)
Pathogenesis
how a disease state develops
Degeneration
cell injury that falls short of cell death, usually reversible
programmed cell death
regulated, controlled cell death
apoptosis
a specific form of PCD, may be pathological or physiological
Necrosis
pathological cell death in the tissues of a living animal due to lethal cell injury
Autolysis
cell death that occurs after the animal dies
Putrefaction
bacterial lysis and fermentation of tissue in a dead animal
Cell injury concepts
normal cells –>injurious stimulus–>injured cell–>necrosis/apoptosis
normal cell–>adapted cell–>adaptive capacity exceeded–>injured cell–> necrosis/apoptosis
Cellular responses to sublethal injury
-metabolically active cells are susceptible to injury
-constant import, export, and synthesis of molecuels
-sublethal injury may shift metabolic pathways such that these molecules accumulate in large amounts
-intracellular inclusions
-
Are all intracellular inclusions the product of cell damage?
no, many accumulate in cells carrying out normal function
hepatocytes, macrophages, aging cells
Mechanisms of accumulation
- increased biosynthesis
- decreased excretion/secretion
- diminished intracellular consumption
- reduced metabolism/decreased transformation of a precursor molecule into its product
- increased uptake from the extracellular compartment
- inability to enzymatically degrade endogenous or exogenous substances
Categories of intracellular material
- normal cellular molecules accumulated to excess (h20,lipids,glycogen)
- foreign substances
- pigments
- metal ions (Cu,Fe) that accumulate to excess or are not excreted properly
- Ca in necrotic cells
- microbial (bacterial, viral, protistan) structures
Physiological causes for hepatic lipidosis
alcoholism
fatty diet
changes in metabolism
starvation
Characteristics of fatty liver
liver is enlarged, friable, rounded edges, more yellow, greasy
Cell death may be? How?
physiological or pathological
- physiologic- skin cells die as they mature
- pathological-due to disease/cell injury
Causes of cell injury and death
- chaotropic chemical and physical insults
- lytic cell insults- lysis (viral infections), pores (complement proteins, cytoxic T-cell)
- hypoxia
- impaired cell membrane function or integrity
- damage to nucleic acids
- ligand-receptor mediated signals
Apoptosis important for?
involution atrophy t-cell removal embryogenesis glucocorticoids tumours injurious stimuli that are too weak to cause necrosis
Disorder associated with disregulated apoptosis include?
increased apoptosis causing abnormally high reates of cell death- ex virus associated with lymphocyte depletion (AIDS)
Inhibited apoptosis and increased cell survival
-tumours- related to p53 mutations/hormone dependence
-autoimmune disorders- autoreactive lymphocytes not removed
Describe the process of apoptosis
Signalling
-transmembrane or intracellular; numerous signals
Control/integration
-biochemical integration of pro- and anti-apoptotic factors in the cell dictate outcome of signal
Execution phase
-death program mediated mainly by caspasese; cysteine-ASPartic residues, bioamplification system
Phagocytosis
-membrane flipping-cell displays signals on the surface that say eat me- get phagocytosed
Is there inflammation involved in apoptosis?
NO
Four main mechanisms of cell injury
depletion of ATP
damage to nucleic acids, especially DNA
interference with protein synthesis
injury to cell membranes
How does necrosis work?
lethally injured cells accumulate large amounts of intracellular Ca
-activation of phospholipases–>progressive cell lysis of all membranes–> activate proteases–>dissolve cytoskeleton–>inactivate enzymes–>denature proteins
What is the overall effects of marked increase of intracellular Ca in necrotic cells
it results in inappropriate activation of proteases, phospolipases, ATPases and endonucleases
Ischemia
lack of blood flow
- castration of cattle with elastic bands
- thrombosis- blood clots- heart attack/stroke
