Cell and Tissue Injury Flashcards
Understand major causes (etiologies) of cell injury
Physical agents- trauma, heat, etc.
Chemical and drugs- drug toxicity, poisoning
Infection- pathogenic bacteria, virus, fungi, protozoa
Immunologic insults- anaphalaxis, autoimmunity
Genetic derangement- phenylketonuria, cystic fibrosis
Nutritional imbalance- atherosclerosis, protein and vitamin deficiency
Hypoxia- primary lung disease, heart failure, shock, arterial or venous thrombosis
Understand how cell injury contributes to the pathogenesis of disease
Cell injury perturbs normal physiology; the injuryed cell cannot function at full capacity (i.e. metabolizing nutrients, synthesizing need products)… this results in illness. Cell injury can occur acutely or chronically.
Injury to one tissue invariably affects other types of tissue that are adjacent.
Describe major mechanisms of cell injury
Cell membranes: Usually the first cellular component to be damaged; lipids within membrane are easily oxidized a supports and oxidative change reaction called lipid peroxidation. Damage to the membrane may physically break membrane or inactivate ion pumps that control ionic concentration in cytoplasm. Thus, membrane damage often results in cell swelling.
Mitochondria: Mitochondrial swelling due to the accumulation of water in the matrix. Swelling results from a decrease in O2-dependent synthesis of ATP required to fuel the ion pumps of the mitochrondrial membrane
ER: Cisternae of ER are also distended, polyribosomes detach from RER–> decrease in the ability to synthesize new proteins.
Nucleus: Alterations in the appearance of the nucleolus, probably has some effect on the synthesis of rRNAs, causing decrease in protein synth.
Cell/tissue injury produces morphologic change
Injury almost always produces a characteristic change in the appearance of the affected tissue that can be seen grossly and/or microscopically. Different kins of morphological changes can be indicative of different diseases.
Free radicals
A free radical is a chemical species with an unpaired electron (important ones are superoxide and the hydroxyl free radical).
Free radicals are generated by intrinsic oxidases (present in the ER of all cells and in PMNs) and radiation, especially in the setting of high pO2.
Free radicals can chemically damage proteins, DNA, and RNA, and trigger lipid peroxidation in cell membranes.
Understand how ischemia/hypoxia creates a setting where free radical damage becomes an important cause of cell injury.
Hypoxic tissue is often infiltrated with PMNs which have enzymes such as myeloperoxidase, which produces oxygen radicals.
Also in hypoxia, the enzyme xanthine dehydrogenase is proteolytically converted to xanthine oxidase. Once the hypoxia is corrected, xanthine oxidase produces oxygen radicals.
O2 therapy can generate high levels of O2 radicals.
What are examples of free radicals and how does the body get rid of them?
Examples of free radicals are the superoxide radical and the hydroxyl radical.
Antioxidants (uric acid, vitamin E), catalase, and glutathione peroxidase eliminate free radicals.
Understand how necrosis differs from apoptosis.
In necrosis, large portions of tissue containing thousands of contiguous cells die all at once. Intracellular [Ca2+] rises which shuts down mitochondrial ATP synthesis. The cell then swells, plasma membrane blebs, and the membrane loses its integrity.
In apoptosis, individual scattered cells are affected rather than a large area of tissue. Apoptosis is highly regulated by the binding of specific extracellular ligands to specific surface receptors., as well as siginals from the mitochondria. Eventually the cell breaks up into small membrane bound vesicles that are taken up by macrophages.
Understand how chronic injury leads to adaptation
Some forst of cell/tissue injury and stress don’t kill the cell and persist for long periods of time. In order to main tissue homeostasis, the tissue adapts.
Hypertrophy: Increase in the size of the cell secondary to an increase in function.
Atrophy: decrease in the size and function capacity of the cell.
Metaplasia: Replacement of one type of tissue with another in response to an injury.
Hyperplasia: Increase in the number of cell of a tissue in response to a stimulus or injury.
Understand the four major types of necrosis seen in human disease.
Coagulative necrosis: dead cell remains a ghost-like remnant of its former self.
Liquefactive necrosis: dead cell dissolves away as lysosomal hydrolases digest cellular components.
Caseous necrosis: seen only in tuberculosis, central portion of an infected lymph node is necrotic (b/c of mycobacteria).
Fat necrosis: fats are hydrolyzed into free fatty acids which precipitate with Ca2+ producing chalky gray material. Typically follows acute pacreatitis or trauma.
Know which morphologic and biochemical alterations during hypoxic injury are reversible and which are irreversible
Reversible changes:
- Decreased ATP
- Decreased action of Na+ pump, causes cell swelling
- Increased glycolysis, decreased pH
- Decreased protein synthesis
Irreversible changes:
- Increased activation of lysosomal enzymes
- DNA and protein degradation
- Increased Ca2+ influx
