General Pathology - Causes of Cell Injury

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With regards to differential diagnosis, what does VINDICATE mean?

- Vascular
- Infection/ Inflammatory/ Immune-mediated
- neoplasm
- Drugs
- Iatrogenic
- Congenital/ Developmental/ Inherited
- Anatomic
- Trauma
- Environmental Exposure/ Endocrine

What is cell injury?

damage or pathologic alterations in molecules and structure that can occur in cells and extracellular components

What 4 things can cause injury?

- persistent stress
- injurious stimuli
- deprived of essential nutrients
- compromised by mutations

When heart muscle accumulates fat droplets, is this the reversible or irreversible stage?

- reversible

What 4 cell systems are particularly vulnerable to injury?

- membranes
- aerobic respiration
- protein synthesis
- genetic apparatus (DNA, RNA)

What is ischemia?

reduced blood flow to the organ or part of the body

What is hypoxia?

inadequate oxygenation of tissues

what is anoxia?

complete loss of oxygen in the tissues

What is anemia?

decreased number of red blood cells in blood or volume or are deficient in hemoglbin

What are the 6 causes of oxygen deprivation?

- hypoxia
- ischemia
- anoxia
- anemia
- CO2 toxicity
- cyanide toxicosis

What is the pathogenesis of cyanide toxicosis?

- plants containing cyanogenic glycosides yield free hydrocyanic acid when hydrolyzed or plant cell structure is disrupted
- cyanide is absorbed and reacts with Fe3+ in cytochrome oxidase= stops cellular respirationvia oxygen deprivation bc the oxyhemoglobin cannot release O2

What type of physical agent causes direct rupture or death of large #s of cells and damage to blood supply to cells?

trauma

What type of physical agent denatures essential cell enzymes and other proteins?

extreme heat

What type of physical agent can increase the rate of metabolic reactions so that substrates, H2O, and pH changes reach lethal levels?

excessive heat

What type of physical agent generates great heat at it passes through tissue and alters conduction to nerves and muscles?

electricity

What type of physical agent causes ionization of cellular water with production of highly reactive free radicals?

Ionization radiation

What type of physical agent damages genetic material producing reproductive cell death of cells, genetic defects, and neoplasia?

radiation

How does extreme cold cause cell injury?

- impairs blood flow
- intracellular ice crystals rupture cell membranes

What does lead poisoning cause?

neuronal necrosis and renal tubular necrosis

What is type of toxin does not need to be converted to cause toxicity?

direct toxin

What type of toxin must be converted into another molecule to have a toxic affect?

indirect toxin

What is an exotoxin?

toxin secreted by gram positive bacterial that causes membrane damage

what is an endotoxin?

toxin (LPS) secreted by gram-negative bacteria from their walls upon cell death
- toxic to membranes

Endotoxin induced damage to endothelial cells activates what response in the host?

- coagulation pathway
- complement system
- results in inflammatory reaction and cell injury

What effect do endotoxins have on macrophages?

- activates them to release cytokines:
- TNF-alpha

What does TNF-alpha induce?

apoptosis

How do viruses act to kill cells?

- shuts down host cell protein synthesis
- inc. membrane permeability of Ca entry
- stimulates cytoxic Tcells taht kill infected cells via FAS-FAS ligand
- induce apoptosis

Vitamin E deficiency causes what in pigs?

hepatocellular necrosis

High dietary copper causes what in sheep?

hemolysis of redblood cells

Why does too much copper cause hepatocyte necrosis in bedlington terrier dogs?

- deletion of MURR1 gene cause them not to be able to get rid of copper

What is premature loss of vitality or degeneration of cells or tissues, especially when due to genetic causes?

abiotrophy

What does cellular response to an injurious stimuli depend on?

type, duration, and severity of the injury

What is cell death the result of?

irreversible cell injury

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