Ch 4. Altered Cellular and Tissue Biology Flashcards
When does a cell become irreversibly injured?
Once changes to the nucleus occur and cell membranes are disrupted, the cell moves to irreversible injury and death.
Pathology
Conditions typically observed during a disease state.
Physiology
Biological discipline that describes processes or mechanisms operating within an organism
Discuss the pathogenesis of hypoxic injury?
Decreased ATP production, leading to Na and Ca accumulation, acute swelling, decreased protein synthesis, lipid deposition, and anaerobic glycolysis.
What are the mechanisms of ischemia-reperfusion injury?
- Oxidative stress - Reoxygenation causes the increased generation of reactive oxygen species (ROS) and nitrogen species.
- Increased intracellular Ca cxn
- Inflammation- danger signals from cytokines are released by resident immune cells when cells die.
- Complement activation
Why are children more susceptible to the toxic effects of lead exposure?
- More prone to hand-to-mouth behavior. Ingestion of Pb dust.
- blood-brain barrier is immature during fetal development, contributing to greater accumulation in developing brain.
- infant absorption of Pb is greater than in adults and bone turnover from skeletal growth results in continuous leaching of Pb into blood, causing constant body exposure.
Discuss the sources of lead exposure?
Particulate lead from smelters, and previous leaded gasoline emissions. Drinking water, particularly well water. Paint.
Discuss the mechanisms of cell injury related to chronic alcoholism?
Nutritional factors - Mg, Vit B6, thiamine, phosphorous, and folic acid deficiencies.
Limits intestinal absorption of folate, leading to fetal alcohol syndrome.
What are the sources of mercury exposure?
gold mines, natural emissions, coal plants.
Anoxia
Total lack of oxygen.
Vacuolation
Formation of vacuoles.
Lipid Peroxidation
The destruction of polyunsaturated lipids (the same process by which fats become rancid), leading to membrane damage and increased permeability.
Pathologic effects of ROS?
- Lipid peroxidation - membrane damage.
- Protein modifications- breakdown, misfolding.
- DNA damage - mutations.
Pathologic effects of ROS?
- Lipid peroxidation - membrane damage.
- Protein modifications- breakdown, misfolding.
- DNA damage - mutations.
Xenobiotics
Compounds that include toxic, mutagenic, and carcinogenic chemicals.
Biotransformation
Metabolism of lipophilic xenobiotics to more hydrophilic forms by the liver.
Toxicophores
Short-lived unstable highly reactive chemical intermediate products of biotrasformation. Includes electrophiles, nucleophiles, free radicals, and redox-active reactants.
Electrophiles
Atom or molecule that accepts e- pair to make covalent a bond.
Nucleophile
Atom or molecule that donates e- pair to electrophile to make a chemical bond.
Protein adduct
Chemical bound to protein.
e.g. Environmental factors
co-exposure to multiple xenobiotics.
e.g. Pathologic factors
inflammation, underlying liver diseases
e.g. Physiologic factors
age, gender
e.g. Physiologic factors
age, gender
Cellular Accumulation (Infiltration)
Intracellular accumulation of abnormal amounts of various substances and the resultant metabolic disturbances.
e.g. Endogenous
a product of abnormal metabolism or synthesis
Why is an increase in cxn of intracellular calcium injurious?
Can lead to dystrophic calcification. Calcium salts cluster and harden, interfering with normal cellular structure and function.
Compare and contrast necrosis and apoptosis.
Necrosis - cell disintegration. Accompanied by inflammation. Cell swells. Cells die long before autolysis, cellular self-digestion.
Apoptosis - Cell shrinks. DNA clumps. Cell buds off to be phagocytized. characterized by the “dropping off” of cellular fragments called apoptotic bodies. Release chemical factors to recruit phagocytes.
Why is apoptosis significant?
Cells need to die; otherwise, endless proliferation would lead to gigantic bodies.
Define autophagy.
Self eating. Involves delivery of cytoplasmic contents to lysosomes for degradation. Can maintain cellular metabolism under starvation conditions and remove damaged organelles, improving survival of the cell.
Oncosis (Vacuolar degeneration)
Progressive vacuolation resulting in cytoplasmic swelling.
e.g. Endogenous
a product of abnormal metabolism or synthesis. Produced within the body.
e.g. Exogenous
infectious agents or a mineral. Produced outside the body.
Oncosis (Vacuolar degeneration)
Progressive vacuolation resulting in cytoplasmic swelling.
Steatosis
Intracellular lipid accumulation.
Diseases of lipid accumulation?
Tay-Sachs disease, Niemann-Pick disease, and Gaucher disease.
Diseases of carbohydrate accumulation?
mucopolysaccharidoses.
Russell bodies
excessive aggregates of protein.
Cytochromes
Oxidative enzymes.
Hemosiderin
yellow-brown pigment derived from hemoglobin. Stores excess iron in tissues. Yellowish color in bruising.
Hemosiderosis
condition in which excess iron is stored as hemosiderin in the cells of many organs and tissues.
Bilirubin
yellow-green pigment of bile derived from the porphyrin structure of hemoglobin.
Jaundice (icterus)
Excess bilirubin within cells and tissues, causing yellowing of the skin. Occurs when level excess 1.5 to 2 mg/dl of plasma. (normal values of 0.4 to 1 mg/dl).
4 types of necrosis
Coagulative, liquefactive, caseous, fatty.
Coagulative necrosis
Primarily in kidneys, heart, and adrenal glands. commonly results from hypoxia. Result of protein denaturation, causes albumin to change from transparent to firm, opaque state. Area of coagulative necrosis called an infarct.
Liquefactive Necrosis
Commonly results from ischemic injury to neurons and glial cells in the brain.Cells are digested by their own hydrolases, so the tissue becomes soft, liquefies, and segregates from healthy tissue, forming cysts. Can be caused by bacterial infection.
Caseous Necrosis
Usually results from TB infection. combo of coagulative and liquefactive necroses. Dead cell disintegrate, but debris not completely digested by hydrolases. Tissue soft and granular.
Fatty Necrosis
Lipases break down triglycerides, releasing free fatty acids that then combine with Ca, Mg, and Na ions, creating soaps (saponification). Tissue appears opaque and chalk-white.
