Four aspects of a disease process
Etiology (cause), pathogenesis (mechanism), morphology (appearance), functional consequences (clinical significance)
Mechanisms by which a cell achieves homeostasis (protect cell integrity)
cell membrane, phagocytosis, excretion of exogenous chemicals, host defense mechanisms, systems of repair
Mechanisms of cell injury (pathogenesis)
Most vulnerable -> maintenance of integrity of cell membrane, aerobic respiration (with ATP production), synthesis of structural proteins and enzymes, preservation of the genetic apparatus -> most susceptible cells are the most metabolically active
Causes of cell injury (etiology)
physical, metabolic, chemical, immunologic, genetic, biologic (microbes)
Cell injury (outcomes)
temporary alteration of cell function followed by complete recovery by normal homeostatic mechanisms OR structural damage causes permanent impairment of function OR DNA damage with mutation and its consequences
REVERSIBLE: Dilatation of organelles and general cell swelling, ribosome disaggregation, blebbing; IRREVERSIBLE: membrane ruptures, dispersal of organelles, mitochondrial damage, breakdown of lysosomes, activation of inflammatory response
using any example of cell injury, explain the sequence of events that take place when a cell is injured, including the target intracellular systems affected and the morphological changes culminating with cell death.
Point of no return
permanent mitochondrial damage or rupture of large cell membrane blebs
SER
target of indirectly toxic substances -> suffer metabolic activation by target cell -> ex. CCl4 converted to CCl3 free radical
Lysosomes
when this is damaged, cell degeneration occurs -> may produce: increased or incomplete autophagy, hereditary absence of an enzyme in primary lysosomes, failure of degradation of phagocytosed material, liberation and activation of lysosomal enzymes -> usua
Mitochondria
target that affects oxidative phosphorylation (hypoxia and hypoglycemia) -> results in energy deficiency (low ATP)
Four main mechanisms of cell injury
hypoxia (may be involved in all 4), injury by free radicals (including activated oxygen), chemical injury, viral injury
Ischemic injury
interruption of blood flow
Reversible ischemic injury
impaired aerobic respiration (mitochondria) -> decreased ATP (energy) -> anaerobic glycolysis -> glycogen depletion -> accumulation of lactic acid (intracellular acidosis) with associated nuclear chromatin clumping; ATP is needed for cell membrane integri
Irreversible ischemic injury
severe vacuolization of mitochondria, damage of plasma membranes, cell swelling of lysosomes and massive Ca2+ influx into cell -> marked intracellular acidosis, ruptured lysosomal membrane -> cell digestion and cell death; INABILITY OF MITOCHONDRIA TO REC
Marked influx of Ca2+
denatures proteins and causes cell coagulation
Injury by free radicals
activated oxygen radicals are most common (aging, chemical, X-rays, infections, inflammation, tumor necrosis) -> combine with substances in cell membranes (lipid peroxidation) and nucleic acids (mutations), and promote cross-linking of proteins with incre
Chemical injury
either directly affects specific organelle or cell component OR (most commonly) indirectly through metabolic activation (reactive toxic metabolites) -> ex.
CCl4 poisoning (becomes CCl3)
a type of chemical injury which causes lipid accumulation within the cytoplasm (can't synthesize lipoproteins for TGs to leave the hepatic cell) -> causes characteristic fatty liver of this poison
Virus induced injury
can have cytopathic, cytolyitic (cell killing) or oncogenic effect (tumor production -> can also affect cells by interfering with cellular skeleton (ciliated cells of respiratory epithelium) or producing fusion of cells (giant cells) and by producing incl
Cytolytic effect
this type of viral injury is often cell specific through receptors and causes cell death
Cell injury in microscope
cell swelling, bleb formation, myelin figures, swelling of mitochondria, accumulation of dense material in mitochondria (Ca2+, lipoprotein complexes), dilatation of ER, increase in lysosomes (autophagia)
Apoptosis
selective removal of individual cells -> usual physiological processes -> cell shrink, fragmentation of nucleus and cell (karyorrhexis) -> apoptotic bodies are released and phagocytosed -> residual (acidophilic) body -> NO INFLAMMATION
Necrosis
pathological cell death -> cell swelling (hydropic change, cloudy swelling and feathery degeneration) and rupture (karyolysis -> loss of nuclear staining -> cell fading) -> cells are typically found in contiguous sheets and often associated with striking
Coagulative necrosis
ischemic, coagulation of cells -> proteins are denatured and the cell becomes histologically an opaque, acidophilic mass, nucleus disappears -> cells usually removed by phagocytosis and enzymatic destruction by inflammatory cells
Liquefaction necrosis
hydrolytic enzymes cause protein denaturation in brain tissues and in some bacterial infections (ex. cerebral infarct, bronchopneumonia
Fat necrosis
occurs in adipose tissue as a result of the release of lipases from dead cells (ex. acute pancreatitis) -> lipases break down TGs and generate free FAs -> react with Ca2+ and make soaps (chalky-cheese nodules in the fat surrounding the pancreas or in the
Caseous necrosis
characteristic of tuberculosis -> combination of Coagulative and liquefactive necrosis -> macroscopically have cheesy-milk appearance, eosinophilic
Gangrenous necrosis
not a distinct type of cell death but is a common clinical term that refers to combination of ischemic coagulative necrosis (typically a limb) with a superimposed infection (wet gangrene)
Intracellular accumulations
normal cell components, abnormal substance, pigments, lipids (fatty change -> reversible), protein (Ig = Russell bodies), glycogen (seen in diabetics, storage disorders), mucopolysaccharides (mixture of fats and carbohydrates) -> can have no effect, trans
Atrophy
decreased size and function of cell -> caused by decreased workload/blood supply, loss of innervation, interruption of trophic signal, aging -> if persists cells may die
Hypertrophy
increase in size of cell -> caused by increased functional demand (myocardial, muscle) or physiologic (hormone) hypertrophy (ex. sex organs at puberty)
Hyperplasia
increase in number of cells in an organ or tissue) -> caused by increased functional demand (increased RBC's in high altitude), hormonal stimulation (endometrium in early phase of menstrual cycle) or persistent cell injury (skin in calluses)
Metaplasia
conversion of one differentiated cell type to another -> not precancerous -> conversion of bronchial ciliated columnar epithelium to squamous epithelium in smokers -> protective mechanism but has loss of function (also seen in Barrett's esophagus)
Dysplasia
premalignant condition -> alteration of size, shape and organization of the cellular components of a tissue -> irregularity and hyperchromatism (dark) of nuclei, disordered arrangement of cell -> due to persistent injury (ex. in bronchial epithelium or ce
Cellular aging (senescence)
progressive deterioration of the cell functions with age -> irregularly lobed nuclei, vacuolated mitochondria -> free radical damage through life -> accumulation of lipofucsin granules (non-toxic)