General Pathology Flashcards
Etiology
Science and study of the causes of disease.The term identifies the causes of disease
Pathogenesis
The cellular and molecular mechanisms resulting in the development of a pathologic lesion.The term identifies the mechanisms of a disease process
Pathophysiology
Derangement of function seen in diseaseThe term emphasizes the alterations in function resulting from the structural changes occurring in cells, tissues and organs during a disease process
Causes of cell injury
Ischemia (decreased blood flow) /anoxia-hypoxia (suboptimal or lack of O2 supply) (most common cause)Physical agents Chemicals Microorganisms Immune reactions Nutritional imbalance Genetic changes
Anoxia/hypoxia: possible mechanism
Mediated via hypoxia-inducible factorIf we could create an HIF analog –> decrease hypoxia
Hypoxia-inducible factor: important impacts
Angiogenesis Erythropoiesis Anaerobic glycolysis Glucose uptake Extracellular matrix turnover pH control Apoptosis Mitogenesis
Cell injury and free radicals
Most causes of cell injury act through the generation of free radicals May increase membrane permeability, inhibit cation pumps, deplete ATP and increase cytosolic free calcium
Free radicals: what are they
Oxygen-derived (reactive oxygen species = ROS) are produced by neutrophils and macrophages. Important ROS are superoxide anion (O2-·) and peroxide ion (O2-) ROS are generated during the reduction of molecular oxygen (O2) to water.Nitric oxide (NO) is a free radical gas produced by a variety of cells (macrophages, Kupffer cells and vascular endothelium)
Free radicals: effects
Cause peroxidation of lipids (in membranes, mitochondria and in circulation) Cause peroxidation of proteins (especially thiol-containing proteins, e.g., Ca-ATPase and Na-K ATPases of plasma membranes) Interact with DNA, causing strand breaks and inducing the enzyme poly(ADP-ribose) polymerase Alter the redox activity of the cell, with profoundeffects on enzyme systems sensitive to redox potential
Variability of cell response to injury
Intensity, duration and type of traumatic event (striated muscle can be ischemic for hours vs heart only 20-30 mins)Differences in cell type Production of cytokines/growth factors Expression of cell receptors
Consequences of trauma
Strong, acute, very persistent trauma –> irreversible cell injury
Less intense/temporary trauma –> reversible cell injury
Non-excessive trauma –> cell adaptation
Cell adaptation: hypertrophy
A reversible adaptive response characterized by an increase in cell size (cells do not divide but become larger) –> occurs in cardiac muscle, skeletal muscle, & nerve)
Occurs when there is an increase in protein synthesis, structural components, and organelles
Normal: Increased exercise –> increased muscle hypertrophy
Pathological hypertrophy:
Cardiac hypertrophy in: systemic hypertension restricted aortic outflow(aortic valve stenosis)
Cell adaptation: Atrophy
Decrease in cell size due to decrease in structural components of the cell (mitochondria, myofilamentsand endoplasmic reticulum)
Pathologic atrophy:
Reduced functional activity and/or prolonged pressure Loss of innervation
Reduced blood supply
Insufficient nutrition
Loss of hormones and/or cytokines/growth factors
Cell adaptation: Hyperplasia
A reversible adaptive response characterized by an increase in the number of cells (cells divide more)
Pathologic hyperplasia
Hormonal: Cushing’s syndrome, nodular prostatic hyperplasia Autoimmune: psoriasis vulgaris, Graves’ disease
Viral: warts
Inflammation and wound healing:keloids
Relationship of hyperplasia & hypertrophy
Cells adapt to trauma by increasing both number (hyperplasia) and size (hypertrophy) Examples: thyroid cells of Graves’ disease, bronchial smooth muscle cells in asthma
Cell adaptation: Metaplasia
One adult cell type is replaced by another adult cell type (–> patch of ectopic tissue) Mechanism: stem cells undergo reprogramming
Types of metaplasia
Change from one cell type to another
Squamous, Glandular, Connective tissue (named by what the new cell type is)
Most common: columnar –> squamous
Persistent –> increase likelihood of malignant transformation
Pathologic metaplasia:
Trachea and bronchi of cigarette smokers
Barrett’s esophagus
myositis ossificans (bone formation in muscle after intramuscular hemorrhage
Keratomalacia (vitA deficiency: Retinoic acid needed for proper stem cell differentiation)
Reversible Cell Injury: Hydropic change
Cell is incapable of maintaining ionic and fluid homeostasis due to failure of energy driven pumps
Na/K ATPase
More Na in the cell –> increased water drawn into organ
Reversible Cell Injury: Fatty change
Infiltration of fat (mainly triglycerides) inside hepatocytes, usually exceeding 5% of liver weight:
Histology: empty white spaces where lipid droplet were in vivo
Irreversible Cell injury: types
Apoptosis (cell death with shrinkage, activation-induced cell death, cell suicide, programmed cell death)
Necrosis (cell death with swelling, oncosis, accidental cell death)
Ultrastructural changes of reversible injury
Plasma membrane: blebbing, loss of microvilli…
Mitochondria: swelling, amorphous densities
Dilation of ER
Alterations to the nucleus
Apoptosis: definition
Programmed cell death mediated by a tightly controlled cell program
Apoptosis: Fate of dead cells
Apoptotic cells breakdown into fragments and the plasma membrane of dead cells are marked to signal their phagocytosis
Phagocytosis is usually VERY rapid –> USUALLY there is NO inflammation
Physiological apoptosis
Occurs during:
programmed cell death during embryogenesis
involution of hormone-dependent tissues once the hormone is removed
Elimination of potentially harmful self-reactive lymphocytes
Death of cells that have already served their purpose (neutrophils after immune response)
Cell loss in proliferating cell populations
Inflammation is NOT present