Exam I: Pathology I Flashcards
Four Aspects of Disease Process
- Cause (etiology)
- Mechanisms of its development (pathogenesis)
- Biochemical and structural alterations (molecular and morphologic changes)
- Functional consequences of these changes (clinical manifestations)
Etiology
Two major classes
1. Genetic: Inherited mutations & Disease-associated gene variants
- Acquired: Infectious, Nutritional, Chemical, Physical
Pathogenesis
Sequence of events: follows the exposure of cells or tissues to an injurious agent; from the initial stimulus to the ultimate expression of the disease
One of the main domains of pathology
Even when initial cause is known, there are several steps from the expression of the disease ex. cystic fibrosis
Molecular and Morphological Changes
Structural alterations in cells or tissues that are characteristic of a disease and diagnostic of an etiologic process
Morphology: diagnostic cornerstone of pathology with limitations requiring molecular analysis
Example: Breast Cancer- morphologic change in the cells, but also look at molecular aspect such as the HER2 receptor +/- or ER +/-
Clinical Manifestations
Functional abnormalities: end results of genetic, biochemical, and structural changes in cells and tissues causing signs and symptoms, which lead to the clinical manifestations and to the progression of disease (clinical course and outcome)
Clinicopathologic correlations—very important!
Disease: starts with molecular or structural alterations in cells
Concept first put forth by Rudolf Virchow (19th century)
aka father of modern pathology
Injury to cells and to extracellular matrix leads to tissue and organ injury, which determine the morphologic and clinical patterns of disease
Cellular Responses to Stress and Noxious Stimuli
Normal cell: confined to a narrow range of function and structure; is in a state of metabolism, differentiation, and specialization - maintains homeostasis
Constraints of neighboring cells and availability of metabolic substrates
Normal cell during stress usually adapts, but to injuries it can either recover or undergo necrosis/apoptosis depending on the situation
Cellular Responses: Adaptations
hypertrophy, hyperplasia, atrophy, metaplasia
Reversible functional and structural responses usually due to physiologic stresses and pathologic stimuli
Hypertrophy- increase in the size of cells
Hyperplasia- increase in the number of cells
Atrophy- decrease in the size and metabolic activity of cells
Metaplasia- change in the phenotype of cells
Cellular Responses: Injury
Exposure to injurious agents or stress
Deprivation of essential nutrients
Compromised by mutations that affect essential cellular constituents
Reversible- up to a certain point
Irreversible injury and cell death- stimulus persists
Cellular Responses: Death
Cell death: end result of progressive cell injury
One of the most crucial events in the evolution of disease
Results from diverse causes such as ischemia (reduced blood flow), infection, nutrient deprivation, and toxins
Normal and essential process ex. embryogenesis
Maintenance of homeostasis
Two principal pathways of cell death: necrosis and apoptosis
Autophagy due to low nutrients, and may lead to cell death
May see intracellular accumulations like proteins, lipids, carbohydrates
Adaptations: General
Adaptations: reversible changes of cells in response to changes in their environment Size Number Phenotype Metabolic activity Functions
Hypertrophy
Increase in cell size usually due to increase in synthesis and assembly of intracellular components within organelles, but the nucleus does not change size
This occurs due to an increase in functional demand, stimulation of hormones/growth factors, production of cellular proteins, switch of contractile proteins (fetal to adult)
Subcellular organelle may undergo selective hypertrophy
Examples of Hypertrophy (7)
- Myocytes that die cause a need for increased blood flow and mechanical effort leading to hypertrophy
- Striated muscle cells (cardiac/skeletal) have a limited capacity for division and respond to an increase in metabolic demands (increase in workload/ body building) leading to hypertrophy
- Hypertrophy of uterus during pregnancy
- Cardiac Hypertrophy- activation of signal transduction pathways and transcription factors that increase the production of cellular proteins
- Fetal stage have alpha isoform of myosin heavy chain, but switches the contractile protein to beta for adults
- Genes during development re-expressed in hypertrophied cells ex. ANF
- Hypertrophy of smooth ER in hepatocytes as an adaptive response to increased amount of enzymes needed for detox of drugs and alcohol
Hyperplasia
increase in the number of cells, which can lead to increased mass
Physiologic Hyperplasia
Hormonal: increase in functional capacity of a tissue ex. increase in glandular epithelium in breasts during puberty and pregnancy (usually with hypertrophy)
Compensatory: increase in tissue mass after damage or resection ex. liver donation
Pathologic Hyperplasia
caused by excess or inappropriate actions of hormones/ growth factors
- Endometrial: abnormal menstrual bleeding- can cause cancer
- BPH in prostate via androgens- can cause PCa
- Viral Infection (HPV) causing warts and lesions on skin/epithelium
