Lec 1 introduction.pdf

Dr.Sarab Department of Pathology 2024.  Define pathology and main anatomic concepts of disease: Degenerative, Inflammatory, Neoplastic  Recognize aspects about every disease  Discuss the concepts of cellular growth adaptations: Hyperplasia, Hypertr...

Dr.Sarab Department of Pathology 2024.  Define pathology and main anatomic concepts of disease: Degenerative, Inflammatory, Neoplastic  Recognize aspects about every disease  Discuss the concepts of cellular growth adaptations: Hyperplasia, Hypertrophy, Atrophy, Metaplasia Pathology is the study (logos) of disease (pathos→ suffering)  GENERAL  SYSTEMIC  ETIOLOGY (“Cause”)  PATHOGENESIS (“Insidious development”)  MORPHOLOGY (Abnormal anatomy)  CLINICAL EXPRESSION  ETIOLOGY→ is the origin of adisease why a disease arises Cause→ 𝑮𝒆𝒏𝒆𝒕𝒊𝒄 vs. Risk Factors→ 𝑨𝒄𝒒𝒖𝒊𝒓𝒆𝒅  𝐏𝐀𝐓𝐇𝐎𝐆𝐄𝐍𝐄𝐒𝐈𝐒 →how a disease develops Sequence of events from the initial stimulus to the ultimate expression of the disease  MORPHOLOGY  Abnormal Anatomy  Gross  Microscopic  Radiologic  Molecular  Cells normally maintain a steady state called homeostasis.  As cells encounter physiologic stresses or pathologic stimuli, they can undergo adaptation, achieving a new steady state and preserving viability and function. Stages in the cellular response to stress and injurious stimuli.  Hypoxia and ischemia  Toxins.  Infectiousagents.  Immunologic reactions  Genetic abnormalities  Nutritional imbalances.  Physical agents.  Aging. Adaptations are reversible changes in the number, size, phenotype, metabolic activity, or functions of cells in response to changes in their environment  Physiologic adaptations  Pathologic adaptations Hypertrophy Hyperplasia Atrophy Metaplasia  Hypertrophy is an increase in the size of cells resulting in increase in the size of the organ.  There are no new cells, just bigger cells containing increased amounts of structural proteins and Organelles  Hypertrophy can be physiologic or pathologic  Caused either by increased functional demand or by growth factor or hormonal stimulation. Physiologic hypertrophy of the uterus during pregnancy  Increase in number of cells in an organ or tissue usually resulting in an increase in the mass of organ and tissue. Hyperplasia can be  Physiologic →hormonal and compensatory e.g pregnancy  Pathologic.→e.g viral infections  Cellular proliferation is stimulated by growth factors  Usually, hyperplasia and hypertrophy occur together  Pathologic hyperplasia can progress to dysplasia and cancer. (Exception is benign prostatic hyperplasia)  Shrinkage in the size of the cell by the loss of cell substance  Can occur by decrease in cell number (apoptosis) or decrease in cell size  Causes: physiological or pathological  Physiological →menopause  Pathological→e.g., denervation  Mechanisms : decreased protein synthesis and increased protein degradation in cells. Senile atrophy in brain  Is a reversible change in which one adult cell type (epithelial or mesenchymal) is replaced by another adult cell type  E.g Squamous change that occurs in the respiratory epithelium of habitual cigarette smokers  Can progress to dysplasia and cancer  Columnar→Squamous (Cervix)  Squamous → Columnar(Glandular) (Stomach)  Fibrous→Bone (Connective tissue metaplasia) Metaplasia of normal columnar (left) to squamous epithelium (right) in a bronchus  Failure of cell production during embryogenesis.  Ex – unilateral renal agenesis (failure to make 1 kidney)  Decrease in number of cells  Decrease in cell production in embryogenesis. Results in relatively small organ.  Ex – streak ovary in Turner syndrome.  Cell injury?  If cellular stress overcomes cell's ability to adapt, then cell gets injured.  cellular injury depend on?  Type of stress  Severity  Type of cell  Reversible cell injury.  IRREVERSIBLE = DEATH  REDUCED oxidative phosphorylation  ATP depletion  Cellular “swelling” and fatty changes  loss of microvilli, membrane blebing as it pulls away from the  cytoskeleton  Swelling of RER and ribosomes fall off (low protein synthesis) INJURY MECHANISMS (REVERSIBLE)  Decreased ATP  Mitochondrial damage  Increased intracellular calcium  Increased free radicals  Increased cell membrane permeability  Mitochondrial irreversibility (Amorphous densities)  Irreversible membrane defects  Lysosomal digestion  Membrane damage. End result is cell death.  Cellular enzymes leak out increases.  Cytochrome C from mitochondria leaks out to cytosol and activates apoptosis  Lysosome enzymes will leak out and digest the cells. Ca in cytosol activates them.  C-Necrosis B-Reversible injury A-Normal kidney tubule