Cellular Adaptation PDF

Cellular Adaptation Michael Yakubovskyy, MD, PhD Content of the Course of Cellular Pathology Introduction to Pathology Cellular Pathology 1. Cellular Adaptation Cellular Pathology 2. Cell Injury Cellular Pathology 3. Accumulations, Calcifications, and Aging (Self-Study) Cellular Pathology 4. Ce...

Cellular Adaptation Michael Yakubovskyy, MD, PhD Content of the Course of Cellular Pathology Introduction to Pathology Cellular Pathology 1. Cellular Adaptation Cellular Pathology 2. Cell Injury Cellular Pathology 3. Accumulations, Calcifications, and Aging (Self-Study) Cellular Pathology 4. Cell Death - Necrosis Cellular Pathology 5. Cell Death - Apoptosis Cellular Pathology 6. Cellular Pathology Labs (Fusion/Flipped Classroom/FCR) Introduction to Pathology Pathology: The Study of Disease (Greek “pathos” - suffering) Etiology (Greek “aitia” - cause) Pathogenesis Morphologic changes Functional derangements Clinical manifestations Causes of diseases (etiologic factors) Mechanisms of disease development Structural alterations caused by a disease • Gross (macroscopic) appearance: changes seen by a naked eye • Histologic (microscopic) appearance: changes seen by an armed eye As background for clinical manifestations • • • Other aspects • • • Symptoms: a patient feels Signs: a physician discovers Complications Causes and mechanisms of death Outcomes Prognosis for recovery and life Cellular Pathology 1: Adaptation Michael Yakubovskyy, MD, PhD Recommended Resources for Cellular Pathology • Robbins family o o o o • V. Kumar, A. K. Abbas, J. C. Aster. Robbins and Cotran Pathologic Basis of th Disease, 10 Ed. Ch. 2 th E. C. Klatt, V. Kumar. Robbins and Cotran Review of Pathology, 5 Ed. Ch.2 rd E. C. Klatt. Robbins and Cotran Atlas of Pathology, 4 Ed. nd E. C. Klatt, R.N. Mitchell. Robbins and Cotran Pathology Flash Card, 2 Ed. Unit I.1: not on VitalSource Extra o o WebPath https://library.med.utah.edu/WebPath/webpath.html USMLE-Rx, UWorld, Kaplan, etc. resources Content and Learning Objectives Content Learning Objectives Cellular response to stress LO1. Discriminate between physiologic and pathologic adaptation, and cell injury. Characteristics of adaptive responses LO2. Compare and contrast hypertrophy, hyperplasia, atrophy, and metaplasia with examples, in terms of etiology, pathogenesis, morphology, and clinical features. Cellular Response to Stress LO1. Discriminate between physiologic and pathologic adaptation, and cell injury. Adaptation vs. Injury A normal cell maintains a steady structural and functional state known as homeostasis. • Adaptation: an altered, but reversible and steady state of response • o o • to physiologic stimuli (physiologic adaptation) e.g., breast in pregnancy) to pathologic stimuli (pathologic adaptation) e.g., denervation atrophy of skeletal muscles Cell injury: a sequence of events that occur, if the limits of adaptive capability are exceeded, or no adaptive response is possible Classification of Adaptive Responses • Hypertrophy: an o o Physiologic Pathologic • Hyperplasia: o o o an increase in cell number Physiologic Pathologic • Atrophy: a o increase in cell size decrease in cell size Physiologic Pathologic • Metaplasia: replacement of one cell type by another cell type Cell Type, Cell Cycle and Adaptive Potential Cell Type Tissue/Cell Potential Mitotic Activity Adaptive Potential Labile cells Epithelia, hemo- and lymphopoietic cells, and spermatogonia Continuously dividing (M—>G1) Multiply, but can not become larger —> only hyperplasia Stable cells Glandular organs (liver, etc.), smooth muscles, and fibroblasts Usually in G0, but can enter the cell cycle upon stimulation Can multiply and become larger —> hyperplasia and hypertrophy Neurons Unable to divide, permanently in G0 Permanent cells Cannot multiply, but can become larger —> only hypertrophy Characteristics of Adaptive Responses LO2. Compare and contrast hypertrophy, hyperplasia, atrophy and metaplasia, with examples, in terms of etiology, pathogenesis, morphology, and clinical features. Hypertrophy vs. Hyperplasia • Hypertrophy: o an increase in cell size Seen in stable and permanent cells. • Hyperplasia: an o increase in cell number Seen in labile and stable cells. • Hyperplasia and hypertrophy may occur simultaneously (in stable cells). • Both hyperplasia and hypertrophy result in an increase of organ weight and size. Hypertrophy, Physiologic: Causes and Examples Increased mechanical demand in physiologic conditions •Skeletal muscles and LV myocardium in athletes Increased endocrine stimulation within physiologic limits •Smooth muscle cells in the myometrium during pregnancy (along with hyperplasia) •Ductal epithelium in the lactating breast Pathologic Hypertrophy: Causes and Examples • Increased mechanical demand due to pathologic processes • LV myocardium in hypertension • RV myocardium in chronic pulmonary diseases with increased resistance in the pulmonary circulation Mechanism of Mechanical-Demand-Induced Hypertrophy Increased mechanical load Activation of mechanical sensors Activation of transcription factors PI3K/AKT pathway in physiologic conditions Activation of signaling pathways G-protein-coupled receptorinitiated pathway in pathologic conditions Skeletal/cardiac muscle hypertrophy • Increase Hypertrophy: Structural Changes in size nucleus (nuclear hypertrophy) • Increase in size (hypertrophy) and number (hyperplasia) of o o o Cisterns of endoplasmic reticulum Cisterns and vesicles of Golgi apparatus Mitochondria Cardiac Hypertrophy: Gross and Histo Boxcar nucleus 1 cm . Boxcar nuclei: https://commons.wikimedia.org/wiki/File:Histopathology_of_moderate_myocardial_hypertrophy.jpg By Mikael Häggström, M.D. Author info- Reusing images- Conflicts of interest:NoneMikael Häggström, M.D.Consent note: Consent from the patient or patient&#039;s relatives is regarded as redundant, because of absence of identifiable features (List of HIPAA identifiers) in the media and case information (See also HIPAA case reports guidance). - Own work, CC0, https://commons.wikimedia.org/w/index.php?curid=96249823 Physiologic Hyperplasia: Causes and Examples • Hormone-induced o o hyperplasia in physiologic conditions Proliferation of glandular epithelium of the female breast during pregnancy and puberty Gravid uterus: smooth muscle cell hyperplasia • Compensatory hyperplasia after organ damage or partial resection o Liver regeneration after partial hepatectomy (in donors) • NB: in many organs, hyperplasia and hypertrophy coincide Pathologic Hyperplasia: Causes and Examples • Excessive hormonal stimulation e.g., endometrial hyperplasia, or benign prostate hyperplasia • Viral infections e.g., HPV —> epithelial hyperplasia (skin warts) • Environmental hazards e.g., tobacco smoking —> hyperplasia of the submucosal glands in the bronchial wall Benign Prostate Hyperplasia (Normal Diameter <4 cm): Diagram 5. BPH: https://commons.wikimedia.org/wiki/File: Benign_prostatic_hyperplasia.jpg Unknown Illustrator, Public domain, via Wikimedia Commons • Hyperplasia o Pathologic Hyperplasia vs. Neoplasia o o Responds to normal regulatory mechanisms. Resolves after the stimulus stops acting i.e., is reversible. Does not progress to neoplasia with exception of endometrial hyperplasia. • Neoplasia o o Does not respond to regulatory mechanisms. Non-reversible • Atrophy: a decrease in cell size due to loss of cell substance o Atrophy —> A decrease in organ/tissue weight and size is large number of cells is involved. • Mechanisms o o Decreased protein synthesis or Increased protein degradation • In the ubiquitin-proteosome pathway, or • Via lysosomal degradation with formation of autophagic vacuoles and residual bodies containing lipofuscin • Early o Atrophy: Morphology o stage: reduced cell size due to Decreased number and size of organelles Increased number and size of autophagic vacuoles lipofuscin accumulation —> brown atrophy • Advanced stage: cell death (apoptosis) Lipofuscinosis, Myocardium: Micro Physiologic Atrophy • Embryonic structures (notochord, thyroglossal duct) during fetal development • Myometrium after delivery • Endometrium and breast after menopause Pathologic Atrophy: Causes and Examples • Chronic ischemia (heart, brain, kidney) —> organ atrophy • (Protein) metabolism abnormalities —> neurodegenerative diseases, e.g., Alzheimer disease —> brain atrophy • Bone fracture —> immobilization —> skeletal muscle atrophy and osteoporosis • Denervation (peripheral nerve damage) —> skeletal muscle atrophy • Hypothalamic/pituitary injury —> atrophy of target organs (e.g., thyroid or adrenal glands) • Pressure atrophy (refer to below) • Inadequate nutrition (refer to below) Brain Atrophy in Alzheimer Disease: Gross Pathologic Atrophy: Examples of Pressure Atrophy Hydrocephalus (accumulation of cerebrospinal fluid in the ventricles and subarachnoid space) —> raised intracranial pressure —> brain atrophy • Urolithiasis (renal stones) —> obstruction to urinary flow —> hydronephrosis —> kidney atrophy • Severe acute malnutrition Generalized Pathologic Atrophy •Marasmus: severe caloric deficiency —> generalized atrophy •Kwashiorkor: severe protein-caloric deficiency —> hypoalbuminemia —> generalized edema Cachexia: skeletal muscle wasting •TNF release in patients with cancer and chronic infectious diseases, e.g., TB Marasmus vs. Kwashiorkor Metaplasia • Metaplasia: replacement of one adult cell type by another adult cell type o o o Within the same germ layer Purpose: to withstand an action of a harmful stimulus Reversible • Clinical significance: epithelial metaplasia —> background for malignant transformation Metaplasia: Clinically Significant Examples • Columnar epithelium —> non-keratinizing squamous epithelium • In the bronchi as a reaction to pathologic stimuli • In the uterine cervix as a normal process in women of reproductive age • Non-keratinizing squamous epithelium—> columnar/intestinal epithelium in the esophagus (Barrett esophagus) • Skeletal muscles —> bone in myositis ossificans Bronchial Squamous Metaplasia: Histo 8. https://commons.wikimedia.org/wiki/File:Bronchial_squamous_metaplasia.jpg Yale Rosen, CC BY-SA 2.0 <https://creativecommons.org/licenses/by-sa/2.0>, via Wikimedia Commons Barrett Esophagus, Intestinal/Columnar/Goblet Cell Metaplasia: Histo Normal esophageal mucosa Intestinal epithelium Gastric epithelium [[File:Histopathology of Barrett's esophagus, original.jpg|Histopathology_of_Barrett’s_esophagus,_original]] Mikael Häggström, M.D. Author info - Reusing images- Conflicts of interest: None Mikael Häggström, M.D.Consent note: Consent from the patient or patient's relatives is regarded as redundant, because of absence of identifiable features (List of HIPAA identifiers) in the media and case information (See also HIPAA case reports guidance)., CC0, via Wikimedia Common Control, non-keratinizing squamous epithelium Intestinal metaplasia Barrett Esophagus: Gross Esophagus Stomach Myositis Ossificans: X-Ray The End