Mechanisms of Tissue Injury PDF

Intro to Clinical Medicine Lecture (3) Mechanisms of tissue injury Thomas G. Forsthuber, M.D. Dr. Med. Professor of Immunology Office: BSE 3.250B E-mail: [email protected] Office Hours: Monday 4:30 – 5:30 – ZOOM link Canvas Pathological Diagnosis b...

Intro to Clinical Medicine Lecture (3) Mechanisms of tissue injury Thomas G. Forsthuber, M.D. Dr. Med. Professor of Immunology Office: BSE 3.250B E-mail: [email protected] Office Hours: Monday 4:30 – 5:30 – ZOOM link Canvas Pathological Diagnosis based on macroscopic/microscopic changes Living cells and tissues adapt to a changing environment or stress Failure of adaptive mechanisms leads to cell injury or cell death. Cellular changes/injury can be visible at the organ or at the cellular level Tissues can also show changes related to aging Macroscopic or microscopic changes to tissues are important for pathological diagnosis Macroscopic changes (Organ level): – Hypertrophy, atrophy, dysplasia – Pigmentation, calcification – Fatty change Microscopic changes (Cellular level) – Pigmentation, inclusions (e.g. iron, fat, Lipofuscin) – Multi-nucleation – Apoptosis, necrosis  Macroscopic changes in liver disease Which one is the “fatty” Liver? A B Microscopic changes in liver disease Normal liver Fatty liver Portal vein Hyaline inclusions in the liver = Mallory bodies Alcohol! Hemosiderin H&E Prussian blue (Iron)  Tissue responses to stress Increased demand or Hypertrophy, hyperplasia chronic stimulation Decreased demand, lack of Atrophy stimulation Chronic injury Metaplasia Hypertrophy: Cells increase in size, organs may increase in size Hyperplasia: Increase in the number of cells Atrophy: Shrinkage in cell size (or organ) Metaplasia: Cells change from one cell type to another Hypertrophy: In dividing and non-dividing cells Hyperplasia: Only with dividing cells Physiologic hypertrophy Uterus Uterus histology Pregnant Normal Normal Pregnant  Pathologic Hypertrophy Hyperplasia Prostate Hyperplasia (Nodular hyperplasia, BPH= benign prostatic hyperplasia) Prostate hyperplasia (proliferation of glands) Testosterone converted in prostate stromal cells to dihydrotestosterone (x10 more potent)  Atrophy Physiologic atrophy: Shrinkage of the uterus after pregnancy, – Mechanism: loss of hormonal stimulation, developmental gene regulation, Pathologic atrophy: muscle atrophy after fracture, brain with Alzheimer's – Inactivity, loss of innervation, loss of perfusion/blood supply, lack of nutrition, loss of hormonal stimulation, aging, pressure Atrophy A B  Quick histology primer epithelial cells Most body surfaces are lined by Epithelial cells Agnes Lacombe, University of British Columbia Three types of epithelium: “Simple epithelium” SQUAMOUS Epithelium: Lining of body cavities, Vessels, alveoli (lung) CUBOIDAL Epithelium: Lining nephrons, Thyroid glands, surface of ovaries COLUMNAR Epithelium: Gut including stomach & large intestine, gallbladder, Lining of uterus Upper respiratory tract  Epithelial cells form ONE layer (simple epithelium) or SHEETS (stratified epithelium) Single layer Arranged in sheets or layers Metaplasia Squamous metaplasia: Upper airways = smokers Stress Columnar Squamous Epithelium Epithelium Intestinal metaplasia: Intestinal metaplasisia Gastro-esphageal junction= Barrett’s esophagus GERD Squamous Columnar Epithelium Epithelium (glandular type)  Metaplasia Curtesy Medbullets “Fatal” stress – cells die! Causes of cell death: Oxygen deprivation Physical insult (heat, cold, electric) Chemical Infectious Immune Genetic Nutrition Death by Necrosis Apoptosis necrosis or Inflammation! Silent! apoptosis  Classical apoptosis sign: DNA laddering Apoptosis Necrosis Normal - Caspase = Cysteine- Aspartate protease -Laddering is due to caspase-activated Dnase (CAD) - CAD cuts DNA into small fragments - Fragments are multiples of 280 bp (length of DNA wrapped around histones) Apoptosis pathways Extrinsic (death receptor-mediated) apoptosis pathway Intrinsic (mitochondria-mediated) apoptosis pathway Third pathway: Endoplasmic reticulum stress pathway (mediated by too much or to little Ca++) Extrinsic apoptosis pathway Intrinsic apoptosis pathway  Necrosis Violent tissue death: necrosis Normal tissue Necrotic tissue Myocardial infarct: ischemic necrosis of myocardium  Necrosis Coagulative Necrosis: Liquefactive Necrosis: “Dry necrosis”. Basic “Liquid necrosis”. Tissue cell outline maintained. dissolves. Every structure lost. Nuclei lost, cytoplasm No cells visible. eosinophil. Hypoxic cell Brain shows liquefactive death necrosis! Seen in Infarcts Seen in severe Infections “Clinical” types of necrosis Gangrene (gangrenous necrosis): – Dry or wet gangrene – Often after loss of blood supply -> coagulative necrosis – Example: diabetic foot, peripheral arterial disease, frost bite Caseous necrosis: Tuberculosis, lung cavity filled with “cheesy” white-yellow material. -> liquefactive necrosis Fat necrosis: Fat destruction of the mesentery (tissue-fat- sheet in the belly). Frequently after pancreatitis.  Important: The brain usually shows liquefactive necrosis