L1- Cell injury-adaptation.pdf

Prof. Layla S. Abdullah ,MD,FRCPC Pathology Department Faculty of Medicine KAU Cell Injury and Adaptation Prof. Layla S. Abdullah ,MD,FRCPC Pathology Department Faculty of Medicine KAU Homeostasis: steady state in which the cells are able to handle normal physiologic demands Stress: changes...

Prof. Layla S. Abdullah ,MD,FRCPC Pathology Department Faculty of Medicine KAU Cell Injury and Adaptation Prof. Layla S. Abdullah ,MD,FRCPC Pathology Department Faculty of Medicine KAU Homeostasis: steady state in which the cells are able to handle normal physiologic demands Stress: changes in cell environment If the cell adaptive capability is exceeded Cell Injury develops Adaptation: A new steady state Cellular Adaptation to Injury Cellular Adaptation to Injury Physiologic Responses to normal processes Pathologic Allows cells to modulate environment and hopefully escape injury Mechanism of Cellular Adaptation to Injury Cellular adaptive responses can occur at any of these Steps: Receptor binding signal transduction protein transcription translation export 4 Main Forms of Adaptation o o o o o o o o Atrophy: Reduced size of an organ or tissue resulting from a decrease in cell size Hypertrophy: Increased size of cells and increased size of the organ Hyperplasia: Increase in the number of cells in an organ or tissue Metaplasia: A reversible change in which one adult cell type (epithelial or mesenchymal) is replaced by another adult cell type Atrophy • o – Defintion: Reduced size of an organ or tissue resulting from a: Cell size (loss of cell substances = cell atrophy) • o o o Biochemical Mechanisms Decreased protein synthesis Increased protein catabolism (degradation) Or/ Both Atrophy • Causes, like: – Decreased workload – Limb atrophy (Disuse atrophy, casts) Atrophy • Causes, like: – Loss of innervations (e.g. brain stroke) hemiplegia Atrophy • Causes, like: – Loss of endocrine stimulation Normal testis Testicular atrophy Atrophy • Causes, like: – Aging Atrophy • Causes, like: – Diminished blood supply Kidneys, left side normal size right side atrophy Atrophy • Causes, like: – Inadequate nutrition – Nutritional atrophy (Cachexia in malignancy and famines) Other Important examples of atrophy • • • • • • • • Skeletal muscle atrophy (Poliomyelitis) Pressure atrophy (aneurysm, amyloidosis of liver) Ischemic atrophy (brain in late aquired syphilis) Brown atrophy , heart (lipofuscin pigment) Genital organ atrophy in aging Gastric atrophy due to inflammation or autoimmune disease) Villous atrophy in celiac diaease Renal atrophy in hypertension and inflammation Atrophy • Histologic Changes – • Decreased cell size Atrophy represents a reduction in the structural components of the cell. In muscle, the cells contain fewer mitochondria and myofilaments and a lesser amount of endoplasmic reticulum • – – Increased autophagic vacuoles Increased residual bodies (lipofuscin) Forms of Adaptation o Atrophy o Hypertrophy o Hyperplasia o Metaplasia Hypertrophy Definition: Increased size of cells and increased size of the organ. Thus, the hypertrophied organ has no new cells, just larger cells • • • • Prominent in organs with cells incapable of mitosis Pathogenesis: Increased Synthesis of Structural Proteins Increased Cellular Organelles Hypertrophy Causes: • Physiologic o E.g. skeletal muscle with exercise • o Pathologic E.g. myocardium in hypertension Hypertrophy Mechanism: – Increased functional demand • skeletal muscle in exercise • myocardium in hypertension – • • Specific hormonal stimulation uterus in pregnancy Acromegaly Heart, normal Heart, left ventricular hypertrophy N Heart, left and right frames hypertrophy/middle frame normal Forms of Adaptation o Atrophy o Hypertrophy o Hyperplasia o Metaplasia Hyperplasia Definition: Increase in the number of cells in an organ or tissue • Hyperplasia and Hypertrophy often occur together • Hyperplasia can be physiologic or pathologic Hyperplasia causes Physiologic: 1. Hormonal (breast during pregnancy) 2. Compensatory (after partial hepatectomy) • Pathologic: 1. Hyperplasia causes Excessive hormonal • absolute or relative increase in estrogen over progesterone endometrial hyperplasia • Prostatic hyperplasia. 2. • Excessive growth factor sensitivity Papilloma virus skin wart – Hyperplasia is a Controlled Process if stimulation is ceased – if stimulation continued Soil for Cancer pathologic hyperplasia is Fertile Other Clinical Examples • • • • • Follicular hyperplasia of the lymph nodes Reactive hyperplasia in the bone marrow Fibrocystic disease of the breast (cystic mammary hyperplasia) Nodular goiter (thyroid) Hyperplasia of mucous glands in chronic bronchitis Hyperplasia, uterus Thick mucosal polyps Prostate, Normal: Prostate, benign prostatic hyperplasia: Prostate, normal Prostate, Hyperplasia Nodular goiter, thyroid Forms of Adaptation o Atrophy o Hypertrophy o Hyperplasia o Metaplasia Metaplasia Definition: A reversible change in which one adult cell type is replaced by another adult cell type • Arise by “Genetic reprogramming” of stem cells Metaplasia Metaplasia Epithelial Metaplasia: • – • • • – • Squamous Metaplasia Respiratory epithelium (ciliated columnar is replaced by stratified squamous epithelium) due to: cigarette smoking Vit. A deficiency Gastric Metaplasia Lower esophageal epithelium in “Barrett oesophagus” transformed from (squamous epithelium columnar) due to: chronic gastric reflux Other examples • Gastric to intestinal epithelium – in chronic gastritis • Columnar to stratified squamous epithelium – • in the cervix Transitional epithelium of the urinary bladder to squamous or glandular epithelium – due to stones or shistosomiasis. Metaplasia • Epithelial metaplasia is a two-edged sword and, in most circumstances, represents an undesirable change • if persistent cancer transformation can occur in the same place of metaplastic epithelium Metaplasia Mesenchymal Metaplasia •not clearly an adaptive response For example: Bone formation in muscle in myositis ossificans. Fibroblasts transformation into osteoblasts or chondroblasts