Cellular Adaptations to Injury PDF

Cellular Adaptations Dr. Mahmoud Kiswani Al-Quds University Faculty of Medicine Pathology Department ١  Cellular Adaptation to Injury A new steady state which lies between normal unstressed cell, and the injured overstressed cell, in which the cell can function and preserve viability....

Cellular Adaptations Dr. Mahmoud Kiswani Al-Quds University Faculty of Medicine Pathology Department ١  Cellular Adaptation to Injury A new steady state which lies between normal unstressed cell, and the injured overstressed cell, in which the cell can function and preserve viability. ٢  Cellular Adaptation 1) Physiological adaptation responses of cells to normal stimulation by hormones or endogenous chemical mediators e.g. hormones leading to enlargement of the breast and the uterus during pregnancy 2) Pathological adaptation allows the cells to modulate their environment and ideally escape injury e.g. hormones produced by tumors leading to endometrial hyperplasia ٤ Mechanisms of Cellular Adaptation – up- or down-regulation of specific cellular receptors – receptor binding – Increase or decrease of protein synthesis – switch from producing one type of protein to another ٥  Cellular adaptation Types of adaptive responses: Atrophy - decrease in cell size Hypertrophy - increase in cell size Hyperplasia - increase in cell number Metaplasia - change in cell type Others: aplasia, hypoplasia ٦  Cellular Adaptation to stress normal bronchial epithelial cell adaptation cell injury atrophy hypertrophy hyperplasia metaplasia dysplasia reversible irreversible necrosis ٧  Atrophy Shrinkage in the size of the cell by loss of cell substances, leading to diminished function of the cell and a new equilibrium is reached. Accompanied by decrease in the organ size, if sufficient number of cells is involved. The cells are not dead ٨  Causes of Atrophy 1) Physiological: thymic involution, aging loss of hormonal stimuli (menopause) 2) Pathological: Decrease work load (immobilization of a limb to permit healing of a fracture) loss of innervation (Denervation atrophy) diminished blood supply (ischemic atrophy) inadequate nutrition ٩ A, Atrophy of the brain in an 82-year-old male with atherosclerotic disease. Atrophy of the brain is due to aging and reduced blood supply. The meninges have been stripped. B, Normal brain of a 25-yr-old male. Note that loss of brain substance narrows the gyri and widens the sulci ١٠ Normal These kidneys are from a patient who had atherosclerotic stenosis of one renal artery ١١  Mechanisms of Atrophy Imbalance between protein synthesis and degradation is the fundamental step, leading to reduction in structural components. Decreased synthesis, increased catabolism, or both the fundamental cellular changes are identical in physiological and pathological causes. Sometimes the number of cells can be reduced by the process apoptosis ١٢ Atrophy: increase catabolism Proteolytic systems for degradation: 1) Lysosomes contain hydrolases and other enzymes degrade exogenous proteins engulfed by endocytosis degrade subcellular components (e.g. organelles) leading to the formation of autophagic vacuoles ١٣ 2) The ubiquitin-proteasome pathway: Degradation of cytosolic and nuclear proteins Responsible for the accelerated proteolysis in hypercatabolic states (e.g. cancer) The protein/ubiquitin complexes are engulfed by the cytoplasmic proteasome Ubiquitin: An abundant protein found in normal cells. It has a role in removing old or damaged proteins by acting as a cofactor for proteolysis. Proteasomes: non lysosomal proteinases. ١٥ The ubiquitin-proteasome pathway: ١٦  Hypertrophy Increase in the size of cells by an increase in the number and density of the cellular substances, leading to an over all increase in the size and the function of the organ, and a new equilibrium is reached. Mainly occurs in organs composed of cells that can’t divide (cardiac & skeletal muscles). NO NEW CELLS, JUST BIGGER CELLS ١٨  Causes of Hypertrophy: Physiological or pathological: – Increase in functional demand or work load e.g. body building, hypertension, aortic valve disease – Increase in hormonal stimulation. This involves both hypertrophy and hyperplasia and both result in an enlarged (hypertrophic) organ. e.g. the gravid uterus occurs as a consequence of estrogen stimulation of both smooth muscle hypertrophy and smooth muscle hyperplasia ١٩  Mechanisms of Hypertrophy an increased synthesis of structural proteins and organelles leading to an overall increase in the workload of the organ. ٢٠ hypertrophy after myocardial infarction The mechanisms of cardiac hypertrophy: 1. mechanical triggers, such as stretch 2. trophic triggers, such as activation of α-adrenergic receptors ٢١  Hypertrophy in hypertension Adaptive changes may not be completely benign; they can also result in a dramatic change in the cellular phenotype: Reactivation of certain genes. Switch of contractile proteins to a different type. Degenerative changes overtime leading to failure of organ ٢٢ Skeletal muscle hypertrophy in body building: ٢٣  Hyperplasia an increase in the size of the organ due to increase in the number of the cells in the organ, leading to increase in the function. SEEN IN CELLS THAT CAN DIVIDE ٢٤  Hyperplasia Gravid uterus ٢٥  Causes of Hyperplasia: Physiological: 1. hormonal hyperplasia (e.g. female breast at puberty and during pregnancy) 2. compensatory hyperplasia: occurs when a portion of the tissue is removed or diseased which is under the influence of growth factors (e.g. liver resection, wound healing) Pathological: – Under the effect of hormones or growth factors. (e.g. Endometrial hyperplasia, skin wart) ٢٦  Hyperplasia Both hypertrophy and hyperplasia are reversible, if the stimulus is removed. This differentiates these processes from cancer, in which cells continue to grow despite the absence of hormonal stimuli. pathologic hyperplasia constitutes a fertile soil in which cancerous proliferation may eventually arise. e.g. patients with hyperplasia of the endometrium are at increased risk of developing endometrial cancer e.g. papillomavirus infections predispose to cervical cancers ٢٧ Hypertrophy & hyperplasia Summary ٢٨  Metaplasia Replacement of one type of adult cell, whether epithelial or mesenchymal, by another type of adult cell aiming at replacing cells that are sensitive to certain stimuli by a more resistant cell type. This happens through reprogramming of stem cells or undifferentiated mesenchymal cells. the influences that induce metaplastic transformation, if persistent, may induce cancer transformation in the metaplastic epithelium ٢٩ Examples of Metaplasia (respiratory epithelium) ٣٠ Metaplastic transformation of esophageal stratified squamous epithelium (left) to mature columnar epithelium (so-called Barrett metaplasia) ٣١  An investigator is studying the cell morphologies of the respiratory tract. He obtains a biopsy from the mainstem bronchus of a patient. On microscopic examination, the biopsy sample shows uniform squamous cells in layers. Which of the following best describes the histologic finding seen in this patient? A. Metaplasia B. Normal epithelium C. Dysplasia D. Hyperplasia E. Hypertrophy F. Anaplasia