CELLULR ADAPTATION, CELL INJURY AND CELL DEATH. DR(Med) YOLANDA ASHIE KNUST-KSMD OBJECTIVES • Identify the various types of cellular adaptation • Describe the conditions leading to these adaptive changes. • Categorize injurious agents and their resultant effects on the cell. • Describe the cellular changes in necrosis and apoptosis. Remember! CELL TISSUE ORGAN ORGAN SYSTEM ORGANISM Cellular Differentiation and Cell Types Differentiation is the process by which cells become specialized to perform distinct functions. E.g. cardiac cells, nerve cells, fibroblasts, epithelial cells, erythrocytes, osteocytes, etc. CELL TYPES CHARACTERISTIC EXAMPLE LABILE CELLS Continuously replicating. Squamous epithelia of skin and mucous membranes, haematopoietic cells, epithelia of ducts of glands, gastrointestinal tract and genitourinary tract Mostly quiescent. Can proliferate due to cell loss or injury. Cells of the liver, kidney, glands; mesenchymal cells(fibroblasts, endothelial cells, smooth muscle cells, etc) No proliferative ability Cardiac cells, skeletal cells and neurons Cells can be classified into three main categories based on their replicative STABLE CELLS potential: PERMANENT CELLS Types of Injurious Agents Nonlethal injurious stimuli to the cells such as increased physiological demands, hormonal stimulation, chronic irritation, malnutrition and physical disuse usually result in Cellular adaptations. Infections, ischaemia, chemical injuries, ionizing radiation, and oxidative stress will result in Reversible or Irreversible cell injury. Metabolic alterations and chronic injury culminates in Intracellular accumulations. Cellular aging/senescence. CELLULAR ADAPTATION Reversible changes in the structure and function of cells in response to external stresses. HYPERTROPHY An increase in the size of the cells and thus function. Caused by increased functional demand or hormonal/growth factor stimulation. • Physiologic hypertrophy: e.g. exercised-induced cardiac hypertrophy. • Pathologic hypertrophy: e.g. left ventricular hypertrophy of heart secondary to hypertension, bladder hypertrophy from lower urinary tract obstruction, and compensatory hypertrophy of kidney after unilateral nephrectomy. HYPERPLASIA Increase in the number of cells and size of the organ. Occurs in labile/stable cells. Triggered by increased functional demand, hormonal/growth factor stimulus. Usually coexists with hypertrophy. Types: • Physiologic: e.g. female breast in puberty and pregnancy, also uterine hyperplasia in pregnancy. Hepatic hyperplasia post lobectomy(compensatory). • Pathologic: e.g. Benign prostatic hyperplasia, endometrial hyperplasia ATROPHY Decrease in cell size and number and thus function and structure of organ. Types: • Physiologic; e.g. during embryogenesis and postpartum shrinkage of uterus. • Pathologic; results from a decreased workload, nutritional deficiency, ischaemia, undernutrition, denervation, pressure effects, and loss of hormonal stimulation. E.g. loss of muscle mass and strength after immobilization in a cast, endometrial atrophy. Endometrial atrophy METAPLASIA A reversible change from one adult/matured cell type to another matured cell type in response to a chronic persisting irritation or inflammation. Involves the differentiation of stem cells. Examples include Barrett’s oesophagus due to GERD and squamous metaplasia of the respiratory epithelium in chronic smokers. These metaplastic cells are better able to withstand the persistent stress and irritation. • NB: Dysplasia is usually not regarded as a true adaptation. It is an abnormal/disordered growth of cells displaying atypical features and mostly become precursors of malignancy. CELLULAR INJURY & CELL DEATH CAUSES OF CELL INJURY 1. Physical agents: extremes of temperature, mechanical trauma, changes in atmospheric pressure, electrical shock and radiation injuries. 2. Chemical agents: environmental pollutants, alcohol, poisons(arsenic, cyanide, mercuric salts), hypertonic concentrations saline or glucose , therapeutic agents. 3. Infectious agents: viruses, helminths, prions, bacteria, fungi,etc. 4. Immunologic reactions: autoimmune disease and anaphylactic reactions. 5. Nutritional deficiencies: protein-energy malnutrition, vitamin deficiencies, obesity, etc. 6. Genetic abnormalities: haemoglobinopathies, inborn errors of metabolism, misfolded proteins, congenital disorders. Mechanisms of Cell Injury 1. Formation of free radicals 2. Hypoxia and ATP depletion 3. Disruption of intracellular calcium homeostasis Reversible cell injury Biologicial functions and structural integrity of the cell is maintained in the face of stressors and also because the offending agent is withdrawn before fatal damage ensues. Features include depleted ATP due to reduction in oxidative phosphorylation, cellular swelling resulting from defective ion pumps and swelling of ER and mitochondrion and fatty change. Irreversible cell injury Persistence of stressors or injurious agents renders cells depleted of reserves, and adaptive mechanisms fail to maintain integrity of cell. Eventually there is breakdown of the cellular components resulting in death. Cellular death can occur via the process of Necrosis or Apoptosis. NECROSIS • Persistent or intense injury results in severe damage to the cells with loss of membrane integrity(denaturation of membrane proteins) and release of lysosomal enzymes(enzymatic digestion of cellular components). • Cellular debris from necrosis further elicits inflammation. Patterns of Necrosis 1. Coagulative necrosis: the necrotic tissue is firm with a maintained architecture. Vascular occlusion leading to ischaemia of all organs, except the brain, results in coagulative necrosis(Infarct). 2. Liquefactive necrosis: results from digestion of cell debris by the action of leukocytes. Tissue becomes a liquid viscous mass and may form pus. In the brain, hypoxic injury results in liquefactive necrosis. 3. Caseous necrosis: commonly found in necrotizing granulomatous lesions caused by TB infection. The area of necrosis is easily friable rendering a cheese-like appearance. 4. Fat necrosis: usually results from traumatic injury to areas of fat deposition such as breast. In acute pancreatitis, the release of pancreatic enzyme, lipase, results in the digestion of surrounding fat. The fatty acids combine with calcium to produce chalky white deposits(fat saponification), characteristic of this condition. 5. Gangrenous necrosis: usually describes a necrotic limb resulting from lack of blood supply. Bacterial superinfection leads to liquefactive necrosis and is termed Wet gangrene. 6. Fibrinoid necrosis: occurs in blood vessels as a result of immune complex reactions with the deposition of fibrin with the wall of the vessels(vasculitis). APOPTOSIS • A programmed cell death mediated by a well-regulated mechanism targeted at eh cellular DNA and proteins. • Physiologic apoptosis occurs in: Embryogenesis Involution of hormone dependent tissues when hormone is withdrawn, e.g. ovarian follicular atresia or endometrial atrophy in menopause. Cell loss in proliferating polpulations, e.g. loss of epithelial cells in intestinal crypts to maintain homeostasis Loss of potentially harmful self-reactive lymphocytes. COMPARISON BETWEEN APOPTOSIS AND NECROSIS APOPTOSIS NECROSIS Occurs in single or few groups of cells Numerous cells or groups of cells affected at a time Progresses from reversible to irreversible Irreversible once initiated Passive process Active process dependent of ATP Destruction of cell membrane and organelles Formation of apoptotic bodies(membrane bound cellular components) References and Resources 5. Robbins and Cotran pathologic basis of diseases, 9th Edition. https://images.search.yahoo.com/search/images;_ylt=AwrEtymIx61l9.kQEQBXNyoA;_ylu=Y29s bwNiZjEEcG9zAzEEdnRpZAMEc2VjA3BpdnM-?p=cell+tissu+organisation&fr2=pivweb&type=C210US91075D20160906&fr=mcafee#id=95&iurl=https%3A%2F%2Fimgnm.mnimgs.com%2Fimg%2Fstudy_content%2Flp%2F2%2F7%2F6%2F606%2F974%2F2104%2F 2156%2FLP_2.7.6.1.2.1.1_Ruchika_html_38370136.png&action=click https://s3.studentvip.com.au/notes/40555-sample.pdf?v=1601901269 https://medicine.nus.edu.sg/pathweb/wp-content/uploads/2019/06/normal-uterus-21024x662.jpg http://www.patologia.cm.umk.pl/atlas/reproductive/female/complexatypia/img/large/2.jpg 6. https://www.duncansportspt.com/2018/01/unexplained-body-pain/ 1. 2. 3. 4.
