Cellular Injury: A Detailed Study PDF

1 Cellular Injury Cell damage (also known as cell injury) is a variety of changes of stress that a cell suffers due to external as well as internal environmental changes. Amongst other causes, this can be due to physical, chemical,...

1 Cellular Injury Cell damage (also known as cell injury) is a variety of changes of stress that a cell suffers due to external as well as internal environmental changes. Amongst other causes, this can be due to physical, chemical, infectious, biological, nutritional, or immunological factors. leading to long term damage or cell death I.​ Effect of stressors such as aging. illness, or injury (crush injury, major burn) A.​ Adaptive changes: ensure survival and maintain function​ -​ exhaustion of, or inappropriate adaptive efforts can happen → not able to withstand or adapt to injury → damage and disease to the cells, tissues, and organs B.​ Exhaustion of or inappropriate adaptive efforts When there is too much cell damage that it can no longer repair itself, then disease process begins If a cell has injury or stress, it can reverse the injury or adapt, or else it has an irreversible injury Irreversible injury → necrosis (tissue/cell death) → apoptosis (programmed cell death) Removing the stimuli causing injury can reduce injury and make it more reversible/adaptable. II.​ Stimuli Causing Cellular Injury​ A.​ Physical agents​ (outside agent) 1.​ Trauma, temperature changes, radiation, electrical stimulation 2.​ Direct damage → cell rupture or damage to cell membrane -​ hard to recover from cell membrane damage, internal contents can spill out B.​ Chemical agents​ -​ can injure cellular structures, block enzymatic pathways, cause problems with blood coagulation, and disrupt osmotic environments 1.​ Simple compounds: glucose need in moderation 2.​ Complex a.​ Toxins -​ liver tries to break down and eliminate as much possible, until build up occurs -​ Too much leads to poisoning or death ​ ​ Ex: Lead, strong acids/bases b.​ Therapeutic agents ​ ​ Ex. Tylenol (liver), chemotherapy, Ibuprofen (kidney) 3.​ Damage to cell or taken into the cell C.​ Microorganisms (infectious agents: viruses, bacteria, fungal spores) 1.​ Secretion of toxins 2.​ Interfere with cellular metabolism 3.​ Viruses cause cellular injury by releasing viral proteins that affect the cell’s DNA D.​ Genetic defects/disorders 1.​ Inborn problems of metabolism (congenital disorders/birth defects 2.​ Gross malformations: actual defect in DNA such as issues metabolizing a protein E.​ Nutritional imbalances (self-induced or disease induced) 1.​ Deficiencies of vitamins and proteins primarily 2.​ Excessive food intake: especially lipids → cause of atherosclerosis → cardiovascular disease  2 ​ ​ Cachexia: wasting syndrome where muscle and fat are lost F.​ Hypoxia: Most common cause 1.​ Inadequate oxygen in blood (hypoxemia) leads to decreased oxygen to cells (hypoxia) a)​ Leads to decreased ATP generation 2.​ Less ATP → Decreased perfusion to tissues 3.​ Lack of O2 in cell = Anaerobic glycolysis/metabolism increases a)​ Accumulation of lactic acid (sore muscles) o​ Higher lactate levels → lower pH → lactic acidosis → cell injury/death b)​ Reduction in pH results in impaired enzyme processes → impaired function 4.​ May result in cell death III.​ Intracellular changes in response to stimuli​ A.​ Inability of cell to process materials (fat solubles are stored while water solubles can be wasted) 1.​ Accumulation of waste materials/toxins in the cytoplasm 2.​ Metabolic processes slow; impaired ability to synthesize adenosine triphosphate (ATP) 3.​ Energy stores depleted (decreased ATP) B.​ Lipid and carbohydrate accumulation: triglycerides -​ Build up of fat deposits → plaque forms/grows (atherosclerosis) → decreased blood flow → when unstable a piece can rupture off and form a clot to go to other areas → heart attack/ stroke 1.​ Cytoplasm of parenchyma of certain organs 2.​ Accumulation of fat droplets intracellularly due to improper metabolism a)​ Stimulates scarring of the organ or tissue 3.​ Commonly seen atherosclerosis in Liver, spleen and CNS, heart and blood vessels 4.​ Example: Tay-Sachs disease (genetic disorder) a)​ Lack of enzyme that metabolizes lipids b)​ Lipid accumulation in brain c)​ Interference with normal CNS and brain function/development C.​ Pathologic calcification due to improper metabolism 1.​ Impaired calcium homeostasis with cell membrane damage 2.​ Increased intracellular Ca++ due to increased accumulation released from mitochondria and endoplasmic reticulum 3.​ Activates potentially damaging enzymes 4.​ Builds up in skin, soft tissues, blood vessels, heart, kidneys 5.​ Causes organ dysfunction (calcium is a hard mineral) with increased uptake of calcium into injured cells -​ tissues are calcified/hardened -​ impaired cell/tissue function IV.​ Disruption in cell membrane: main effects ​ The cell membrane is in charge of keeping a controlled intracellular environment ​ Selectively permeable (things move in and out, selectively) ​ Na; extracellular, K; intracellular  3 A.​ Impaired transport processes 1.​ Electrolyte imbalances 2.​ Failure of Na+,K+-ATPase pump a)​ Increased Na+ intracellularly and increased K+ extracellularly b)​ Increased permeability of cell membrane ​ shift in extracellular fluid to intracellular space → cloudy intracellular swelling with cell enlargement ​ more sodium in the cell = more water pulled into the cell = swelling CELL MEMBRANE ISSUES = CELL PERMEABILITY ISSUES c)​ Shift in electrolytes → problems with electrical impulses necessary for nerve transmission, muscle contraction, active transport (1)​ Which is Eventually irreversible 3.​ Poor tissue defense (due to cellular swelling) a)​ increase the risk of infection from microorganisms 4.​ Bleeding disorders a)​ resulting from disruption/damage within smaller blood vessels ​ ​ B.​ Dysfunction of receptors occurs through: 1.​ Binding and destruction or blocking of receptors a)​ damages receptor b)​ due to waste product buildup, obstructing receptor sites 2.​ Inappropriate triggering of responses or activity in and out of cell Ex. diabetes 2; long term exposure that causes issue to our receptors C.​ Free radical effects (unstable reactive chemicals) Ex. Ozone exposure, pollution, cigarette smoke, radiation, chemicals 1.​ Destruction of phospholipids in cell membranes 2.​ Damage to cell proteins 3.​ DNA damage a)​ results in cancer, heart disease, neuro diseases, Alzheimer’s, diabetes V.​ Cellular Adaptations in response to Injury or pathological Stimuli: Porth: Figure 3-1, p. 41.​ ​ *These changes allow stressed and injured cells to survive or maintain as much function during an injury A.​ Atrophy: Decrease in size of cells 1.​ Physiologic (Normal; No disease process involved): Aging 2.​ Disuse: decreased workload = decreased size of muscle, or due to disease a)​ Other causes: starvation, cellular hypoxia/ischemia B.​ Hypertrophy 1.​ Increase in size of cells 2.​ Results in increased tissue size 3.​ Response to increase in workload = Increased number of intracellular organelles ​ Physiologic: exercise; Ex. weightlifters ​ Pathologic: disease; Ex. left ventricular hypertrophy (causes excess strain on heart, which increases heart muscle size), not good → ineffective contraction C.​ Hyperplasia 1.​ Increase in number of cells  4 2.​ Cells that are capable of dividing a)​ usually due to hormone stimulation 3.​ Normal in some instances a)​ Physiologic: common in skin, glands, wound healing, uterus growth during pregnancy b)​ Pathologic: abnormal; Ex. benign prostatic hyperplasia, prostate gland grows indefinitely D.​ Metaplasia 1.​ One adult cell type is replaced by another cell type 2.​ Chronic irritation or exposure and inflammation a)​ Ex. smoking, recurrent infections, coal miners 3.​ Protective functions are lost 4.​ Changes may predispose cells to cancer (i.e. habitual cigarette smoking) **Can be reversed if stopped in time!!** E.​ Dysplasia 1.​ Cells have undergone atypical changes 2.​ Presumably controlled, may transform into uncontrolled reproduction of cells → cancer​ *possible reversal with removal of irritation or stimulus. Ex. skin cancer; precursors to cancer VI.​ Cell death: See Porth Figure 3-8, p. 51. A.​ Apoptosis: destroys cells no longer needed normally older, lower functioning, aging cells 1.​ Suppression of apoptosis = pathology ​ No apoptosis = no autoregulation → more dangerous cells survive​ B.​ Necrosis: cell death in a living organ or tissue ​ occurs when cells do not heal 1.​ Must be removed if not then infection develops (Ex. ulcers), or scarring can happen C.​ Gangrene: considerable mass of tissue undergoes necrosis (lots of dead tissue, hard to get rid of) common in toes, fingers, feet dead tissue needs to be removed/cut out or else toxic substances from it will spread **Apoptosis is normal and necessary for cell function** ​