Flashcards - Cell Adaptation and Injury - Final Format PDF

Cell Adaptation – Low yield Apoptosis  Definition – Reversible changes in Number, Size, Phenotype, Metabolism, Function of cells in  Definition – ATP-dependent programed cell death response to changes in environment...

Cell Adaptation – Low yield Apoptosis  Definition – Reversible changes in Number, Size, Phenotype, Metabolism, Function of cells in  Definition – ATP-dependent programed cell death response to changes in environment o No loss of membrane integrity, cellular contents do not leak out, no inflammatory reaction o Defective apoptosis seen in cancer o Increase/Decrease in cellular activity  Phases – Priming, Execution, Degradation, Phagocytosis o Altered morphology  Mechanism – Activation of Caspases pathway  Physiologic – Response to normal hormonal stimulation o Intrinsic (mitochondrial)– internal stimulation. Major pathway  DNA damage/ Misfolded proteins accumulation - ↑ p53 and mitochondrial Ca2+ leakage  Pathologic – Response to stress  ↓ hormonal stimulation – as seen in embryogenesis, menopause  Mechanisms o Extrinsic – external stimulation o Hypertrophy  TNF Receptor Family (TNF-R and FAS) o Hyperplasia  Immune cells - Cytotoxic T Cells  Morphologic appearance o Atrophy o Cell shrinkage, Eosinophilic cytoplasm o Metaplasia o Chromatin condensation followed by fragmentation o Anaplasia o Membrane blebing and phagocytosis of apoptotic bodies by macrophages o Aplasia  Physiologic examples o Hormonal stimulation- menstrual cycle, thymus in adults. Intrinsic o Inflammatory cells that accomplished their purpose (after recovering). Extrinsic  Pathologic examples o DNA damage (radiation, cytotoxic drugs, temperature, hypoxia). Intrinsic o Cell injury due to viral infection. Extrinsic Cell Injury – Low yield Cell injury- reversible and irreversible – Low yield  Definition – Stressful stimuli exceeds ability to adapt  Reversible – Early stages / Mild injuries – Morphology is reversible if injurious stimuli removed  Outcome – Depends on type of injury, duration, pattern, intensity, severity, type of cell o ↓ATP and cell swelling – Inability to maintain ionic and fluid homeostasis affected and cell’s ability to adapt  First evidence of injury  Mechanisms o Detachment of ribosomes and ↓ protein synthesis o ATP depletion o Mitochondrial swelling o Mitochondrial damage o Switch go glycolysis →↓ pH o Membrane damage (inability to maintain ion and fluid homeostasis) o Specializations loss (microvilli, cilia) o ROS o Fatty change (Steatosis) [seen in cells participating in fat metabolism- e.g. liver]  Causes o Hypoxia/ischemia  Irreversible – Severe / Persistent injuries, will cause cell death o Physical agents o Cellular membrane damage→ ↑ Intracellular Ca2+  Apoptosis o Chemical agents  Mitochondrial dysfunction → cytochrome C leakage  Apoptosis o Infectious agents/ Immune reactions o Rupture of lysosomes- Autodigestion o Genetic derangements o Nuclear degradation - Hallmark of cell death o Nutritional imbalances  Types – reversible vs irreversible Necrosis Apoptosis vs Necrosis  Definition – Unregulated death of large cell population, resulting from severe damage to cell membranes and loss of ion homeostasis Apoptosis Necrosis  Mechanism Cause Programmed Damage/trauma o Plasma membrane damage  cell undergoes enzymatic degradation and protein Cell size Shrinkage Swelling denaturation, intracellular components leak  local inflammatory reaction Intrinsic/extrinsic Both Extrinsic only o Cell swelling due to inability to maintain ion and fluid homeostasis Physiologic/pathologi Both Pathological only o Nuclear Changes (Pyknosis, Karyorrhexis, Karyolysis) [shrinkage, fragmentation, fading] c  Causes – Always pathological, caused by exogenous injury Cellular content Packed into vesicles Leak out of the cell o Ischemia Nucleus Fragmentation, packed Breakage o Physical trauma Inflammation No Yes o Radiation Requires ATP Yes No o Biological – Infections o Chemical injuries/ toxins  Types – Coagulative, liquefactive, caseous, fat, fibrinoid, gangrenous Coagulative (Denaturative) necrosis Liquefactive necrosis  Definition – The most common form of necrosis  Definition – Characterized by digestion of the dead cells due to ischemia  tissue o Usually results from ischemic injury (infarction) in most tissues (except brain, which is transformed into liquid viscous mass liquefactive) o Results from cellular destruction by hydrolytic enzymes o Common organs are heart, liver, kidney o Neutrophils release lysosomal enzymes that digest the tissue  Pathogenesis – Ischemia → denaturation of cytoplasmic proteins  Morphology – Material is creamy yellow - presence of dead leukocytes (pus) o Architecture of dead tissues is preserved for a span of at least some days  Outcome o Loss of nucleus is observed o Early – cellular debris and macrophages  Outcome – Ultimately, necrotic cells are removed by phagocytosis of cellular debris by o Later – cystic spaces and cavitation (brain). Neutrophils and cell debris seen with leukocytes and their enzymes → replaced by scar tissue bacterial infection  Examples o Brain infarcts – Ischemic death of cells within the CNS o Bacterial abscess – Accumulation of leukocytes and liberation of enzymes o Pancreatic necrosis – Proteolytic enzymes liquefy pancreatic parenchyma  Treatment – Surgically hard, washing and antibiotics Coagulative (Denaturative) and Liquefactive Necrosis Coagulative Necrosis  Definition – The most common form of necrosis o Usually results from ischemic injury (infarction) in most tissues (except brain, which is liquefactive) o Common organs are heart, liver, kidney  Pathogenesis – Ischemia → denaturation of cytoplasmic proteins o Architecture of dead tissues is preserved for a span of at least some days  Outcome – Necrotic cells are removed by phagocytosis and replaced by scar tissue Liquefactive necrosis  Definition – Characterized by digestion of the dead cells due to ischemia  tissue transformed into liquid viscous mass o Results from cellular destruction by hydrolytic enzymes  Morphology – Material is creamy yellow - presence of dead leukocytes (pus)  Outcome - Cystic spaces and cavitation (brain). o Neutrophils and cell debris seen with bacterial infection  Examples o Brain infarcts – Ischemic death of cells within the CNS o Bacterial abscess – Accumulation of leukocytes and liberation of enzymes Caseous necrosis Fat Necrosis  Definition – Combination of liquefactive and coagulative necrosis  Definition – Death of fat tissues, caused by action of lipases on adipocytes o Macrophages wall off the infecting microorganism → granular debris  Types - Enzymatic vs. non-enzymatic o Characteristic of o Enzymatic - Acute pancreatitis → liquefy the membrane of fat cells in the peritoneum  Granulomatous infection (Tuberculosis/Fungal)  Causes – Alcohol, Drugs, diet  Atheroma  It is a life threatening situation  Malignant tumors o Non-enzymatic - traumatic (e.g., injury to breast tissue), or ↓ Perfusion  Macroscopically – Soft friable white cheese-like appearance  Macroscopically – Saponification- fat + calcium – Chalky Yellow-White deposits Fibrinoid necrosis – Low yield Gangrenous necrosis – Low yield  Definition – Form of necrotic connective tissue, histologically resembles fibrin  Definition – Not a specific pattern of cell death, usually applied to prolonged ischemia of the  Causes lower limb involving multiple tissue planes o Vascular hypertensive damaged → leakage of plasma protein (e.g., fibrin) → Necrotic o Other common sites – gallbladder, GIT, testis damage o Common in war zones o Acute immunologic injury - Immune complex deposition (Hypersensitivity reactions II, III)  Types  Example – Malignant hypertension causing vasculitis o Dry Gangrene – coagulative necrosis dues to ischemia. o Immune vascular reactions (e.g., Polyarthritis Nodosa)  Most common in limbs o Nonimmune vascular reactions (e.g., hypertensive emergency, preeclampsia)  Grey-black color o Wet Gangrene – Bacterial superinfection - liquefactive necrosis  Most common in bowel  Green color, smelly  Treatment – Resection within healthy margins Acute Myocardial Infarction Acute pancreatitis  Definition - Heart muscle necrosis resulting from ischemia due to obstructed artery (infarction)  Definition – Reversible pancreatic parenchymal injury associated with inflammation o Severe ischemia lasting 20-40 minutes → irreversible damage  cardiomyocytes death  coagulative necrosis o varies in severity  Types  Risk Factors – 80% either Biliary tract disease (stones) or excessive alcohol intake o Transmural (regional) Myocardial Infarction (90%)  Thrombus occlusion of atherosclerotic artery  Causes  STEMI (ST-elevation MI) o Pancreatic duct obstruction  Single anatomic area corresponding to a specific coronary artery o Primary acinar cell injury o Subendocardial Infarction (10%)  Severe hypoperfusion of the main coronary arteries due to high grade atherosclerotic stenosis o Defective intracellular transport of pro-enzymes  Non-STEMI. ST depression, non-Q wave  Pathogenesis  Multiple foci. May be circumferential o Inappropriate release and activation of pancreatic enzymes → Destruction of pancreatic  Complications and peritoneal substance → Acute inflammatory reaction o Reinfarction/ Death o 0-24 hours [CCCP] o Accompanied fat necrosis and deposition of calcium soaps (hypocalcemia)  Cardiac Arrhythmia- the most common cause of death  Clinical manifestation – Epigastric pain radiating to the back, ↑ serum amylase, ARDS  Congestive Heart Failure (especially left)  Morphology  Cardiogenic Shock o Focal hemorrhage  Pulmonary Edema o Pancreas - Semi-liquid parenchymal destruction o 1day-7day  Transmural MI (Pericarditis) 1-3 days o Fat Saponification- chalky, white-yellow appearance- fat necrosis with inflammation  Myocardial rupture, may results in cardiac tamponade. 4-7d  Complication – Rupture → enzymatic fat necrosis  Ruptured papillary muscles  Mural thrombosis → left-sided embolism  Ventricular aneurysm - Day 5 o Weeks-Months- Thromboembolic events, Dressler syndrome (secondary pericarditis) Encephalomalacia – Low yield Autophagy – Low yield  Definition – The end result of liquefactive necrosis of brain parenchyma following insult,  Definition – Natural, regulated mechanism of the cell that removes unnecessary or usually occurring after cerebral ischemia, infection, hemorrhage, or traumatic brain injury dysfunctional components  Types- Thrombotic, embolic, hemorrhagic o Starved cell can eat its own components to reduce nutrient demand  Location - Can occur anywhere, however has characteristic locations are anteroinferior  Mechanism – lysosomal digestion of cellular components frontal and temporal lobes o Impaired mechanism is the basis of lysosomal storage diseases  Progression  Outcome o 6-48 hours (Early changes) – swollen tissue (edema), pale and soft o Residual bodies – Cell debris within vacuoles that resist digestion and persist in the o 2-10 days (Subacute changes)– Beginning of liquefactive necrosis, gel-like tissue cytoplasm as membrane-bound residual bodies o After 2 weeks (repair)– Tissue liquefied by lysosomal enzymes, Debris removed – leaving  Example – Lipofuscin granules – In sufficient amounts, impart brown discoloration CSF-filled cavity. Dark-grey tissue. to the tissue (brown atrophy)  Outcomes o Neurologic deficits o Hemosiderin deposition o Cystic space- Enlarged spaces in the brain Atrophy – Low yield Brown Atrophy – Low yield  Definition – Decrease in a cell/organ size and functional ability  Definition – Symptom, not disease. Accumulation of lipofuscin granules in shrunken cells of o Reduce metabolic needs and permits survival by achieving new equilibrium atrophic tissue o Early – Cells have diminished function, but cell death is minimal o Associated with elderly and Long/end stage diseases o Later – Irreversible injury causes death by apoptosis o Occurs due to indigestible material within lysosomes, usually in the heart and liver  Mechanism – ↓protein synthesis and ↑degradation because of reduced metabolic activity  Locations 1) Autophagy – cell consumption of own components 2) Degradation by ubiquitin-proteasomes pathway o Heart 3) Apoptosis -programed cell death o Liver  Causes o Kidney o ↓ Workload - Muscle atrophy due to cast after fracture o Colon o ↓ Innervation - Muscle fiber atrophy due to denervation o Eye o ↓ Blood Supply (ischemia/hypoxia)- Brain and heart due to atherosclerosis  Morphology – Yellow-brown “wear and tear” pigment o ↓ Nutrition- Chronic Inflammation, Cancer o ↓ Endocrine Stimulation- Uterus shrinks in menopause, Thymus in adults o Pressure (compression)- Tumor → Pressure on vessels  ischemia  atrophy o Aging- Brain in Alzheimer Calcification – Dystrophic and Metastatic o Dystrophic Calcification  Definition – Abnormal deposition of crystalline calcium phosphate, in dying or necrotic tissues o Localized – normal serum levels of calcium o For life o Together with smaller amounts of iron, magnesium and other minerals  Mechanisms o Intracellular initiation is in the mitochondria of dead or dying cells o Extracellular initiation is in membrane bound vesicles derived from degenerative or ageing cells  Examples o Fat necrosis – saponification o TB (lungs and pericardium) and other granulomatous infections o Aging/Damaged heart valves o Atheroma's of advanced atherosclerosis o Microcalcification in the breast → carcinoma Metastatic Calcification  Definition – Precipitation of calcium phosphate in normal tissue due to hypercalcemia o Systemic hypercalcemia secondary to some disturbance in calcium metabolism o Mainly interstitial tissues in stomach, Kidneys, Lungs, blood vessels  Causes of hypercalcemia o Hyperparathyroidism - ↑ PTH (Parathyroid Adenoma) o Bone destruction (Leukemia, Metastasis, Sarcoma) o Vit D disorders (Intoxication, Sarcoidosis) o Chronic kidney disease / renal failure (Phosphate retention) Fatty Change (steatosis) – Low yield Anthracosilicosis – Low yield  Definition – Accumulation of intracellular parenchymal triglycerides  Definition – Massive fibrosis of the lungs caused by inhalation of carbon and silica particles o Damaged cells unable to metabolize fat→ vacuoles of fat accumulate in cytoplasm and their accumulation in the lungs (steatosis) squeezing nucleus.  Pathogenesis – Ingestion of free silica dust and carbon by alveolar macrophages  o Mostly in cells participating in fat metabolism (liver, kidney, heart, skeletal muscles) macrophages unable to digest  Dust Cells formation  Cytokine secretion  Inflammation  Causes – Imbalance among the uptake, utilization, and secretion of fat and Fibrosis  Mechanism  Outcome – Can lead to nodules which can obstruct airways and blood vessels o ↑ transport of triglycerides or fatty acids to affected cells  Complication – Increased susceptibility to tuberculosis and neoplasia o ↓ mobilization of fat from cells o ↓ use of fat by cells o Overproduction of fat in cells  Examples o Hepatocytes- acute hepatic congestion o Myocardium- cardiac steatosis o Kidney- fatty kidney disease Hemosiderosis Hemochromatosis  Definition – Symptom, not a disease. Local or systemic excess of iron causes ferritin to form  Definition – Hereditary disease, ↑ serum Iron levels and hemosiderin deposition in hemosiderin granules which are deposited inside the cell parenchymal organs (Liver, Heart, Pancreas), can lead to organ damage o Hemosiderin – Hemoglobin-derived, yellow-brown granular or crystalline pigment  Etiology – Genetic mutation in HFE gene causing increased absorption of iron in GI  Local excess – hemorrhage or breakdown of hemoglobin o Secondary hemochromatosis is most often caused by multiple blood transfusions or in  Systemic excess - Generalized hemosiderin deposition without tissue or organ damage chronic viral hepatitis C. o Mainly from hemorrhage, multiple blood transfusions, hemolysis, and excessive dietary  Outcome – Bronze diabetes. A triad of: intake of iron o Cirrhosis  Examples o Diabetes Mellitus o ↑ Absorption dietary iron due to an inborn error of metabolism o Skin pigmentation o Blood transfusions→ iron overload o May also lead to cardiac Arrhythmias o Hemolytic anemia  Diagnosis – Serum ferritin, genetic tests, liver biopsy Anaplasia, dysplasia, neoplasia Hyperplasia, hypertrophy, and metaplasia Anaplasia – Loss of structural and functional differentiation within cell or group of cells. Hyperplasia  When anaplasia occurs in neoplastic cells they are far distinct from original cells. Complete change=malignant  Definition – ↑# of cells in tissue/organ, only in cells capable of division  Morphology – Pleomorphism, Hyperchromatism, Nuclear enlargement, Mitosis abnormality o Frequently together with hypertrophy  Mechanisms – Controlled proliferation of stem cells and differentiated cells by growth factors Dysplasia - Disordered, precancerous epithelial cell growth, potentially reversible  Physiologic - Controlled, hormonal stimulation. ↓signal→↓ hyperplasia. Uterus during pregnancy  Cause – Occurs after prolonged pathologic stimuli causing hyperplasia/metaplasia  Pathologic (excessive/inappropriate trophic action). Endometrial hyperplasia, Benign Prostate Hyperplasia  Characterized by: o Disorderly maturation and spatial arrangement of cells Hypertrophy o Marked variability in nuclear size and shape (pleomorphism)  Definition – ↑cell size and functional capacity due to synthesis of intracellular structural proteins and organelles o Increased, often abnormal mitosis → mitotic figures o Occurs in cells that are not capable of division (cardiac, skeletal muscle, neurons)  Examples – Cervical dysplasia, Actinic (solar) keratosis  Mechanism – Mediated by growth factors, cytokines, and hormones  Genes expression  Physiologic - Striated muscles in increased workload (Functional demand). Hormonal – Lactating Breast, Neoplasia – Uncontrolled, disorderly proliferation of cells, grow more rapidly than normal cells or tissue.  Pathologic - Hypertrophic cardiomyopathy, Thyroid gland goiter  Caused by failure of regulation mechanism (proliferation and maturation) of cells.  Resulting in a benign or malignant growth known as a neoplasm. Metaplasia  Sporadic, Familial >3 cases in family, no specific gene. Genetic–specific gene, high possibility for malignancy  Definition – Change in cell type (epithelial or mesenchymal) usually due to stress. Can be adaptive or pathological  Common locations – Breast (woman)/prostate (men), skin, lungs o Cell is replaced by another cell which can withstand the adverse environment  Classification – Classified as either malignant or benign, based on their behavior o Not a change in already differentiated cell phenotype o Benign – Tissue name+"-oma”. Slow growth, well demarcated, no metastasis. Tend to be encapsulated o Can be reversible, usually is not  Papilloma, Lipoma  Epithelial- Columnar  Squamous (most common): Trachea in cigarette smokers, Cervix junction o Malignant – "-sarcoma", "-carcinoma". Fast growth, less differentiated, metastasizes Squamous  Columnar – Barret's esophagus, If stimuli continues  Adenocarcinoma  Colonic adenocarcinoma – epithelial origin. Osteosarcoma – Bones  Mesenchymal – pathologic and not adaptive. Myositis ossification - Calcification of muscles  Astrocytoma – Glial (CNS). Melanoma – Skin  Complication – Can progress to dysplasia or neoplasia (squamous cell carcinoma) Hypertrophy Hyperplasia  Definition – Increase in cell size and functional capacity due to synthesis of intracellular  Definition – Increase in number of cells in tissue/organ, only in cells capable of division structural proteins and organelles  Resulting in increase of tissue/organ size o Frequently together with hypertrophy o Occurs in cells that are not capable of division (cardiac, skeletal muscle, neurons)  Mechanisms – Controlled proliferation of stem cells and differentiated cells by growth factors o Frequently together with hyperplasia  Physiologic (due to hormones or growth factors)  Mechanism – Mediated by growth factors, cytokines, and hormones  Genes expression o Controlled, hormonal stimulation. When signals diminish, hyperplasia decrease  Physiologic o Examples o Functional (mechanical) Demand – Striated muscles in increased workload (Functional),  Liver regeneration after partial hepatectomy Thyroid gland in pregnancy  Uterus during pregnancy o Hormonal – Lactating Breast, Uterus during pregnancy (↑Estrogen)  Breast development in puberty  Pathologic  Pathologic (excessive/inappropriate trophic action) o Hypertrophic cardiomyopathy o Endometrial hyperplasia o Thyroid gland goiter o Benign Prostate Hyperplasia Metaplasia Dysplasia  Definition – Change in cell type (epithelial or mesenchymal) usually due to stress  Definition – Disordered, precancerous epithelial cell growth, potentially reversible o Cell is replaced by another cell which can withstand the adverse environment  Cause – Proliferation of pre-cancer cells after prolonged pathologic stimuli causing o Not a change in already differentiated cell phenotype hyperplasia/metaplasia o Can be reversible, usually is not  Characterized by:  Mechanism - Reprogramming of stem cells or Undifferentiated mesenchymal cells  Types o Disorderly maturation and spatial arrangement of cells o Epithelial o Marked variability in nuclear size and shape (pleomorphism)  Columnar  Squamous (most common) o Increased, often abnormal, mitosis → mitotic figures  Trachea in cigarette smokers (→ loss of cilia, not specialized)  Outcomes  Cervix junction o Mild / moderate dysplasia (i.e., do not involve entire thickness of epithelium) may regress  Squamous  Columnar – Barret's esophagus, mucus secreting to withstand acid with alleviation of inciting cause.  If stimuli continues  Adenocarcinoma o Severe dysplasia often becomes irreversible and progresses to carcinoma in situ. o Mesenchymal – pathologic and not adaptive  Myositis ossification - Calcification of muscles  Examples  Myeloid metaplasia – Proliferation of hematopoietic tissue in liver and spleen o Cervical dysplasia  Complication – Can progress to dysplasia or neoplasia (squamous cell carcinoma) o Actinic (solar) keratosis o Oral leukoplakia Myocardial Hypertrophy – Low yield Endometrial Hyperplasia  Definition – Hypertrophy of the myocardium causing the wall to thicken and reduction in  Definition – Abnormal endometrial gland proliferation usually caused by excess estrogen ventricle lumen size stimulation.  Causes – ↑Estrogen, ↓Progesterone → ↑Gland/Stroma ratio  Cause – Most cases are due to genetic mutations in genes encoding sarcomeric proteins  Risk Factors (↑Estrogen) [PROMO] o Hypertension (atherosclerosis) or aortic valve disease o PCOS/ Ovarian tumor o Connective tissue disorder, such as Friedreich ataxia o Replacement therapy  Outcomes o Obesity o Reduced diastolic function o Menopause o Usually normal systolic function  Classification o Causes syncope during exercise and may lead to sudden death o Simple - Gland Pleomorphism, cystic/mild hyperplasia. Rarely progress to CA (1-3%) o Complex - Irregular gland shape, Gland crowding, ↑Stratification. o S4, systolic murmurs o Atypical (Simple/Complex) – Irregular epithelial lining (Stratification, Tufting)  Complications  ↑mitotic activity, enlarged nuclei and loss of nuclear polarity o Prolonged left hypertrophy will lead to congestion  ↑ risk for endometrial carcinoma o Left  Right Hypertrophy = Cor Bovinum  Signs and Symptoms – Presents as postmenopausal vaginal bleeding  Treatment o Atypical – Hysterectomy o Non-Atypical – Progestin, Dilation & Curettage Gastritis – Low yield Acute Gastritis – Low yield  Definition – Inflammation, irritation, or erosion of the lining of the stomach (mucosa and  Definition – Superficial acute inflammation of the gastric mucosa submucosa)  Pathogenesis – Due to imbalance between mucosal defences and acidic environment o It can occur suddenly (acute) or gradually (chronic).  Causes o NSAIDs  Diagnosis – Assessed by endoscopic examination of the mucosa, confirmed by biopsy o Acute heavy alcohol ingestion  Types of gastritis o Stress-induced injury (burn, shock, ↑ICP) o Acute (e.g. excessive alcohol use, NSAIDs, Chemicals) o Chemicals (acid/alkali) o Chronic (chronic vomiting, stress, or the use of NSAIDs) o Radiation + chemotherapy  Helicobacter associated  Autoimmune chronic  Symptoms – Can be asymptomatic, or: o Epigastric pain, nausea, vomiting  Reactive o In severe cases: erosion, ulceration, hemorrhage, hematemesis, melena (dark feces)  Complication – If left untreated, it can lead to a severe blood loss and may increase the risk of developing stomach cancer Chronic Gastritis – Low yield Gastritis- Acute vs. Chronic – Low yield  Definition – Presence of chronic mucosal inflammatory changes o Sometimes  mucosal atrophy and epithelial metaplasia Acute Chronic  Causes Onset Abrupt Gradual o #1- H. pylori 90% of cases  Urea breath test. Triple therapy Duration Up to 6 moths More than 6 months o #2- Autoimmune associated (Antibodies against parietal cell and intrinsic factor)  →↓HCL, megaloblastic anemia Intensity Mild, moderate, severe Mild, moderate, severe o NSAIDs o Chronic alcohol consumption Etiology Acute heavy alcohol ingestion H. pylori o Bile reflux Chemicals (acid/alkali) Autoimmune associated o Smoked sea-food burn, shock, ↑ICP NSAIDs  Symptoms Chronic alcohol consumption o Dyspepsia (impaired digestion) o Upper abdominal discomfort Physical response Increase BP, HR, dilated pupils, No ANS response. o Vomiting nausea and vomiting nausea and vomiting  Complication Gastric hemorrhage Pernicious anemia o Peptic ulcer disease Dyspepsia, anorexia Anorexia o Malignancy- adenocarcimoma of stomach (2-4%) Helicobacter Associated Gastritis – Low yield Autoimmune Chronic Gastritis – Low yield  Definition – Most common form of chronic gastritis, caused by H. Pylori infection  Definition – Autoimmune associated gastritis affects the body of the stomach  Pathogenesis  Mechanism o Colonize epithelium beneath mucus o Antibodies against gastric parietal cells (90%) o Pyloric antrum is most severely affected area o Antibodies against intrinsic factor (60%) o Epithelial damage, mixed acute and chronic inflammatory reaction  Outcomes  Diagnosis – Breath test, blood tests o ↓ HCL (Hypo/A-Chlorhydria)  Treatment – Only if clinical signs plus positive breath test o Failure of absorption of dietary vitamin B12  Megaloblastic anemia o Triple therapy- 2 antibiotics + PPIs (proton pump inhibitors)  Complication – Severe atrophy of the mucosa in elderly patients  Complication o Intestinal metaplasia - Gastric epithelium replaced by small intestine epithelium Placental Villi – Low yield – Low yield Stomach Intestinal Metaplasia – Low yield  Definition – Placenta is pregnancy-specific organ. During pregnancy, it will go hyperplasia and  Definition – Replacement of gastric epithelium with intestinal epithelium hypertrophy to support the fetus. o More common in people who have chronic acid reflux / GERD o Placental villi contain:  Causes – Chronic Atrophic gastritis/ H. pylori gastritis  Loose connective tissue  Classification by type  Capillary blood vessel o Small bowel metaplasia – Sialomucin production (aqua blue staining)  Layer of cytotrophoblast o Large bowel metaplasia – Sialomucin and Sulfomucin (brown-black staining)  Layer of syncytiotrophoblast  Classification by level (both types)  Complication o Incomplete – ↓Columnar cells, ↓Mucin content → acidic mucus o Incomplete placental birth or intrauterine death of embryo can cause placental remains o Complete – Total loss of columnar mucus-secreting cells → replacement by goblet cells in uterus and absorptive cells o Placental abruption is when the placenta separates before childbirth  Complications  Treatment – Preterm delivery / removal of remnants by abrasion o ↑ gastric adenocarcinoma o MALT lymphoma Peripheral Edema – Low yield Pulmonary Edema  Definition – Presence of excess fluid in interstitium  Definition – Leakage of excessive interstitial fluid which accumulates in alveolar spaces  Causes  Causes – Disruption of Starling forces or endothelial injury o ↑ Hydrostatic pressure in blood vessels - Congestive heart failure, portal HTN/cirrhosis, renal salt and water retention, venous thrombosis o ↑ hydrostatic pressure - seen in left-sided heart failure, mitral valve stenosis, and fluid o ↓ Oncotic pressure - liver disease, nephrotic syndrome, and protein deficiency overload. o Microvasculature o ↓ oncotic pressure - seen in nephrotic syndrome and liver diseases  Lymphatic obstruction - Inflammatory, Neoplastic, Postsurgical o ↑ capillary permeability - due to infections, narcotics, shock, and radiation.  Increase endothelial permeability - inflammation, hypersensitivity reaction, some drugs  Sodium retention - ↑intake, primary aldosteronism, renal failure  Clinical manifestation  Decompression disease - High mountain climbers o Left Heart Failure  Poor systemic perfusion, congestion of pulmonary circulation  Chemicals (weapons, industry)  Wet and heavy lungs  Classification o Local – seen in inflammation o Presence of hemosiderin-laden macrophages (“heart failure” cells) in lungs o Generalized – seen in heart Failure o Fibrosis in interstitium – Brown induration o Anasarca – severe generalized edema o Effusion- fluids within the body cavity. (e.g. pleural effusion)  Types of edema fluid o Transudate - low protein content o Exudate - high protein content and cells o Lymphedema - related to lymphatic obstruction o Glycosaminoglycan-rich - ↑ hyaluronic acid and chondroitin sulfate → myxedema edema Left Failure – Low yield Right Failure – Low yield  Left Failure - Pulmonary edema (blood flows from lungs →left heart →systemic circulation)  Right Failure – Usually outcome of left Heart Failure  Causes  Causes o Ischemic heart disease, especially myocardial infarction o Left-sided lesions, such as mitral stenosis o Hypertension o Pulmonary hypertension often caused by chronic lung disease (cor pulmonale) o Aortic and mitral valvular disease (e.g. calcification/stenosis) o Various types of cardiomyopathy and diffuse myocarditis o Myocardial diseases o Tricuspid or pulmonary valvular disease  Mechanism – left ventricular hypertrophy and dilatation  Mechanism – right ventricular hypertrophy and dilatation o Stasis of blood in left chambers of the heart o Increased pressure in systemic venous system o Passive congestion of pulmonary circulation→ pulmonary edema o Poor pulmonary perfusion o Poor systemic perfusion→ organ dysfunction o Transudation of fluid in peripheral tissues (lower limbs)  Clinical manifestations o Transudation of fluid in the abdominal cavity o Dyspnea and orthopnea caused by pulmonary congestion and edema  Symptoms o Pleural effusion - often results with hydrothorax o Jugular vein distension o Reduction in renal perfusion o Liver and spleen congestion → hepatosplenomegaly o Cerebral anoxia - less frequent o Peripheral edema, ascites, pleural/pericardial effusion  Outcomes o Renal hypoxia o Hemosiderin accumulates in heart Failure Cells  Complications - Chronic passive liver congestion → Cardiac cirrhosis o Fibrosis of interstitium – Brown induration Thrombosis – Low yield Embolism – Low yield  Definition – Intravascular coagulation of blood, often causing significant interruption of blood flow.  Definition – Intravascular solid / liquid / gaseous mass that has been carried down the  Physiological– Occurs normally to plug small defects in blood vessel walls, removed after vessel is repaired bloodstream from its site of origin, resulting in the occlusion of a vessel  Pathological - Causes of thrombosis - Virchow's Triad: o Endothelial damage - atherosclerosis, vasculitis, etc.  Types o Abnormal blood flow - Alterations in laminar blood flow or turbulence (e.g., aneurysms), and hyperviscosity o Pulmonary embolism – An important cause of sudden death, usually occurring in of blood immobilized postoperative patients and in those with congestive heart failure o Hypercoagulability- primary (genetics)/secondary (acquired)  Types  Thromboembolism -95%. Immobilization → DVT (lower extremities) o By location  Fat embolism (car crash → bone marrow embolism)  Arterial thrombi – usually occlusive (coronary, cerebral, femoral), lines of Zahn  Amniotic fluid embolism - occurs during labor or postpartum  Venous thrombosis (phlebothrombosis) is almost invariably occlusive  Air embolism (trauma – Jugular vein, injection >40mL of air, decompression)  Mural thrombosis- Vessel wall/heart chambers. No occlusion o Systemic embolism – Ischemic necrosis of downstream tissues  Heart valves – Vegetations (Polypoid Masses) o By color/ composition  Abdominal Aorta  Kidneys  Fast-moving blood – Contains platelet + Fibrin content. Firm, Pale  Heart  brain, kidneys, GI, lower limbs  Slow-moving blood – More RBCs relative to Platelets + Fibrin. Red, Soft, Gelatinous  Common Carotid artery  Cerebral arterial circulation (stroke)  Outcomes  Outcomes o Re-canalization o Thromboembolism o Silent- no sequelae o Propagation- vascular occlusion and Infraction o Infarction o Organization o Sudden death o Secondary pulmonary HTN Pulmonary Embolism – Low yield Disseminated Intravascular Coagulation (DIC) – Low yield  Definition – Occlusion of pulmonary circulation due to embolism  Definition – An acquired coagulopathy caused by deposition of fibrin in small blood vessels, o The most common preventable cause of death in hospital patients leading to thrombosis and end-organ damage. o If 60% of pulmonary vasculature is suddenly blocked, the heart cannot pump blood o Associated with many severe illnesses and is often seen in hospitalized patients. through the lungs  Causes- DIC is always secondary to another disorder: o Severe infections/ sepsis  Cause – Vast majority from DVT (thrombus), but also: o Trauma- surgery/ burn o Fat embolism (car crash → bone marrow embolism) o Obstetric complications o Amniotic fluid embolism- occurs during labor or postpartum o Hemolysis/ vascular disorders (aortic aneurysm) o Air embolism (trauma – Jugular vein, injection >40mL of air, decompression sickness) o Malignancy  Outcomes  Outcomes - Depletion of clotting factors and platelets leads to: o Small – Silent, rapidly removed. Can lead to pulmonary HTN o Bleeding diathesis (unusual susceptibility to bleed) o Thrombosis and end-organ damage o Medium – Haemorrhagic pulmonary infarction. Dyspnea, shallow breath.  Diagnosis – Thrombocytopenia (↓platelets), ↑D-dimer o Large – Death. Cyanosis, JVD, pulse is rapid and weak, BP is low. o DIC may be confused with liver disease, (unlike liver disease, factor VIII is depressed)  Complications- Secondary pulmonary HTN → right sided heart failure  Treatment o Reverse the underlying cause o Transfusion of blood (RBCs) and platelets o Manage shock as necessary Hemorrhage Cerebral hemorrhage  Definition – Extravasation of whole blood from its vessels Definition - Ruptured blood vessels in the brain, causing localized bleeding and death of brain cells o Most often caused by trauma Causes  Stroke, Trauma, Aneurysm  Classifications  Tumor, Amyloid angiopathy o Internal, External, Semi-external (bleeding in urinary bladder) Types o Arterial (red, fast), Venous (purple, slow), Parenchymal (capillaries, small red dots on the  Epidural - Arterial bleeding, between the skull and the dura mater. skin) o Almost always traumatic, usually associated with skull fracture  Types o Clinical- Trauma→ ↑ ICP → herniation → death. Lucid interval before loss of consciousness o Hematoma – Hemorrhage into a soft tissue/ organ → Hemosiderosis o Petechiae – Pinpoint haemorrhages 1-2mm in diameter.  Subdural - Venous bleeding between dura + arachnoid mater. The most common type. o Can be due head trauma, brain atrophy, aging, or alcoholism  Bleeding from small vessels into Skin, Mucosa, Serosa o Clinical- Headache, confusion, slowly progression of neurological deficits  Causes – Coagulopathy (↓platelet/ defective function), ruptured vasculature o Purpura – Diffuse superficial (skin), up to 1cm  Subarachnoid - Bleeding into subarachnoid space  Causes – As above and trauma, vasculitis, increased vascular fragility o Usually due ruptured “Berry’s aneurysm”, trauma, or arteriovenous malformation o Ecchymoses – Diffuse, Larger (1-2cm). skin and subcutaneous tissues o Clinical- Neck rigidity, sudden excruciating headache, rapidly loss of consciousness  Discoloration of the skin due to hemoglobin metabolism (Red-Blue) o Increased risk for developing hydrocephalus (obstructive/communicating) and ischemic infarcts Biliverdin/Bilirubin(Blue-Green) Hemosiderin (Golden-Brown).  May appear with coagulation disorders (Cushing syndrome)  Intracerebral - Bleeding into brain parenchyma, usually basal ganglia o Usually due to systemic hypertension. Also due to amyloid angiopathy, vasculitis, neoplasm o Clinical- Compression of adjacent parenchyma → Liquefactive necrosis, Hemosiderosis, death Hyperemia vs. Congestion (passive hyperemia) – Low yield Shock – Low yield  Definition – Disproportion between volume of circulating blood and its blood vessels Hyperemia Congestion o Characterized by vascular collapse and systemic hypoperfusion Type Active Passive o Cellular injury is initially reversible, if hypoperfusion persists → hypoxia → irreversible cell damage  Types Etiology Physiological/pathological Always pathological o Cardiogenic shock – Pump Failure  MI, Arrhythmias, Pulmonary embolism, Cardiac tamponade Mechanism Vasodilatation mediated by: Decreased venous outflow → o Hypovolemic shock – Reduced blood volume Vasoactive mediators stasis of blood inside the organ  Haemorrhage, Burns, Dehydration Hormones o Septic Shock – Bacterial infection (gram negative bacteria) Neurogenic reflexes o Neurogenic shock – Distributive shock (generalized vasodilation)  Anaesthesia, Toxins, CNS Injury Tissue color Redder than normal Blueish (cyanotic) o Anaphylactic shock – Distributive shock (generalized vasodilation)  Allergy (type I hypersensitivity response) Examples Inflammation Congestive heart failure  Stages Exercise Deep venous thrombosis o Compensated – Vital organ perfusion is maintained by reflex. ↑ sympathetic tone, hormones Blushing Budd-Chiari syndrome o Decompensated – Progressive ↓in tissue perfusion → metabolic acidosis, renal insufficiency o Irreversible – Organ failure and death Hyperemia – Low yield Congestion (passive hyperemia) – Low yield  Definition – Localized increase in blood volume within a tissue  Definition – Stasis of venous blood within a tissue  Mechanism – Active process resulting from arteriolar dilation and increased blood flow o Passive process resulting from impaired outflow of venous blood from a tissue o Vasoactive mediators o Always pathological o Hormones o Congested tissues are cyanotic o Neurogenic reflexes  Types  Clinical manifestation – Hyperaemic tissues are redder than normal o Acute – Occurs in shock, acute inflammation, right heart failure  Examples  Also seen in: Venous obstruction, Immobility (long flights), and dehydration o Inflammation (alcohol/caffeine consumption, sweating, ↓humidity) o Exercise o Chronic o Erection  Pulmonary congestion – due to left heart failure or mitral stenosis  Liver congestion - due to right heart failure  Complications – Chronic congestion may lead to parenchymal cell death and secondary tissue fibrosis  Treatment – Anticoagulants (e.g. aspirin)/Antiplatelets Infarction Liver congestion  Definition – Localized area of necrosis secondary to ischemia  Definition – Liver dysfunction due to long-term venous congestion within the liver results from  Causes right-sided heart failure o 99% are due to thrombotic or embolic occlusion of blood vessels o Usually due to a cardiomyopathy, tricuspid regurgitation, mitral insufficiency, cor o Less common- vasospasm or torsion pulmonale, or constrictive pericarditis.  Classification  Mechanism – Right heart failure  Impaired hepatic venous drainage  Massive hepatic o Anemic infarcts – Pale or white color. Caused by thromboembolic events in solid organs congestion  Liver dysfunction with single blood supply- heart, kidney, spleen o Prolonged stage → nutmeg liver, (cardiac) cirrhosis, necrosis o Haemorrhage infarcts – Red color. Occurs in:  Symptoms  Venous occlusion – testicular/ovarian torsion o Hepatomegaly  Loose tissues – lung o Jaundice  Tissues with dual circulations - lung and small intestine, liver, thyroid, uterus, o Ascites testis, tongue, urinary Bladder o Varices  Also occurs after reperfusion (after angioplasty) o Abdominal pain  Complications – Coagulative necrosis (most organs) or liquefactive necrosis (brain) →inflammation and scarring  Treatment – If necrosis → resection with healthy margins Hemorrhagic Lung Infarction – Low yield Inflammation  Definition – Ischemic necrosis in the lung within area of hemorrhage  Definition – Response to eliminate initial cause of cell injury, to remove necrotic cells resulting from the o Appears only in patients with inadequate circulation – with heart or lung disease original insult, and to initiate tissue repair.  Consequence – Can cause considerable harm if prolonged, severe or inappropriate.  Cause – Trauma/ reperfusion (after angioplasty)  Cardinal signs – Rubor (redness), Calor (heat), Dolor (pain), Tumor (swelling), Loss of function  Location  Causes – Infection, Trauma (Physical/ Chemical), Immunological injury, Tissue death (necrotic areas) o Usually develops in sub-pleural region of lower lobes  Classifications o Affecting the alveolar walls, bronchioles and vessels  Basic o Acute- Neutrophils. o Single/Multiple lesions  Serous - protein poor. Transudation into body cavities. Seen in burns and viral infection.  Outcomes  Purulent (suppurative)- edema, Pus – Exudate containing neutrophils→ abscess formation o Early stages – Raised, red-blue area  Fibrinous- ↑increase vascular permeability, ↑fibrin.  Ulcer - Local defect / excavation of organ/tissue surface o Within 48 hours - Red blood cells begin to lyse o Subacute – Relatively rapid onset  Necrotic area is paler or red-brown (Hemosiderosis) o Chronic- Lymphocytes, Plasma cells. Simultaneous tissue destruction and repair  Lung fibrosis and scarring  Non-specific/granulomatous (Caseating- fungal. Non-Caseating- sarcoidosis, foreign  Complications – Sudden death (if occurs in main pulmonary arteries) material) o Mixed  Exudate - Serous, Purulent, Hemorrhagic (Ebola), or Fibrinous  Superficial / Deep (Abscess – Deep)  Limited / Diffused (Abscess – Limited)  Specific (Crohn’s disease, ulcerative colitis) Acute Inflammation Chronic Inflammation  Definition – Immediate response with limited specificity (innate immunity)  Definition – Prolonged inflammation characterized by mononuclear infiltration, which leads o Rapid onset (seconds to minutes) to simultaneous tissue destruction and repair (including angiogenesis and fibrosis). o Short duration (minutes to days)  Causes - Infection, trauma, necrosis, foreign body  Causes  Mechanism o May be preceded by acute inflammation o Vascular- vasodilation, ↑blood flow and endothelial permeability o Persistent infections – TB, syphilis (Treponema Pallidum) o Cellular – Migration and extravasation of leukocytes and neutrophils o Immune-mediated – Hypersensitivity or autoimmune  Types o Serous– Protein-poor fluid (transudation into body cavities e.g. peritoneum, pleura, pericardium). o Toxins – Prolonged exposure to toxic agents (e.g. Silica) and foreign materials Seen in Burns, Viral Infection  Mechanism o Fibrinous – ↑ Vascular Permeability, ↑Fibrin o Nonspecific inflammation – Mediated by macrophages and lymphocytes o Suppurative (Purulent) – Edema, Pus – Exudate containing neutrophils→ abscess formation o Ulcer – Local defect / excavation of organ/tissue surface o Granulomatous inflammation - Seen in fungal/ some bacterial infections  Outcomes  Outcomes o Resolution and healing (regeneration) o Scarring o Scarring – Substantial tissue destruction o Amyloidosis o Abscess formation–pus (cavity filled with neutrophils and cellular debris walled by fibrous tissue) o Chronic inflammation – Cause not removed o Neoplastic transformation Acute vs chronic inflammation Granulomatous inflammation Acute inflammation Chronic inflammation  Definition – A pattern of chronic inflammation Onset Fast: minutes to hours Slow: days o Granulomas “wall off” a resistant stimulus without completely eradicating or degrading Innate immune system Adaptive immune system Duration Hours to days Weeks to months it → persistent inflammation→ fibrosis, organ damage  Types Causative agent Pathogens, injured tissue Persistent acute inflammation o Caseating - Associated with central necrosis. Caused by infectious agents: /foreign body,  Bacterial: TB, listeria, T. pallidum autoimmune reaction  Fungal Cellular infiltrate Mainly neutrophils Monocytes/macrophages and  Parasitic lymphocytes o Non-caseating - No central necrosis. Seen in non-infectious disorders: Vascular changes Prominent (vasodilation Not prominent; angiogenesis increase permeability)  Autoimmune diseases: Sarcoidosis, Crohn, thyroiditis  Vasculitis: Wegener granulomatosis, giant cell arteritis Tissue injury, fibrosis Usually mild and self-limited Often severe and progressive  Foreign material: berylliosis, talcosis, hypersensitivity pneumonitis  Chronic granulomatous disease Local and systemic signs Prominent Less prominent; may be subtle Outcome Resolution, abscess formation, Tissue destruction, scarring, fibrosis chronic inflammation Immune granuloma – Low yield Foreign Body Reaction – Low yield  Definition – A characteristic form of inflammation associated with Infectious agents  Definition – Foreign material in tissue  Macrophage reaction o Bacterial:  Mechanism – Non-Caseating granulomatous inflammation  Mycobacteria (tuberculosis, leprosy) o Aggregation of macrophages  Giant cells with multiple nuclei in the periphery  Bartonella henselae (cat scratch disease; stellate necrotizing granulomas),  Initiation  Listeria monocytogenes (granulomatosis infantiseptica) o Endogenous – Keratin, Urate, Crystals, degenerate and altered collagen and elastin  Treponema pallidum (3° syphilis) o Exogenous – Non-lysable Suture, Talcum, Thorns o Fungal: endemic mycoses (e.g., histoplasmosis) o Response to fungi – Suppurating granuloma o Parasitic: schistosomiasis  Fungi found within purulent neutrophilic material Granulation tissue – Low yield Healing  Definition – Tissue repair. Organization and repair of acute inflammation leads to healing by Definition – A complex process in which the skin, and the tissues under it, repair themselves after injury collagenous scar Stages o Begins within 24h of injury by migration of fibroblasts and endothelial cell 1.Inflammatory phase (up to 3d after injury) - Clot formation, ↑ vessel permeability, neutrophil migration 2.Proliferative (day 3–weeks after injury) - Deposition of granulation tissue and type III collagen, proliferation angiogenesis, epithelial cell proliferation  Sequence 3.Remodeling (1 week–6+ months after injury) of collagen to ↑ tensile strength of tissue 1. Removal of debris Intentions 2. Formation of granulation tissue  Regeneration (Primary healing) – Replacement of dead cells by proliferation of cells of same type –  Angiogenesis – Formation of new capillaries from pre-existing capillaries involves cell growth & differentiation and cell-matrix reactions – requires intact basement membrane.  Fibroblast proliferation– beginning of scar formation by collagen synthesis Occurs with clean wounds with little tissue damage and adjacent surfaces closely together. 3. Scarring Examples - Surgical suture, muscle fiber damage.  Maturation and organization of fibrous tissues  Repair (Secondary healing) – Replacement of injured tissue w/fibrous scar, NOT w/parenchymatous  Dense Collagenous Scar and progressive contraction of the wound tissue of same kind. Occurs in large tissue defect /Suture impossible / Intense inflammatory response  Longer healing.  Interruptions  Examples - Large surface ulcers and open wounds o Retention of debris Interruptions o Impaired circulation  Foreign body/material, Infection – continued tissue damage o Persistent infection  Ischemia, Diabetes, Obesity, Old age o Metabolic disorders, e.g. diabetes, alcohol abuse  Malnutrition (Vit. C- scurvy, Zinc, water) o Dietary deficiency of ascorbic acid or protein (required for collagen formation) Keloids – Low yield Abscess – Low yield  Definition – A tumor-like scar resulting from abnormal proliferation of connective tissue with  Definition – A cavity filled with pus (neutrophils, monocytes, and liquefied cellular debris). deranged arrangement of collagen fibers o Usually caused by a bacterial infection  Prevalence – Genetic predisposition that is more common in ethnic groups with dark skin (e.g.  Classification – Purulent, Deep, Limited inflammation Afro-Americans)  Types o Skin abscess- usually subcutis  Location – Ears, Face, Upper extremities o Internal abscess- inside the body: in an organ or in the spaces between organs  Causes - Often follows trauma to the skin, such as ear-piercing or surgical wounds  Seen in immune deficiency (Chemotherapy, Transplantation, Autoimmune  Outcomes - Resection is not recommended disease, AIDS) o Keloids have a marked tendency to recur after resection o Acute abscess – Pus surrounded by a layer of acute inflammatory exudate  Treatments o Chronic abscess – Exudate forming abscess wall replaced by scar tissue  Treatment – Can be removed only when mature (capsule is fully formed – roundish structure) o Compression dressing  Examples o Steroids o Ignored appendicitis  Liver abscess o Laser o Perianal abscess in truck drivers o Cicatrix in the Treatment of Hypertrophic Scars and Keloids Scars  Complication o Sepsis (bacteremia)- failure to contain the cause o Hospital viral infection o Cellulitis- If removed before capsule is formed / ruptured capsule Wart – Low yield Amyloidosis – Low yield  Definition – Squamo-Proliferative disorders of skin caused by HPV Definition – A group of disorders characterized by abnormal aggregation of proteins (amyloid), which lead to o Common lesion in children and adolescents cellular damage and apoptosis. o Self-limited, regressing spontaneously within 6 months to 2 years Consequence – Cellular Dysfunction - Prevents diffusion or Physical compression of parenchyma o They are not cancerous Mechanisms – Can be abnormal amounts protein or abnormal AA sequence o They typically do not result in other symptoms Types  Types (Morphology, Location)  Systemic (Generalized) o Verruca Vulgaris – Most common (Everywhere, most frequently - Hands) o Primary – Idiopathic. AL protein (amyloid light chain). Associated with plasma cell disorders.  Rough – Pebble-like  Deposition in tissues of mesodermal origin, such as heart, muscle, and tongue. o Verruca Plana (Flat wart) – Face and Dorsal surface of Hands  The kidney is the most involved organ.  Smaller o Reactive (Secondary) – Idiopathic. Serum amyloid A (AA).  Smooth  Seen in chronic inflammatory diseases (IBD, Rheumatoid Arthritis, Chronic Osteomyelitis) o Verruca Palmaris/Plantaris – Soles and Palms. may be painful o Dialysis-associated– β2 microglogulin. Seen in end-stage renal disease and long-term dialysis  1-2cm diameter o Hereditary (Familial Mediterranean Fever, etc.)  Rough  Localized – Confined to a single organ / tissue o Condyloma Acuminatum (Venereal wart) – External genitalia, urethra, rectum o Alzheimer disease- β-amyloid precursor protein (abnormal clevegae)- APP gene on Chr21  Sexually transmitted infection, HPV type 6 or 11 o Diabetes mellitus- Deposits of amyloid in islet cells  Cauliflower-like masses o Medullary carcinoma of the thyroid- Deposits within the tumor  Soft o Age-related amyloidosis- Heart, brain, and other organs of elderly people Appendicitis Phlegmonous appendicitis – Low yield  Definition – Acute inflammation of the appendix – the most common surgical emergency  Definition – Appendicitis that is spreading through full thickness of wall to serosa, causing an  Cause – Associated with obstruction (Fecalith, Gallstone, Tumor, Worms) acute localized peritonitis and walled off by the adjacent greater omentum or small-bowel  Stages o Acute appendicitis – Obstruction  ↑Intraluminal pressure  Ischemia  Bacterial proliferation loops, resulting in focal abscess  inflammation and edema o Abscess - cavity filled with pus (neutrophils, monocytes, and liquefied cellular debris) o Phlegmonous appendicitis – Spreading through full thickness of wall to Serosa  Acute localized  Gross Peritonitis o Rough o Gangrenous appendicitis – Muscle layer necrotic and inflamed  Perforation  bowel contents in peritoneum  Generalized Peritonitis o Yellow  Symptoms - Pain starts in mid-epigastrium  Migrates to RLQ (McBurney point) o Fibrinous exudate on surface o Pregnancy can mask the pain location o May elicit psoas, obturator, and Rovsing’s signs. Guarding and rebound tenderness on exam  Mimics o Meckel's Diverticulum o Salpingitis (right sided) o Mesenteric Lymphadenitis (swollen lymph nodes)  Treatment – Appendectomy  Complications – A ruptured appendix: o Necrosis of appendix wall, Perforation, Peritonitis→ gangrenous necrosis o Sepsis o Abscess Hashimoto's Thyroiditis – Low yield Neoplasia  Definition – Autoimmune disease against thyroid tissue. The most common cause of  Definition – Uncontrolled, disorderly proliferation of cells, grow more rapidly than normal cells or tissue. hypothyroidism Caused by failure of regulation mechanism (proliferation and maturation) of cells. o Resulting in a benign or malignant growth known as a neoplasm.  Mechanism- Anti-thyroid peroxidase and anti-thyroglobulin antibodies  Etiology o First, Hyperthyroidism – Follicles are destroyed and hormones flow to blood o Sporadic – Statistical (environmental, nutritional etc.) o Then, Hypo after fibrosis and fat tissue o Familial – >3 cases in family, not associated with one specific gene o Genetic – Associated with specific genes. High possibility for malignancy  Diagnosis – Ultrasound  Biopsy  Antibodies  Hashimoto thyroiditis  Common locations – Breast (woman)/prostate (men), skin, lungs o Moderately enlarged, non-tender thyroid  Classification – Classified as either malignant or benign, based on their behavior  Treatment o Benign – "-oma”. Slow growth, well demarcated, no metastasis. Tend to be encapsulated o Resection only in tumor cases  Papilloma, Lipoma o Malignant – "-sarcoma", "-carcinoma". Fast growth, less differentiated, metastasizes o Consider partial resection if possible  Colonic adenocarcinoma – epithelial origin o Don’t resect the parathyroid glands!  Osteosarcoma – Bones  Complication – Some progress to primary atrophic thyroiditis  Astrocytoma – Glial (CNS)  Melanoma – Skin o ↑ risk of non-Hodgkin lymphoma  Lymphoma – Lymphatic  Causes of death o Cachexia – Excessive body weight loss. Accompanied by weakness, anorexia and anemia o Secondary infection. Usually pneumonia o Obliteration of vital organs/system by tumor  Diagnosis – Physical, radiographic, laboratory/biopsy/autopsy Benign tumor (benign neoplasia) Malignant tumor  Definition – Closely resemble tissue of origin (fully differentiated)  Definition – Neoplasm with tendency to become worse o Slow Growth o Grow fast o Well demarcated – Margins well defined. Encapsulated o Margins poorly defined - Not encapsulated o No Metastases! o Invasive and Metastasize (Through Lymph, Blood, Cavities)  Complications  Classification o Compression of adjacent tissues o Well-Differentiated – Constituent cells closely resemble tissue of origin o Blockage of lumen o Poorly-Differentiated – Little resemblance to tissue of origin o Endocrine functions