BIO 307 PATHOPHYSIOLOGY DR. GREENAMYER BASIC TERMS • Vocabulary – – – – – Hyper-- vs hypo---itis --osis --opathy Idopathic, Iatrogenic, Nosocomial • Disease (Syndrome) vs Normalcy • Etiology: causes or reasons for a disease – Virus/bacteria, occupation, age, sex, nutritional status, genetics • Can be used to classify disease – Inherited, congenital, toxic, infectious, traumatic, degenerative, neoplastic, metabolic • Pathogenesis: development/evolution of disease • Manifestations of Disease – Signs: objectively identifiable changes (fever, BP, HR, PCV) – Symptoms: subjective feelings (nausea, pain) FACTORS THAT INFLUENCE DISEASE • Extrinsic factors—outside individual, may or may not be controlled – Diet, medication, exposure to harmful agents • Intrinsic factors—rarely under individual control – Age, sex, genetic inheritance – Congenital vs inherited • Most diseases are a combination (interaction) of factors Genetic disorders • Single gene disorders—may affect any tissue/organ system • Autosomal dominant—need only one bad copy of gene – Equally prevalent in males and females – No skipping of generations, delayed onset common – Typically less severe than recessive, structural protein defect – Huntingdon’s Disease, Adult polycystic kidney disease • Autosomal recessive—need two bad copies of gene • Equally prevalent in males and females • May skip many generations, but often seen in siblings • Early age onset, more often enzymatic deficiency • Cystic fibrosis, sickle cell anemia • Sex Linked disorders—carried on X (most often) or Y (rarely) chromosome • X linked recessive most common • More common in male; females are usually asymptomatic carriers unless unequal X inactivation or 2 copies of the mutated gene • All daughters of affected men are carriers • Hemophilia A, Duchenne’s muscular dystrophy • Mitochondrial gene disorders—passed through maternal line – Extremely rare Chromosomal abnormalities • Aneuploidy—abnormal number of chromosomes • Down’s syndrome (trisomy 21) most common • Result of nondisjunction • Translocations—result in structural abnormalities – Genetic material exchanged between nonhomologus chromosomes – Robertsonian translocations most important clinically – Philadelphia chromosome in chronic myelogenous leukemia Fig. 4-18 Causes of Cellular Injury • Hypoxic injury (ischemia is #1 cause) • Chemical injury (free radicals, heavy metals) • Physical injury (mechanical, thermal, radiation, electric shock) • Infectious injury (bacteria, viruses, fungi, parasites) • Immunological and inflammatory injury Terminology of Cellular Changes • Atrophy – Autophagy in malnutrition • • • • Hypertrophy vs hyperplasia Dysplasia (atypical hyperplasia) Metaplasia Senescence (aging) and death Common themes/results (T 2-2) • • • • ATP depletion Defects in membrane permeability Increased intracellular calcium Increased free radicals Manifestations of Cellular Injury • Accumulate water (cloudy swelling, oncosis, hydropic degeneration) • Accumulate lipids (steatosis), carbohydrates, or proteins • Atrophy—requires autophagy – accumulation of pigments (brown atrophy) Cloudy swelling (oncosis, hydropic degeneration) Cell death (necrosis) • Nuclear changes are most obvious – Pyknosis—shrunken, irregular, dark staining nucleus – Karyorrhexis—fragmentation of nucleus • Karyolysis—dissolution of nucleus • Coagulative necrosis—most common type – Cells retain shape, tissue retains normal architecture – Indicates ischemia—dry gangrene • Liquifactive necrosis—most common in brain – Can result from hydrolases from bacteria – Wet gangrene • Caseous necrosis—cells degenerate but fragments remain--Mycobacterium infections Apoptosis • Active process of programmed cell death (scattered, single) – Deletes excess cells during development – Probably occurs in malignant cells or cells damaged by chemotherapy • NOT accompanied by inflammation – Should not stimulate an immune reaction Apoptosis Systemic Manifestations of Necrosis (Inflammation) • • • • Fever (from pyrogens) Increased heart rate Increased WBCs Elevated presence of tissue specific enzymes • CPK creatine phosphokinase • LDH lactic dehydrogenase • ALT alanine aminotransferase • Loss of some organ function • Pain LOCAL INFLAMMATION Purpose of Inflammation • • • • Destroy and remove insult Wall off and confine damage Stimulate immune response Promote healing Causes of inflammation • Infection • Trauma—physical, chemical, thermal, radiation • Immune hyper-sensitivity reactions INFLAMMATION---types • Acute – Redness, heat, pain, swelling (rubor, calor, dolor, tumor) – Altered function (functio laesa) has been added • Subacute • Chronic---Longer duration – Granuloma formation—massive numbers of macrophages Fig 6-3 Clotting Cytokines in acute inflammation Local Inflammatory Response • Margination and diapedesis of WBC • Vascular Response—increased permeability • Arterial dilation—increased local BP • Endothelial cells of blood vessels (venules) separate • Exudation—significant amounts of protein lost into interstitial space • Water follows protein to maintain osmotic balance Results of water movement • Interstitial swelling pulls flaps of lymphatic capillaries apart • Increased flow of lymph • Protein, cells enter lymphatics • Lymphangitis/lymphadenitis (lymphadenopathy) may result Mediators of inflammation • Histamine—mast cells • Activated Factor XII--Clotting System • Arachidonic acid metabolites • COX and LOX pathways • Complement cascade • Miscellaneous cell factors Fatty acids Chronic inflammation Exudates • Serous—protein in interstitial fluid • Fibrinous—fibrinogen accumulates on serous surfaces • Mucinous—mucous membranes—cellular secretion • Neutrophillic—purulent—bacterial infection/necrotic cells • pus is suppurative exudate of neutrophils and dead bacteria Systemic Manifestations of Inflammation • Fever • Leukocytosis • Increased Erythrocyte Sedimentation Rate Wound Healing • Healing by first intention • Healing by second intention (granulation) Fig 6-21 Indications of wound infection • Abscesses, furuncles (boils), carbuncles • Cellulitis—widespread purulent inflammation • Mixed exudate from wound – Fibrinopurulent – Mucopurulent – Serofibrinous Factors that Delay Wound Healing • • • • • • Oxygen deficiencies/ Ischemia Nutrition deficiencies Fluid/ electrolyte imbalances Age Medications or other disease Extent of tissue damage • Dehiscence/ evisceration may result from premature suture removal Complications of healing • Scaring – strictures, contractures • Adhesions • Keloids