Exam 1 Study Guide: Inflammation, Cells, Tissues, and Cancer PDF

Exam 1 Inflammation ​ Goals of Inflammation ○​ control inflammatory response from spreading ○​ preventing/limiting further damage/infection ○​ activate adaptive immunity and educate ○​ Initiate healing ​ Acute: 8-10 days, self-limiting, heals w/o t...

Exam 1 Inflammation ​ Goals of Inflammation ○​ control inflammatory response from spreading ○​ preventing/limiting further damage/infection ○​ activate adaptive immunity and educate ○​ Initiate healing ​ Acute: 8-10 days, self-limiting, heals w/o treatment ​ Chronic: more than 2 weeks/recurring ​ Signs: redness/erythema, swelling/edema, pain, heat, and sometimes loss of function ​ Exudative fluid ○​ Serous: clear, watery, early inflammation ○​ Fibrinous: yellowish, healing, thick/clotted, more advanced inflammation ○​ Hemorrhagic: blood ○​ Purulent: pus, infection present, bacteria ​ Fever: caused by pyrogens ○​ endogenous=cytokines ○​ exogenous=microbes ​ Cytokines: chemical messages that have effects on cells ○​ IL-1: proinflammatory ○​ IL-10: anti-inflammatory ○​ IFN alpha and beta: antiviral proteins ○​ IFN gamma: increase macrophage phagocytosis ○​ Leukocytosis: increased WBC circulation ​ RBCs vs WBCs vs Platelets ​ Macrophages: phagocytosis, secrete cytokines for inflammatory response to activate plasma systems and mast cells ​ Mast Cells: mature into macrophages at inflammation site, release histamine ​ Plasma systems: Kinin, Complement, Clotting ○​ Complement: 3 pathways= classical, lectin, alternative ​ Activated C3 to C3a and C3b ​ C3a: mast cell degranulation ​ C3b: opsonization and C5 ​ C5a: mast cell degranulation and leukocyte migration ​ C5b: activates MAC (membrane attack complex) ○​ Clotting: Extrinsic vs Intrinsic ​ Extrinsic: factor VII and TF to factor X ​ Intrinsic: factor VII to factor x or Kinin System ​ Factor X to thrombin to fibrinogen to fibrin to fibrin and FP ​ fibrin=blood clot  ​ FP=leukocyte migration and capillary permeability ○​ Kinin ​ Prekallikrein to kallikrein to kininogen to Bradykinin ​ Bradykinin: vascular permeability, pain ​ Margination: leukocytes sticking to vessel wall ​ Diapedesis: Leukocytes leaving vessel to enter tissue ​ Cytokines ○​ Vasodilation: prostaglandin, histamine, nitric oxide ○​ Vascular permeability: histamine, bradykinin, leukotrienes, PAF ○​ Pain: bradykinin and prostaglandin ○​ Limit inflammation: IL-10, Enzymes ​ Histamine effects ○​ H1 receptor: proinflammatory ○​ H2 receptor: anti-inflammatory ​ Cell injury to acute inflammation, then either heals or goes to chronic inflammation, then it either heals or produces granulomas then it heals ​ Chronic Inflammation Causes ○​ Unsuccessful acute inflammation ○​ Chemicals ○​ viruses/microorganisms (hiding tactics) ○​ Toxins ​ Wound healing/Regeneration ○​ Resolution: return tissue to original function and structure ○​ Repair: scar tissue, structure and strength not function ○​ Intention: ​ Primary: clean/close wound, sutured incision(closed wound0, paper cut ​ Secondary: open wound, not closed, more tissue loss ​ Tertiary: leave wound open at first, then close it ​ Epithelialization: sealing wound with epithelial tissue ​ Contraction: bringing 2 sides of wound together/shrinking ​ Phases of wound healing: ○​ 1) Hemostasis: stop bleeding/clot formatting ○​ 2) Inflammation: leukocytes present and release cytokines ○​ 3) Proliferative: epithelialization, macrophages clear debris, clot replaced w/ normal or scar tissue, angiogenesis ○​ 4) Maturation/Regeneration: cellular differentiation of epithelial tissue, scar formation/Remodeling ​ Dysfunctional wound healing: ischemia, excess bleeding, excess fibrin, obesity/diabetes/tobacco/infection/malnutrition/drugs ​ Hypertrophic scar: noticeable/raised  ​ Keloid: protruding scar, outside of wound boundaries, more melanin=more likely ​ Dehiscence: separation of wound edges ​ Contracture: wound healing to close together, limits movement Altered Cells and Tissues ​ Pathogenesis: development of disease from stimulus to expression ​ Pathophysiology: functional changes accompanying syndrome/disease ​ Diagnosis: indication of disease through evaluation of signs/symptoms ​ Etiology: cause of disease/origin ​ Idiopathic: no known cause ​ Iatrogenic: human caused, usually in healthcare ​ Predisposing factors: encompass tendency to promote diseases (ex lack physical activity) ​ Prophylaxis: a process or measure that prevents disease ​ Prevention: linked to etiology and predisposing factors ​ Acute: sudden/short lived, 8-10 days ​ Chronic: 2 weeks or longer, recurring/persisting for a long time ​ Insidious: gradual progression with vague/mild symptoms ​ Subclinical: disease is present, no obvious manifestations ​ Latent: asymptomatic, no distinct change, incubation ​ Signs: objective findings from assessment, observe/measure ​ Symptoms: subjective, reported by patient/felt by patient ​ Manifestations: clinical evidence of disease ​ Lesions: specific local change in tissue (internal or external) ​ Syndrome: constellation of signs/symptoms occurring together to specific conditions, group of diseases sharing signs/symptoms ​ Sequelae: unwanted outcomes ​ Homeostasis: tendency to maintain balanced/constant internal state ​ Stress can either lead to adaptation/new state/preserved cell or exceed adaptive capabilities/cell injury/cell death ​ Neurosis: pathologic cell death ​ Apoptosis: programmed cell death ​ Reversible: cell can recover ​ Irreversible: cell death ​ Hypoxia: lack of oxygen in tissue ​ Ischemia: lack of blood flow to tissue ​ Infarct: death due to ischemia ​ Ischemia reperfusion injury: involves formation of free radicals, after lack of blood flow returns, injury occurs due to free radicals ​ ROS: reactive oxygen species, created from reperfusion of O2 ​ Free radicals: unstable oxygen molecules that can damage cells, impaired electrons=reactive  ​ Infiltration: intracellular accumulation ​ Calcium free floating ○​ Triggers chemical reactions(enzymes) ○​ Causes low ATP and mitochondrial permeability ​ Necrosis Types ○​ Coagulative: in organs that deal with blood (kidney, liver, heart), protein denatured, ischemia/infarction ○​ Liquefactive: CNS, no connective tissue, bacterial/fungal or ischemia, hydrolytic enzymes ○​ Caseous: “cheese-like”, tuberculosis, coagulative and liquefactive, granulomas ○​ Gangrenous: dry or wet, caused by ischemia superimposed with clostridium perfringens ○​ Fats: pancreas/pancreatitis, pancreatic lipase ​ Cellular adaptations ○​ Atrophy: shrinking cell size (muscles w/ age) ○​ Hypertrophy: increase in cell size (myometrium during pregnancy) ○​ Hyperplasia: increase in cell number (mamillary, endometrium) ○​ Metaplasia: change from one adult cell to another, reversible, can lead to malignancy (tobacco smoke, GERD) ○​ Dysplasia: not a true adaptation, high grade= no resemblance to original type=cancer/carcinoma in situ, low grade= abnormal but some resemblance ​ Apoptosis: programmed cell death ○​ Physiological: embryogenesis(webbed fingers) ○​ Pathological: cell injury ○​ 2 pathways ​ Intrinsic: proteins w/ in cell that favor life vs those that favor death ​ Extrinsic: another cell triggers/signals cell death ​ Autophagy: cell eats itself to ensure survival when nutrients is scarce ​ Chaperones: protein that helps other proteins fold correctly Genes and Genetic Diseases ​ 23 pairs/46 chromosomes, 1-22 autosomal, 23=sex chromosomes, euploidy amount ​ Histone: any group of basic proteins found in a chromatin ​ Chromatin: complex of DNA and protein, for packing long DNA molecule into dense, compact structure ​ Chromosome: thread-like structure made of proteins and a single DNA molecule, serve to carry genetic info from cell to cell ​ Gene: sequence of nucleotides in DNA/RNA, basic unit of inheritance ​ Locus: specific, fixed position on a chromosome where a particular gene/genetic marker is located ​ Alleles: different versions of DNA sequence at a given genetic location ​ Genotype: genetic makeup of an individual cell/organism ​ Phenotype: physical expression of genotype and environmental factors ​ Homozygous: HH/hh, 2 same alleles ​ Heterozygous: Hh, 2 different alleles ​ Dominant gene: requires only one allele to express phenotype ​ Recessive gene: often masked and required 2 alleles to express phenotype ​ Codominant: example=blood type AB ​ Carrier: possess the defective gene but does not show symptoms, Hh ​ Centromere: the point on the chromosome to which the spindle attaches during cell division ​ Short Arm: p, top half of chromosome ​ Long Arm: q, bottom half of chromosome ​ Chromosomal aberrations: entire chromosome defective ​ Single gene disorder: specific gene affected ​ Multifactorial: genes and environment ​ Euploidy: 23 pairs of chromosomes, normal # ​ Aneuploidy: abnormal # of chromosomes ○​ Trisomy: 3 chromosomes, can survive ○​ Monosomy: 1 chromosome = LETHAL (except turner syndrome)\ ​ Nondisjunction: causes aneuploidy, failure of chromosomes/sister chromatids to divide during cell division ​ Autosomal Aneuploidy: Trisomy 21/Down Syndrome ​ Sex Chromosome Aneuploidy: Turner Syndrome (X_), Klinefelter’s Syndrome (XXY,XXXY), ​ Trisomy 21: ○​ Risk: mother over the age of 35 ○​ Manifestations; epicanthal fold, congenital heart disease, poor muscle tone, lower intelligence, low nasal bridge, protruding tongue, low set ears, intestinal malformation, broad hands w/ simian crease, wide gap between big toe and second toe, flat occiput ​ Turner Syndrome: ○​ Female with one x chromosome; genotype ○​ Manifestations: underdeveloped ovaries(sterile), short stature, WEBBED NECK, edema, underdeveloped breasts, wide nipples, high number of aborted fetuses(diagnosis) ​ Klinefelter’s Syndrome: ○​ XXY or XXXY, more x’s more problems ○​ Manifestations: male appearances, gynecomastia(breasts), small testes(sterile), sparse body hair, long limbs, wide hips, lack facial hair, tall stature ​ Pedigree table: tool used to study genetic disorders with in a family ​ Single Gene Disease: ○​ Autosomal recessive: 2 defective genes ○​ Autosomal dominant: 1 defective gene ○​ X-linked recessive: more prominent in males because only have one x chromosome ​ Recurrence risk: probability and individual will develop a genetic disease ​ Penetrance: probability of a gene/trait being expressed (GENOTYPE) ​ Expression: variation in phenotypic expression ​ Autosomal Dominant: delayed lethal phenotype ○​ No carriers ○​ Does not skip generations ○​ 50% recurrence risk/chance of getting it if one parent has the allele ○​ Ex: Huntington’s Disease(chromosome 4), Marfan’s Syndrome(connective tissue abnormalities), Neurofibromatosis(chromosome 17, neurofibromas, cafe au lait spots), vonWillebrand’s(slow clotting) ​ Autosomal Recessive: hh ○​ Carriers: Hh ○​ Commonly caused by consanguinity ○​ Commonly die at a young age ○​ Ex: cystic fibrosis(thick mucus in lungs/gi, white people), sickle cell anemia(cells elongate and harden, african decent), phenylketonuria(PKU, lacks PAH), Tay-Sachs disease(lack hexosaminidase, chromosome 15) ​ Cystic Fibrosis ○​ Defect in CFR gene ○​ Affects lungs and gi tract ○​ Pancreas and lungs specifically ○​ Maldigestion due to pancreas not able to secrete mucus containing enzymes ​ Sickle Cell Disease ○​ Replace glutamic acid with valine ○​ RBC sickle under conditions that cause O2 to be low ○​ Manifestations: CVA, Paralysis, Death, Retinopathy, hemorrhage, avascular necrosis(shoulder/hip), hepatomegaly, splenomegaly, gallstones, hematuria, priapism, osteomyelitis, chronic ulcers, anemia ​ X-linked Recessive Inheritance: males affected, female carriers, consanguinity, males give to female offspring, sons of female carriers=50% recurrence rate ○​ Ex: Hemophilia(a=viii, b=ix, c=xi), muscular dystrophy, red/green color blind, alport syndrome ​ Multifactorial: genetic influence and environmental factors  ○​ Ex: cleft palate, congenital hip dislocation, congenital heart disease, type 2 diabetes mellitus ​ Diagnostic Tests: prior to conception, during pregnancy, and after birth ○​ Recommended if family history, previous child with abnormalities, woman over 35, ethnic group with specific disease ​ Alpha-fetoprotein: if levels are low, baby will have down syndrome Cancer Biology/Epidemiology ​ Cancer: disease on which abnormal divide w/o control and can invade other tissue. ​ Neoplasia: uncontrolled abnormal growth of cells/tissues in the body ​ Causes of Cancer: ○​ Genetic: DNA mutation ○​ Heritable: Darwin Selection ​ Benign ○​ Not cancerous ○​ Differentiated ○​ Encapsulated ○​ Slow Growing ○​ Remained localized ○​ Not life threatening ○​ -oma ​ Malignant ○​ Cancerous ○​ Undifferentiated ○​ Not encapsulated ○​ rapid/aggressive growth ○​ Metastasis ○​ Life-threatening ○​ -carcinoma(epithelial), -sarcoma(mesenchymal) ○​ Melanoma ○​ Hodgkin’s lymphoma ○​ Ewing sarcoma ○​ Wilms tumor ○​ Hepatoma ​ Proto-oncogenes: normal cell proliferation ​ Oncogenes: mutated proto-oncogenes/cancerous ​ Tumor-suppressor gene: inhibit proliferation, stop cell division, prevent mutation, Guardians and Governors ​ Governor: stop the growth ○​ Rb gene ​ Guardian: damage the growth ○​ BRCA-1 ○​ BRCA-2 ​ Telomeres: normally present, prevent immortality by limiting cell division by getting smaller w/ every division ​ Telomerase: not normally present, restore and maintain telomeres, unlimited division, 90% of cancer ​ Angiogenesis: creation of new blood vessels ​ VEGF: Vascular Endothelial Growth Factor, secreted by cancer cells to promote angiogenesis to gain nutrients ​ Warburg Effect: cancerous cells ineffective aerobic glycolysis, less ATP ​ Reverse Warburg: other cells doing the ineffective aerobic glycolysis to allow cancerous cells to have lactate and other metabolites ​ Chronic Inflammation: important for cancer, cellular injury leads to adaptations causing more room for error to cancer and mutations ​ Diseases and related cancer ○​ Hep B&C: primary hepatocellular carcinoma ○​ Epstein-Barr Virus: Burkitt’s Lymphoma ○​ HIV/AIDS: kaposi sarcoma herpesvirus (KSHV) ○​ Human Papillomavirus: cervical cancer ○​ Reflux Disease: Adenocarcinoma of lower esophagus ○​ Helicobacter Pylori: gastric carcinoma ​ Local spread: prerequisite for metastasis ​ Metastasis: spread from site of origin to distant site ○​ Routes: blood and lymph because they circulate the whole body ​ Cancer Manifestations: cachexia(wasting away), exhaustion, pain, obstruction, tissue necrosis, anemia, severe fatigue, effusion, infection, bleeding ​ Diagnostics ○​ Routine screening ○​ Blood test ○​ Tumor markers: AFP(liver), PSA(prostate) ○​ Biopsy ○​ Cytology ​ TNM: Tumor Nodes Metastasis, universal language for tumors ○​ Tumor Spread ​ t0=no tumor, t1=5cm ○​ Nodes ​ n0=none, n1-3= nodes infiltrated ○​ Metastasis ​ m0= no metastasis, m1= metastasis ​ Staging: where cancer has spread ○​ Stage 1: confined to origin ○​ Stage 2: local invasion ○​ Stage 3: spread to regional structure (lymph nodes) ○​ Stage 4: distant metastasis ​ Grading: what cells look like/behavior ○​ Grade 1: well differentiated ○​ Grade 2: moderately differentiated ○​ Grade 3: poorly differentiated ○​ Grade 4: anaplastic ​ In situ: presence of abnormal cells, “on site” ​ Localized: where it started ​ Regional: spread to lymph nodes/nearby tissue ​ Distant: metastasis, to distant parts of body ​ Unknown: not enough info ​ Cancer therapy: ○​ Surgery ○​ Chemotherapy: uses drugs to kill cancerous cells, systemic ○​ Radiation: targeted, to kill/shrink cancer cells/tumor ○​ Hormone therapy: slow/stop cell growth ○​ Immunotherapy: boost immune system to fight cancer ○​ Stem cell transplant: restore destroyed stem cells ​ Cancer=25% of all deaths ​ 40% of cancer is preventable ​ Prevalence: percentage affected with disease at given time ​ Incidence: number of new cases within a specific timeframe ​ Morbidity: having signs/symptoms of a disease ​ Mortality: number of deaths due to a disease ​ Sensitivity: able to correctly identify those with disease ​ Specificity: identify those without the disease ​ Male ○​ Diagnosed: prostate, lungs, colorectal ○​ Deaths: lungs, prostate, colorectal ​ Female ○​ Diagnosed: breast, lung, colorectal ○​ Deaths: lung, breast, colorectal ​ Cancer and Fat ○​ Cancer induces lipolysis ○​ Fat supports growth of cancer/metastasis