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Functional GI Disorders Chronic abdominal symptoms with no underlying physical abnormalities A patient is experiencing frank hematemesis. Where is the bleeding? Above the stomach. Hematemesis = vomiting blood A patient has coffee ground vomitus. Where is the bleeding? Into the stomach What is the difference between melena and occult blood? Melena: large volume of blood into the intestines Occult: small volume of blood mixing with feces Mumps may cause...? Parotitis, inflammation of the parotid salivary gland Failure of the propulsive force of the esophagus is? Dysphagia This disease occurs when the LES is unable to relax. Achalasia What occurs in Barrett esophagus? With chronic GERD, the simple squamous epithelium is replaced with columnar epithelium; this predisposes the pt to develop adenocarcinoma. Which disorder is caused by an ectopic gastrin-secreting tumor? Zollinger-Ellison Syndrome; this manifests as increased motility and HCl secretion. This disorder may lead to atrophy of the gastric epithelium? Chronic gastritis, may be caused by H. Pylori and may lead to adenocarcinoma. In contrast, acute gastritis is often self-limiting. Which three protective factors of the stomach are effected by NSAID use? 1. Mucus production 2. HCO3 production 3. Prostaglandin production What are the risk factors for developing a stress ulcer/Curling's ulcer? Acute illness including liver disease, trauma or large area burns. Seen in 5-10% of ICU patients. What are the features of diarrhea causing bacterial enterotoxins? 1. Enhance intestinal secretion 2. Do not impair Na dependent absorbtion What is the cholera toxin MOA? The toxin activates adenylate cyclase, increasing levels of cAMP and increasing secretion of anions into the intestinal lumen. Which disorder is characterized by an inappropriate T-cell reaction to Gliadin? Celiac Disease. Present in 1% of a population, a genetic disorder. What is the cause of IBS? IBS is thought to be a combination of motor and sensory disfunction, as well as psychological stress response. Dx with 3 MONTHS of symptoms. Which two diseases are Inflammatory Bowel Diseases? Crohn's and Ulcerative Colitis What differentiates Crohn's disease and Ulcerative Colitis? Crohn's: distributed lesions, assoc. w/ smoking, does not develop into cancer Ulcerative Colitis: Spec. to colon, assoc. w/ immune hepatitis, pre-cancerous Originally known as "infectious hepatitis", this disease is transmitted via the fecal-oral route. Hep A Originally known as "serum hepatitis", this disease is transmitting by blood or body fluids. Hep B How common is progression from acute HCV t chronic HCV infection? 50-80% What is important about HEV? Hepatitis E is similar to Hep A (oral-fecal, mild) but has a 20% mortality in pregnant pts due to fulminant hepatitis. Which disease is associated with increased cholesterol, xanthomas, jaundice and hyper-pigmentation of the skin? Primary Biliary Cirrhosis; autoimmune destruction of the bile ducts of the liver, associated with Sjogren's syndrome. This liver d/o leads to a build-up of bile in the liver, and is highly associated with Ulcerative Colitis. Primary Sclerosing Cholangitis, an autoimmune disease Name some pre-, intra- and post-hepatic causes of portal hypertension. Pre: Obstruction (leading to edema), Splenomegaly Intra: Cirrhosis Post: Right-sided HF, outflow obstruction What is hepatic encephalopathy? CNS effects associated with liver failure, likely caused by buildup of toxins in the blood; includes flapping tremor What is the difference between obstructive, intrahepatic and hemolytic jaundice? Obstructive/Posthepatic: involves a disruption in bile flow (cholestasis) Intrahepatic: involves decreased liver function (decreased bilirubin uptake, conjugation) Hemolytic/Prehepatic: involves excessive RBC lysis Progressive kidney failure in a pt with liver cirrhosis is called...? Hepatorenal Syndrome (HRS); characterized by progressive azotemia, thought to be caused by decreased renal blood flow. The most common cause of gall bladder problems is...? Cholecystitis, Inflammation of the Gall Bladder What are the features of pancreatitis? 1. Pain radiating to the back 2. Fever, Leukocytosis 3. Hypotension, hypovolemia 4. Increased serum Amylase A complete detachment of a tendon or ligament from its bony attachment point is an...? Avulsion What are the grades of sprains? 1. Mild 2. Hematoma formation 3. Ligament breaks (total disruption) 4. Ligament separated from bone (avulsion) Inflammation of a tendon where it attaches to the bone is...? Epicondylitis; includes tennis, golfer's elbow What is the difference between tendinitis and tendinosis? Tendinitis: Inflammation of the tendon Tendinosis: Chronic inflammation and degradation of collagen fibers In this disorder, chronic muscle inflammation leads to calcification and ossification of the muscle Myositis Ossificans, often occurs in thigh or arm What is the most common cause of toxic myopathy? Alcohol abuse, loss of lean muscle mass is greatest predictor of mortality! In this type of fracture, the bone has been broken into several small pieces. Comminuted What is traction and reduction? Traction: holding bones in alignment Reduction: moving bones into alignment What is the difference b/w dislocation and subluxation? Dislocation: Total separation of articular cartilage Subluxation: Partial separation of articular cartilage What are the four stages of bone healing? 1. Fibrin clot formation, Hematoma 2. Fibrous callus formation, collagen deposition 3. Bony callus formation 4. Remodeling What is osteomyelitis, and what is a common cause? Osteomyelitis is a bone infection, and is often caused by Staph, may be blood borne. In untreated osteomyelitis, reactive bone (involucrum) may grow outside of the infected area. What is Blount's disease? Bowing of the legs which gradually worsens, may lead to necrosis What class of drugs may cause osteonecrosis of the jaw? Bisphosphonates, when administered IV for cancer treatment Which bone is most frequently affected by osteonecrosis? Femoral Head 20% (the biggest portion) of bone cancers are what type? What population is effected most? Osteosarcoma, most commonly in pts younger than 20. 10% of bone cancers are what type? What population is effected? Chondrosarcoma, most commonly in mid to late life This rare cancer forms in muscle and is highly malignant. Rhabdomyosarcoma What causes in-toeing and out-toesing? Torsion or the femur and/or tibia What causes Osteogenesis Imperfecta? Known as "brittle bone disease", this is caused by a deficiency in collagen synthesis. There are four types. This disease is autosomal dominant. What are the types of Osteogenesis Imperfecta? I: Mild, blue sclera, may have postnatal fractures II: Severe, usually leads to death <1year III: Progressive severe d/o IV: Mild, normal sclera, slightly worse then I. What occurs in Osteocondroses? The blood supply is disrupted to the epiphyseal plate and ossification is disrupted. Compare Legg-Calve-Perthes to Osgood-Schlatter disease. Legg-Calve-Perthes disease: Femur, boys 4-8 Osgood-Schlatter disease: Tibia, boys 10-15, usually resolve Differentiate the three causes of scoliosis. Congenital: Vetebral growth disturbance in utero Neuromuscular: Develops from neuro- or myopathic diseases. Idiopathic: most common in girls What ligand controls the actions of osteoclasts? What ligand suppresses osteoclasts? Osteoclasts are stimulated by RANKL, and suppressed by OPG (Osteoprotegerin), secreted by bone marrow and bone cells. What causes Osteomalacia & Rickets? Decreased Bone Mineralization What is the density of normal bone? How many SDs away from a normal female must one be to be dx Osteoporosis? normal 833mg/cm^3 2.5 Std dev's, or <648mg/cm^3 Which disease is characterized by degenerate bone remodeling? Pagets (Osteitis deformans). Likely has a genetic component with mutations in RANK pathway. Which disease is characterized by the formation of a pannus in the joint cavity? A pannus "destructive vascular granulation tissue" forms in Rheumatoid Arthritis; worst in the AM! This disease involves inflammation of fibrous cartilage (often inbetween vertebrae) and may lead to calcification and vertebral fusing. Ankylosing Spondylitis, a immune reaction causing enthesitis, inflammation of the insertion site of ligaments or tendons. What occurs in Reactive Arthritis? In Reactive Arthritis, sterile joint inflammation occurs following GI or GU infection. This disease is characterized by wearing of articular cartilage and formation of bony spurs (osteophytes). Osteoarthritis (degenerative joint disease), worst at night! Mechanical stress causes chondrocytes to release cytokines. What causes muscle contracture? Failure of the Ca pump to remove Ca, which would allow the muscle to relax What is myotonia and what life-threatening crisis is it associated with? Myotonia is slow relaxation of muscles following contraction, and is related to the experience of Malignant Hyperthermia. What is the difference between relative and absolute polycythemia? Relative: Change in plasma volume Absolute: Change in red cell mass If reticulocytes are <2 w/anemia, this is indicative of...? Hypoproliferative Anemia. RBC production is decreased or defective. If reticulocytes are >3 w/anemia, this is indicative of...? Hyperproliferative Anemia. RBC destruction or hemorhhage is occuring. What are normal hgb levels? Approx. 13 - 16 g/dL F: 12 - 15 M: 14-16.5 What can cause absolute polycythemia? 1. Tissue hypoxia 2. Defective EPO Define anemia. Reduction in total number of erythrocytes, or quality or quantity of hemoglobin. In this disease, red blood cells develop spherically instead of bi-concave, and are more susceptible to lysis. Hereditary Spherocytosis Which type of anemia is normally associated with normocytic and normochromic RBCs? Hemolytic Anemia This hemolytic anemia is associated with IgG and is associated with several autoimmune diseases. Warm Antibody Disease This hemolytic anemia is associated with IgM and is associated with Raynauds Phenomenon. Cold Antibody Disease, often a complication of Mono, Mycoplasmal Pneumonia, Epstein Barr Virus What are the three mechanisms of drug-induced hemolytic anemia? http://asheducationbook.hematologylibrary.org/content/2009/1/73.full 1. Auto-antibody reactions 2. Hapten Formation 3. Immune Complex Formation What is the initial cause of sickle-cell anemia? How is it inherited? Single base substitution results in formation of Hb-S, and abnormal hemoglobin. Most frequently autosomal recessive. Why is fetal hemoglobin interesting for sickle-cell treatment? Its has no Beta chains, therefore it cannot sickle. (Adult hemoglobin has Alpha and Beta, Fetal has Alpha and Gamma) Which Thalassemia is more severe? Beta Thalassemia. In Beta Thalassemia, only Alpha chains are formed, may clump together forming HbA4. What is a Heinz body? Seen in BETA thalassemia, a heinz body is a precipitated clump of ALPHA hb chains. What is Virchow's Triad? Three factors which contribute to Thrombosis: 1. Hypercoagulability 2. Hemodynamic changes (stasis) 3. Endothelial injury What factors are associated with Arterial thrombi? Venous? Arterial: 1. Turbulant Flow 2. Sticky Platelets Venous: 1. Decrease Flow 2. Concentration of coagulation factors What disorder results in uncontrolled systemic clotting and may also lead to hemorrhage as clotting factors are consumed? DIC: Disseminated Intravascular Coagulation Which blood disorder is characterized by petichiae and purpura, and may result in hemhorrage? Immune thrombocytopenic purapura (ITP). IgG antibodies coat the platelets, targeting them for removal, increasing bleeding risk. In this rare platelet disorder, platelet aggregate, occluding the small vessels. May be related to excess vWf. Thrombotic Thromocytopenic purpura (TTP) Platelet counts >600,000/mm^3, what could cause this? Thrombocythemia, may be caused by increased production of megakaryocytes. Normal neutrophil range? 2000/uL - 7500/uL Which are which? Bands, Segs Bands: Immature Neutrophils Segs: Mature Neutrophils If bands > segs, "left shift" Which infection is associated with lyphocytosis? Epstein-Barr Virus (Causes Mononucleosis) What are the four different categories of leukemia? What is the most common? Acute: Mostly immature WBCs Chronic: Mature but disfunctional WBCs Myelocytic: Mutation of Mono-, Granulocytes (also may interfere with RBCs and platelets) Lymphocytic: Mutation of Lymphocytes [AML, ALL, CML, CLL] - ALL is the most common Reed Sternberg cells must be detected for dx of this disease? Hodgkin's Lymphoma. Reed Sternberg cells are malignant cells derived from B cells. Most cases of lymphoma are of this type. What causes this type of lymphoma? Non-Hodgkins. In 85%, derived from B-cells, damaged proto-oncogenes and tumor suppressor genes. What is the most common type of non-Hodgkins lymphoma in children? Burkitt Lymphoma, a fast growing tumor of the jaw and facial bones. What is the Philadelphia chromosome? Breaks on chromosomes 9 and 22 allow a proto-onco gene from 9 to be transferred to 22, leading to chronic myelogenous leukemia (CML). Which type of breathing is characterized by deep, rapid breaths? What causes it? Kussmaul breathing. Caused by severe acidosis, renal failure. Which type of breathing is characterized by alternating patterns of heavy breathing and apnea? What causes it? Cheyne - Stokes respiration. May be caused by damage to central breathing centers or heart failure. What is ARDS? What causes it? Acute Respiratory Distress Syndrome. Caused by acute injury or inflammation to the lung (chemical inhalation, aspiration, trauma, septic shock) This disease is characterized by gradual scarring of the lungs, often by chronic exposure to lung irritants. Interstitial lung disease. Often present with SOB, dry cough. Differentiate between typical and atypical pneumonia. Typical: Bacteria in the Alveoli. May be lobar or bronchopneumonia (patchy distribution) Atypical: Virus, Mycoplasma in the alveolar interstitium Clearance of S. pneumonia relies heavily on which organ? The spleen. The spleen plays a role in B-cell generation, and is the main site of macrophage elimination of the bacteria. Which less common type of pneumonia is characterized by pneumonia as well as confusion, diarrhea and hyponatremia? Legionnaire Disease. Caused by inhalation of Legionella pneumophila (Gram -). Not transmitted person to person. What is a granuloma? A collection of macrophages, seen in many diseases- including tuberculosis, leprosy, and aspiration pneumonia. What is contained in a Ghon focus? What is a Ghon complex? Ghon focus: T Cells, Macrophages, Inactive TB bacteria Ghon complex: also includes lymph node involvement This is called the "consumption", it results in development of cavities in the lungs. Secondary Tuberculosis Why are lung cancers differentiated as small cell and non-small cell? Small cell cancers have usually spread by time of detection, greatly influencing treatment options. Why are small cell lung cancers associated with syndrome of inappropriate ADH secretion (SIADH)? Small cell lung tumors may have the ability to secrete hormones, suggesting they develop from the neuroendocrine cells of the bronchial epithelium. Which upper airway infection in children is associated with viral infection? How is it characterized? Croup. Characterized by inspiratory stridor, hoarseness, barking cough. Which upper airway infection in children is associated with certain bacterial infections, and is a medical emergency? Epiglottitis. Characterized by low-pitched stridor, and evident respiratory distress. Normal pO2? pCO2? pO2: >80mmHg. <60mmHg is hypoxemia. pCO2: 35-45mmHg. >50mmHg is hypercapnia In this form of traumatic pneumothorax, air enters the interpleural space from outside, but cannot leave. The trachea is deviated to the unaffected side. Tension Pneumothorax. This is a life-threatening emergency, as intrapleural pressure builds, pressing on the great vessels. Differentiate transudative and exudative pleural effusion. Exudative: fluid contains proteins and LDH, a marker of inflamed pleural tissue Transudative: fluid does not contain proteins or LDH Which type of lung cancer is associated with paraneoplastic hypercalcemia? Squamous cell: found most commonly in men. When does the following occur during development: Type II cells begin secreting surfactant? Sufficient terminal sacs present for survival? Type II cells begin secreting surfactant? 24 weeks Sufficient terminal sacs present for survival? 25 weeks Which disease develops as a result of damage from O2 therapy in the immature lung? Bronchopulmonary Dysplasia (BPD) Which antibody is associated with atopic/intrinsic asthma? IgE. What is Chylothorax? Empyema? Chylothorax: Lymph in the IPS Empyema: Pus/Purulent drainage in IPS Differentiate between "pink puffers" and "blue bloaters" with COPD. Pink Puffer: Emphysema; pursed lips to prevent alveolar collapse, barrel chest Blue Bloater: Chronic Bronchitis; cyanosis and fluid retention like right-sided heart failure (Cor Pulmonale). Which autonomic receptor produces broncho-constriction? Dilation? Ach: Broncho-constriction Beta 2 Adrenergic: Broncho-dilation Differentiate early- and late-phase reactions to an extrinsic asthma trigger (Type 1 hypersensitivity) : Early: Mast cell degranulation via IgE, bronchospasm, increased mucus Late: Inflammation, edema, decreased mucociliary function, cont'd bronchospasm Name some of the mechanisms of COPD development. 1. Inflammation -> fibrosis 2. Mucus gland hypertrophy 3. Loss of alveolar tissue 4. Loss of elastic tissue Which enzyme dysfunction is associated with COPD? alpha 1 - antitrypsin, in early development of emphysema, most pts have genetic decrease in this enzyme. What is Cor Pulmonale? Failure of the right-side of the heart due to chronic hypertension. This rare form of COPD is characterized by dilated bronchi and bronchioles due to destruction of muscle and elastic tissue. Bronchiectasis; develops with chronic infection, present with marked dyspnea, cyanosis and clubbing (not seen in other obstructive lung diseases). What is the inheritance pattern of Cystic Fibrosis? Autosomal Recessive. Carriers display no symptoms. What genetic abnormality appears in CF? Single gene mutation of Chr. 7, non-functioning epithelial Cl channel. Different effects in different organs. In the airways, mucus becomes excessively viscous. What is the progression of CF? Bacterial infections -> chronic bronchitis ->bronchiectasis -> respiratory failure What are the collateral consequences of the CF mutation? Abnormal pancreatic function leading to diarrhea and abdominal pain; hyperglycemia may lead to diabetes mellitus How are the interstitial lung d/os (restrictive d/os) different from the obstructive lung diseases? *Effects are seen in the collagen and elastic tissue of the alveolar interstitium *Difficulty in getting air IN due to decreased compliance What could cause metabolic acidosis, alkalosis? Acidosis: Inadequate perfusion Alkalosis: Diuretic therapy, Fluid loss What is the most common cause of INCREASED anion gap? Acidosis. Why doesn't loss of HCO3 increase anion gap? Loss of HCO3 is almost completely compensated by increased Cl (Hyperchloremic Acidosis) What causes chloride resistant metabolic alkalosis? Hyperaldosteronism, Bicarb retention Normal ranges: pH pCO2 pO2 HCO3 Anion Gap pH: 7.35-7.45 pCO2: 35-45mmHg p02: 80-100mmHg HCO3: 22-26mEq/L Anion Gap: 8-12 What are the three fluid chambers of the body? Intracellular Extracellular Intravascular How do you calculate osmolality? What is normal osmolality? Na x2, +glucose, +urea 275-295 Replace blood with: Replace plasma with: Resuscitate with: Replace ECF depletion with: Rehydrate with: Replace blood with blood. Replace plasma with colloid. Resuscitate with colloid. Replace ECF with saline. Rehydrate with dextrose soln. What causes these types of kidney stones? A. Calcium Oxalate B. MAP (Struvite)/Staghorn C. Uric Acid D. Cystinuric E. Indinavir Calcium Oxalate: Hypercalcemia Struvite: UTI w/ urease activity Uric Acid: Gout Cystinuric: Genetic mutation for cystine in urine Indinavir: This protease inhibitor (HIV drug) may increase risk of developing kidney stones What are the "Four C's"? Clinical Manifestation (Symptoms), Causes, Consequences (Direct), Collateral (Indirect) What is an Anchoring error? Focusing on the 1st abnormal finding What is an Availability error? Focusing on personal/anecdotal experience and knowledge. What is an Attribution error? Focusing on stereotypical data. Which type of receptor can be both ionotropic and metabotropic? Muscarinic Starting with G1, what are the four phases of the cell cycle, and what happens in each phase? G1: Period b/w Mitosis and DNA synthesis S: DNA Synthesis G2: RNA and Protein Synthesis M: Mitosis What do Growth Factors do? Stimulate proliferation, mediate inflammation, stimulate angiogenesis & chemoattract neutrophils, macrophages, fibroblasts, keratinocytes and epithelial cells Groups of cells clustered together with common or similar functions are called? Tissues Which highly differentiated cell types have lost their ability to divide? Muscle, Neurons What are the four cell types? Epithelial Connective Muscle Nerve Change in number of cells is called...? Hyperplasia Chance in form of cells is called...? Metaplasia: An adaptive, reversible response. Cells stay within primary tissue type, ie epithelium. Deranged, precancerous growth in which cells vary in size, shape and organization is called...? Dysplasia: An adaptive, reversible response. Cancerous growth is called...? Neoplasia The most common form of cellular injury is...? Hypoxia Which tumor supressor protein in over-expressed in several cancers? Retinoblastoma (Rb) Which type of necrosis involves protein denaturation, and where would you likely find it? Coagulative. Heart, Kidneys, Adrenal Gland Which type of necrosis is often seen in the brain? Liquefactive Necrosis Which kind of necrosis is a mixture of coagulative and liquefactive, and is seen in Tuberculosis? Caseous Necrosis Which type of necrosis is seen in Breast, Pancreas and Abdominal organs? Fat Necrosis Which term is applied when a considerable amount of tissue has undergone necrosis? Gangrene Dry gangrene is a form of...? Dry gangrene is caused by (A or V) interference? Coagulation Necrosis Arterial Wet gangrene is caused by interference of Arteries or Veins? Veins Gas gangrene most commonly results from infection of tissues by what bacterium? Clostridium perfringens Which apoptotic pathway is dependent on extracellular signals? Extrinsic Pathway What receptors are involved in the extrinsic apoptotic pathway? Tumor Necrosis Factor Receptor Fas Ligand Receptor What activated the intrinsic apoptotic pathway? DNA damage, hypoxia, decreased ATP and activation of p53 following DNA damage How many pairs of chromosomes does a human have? 23 Homologous Pairs How many base pairs in human DNA? 3.12 Billion Pairs All humans are what percent similar to one another? 99.9% The "useful" part of DNA is in the introns or exons? Exons How many genes in the human genome? 120,000 Which Autosomal Dominant disorder involves connective tissues, effecting three systems? Marfan Syndrome Name some autosomal recessive diseases. Tay-Sachs Cystic Fibrosis Albinism PKU Sickle Cell Anemia Name some x-linked recessive diseases. Hemophilia A Duchene Muscular Dystrophy Red/Green Colorblindness Fragile X Name an X-linked recessive disease. Faulty enamel trait The percentage of individuals with a certain genotype who express the expected phenotype is called...? Penetrance The variation in phenotype associated with a particular genotype is called...? Expressivity Expressivity may be caused by...? Modifier Genes Disorders of mitochondrial traits usually cause problems with what three tissue types? CNS, eye, muscle _______ traits are influenced by many genes, where as _________traits are influenced by the environment or lifestyle. Polygenic, Multifactorial Traits that are measure on a continuous numeric scale are...? Quantitative Coronary artery disease is an example of a ----------- disease. Multifactorial A disproportionate amount of mutations occur in ______ hotspots. C/G A somatic cell that does not contain a MULTIPLE of 23 has...? Aneuploidy; this includes Trisomies and Partial Trisomies Normal separation of chromosomes during cell division is called? Disjunction Failure of chromosomes to separate properly during cell division Nondisjunction Addition or loss of complete chromosome sets is called...? Euploidy; always fatal to the embryo An extra portion of a chromosome is present in the cell Partial trisomy Down Syndrome is also known as: Trisomy 21 Metafemales; may be sterile, have menstrual irregularity and/or mental retardation; appear the same as normal females Trisomy X, the most common sex-linked aneuploidy. Worsens with additional Xs. Which disorder is characterized by: Absence of ovaries Short stature Neck Webbing Edema Underdeveloped breasts; wide nipples Abortions Turner Syndrome, Only one X Chromosome Which disorder is characterized by: At least two X's and 1 Y Chromosome Male Phenotype Female Breasts Small Testes Sparse Body Hair Kleinefelter Syndrome These "super males" have a higher incidence of violence, IQs around 80, and are excessively tall Jacob's Syndrome, XYY Those born with this abnormality have microcephaly, mental retardation and low birth weight. Cru du Chat, Deletion of the Short Arm of Chromosome 5 Which type of tumors are named for the tissues of origination, ending with -oma? Benign Tumors Malignant epithelial tumors are known as...? Carcinomas Malignant connective tissue tumors are known as...? Sarcomas Rates of growth in tumor and normal tissue depend on what three things? 1. Number of cells actively dividing 2. Length of cell cycle (time) 3. Loss of cells : gain of cells By the time a tumor is detected by normal means, it has typically reached ---- cm in diameter, has doubled ---- times, and contains more than ---- cells. 1 cm, 30 times, 10^9 (1 billion) p53 damage may cause cancer because....? P53 is involved in the intrinsic apoptotic pathway. What are NORMAL genes, which code for proteins used in cell division? Proto-oncogenes When genes which normally code for proteins used in cell division become deregulated, they are called? Oncogenes The "guardian of the genome", which gene is the most common target for genetic alteration in human cancers? p53. Located on the short arm of chromosome 17, p53 prevents the survival of genetically damaged cells by triggering the intrinsic apoptotic pathway. Which tumor supressor gene is mutated in those who develop retinal cancer? Retinoblastoma (Rb) What happens in the promotion phase of oncogenesis? Mutated cells are stimulated to divide. What happens in the progression phase of oncogenesis? Mutated cells compete and develop more mutations, making tumor more aggressive. What factor, secreted by tumors, stimulates angiogenesis? VEGF: Vascular Endothelial Growth Factor Direct invasion of a tumor to contiguous organs is called...? Local Spread. Mechanical pressure and release of lytic enzymes decreases cell to cell adhesion, allowing the tumor to spread. Preferential growth of tumor in certain organs is known as...? Organ Tropism What is TNM staging? T: size of tumor N: Invasion of lymph nodes M: Level of Metasteses By the World Health Organization What is Cachexia and what causes it? Severe malnutrition and muscle wasting occurring in end-stage cancer, caused by TNF-alpha (tumor necrosis factor) Mutagenicity can be tested with what test? Ames Test for growth of Histidine-independent bacteria. What type of cells produce antibodies? B Cells, after being activated by CD4 Helper T Cells These infectious agents are eukaryotic, thick walled, and have a wide livable spectrum. Fungi What differentiated Specific vs. Nonspecific symptomatology? Specific: Local Nonspecific: Nonlocal What are the first, second and third lines of defense? 1st: Innate Immunity 2nd: Inflammation 3rd: Acquired Immunity What two receptors are involved in innate immunity? Toll-like Mannose These receptors recognize identical antigens on different microbes. How is the inflammatory process activated? Pattern Recognition Receptors (PRRs; usually Toll-like) of the host bind to Pathogen-Associated Molecular Patterns (PAMPs) initiating inflammatory response. Which Toll-like receptor is reactive to Lipopolysaccharide (LPS)? TLR4 Which factors of the complement system act as anaphylotoxins (cause degranulation) and chemotaxins (attract macrophages)? C3a, C5a Which factor of the complement system initiates the MAC attack? C5b Which coagulation pathway involves the activation of factor 12 to 12a? Intrinsic, collagen activated which system causes dilation of blood vessels, pain, smooth muscle contraction, vascular permeability, and leukocyte chemotaxis Kinin System Which cytokine protects against viral infection? Interferons. Interferons bind to unaffected cells and produce anti-viral protein. What is secreted by macrophages in response to PAMP activated toll-like receptor? TNF-alpha -> cachexia Which cytokine promotes inflammation, fever and sepsis? IL-1 Which cytokine acts as both a pro and anti inflammatory? IL-6 Which acute phase reactant protein aids in the clearance of necrotic and apoptotic cells, and activates the complement system? C Reactive Protein