path exam 6 Flashcards

Question

the threshold number of mutations is higher in...than in...

Answer 1

solid tumors than in hematological malignancies

Answer 2

oncogenes = promote cell proliferations and is the mutated (gain of function) form of proto-oncogenes (normal cell proliferation) tumor suppressor genes = inhibit cell division (mutation leads to inactivation so uncontrolled division), 2 groups: stop/slow cell proliferation or sensors of damage to genome regulators of apoptosis = control tissue mass by influencing cell survival genes that reg the interaction between tumor cells and host cells, esp recognition and destruction of tumor cells by host immune system

Answer 3

driver mutations = alters initiation and progression of cancer passenger mutations = alterations due to genomic instability but not involved in initiation or progression of cancer, can help id carcinogen in carcinogen-associated cancer, may confer selective survival advantage to specific tumor clones, and can produce altered proteins that elicit host immune responses

Answer 4

- growth factors - growth factors and hormone receptors - signal-transducing proteins (non-receptor tyrosine kinases) - transcription factors - cell cycle control proteins

Answer 5

proto-onc to --> onc - mutation in coding sequence --> hyperactive protein made in normal amts (RAS) - gene amplification --> normal protein greatly overproduced (MYCN, Her2) chromosome rearrangment - nearby reg DNA seq causes normal protein to be overproduced (BCL2 - follicular lymphoma, MYC- Burkitt lymphoma) - fusion to actively transcribed gene greatly overproduces fusion protein or fusion protein is hyperactive (BCR-ABL - chronic myeloid leukemia)

Answer 6

point mutations in RAS gene constitute the most common genetic abnormalities of oncogenes GTP binding proteins more than 30% of all tumors have muts in Ras (pancreas, colon, rectum, thyroid, and lung) codons 12, 13, 59, 61

Answer 7

for ex MYCN gene in neuroblastoma is found on chr 2p --> after amp, the gene can be seen as double minutes (cell divides and genes are lost) or as homogenous-staining region (HSR) that is integrated into chr

Answer 8

- fusion of TF or tyrosine kinase gene to normally unrelated gene --> CHIMERIC protein with oncogenic properties - repositioning of normally regulated genes next to CONSTITUTIVELY active gene promoters (Ig or T-cell receptor genes)

Answer 9

inhibit gene expression POST-TRANSCRIPTIONALLY

Answer 10

harbors oncogene MYC

Answer 11

harbors tumor suppressor gene (TP53)

Answer 12

overactive regulates tumor suppressor gene and leads to reduced activity of tumor suppressor protein reduced increase activity of oncogene because it can't inhibit it's gene expression

Answer 13

tumors become more aggressive over time tumors become less responsive to therapy over time

Answer 14

avoiding immune destruction --> immune activating anti-CTLA4 mAb evading growth suppressors --> cyclin dependent kinase inhibitors enabling replicative immortality --> telomerase inhibitors tumor-promoting inflammation --> antibiotic treatment of H. pylori activating invasion and metastasis --> inhibitors of HGF/c-Met genomic instability --> MDM2 and PARP inhibitors resisting cell death --> BCL2 antagonists inducing angiogenesis --> inhibitors of VEGF signaling deregulating cell energetics (cells able to keep growing even when there's not enough nutrients to maintain energy) --> aerobic glycolysis inhibitors sustaining proliferative signaling --> EGFR inhibitors

Answer 15

growth factor binds to growth factor receptor, triggers signal transduction of first messenger, signal transduction of second messenger, then transcription factor, DNA repair proteins, cell cycle control proteins, and apoptosis regulating proteins endpoints of this signaling = growth and replication, differentiation and maturation, tissue repair, apoptosis and involution, DNA repair and stability of genome, and cell metabolic processes

Answer 16

cancer may secrete their own growth factors (autocrine effect) or have stromal cells in the tumor microenvironment produce growth factors (paracrine effect) --> ex of autocrine = PDGF produced by glioblastoma many growth factor receptors act as oncoproteins when they are mutated or over-expressed, they are constitutively active mutations in signal transduction genes downstream of growth factors activates pathway without needing growth factor RAS is most commonly mutated oncogene in human tumors

Answer 17

the ones controlled by FB gene and TP53 gene at the G1-S checkpoint RB = governor of cell cycle TP53 = guardian of cell cycle no cell becomes neoplastic unless it deregs or bypas RB-TP53 mechanisms at G1-S

Answer 18

G1 = ensure integrity of genome intra S-phase = ensure proper DNA rep G2/M = correct post-rep erros mitotic = monitor chr alignment before segregation

Answer 19

gain of function mutations in cyclin D and CDK 4 loss of function in CDKIs at least one of 4 key regulators of cycle is mutated in cancers = p16, cyclin D, CDK 4, and RB

Answer 20

they are bi-allelic mutations so if one is inactivated, the other active one can compensate but if both are inactivated then that's when the mutation occurs AD cancer predisposition (risk) and AR at cellular or mutation level (developing cancer)

Answer 21

overactivity is always dominant --> single mutation even in proto-oncogene creates an oncogene --> activating mutation enables oncogene to stimulate cell survival and proliferation hyperactivity is always recessive --> first mutation event inactivates one TSG with no effect --> second mutation event inactivates other TSG --> two inactivating mutations eliminate TSG and stimulates cell survival and growth Knudson's 2 hit hypothesis, 2 hit only occurs in TSGs, but basically indvs who inherit a mutated gene develop cancers earlier in life because they are born with 1 allele already affected which also leads to loss of heterozygosity

Answer 22

- point mutations - deletions - loss of heterozygosity - hypermethylation - epigenetics - Knudson's "two hit" hypothesis

Answer 23

when cancers convert glucose to lactate via the glycolytic pathway despite ample O2

Answer 24

BCL6, BAX, BAK, are all PRO-apoptotic BCL2, BCL-XL are ANTI-apoptotic

Answer 25

telomerases prevent telomere shortening which is not normal active telomerases have been id in lots of cancers and allows them the ability to replicate indefinitely mutations in TERT promoter region account for upregulation of telomerases in cancer cells

Answer 26

by lack of O2 and expression of VEGF

Answer 27

refractive errors

Answer 28

bacterial infection = neutrophils allergy = eosinophils viral infection = lymphocytes chronic inflammation = giant cells and plasma cells

Answer 29

bacteria, fungi, viruses, protozoa descematocele

Answer 30

they can induce ulcers and keratitis

Answer 31

ciliary body --> pos chamber --> pupil ant chamber --> trabecular meshwork --> Schlemm's canal --> episcleral v (major) or uveoscleral route (minor) disruption anywhere = increase IOP --> optic n damage

Answer 32

eyelid cancers choroidal melanoma retinoblastoma

Answer 33

pinguecula and pterygium (solar degen) Fuch's endo dystrophy keratoconus

Answer 34

degene can be uni or b/l, typically NON-FAMILIAL dystrophy = b/l and hereditary

Answer 35

embryonic = chromosomal abnormalities and hormonal/environmental factors fetal - early = chromosomal abnormalities, cervical incompetence, and thrombophilia - late = placental pathology, congenital anomaly, and infection

Answer 36

1-4 years - ACCIDENTS with adverse effects - congenital malformations, deformations, and chromosomal abnormalities - HOMICIDE 5-9 years - ACCIDENTS and adverse effects - malignant neoplasms - HOMICIDE 10-14 years - ACCIDENTS and adverse effects - SUICIDE - malignant neoplasms 15-24 years - ACCIDENTS and adverse effects - HOMICIDE - SUICIDE

Answer 37

in early embryonic period (first 3 wks after fertilization) = injurious agent either damages enough cells to cause and abortion OR damages only a few cells, allowing for recovery without defect between 3-12 wks, embryo/fetus are more susceptible due to organogenesis after 12 wks, structures of organs are mostly formed but functional defects in organs can still occur along with minor structural abnormalities ex of environmetal teratogens and genetic defects - valproic acid = antiepileptic drug that disrupts expression of transcription factors aka HOX proteins which are important for patterning of limb, vertebrae and craniofacial structures, mutations will cause congenital anomalies - vit A = essential for development and differentiation, absence of excessive exposure during development results in malformations of multiple organ systems like use of retinoic acid for acne during pregnancy can cause CNS defects, craniofacial defects

Answer 38

immature and have high risk of hypothermia and hypoglycemia

Answer 39

preterm premature rupture of membranes (PPROM) --> prior Hx of PPROM, vaginal bleeding, maternal smoking, low socioeconomic status, poor maternal nutrition, and immune regulatory gene polymorphisms intrauterine infections (chorioamionitis and villitis) --> inflammation triggers labor anatomic abnormalities of cervix and placenta --> bicornuate uterus, fibroids, placenta previa, abruption multiple gestations

Answer 40

group 1 - hydrophilic glycoproteins SP-A and SP-D - play a role pulm host defense group 2 - hydrophobic surfactant proteins SP-B and SP-C - involved in reduction of surface tension at air-liquid barrier in alveoli of lung - reduced surface tension causes less pressure required to keep alveoli open

Answer 41

fetal anemia = fetal blood sampling followed by IN UTERO TRANSFUSION fetal arrhythmia = meds like diogxin, sotalol, propanolol, flecainide, amiodarone intrinsic thoracic malformations = THORACENTESIS or THORACOAMNIOTIC SHUNT for pleural effusions in select cases twin-twin transfusions = fetoscopic LASER ABLATION of communicating vessels syphilis = penicillin

Answer 42

caput succedaneum cephalhematoma

Answer 43

more benign than malignant -mesenchymal or germ cell derived (hemangiomas, benign mature teratomas) - leukemia/lymphoma - brain tumors - neuroblastoma - wilms tumor (nephroblastoma)

Answer 44

serial or continuous separation of donor's blood into components using specialized equipment, harvesting specific blood elements and reinfusing remainder back into donor allows for higher yield collection than traditional whole blood separation techniques

Answer 45

separated from whole blood or via apheresis collected into sterile collection bag with anticoagulant and one unit can be stored for 35-42 days and at 1-6 degress C as they progress through their shelf life, they will gradually leak K+ almost always LEUKOREDUCED which reduces formation of Ab against foreign HLA Ag, decrease febrile transfusion rxns, and reduce infections (CMV) RBCs can be washed to remove up to 95% of plasma proteins, for pxs with history of SEVERE ALLERGIC RXNS or IgA DEFICIENCY can be frozen and stored for more than 10 years

Answer 46

collection from units of whole blood are pooled --> therapeutic dose made by pooling platelets from 4-8 whole blood units apheresis platelets are single donor units stored on an agitator at 20-24 degrees c for 5 DAYS (SHORT LIFE) --> day 5 gives same platelet count as day 1, pH will decreased during storage due to accumulated lactic acid can also be washed to remove plasma proteins which results in loss of >25% platelet number and function post-transfusion platelet count can be checked 10-60 mins following transfusion goal = increase px's platelet count. by 15-25k/mL at 1 hr

Answer 47

fewer donor exposures lower risk of bacterial contamination/sepsis fewer donor RBCs in unit

Answer 48

plasma from apheresis collection or whole blood is separated and frozen within 8 hrs, resulting in fresh frozen plasma (FFP) stored of <-18 degrees C for up to a year after thawing, FFP can be stored for 24 hrs at 1-6 degrees C or 4 hrs at 20-25 after 24 hrs = thawed plasma that can be kept for additional 4 days (unlicensed by FDA) contains coagulation factors and other plasma proteins for normal hemostatic and fibrinolytic activity common indications for FFP - coagulation factor replacement in massive transfusion, DIC, liver disease - used for plasma exchange, like TTP - used to supply deficient factors when no factor concentrates are available

Answer 49

never frozen before collected from whole blood and stored btwn 1-6 degrees C for 26-40 days, depending on anticoagulant used for storage used within 14-21 days, due to PROGRESSIVE FACTOR LOSS clinical indication = initial tx of HEMORRHAGING PXS who will need massive transfusion

Answer 50

made by slowly thawing FFP at 6 degrees C groups of proteins precipitate during this process, including factors VIII and XIII, as well as FIBRINOGEN and vWF - separated by centrifugation, suspended in small amt of plasma and refrozen - must be stored frozen until it is ordered for clinical use - after thawing, must be used within 6 hrs cryprecipitate has these factors at 2-9x higher conc than regular plasma (not simply concentrated plasma) each unit at >150 mg FIBRINOGEN, so each dose should INCREASE FIBRINOGEN level

Answer 51

whole blood = ACTIVELY BLEEDING TRAUMA pxs who anticipate total blood vol loss is >15% RBCs = SYMPTOMATIC ANEMIA in pxs who require an increase in O2 carrying capacity and red cell mass platelets = bleeding in pxs with THROMBOCYTOPENIA, DEFECTIVE PLATELETS and for prophylaxis against bleeding FFP = bleeding or prophylaxis in pxs with FACTOR DEFICIENCIES cryoprecipitate = FIBRINOGEN deficiency

Answer 52

occurring during or within 24 hrs of transfusion difficult to apply single simple algorithm for specific types of rxn signs and symptoms may include = dyspnea, vol overload, fever, malaise, hypotension/shock, urticaria/hives, pain

Answer 53

unidentified Ab, an incompatible crossmatch, or free urine Hb suggests HTR

Answer 54

accelerated destruction of transfused RBCs due to Ab-mediated incompatibility acute (within 24 hrs) or delayed (24 hrs to 28 days) non-immune causes - osmotic - thermal - mechanical - RBC membrane or enzyme disorders - microangiopathic hemolytic anemias (TTP) - infections

Answer 55

iatrogenic rapid increase in circulating vol --> blood products appear to cause circulatory overload more quickly than other fluids transfused vol overloads heart --> L ventricular diastolic vol increases --> increased hydrostatic pressure in pulm caps --> forces transudate across cap walls and into alveoli --> gas exchange impeded by pulm edema, leading to respiratory distress, dyspnea, and hypoxia lungs are first organ to be symptomatic HTN and tachycardia are result of sympathetic activation as a result of decrease cardiac output via baroreceptor reflexes

Answer 56

inability to comp of sudden increase in circulating vol - extreme ages = young children more prone and elderly with comorbidities that limit comp (atherosclerosis/decreased arterial elasticity, blunting of baroreflexes, physiological decline of renal fxn) - fluid balance = baseline vol status is important factor in developing TACO, hypovolemic pxs should be able to comp - renal and cardiac dysfunction = chronic renal disease --> peripheral edema and chronically increase vol, diuresis can be impaired, cardiac dysfunction --> decreased handling of increased preload --> CHF - transfusion vol and rate = non-emergency settings, rate can be decreased, allowing px to accommodate transfused vol

Answer 57

two hit model first hit is px's underlying clinical condition (sepsis, cardiac surgery, liver surgery, history of liver disease, chronic alc abuse, shock, older age, smoking, high peak airway pressure while on vent, pos intravasc fluid balance, SYSTEMIC INFLAMMATION - increased IL-6,8, and CRP - dysreg of CD4+ cells or dendritic cells, decreased IL-10) second his is exposure to substances in transfused products - anti leukocyte Abs = HLA class II and I ab, HNA Ab, and granulocyte Ab - biological response modifiers = bioactive lipids, mt damage associated molecular patterns, extracell vesicles, aged cell blood products (ceramide, CD40 ligand) both hits together via immunological mechanisms results in damaged lung endo --> increased permeability --> pulm edema --> acute resp distress and ALI

Answer 58

removal of plasma from px's blood not for purposes of donation but to remove a substance or substances and/or provide missing substances these include = pathogenic Igs, immune complexes, and cytokines for most efficient clearance from plasma, substance should - be able to be id and assayed - have high molecular weight - have low distribution vol - half long half life - have low turnover rate degree of substance removal DOES NOT always correlate with alleviation of symps goal is to exchange 1-1.5x px's total plasma vol to remove 65-70% of target substance removed plasma is exchanged with - albumin (lower freq allergic rxns, no risk of infection) - FFP or liquid plasma - saline citrate is main anticoagulant in apheresis but because it chelates Ca2+, it can lead to HYPOCALCEMIA

Answer 59

I = disorders where apheresis is accepted as 1st line therapy (GBS, Goodpature's, catastrophic antiphospholipid Ab syndrome, hyperviscosity in hypergammaglobulinemia, myasthenia gravis, NMDA receptor Ab encephalitis, TTP - give ADAMTS13 - fulminant wilson's disease, acute liver failure II = disorders which apheresis is accepted as second-line therapy (refractory thyroid storm, ANCA, thrombotic microangiopathy-complement mediate, autoimmune hemolytic anemia) III = role of apheresis is not established, no evidence IV = disorders in which apheresis is ineffective or harmful

Answer 60

axons remain intact neuron cell body remains myelin is lost --> causes conduction block ex: acute like GBS or chronic like Charcot-Marie-Tooth

Answer 61

axon connection to neuronal cell body is lost can be traumatic or degenerative clinical ex = acute - trauma (something that cuts thru n fibers and sever axonal connections to neuronal body)

Answer 62

occurs after injury either due to - poor approximation and repair of injury - extensive injury (not able to repair) proximal n regens into tangled mass of n fibers that does not meet the distal end PAINFUL mass path features = admixed mass of fibroblasts, axons, Schwann cells and scar tissue TRICHROME shows disorder orientation of n fiber

Answer 63

type I = slow twitch fiber slow contraction, repetitive, DO NOT fatigure easily rich in mt, myoglobin, and oxidative enzyme stains darkly with ATPase 4.3/4.6 type II = fast twitch fiber fast conduction, fatigues early, specialized for FINE SKILL MOVEMENT poor in mt, myoglobin, and oxidative enzymes stains darkly with ATPase 9.4

Answer 64

vacuolization vacuoles may form in many conditions like glycogen storage diseases, other storage disease, and organelle accumulation or dysfxn fiber hypertrophy increased load, physiologic /iatrogenic or pathologic phys/iatro = weightlifting, exercise, males patho = early stages or many myopathies to compensate for muscle fiber loss

Answer 65

muscle weakness abnormality in motor neuron paths - poliomyelitis - ALS - spinal muscular atrophy abnormality in neuromuscular synapse - myasthenia gravis abnormality in muscle fiber proper - muscular dystrophy eval disorders - clinical hx - determine pattern of transmission - special studies = molecular genetic tests, EMG, lab tests, muscle biopsy

Answer 66

polymyositis (w/o skin) dermatomyositis (w/ skin) inclusion body myositis diseases may occur on their own or as a component of an immune mediated systemic disease like systemic sclerosis most have immune component

Answer 67

building block cell of the CNS responsible for form and structure forming BBB forming gliosis (scar) in response to CNS injury silver stain will show long cytoplasmic processes

Answer 68

form the myelin sheath in the CNS concentrated in the white matter and appearing to be lines (linear) as they form around the axons look like a fried egg on histo

Answer 69

cells that line the ventricular spaces have cilia and terminal bars responsible for regulation of CSF flow in and out of ventricular spaces

Answer 70

phagocytic cells that act as the macrophages of the CNS normal brain, there's not many in response to insult, they will activate and form MICROGLIAL NODULES which are common in viral infections like encephalitis, fungal infections, and some autoimmune diseases on histo they might have tails or projections

Answer 71

malformation = primary, tissue that was never normal, formed abnormally INTRINSIC abnormality occurs during development --> 50% cases of unknown etiology, 80-90% die in utero, ex: spina bifida and heart defects disruption = secondary, tissue was growing normally until something external affected it --> resulted from destruction of normally developed brain and are caused by external factors ex: infections, chem exposure, radiation, hypoxia/ischemic injury, amniotic bands like TORCH infections, retinol in pregnancy, and trauma deformation = caused by mechanical forces on normal tissue biochem factors low risk of recurrence in siblings most commonly due to uterine constraint because the fetus is growing faster than the uterus ex: clubfoot

Answer 72

failure of closure of neural tube of folic acid deficiency

Answer 73

infarction = ischemic tissue necrosis localized to a particular territory of vascular supply ischemic infarction - gross = 8-48 hrs, poor demarcation between gray and white matter, edematous SWELLING and vascular congestion, 2-10 days = tissue softening -micro before 6-12 hrs = no histo changes 6-12 hrs = acute ischemic neuronal injury (eosinophilic cytoplasm, dispersed Nissl substance, shrunken nucleus, no visible nucleolus) 24-48 hrs = neutrophils (rarely see this stage) 48 hrs+ = macrophages replace neutrophils 10 days + = reactive gliosis and macrophages (cavitation) a

Answer 74

for spontaneous intracranial hemorrhage, HTN is the most common cause

Answer 75

contusion = direct parenchymal injury crest of gyri that comes into contact with bony protuberances - frontal poles - orbital surface of frontal lobes - temporal poles

Answer 76

gliomas - astrocytoma - ependymoma - oligodendroglioma primitive neuroectodermal tumors - medulloblastoma other tumors - meningioma - acoustic neuroma/Schwannoma metastatic tumors

Answer 77

BAP1 mutations

Answer 78

detailed exam of an indv who died with an emphasis on the manner of death in addition to cause of death 3 basic components - scene/death investigation - autopsy - toxicology does not require family consent not performed on an embalmed body

Answer 79

disease, injury, or combo of conditions that leads to death of an indv divided into - immediate COD = condition that occurred last and immediately resulted in death (result of underlying cause) - intermediary COD = condition that was caused by underlying COD and resulted in immediate COD - underlying COD = condition that started the downhill course of events leading to death ex - intermediate COD = cardiac tamponade - intermediary COD = ruptured MI - understing COD = atherosclerotic CAD

Answer 80

include terminal events, nonspecific anatomic processes, and nonspecific physiologic derangements that result in death can be listed as immediate or intermediary COD with exception of terminal event terminal event = final common path of death like cardiopulm arrest, asystole, and respiratory arrest --> DO NOT REPORT ON CERTIFICATE nonspecific anatomic processes = like pneumonia and cirrhosis nonspecific physiologic derangements = non-anatomical findings like hyperkalemia and hypoglycemia

Answer 81

class of death based on how the cause of death came about - natural - accident (falls, overdose, traffic collision) - suicide - homicide - undetermined indvs with sig natural disease and illicit substance detected on toxicology should be classed as ACCIDENT as well as indvs with sig falls/trauma that results in sudden decline in their health from baseline manner must match underlying COD ex: indv dies as a result of urosepsis that originated from an infect indwelling urinary catheter. indv is paralyzed from being shot in the spine by another indv 20 years ago. manner of death is HOMICIDE.

Answer 82

infants child abuse all homicides unid bodies decomp bodies mass fatalities/plane crashes gunshot wounds

Answer 83

femoral or peripheral blood if antemortem present if not, heart or cavity blood blood sample for toxicology = gray top tube (sodium fluoride) --> prevents degradation of certain drugs vitreous electrolyte sample = red top tube (no preservatives_ --> can help detect hyperglycemia, dehydration, renal failure, etc.)

Answer 84

green discoloration - 24-36 hrs due to sulfhemoglobin firmed when hemoglobin binds to hydrogen sulfide (produced by microbes breaking down organic matter without O2) marbling = vein pattern, green to purple, due to breakdown of blood and reaction of Hb and hydrogen sulfide bloating skin and hair slippage, blister formation greenish-black discoloration of entire body mummification = occurs when body has been left in very dry, hot environment adipocere = formed in cold and wet climates secondary to hydrolysis of fats by CLOSTRIDIUM species --> gray waxy substance (grave wax)

Answer 85

flies most commonly associated eggs laid 1-2 days after death eggs hatch and become larvae in 1-3 days maggots undergo 3 growth phases, 6-10 days, getting larger until pupation pupae hatch into flies 12-18 days

Answer 86

early (24-48 hrs postmortem) - absent rigor, fixed livor - green discoloration of RLQ of ab - marbling begins - mild purge fluid from body orifices - early skin slippage - drying of fingertips, lips, genitalia, in dry climates mod (48-72 hrs) - generalized bloating - diffuse green-black discoloration of head and neck - significant purging of fluids - vesicle formation and skin slippage - protrusion of tongue and distention of ocular globes advanced (> 4-5 days) - continued progression of above changes - hot and dry = mummification - cold and wet = adipocere formation - skeletonization

Answer 87

entrance round or ovoid central perforation (missing skin) abrasion ring soot, muzzle imprint stippling (gunpowder tattooing) internal beveling of bone close has more condensed stippling while intermediate range has more dispersed stippling distant/indeterminate range has no soot or gunpowder around wound but has abrasion exit IRREGULAR, usually can reapprox the wound edges radiating lacerations no gunshot residue external beveling of bone shored exit wounds injury depends on 3 principles amount of energy --> KE = 1/2 mv^2 anatomic location cavitary effect - temporary cavity = laceration or contusion - permanent cavity

Answer 88

incised wounds = cut, slash --> wound LONGER than it is deep stab wound = caused by pointed instrument with or without sharp edge --> wound DEEPER than it is long chop wounds = caused by heavy object with cutting edge

Answer 89

one of the most pernicious air pollutants formed by rxn of nitrogen oxides and volatile orgo compounds in presence of sunlight toxicity due to production of free radicals, which injure epi cells along respiratory tract

Answer 90

radon - radioactive gas from uranium present in soil and homes - lung cancer in uranium miners - low level chronic exposures in home won't increase lung cancer risk for nonsmokers formaldehyde in manufacturing of building materials - classed as carcinogen for humans and animals - high concs, causes breathing difficulties and eye irritation

Answer 91

phase I = chemicals undergo hydrolysis, oxidation, and reduction most important catalyst of phase I rxn is CYTOCHROME P-450 located in the smooth ER of liver --> can detoxify xenobiotics or convert xenobiotics into active compounds that cause cell injury, bot rxns may produce ROS which can cause cellular damage CYPs participate in metabolism of acetaminophen, barbiturates, warfarin, anticonvulsants, and alc drugs, smoking and alc activate oxidation by binding to nuclear receptors fasting or starvation inhibition oxidation phase II = products of phase I rxns are often metabolized into water-soluble compounds thru - glucuronidation, sulfation, methylation, and conjugation with glutathione - WATER-SOLUBLE COMPOUNDS READILY EXCRETED

Answer 92

arsenic = herbicides cadmium = fertilizers

Answer 93

lead = bone, blood, nervous system, GI, and kidney mercury = CNS and kidney arsenic = GI, nervous system, skin, heart, and cancer cadmium = lung, kidney, bone

Answer 94

COTININE a metabolite of nicotine second hand smokers = increased risk of lung cancer, coronary atherosclerosis, and MI tobacco effect is dose dependent effects that is expressed as pack-years, average number of cigarette packs smoked each day multiplied by number of years of smoking cessation of smoking - greatly reduces, within 5 years, overall mortality and risk of death from cardiovascular diseases - lung cancer mortality decreases within 5 years, but excess risk persists for 30 years

Answer 95

MI increase platelet aggregation increased O2 demand decreased threshold for ventricular fibrillation decreased myocardial O2 supply - sig lung disease - hypoxia related to the CO content of cigarette smoke

Answer 96

drunk driving = conc of 80 mg/dL (.08%) in blood drowsiness occurs at 200 mg/dL stupor at 300 mg/dL coma and possible respiratory arrest can occur at higher levels mutated ALDH2*2 reduces acetaldehyde dehydrogenase activity significantly indvs homozygous for ALDH2(2 allele are completely UNABLE to oxidize acetaldehyde and CANNOT TOLERATE ALC, experiencing nausea, flushing, tachycardia, and hypervent acetaldehyde is responsible for some acute effects of alc and for development of oral cancers alc oxidation by alc dehydrogenase causes - reduction of NAD to NADH NAD is required for fatty acid oxidation in liver --> deficiency is main cause of accumulation of fat in alcoholics (steatosis, fatty liver) NAD is required for conversion of lactate into pyruvate --> increase in NADH/NAD ration in alcoholics also cause lactic acidosis

Answer 97

acute = CNS, liver, and stomach mainly in CNS --> alc is depressant first affecting subcortical structures, stimulation and disordered cortical, motor, and intellectual behavior higher blood levels lower medullary centers are depressed and respiratory arrest may follow reversible hepatic and gastric changes fatty change or hepatic steatosis acute gastritis and ulceration chronic = liver, GI, pancreas, CNS, PNS, alcoholic baby syndrome, cancer, malnutrition (thiamine and vit Bs) liver is main site of chronic injury - fatty change - alcoholic hepatitis - cirrhosis --> portal HTN and increased risk of hepatocellular carcinoma GI = massive bleeding from gastritis, gastric ulcer, or esophageal varices acute and chronic pancreatitis bc alc is empty calories, chronic alcoholism leads to malnutrition and nutritional deficits, particularly B vits dilated congestive cardiomyopathy increase incidence of HTN decreased levels of HDL, increasing the likelihood of CHD

Answer 98

ALDH2*2 higher risk for developing cancer of ESOPHAGUS

Answer 99

warfarin (antagonist of vit K) dabigatran (direct inhibitor of thrombin) - bleeding - thrombotic complications like emboli warfarin is inexpensive and its effects are easy to monitory but many drugs and foods rich in vit K either interfere with its metabolism or block its fxn

Answer 100

estrogen with progestogen - combo of these will increase risk of breast cancer in women after 5-6 years - estrogen alone in women is hysterectomy is associated with borderline reduction of breast cancer - MHT may have protective effect against atherosclerosis and coronary disease in women younger than 60 but should NOT be used for prevention of cardiovascular disease or other chronic conditions MHT increases risk of stroke and venous thromboembolism, like DVT and PE - more common during frst 2 years of tx - women who have other risk factors like immobilization and hypercoagulable states caused by prothrombin or factor V Leiden mutations

Answer 101

always contain small amount of estradiol and some progestin act by inhibiting ovulation or preventing implantation transdermal and implantable formulations also available OCPs minimally increase risk of breast cancer has a protective effect against these endometrial and ovarian tumors may increase risk of cervical cancers in women infected with HPV thromboembolism - hypercoagulable state induced by elevated hepatic synthesis of coagulation factors - increases risk of venous thrombosis and pulm thromboembolism - higher risk with 3rd gen OCs that contain synthetic progestins - in in women who are carriers of factor V Leiden mutation - risk lower than risk of thromboembolism associated in pregnancy cardiovasc = risk doubles in women older than 35 years who smoke hepatic adenoma = rare benign hepatic tumor (risk of BLEEDING)

Answer 102

contains testosterone which inhibits the production and release of LH and FSH, increases amt of estrogen - stunted growth - gynecomastia and testicular atrophy - growth of facial hair and menstrual changes - psychiatric disturbances - MI - hepatic cholestasis in invds receiving oral anabolic steroids

Answer 103

detox in liver by phase II enzymes and is excreted in urine as glucuronate or sulfate conjugates about 5% or less is metabolized through activity of CYPs to NAPQI (highly reactive metabolite that is very toxic to the liver and normally conjugated with glutathione) accumulation of NAPQI causes hepatcellular injury, leading to centrilobar/zone 3 necrosis that may progress to liver failure clinical manifestations - n/v, diarrhea, and sometimes shock - jaundice in a few days - overdoses can be treated in FIRST 12 HOURS by administration of N-ACETYLCYSTEINE which restores GSH levels - centrilobular necrosis may extend to entire lobules, causing liver failure, so liver transplant is only tx

Answer 104

ingestion of 2-4 gm by children and 10-30 gm by adults may be fatal acute salicylate overdose - resp alkalosis due to stim of resp center in medulla (hypervent) - followed by metabolic acidosis and accumulation of pyruvate and lactate metabolic acidosis enhances formation of non-ionized forms of salicylates which diffuse into brain and produce effects from nausea to coma chronic aspirn toxicity - 3 gm or more daily for long periods - HAs, dizziness, ringing in ears, hearing impairment, mental confusion, drowsiness, convulsions and coma - n/v, diarrhea, erosive gastritis, ulceration and GI bleeding (aspirin inhibits COX = reduced PGE2 which protects stomach mucosa) - bleeding tendency bc it acetylates platelet cyclooxygenase and irreversibly blocks production of thromboxane A2 (activator of platelet aggregation)

Answer 105

tubulointerstitial nephritis with renal pap necrosis aka analgesic nephropathy

Answer 106

intense euphoria and stim no physical dependence profound psychological withdrawal dopaminergic and adrenergic effects facilitates neurotransmission in CNS where it BLOCKS REUPTAKE OF DOPAMINE and at adrenergic n endings where it BLOCKS REUPTAKE OF EPI AND NOREPI while stimulating presynpatic release of norepi can cause tachycardia, HTN, and PERIPHERAL VASOCONSTRICTION myocardial ischemia by coronary a vasoconstriction and by enhancing platelet aggregation and thrombus formation cigarette smoking potentiates cocaine-induced coronary vasospasm lethal ARRHYTHMIAS dilated cardiomyopathy CNS = hyperpyrexia and seizures can also lead to perforation of nasal septum in snorters and decreased lung diffusing capacity in those who inhale the smoke decrease blood flow to placenta, resulting in fetal hypoxia and spontaneous abortion impaired neuro development in fetus or chronic drug users

Answer 107

CNS = euphoria, hallucinates, somnolence, and sedation binds to mu opioid receptor at neuron and blocks pain sudden death - profound resp depression, arrhythmia, and severe pulm edema pulm injury - pulm edema - abscess and infections - foreign body granulomas from talc skin and subcutaneous tissue - acute = abscesses, cellulitis, and ulcerations due to subcutaneous injections - chronic = scarring, hyperpig, and thrombosed veins heart valves most common = R-sided heart valves particularly TRICUSPID, most common agent = S. aureus liver = viral hepatitis thru sharing of needles lungs HIV kidney - amyloidosis (secondary to skin infection - focal and segmental glomerulosclerosis - induce proteinuria and nephrotic syndrome

Answer 108

induces dopamine release feeling of euphoria followed by a crash long term use leads to violent behaviors, confusion, paranoia, and hallucinations

Answer 109

leaves of Cannabis sativa plant, contains THC in CNS --> distorts sensory motor coordination for first few hrs chronic use can cause cognitive and psychomotor impairments like inability to judge time, speed, distance potential use to treat nausea secondary to chemotherapy and decrease IOP resp = laryngitis, pharyngitis, bronchitis, cough and hoarseness, and asthma-like symps, carcinogenesis, more inhaled tar compared to cigarettes cardio = increases HR and sometimes BP, may cause angina in ppl with CAD

Answer 110

superficial (1st degree) = epidermis partial thickness (2nd degree) = involve injury to dermis (pink or mottled with BLISTERS -wet and red- and PAINFUL) full thickness (3rd degree) = extend to subcutaneous tissue, sometimes muscle (white or charred, dry, and PAINLESS) pxs usually die due to infections shock in large burns/orthostatic hypotension --> rapid shift of body fluids into interstitial compartments due to systemic inflammatory response syndrome sepsis = MOST COMMON CAUSE OF DEATH specifically P. aeruginosa resp insufficiency = pulm edema hypermetabolic state = results in ecess heat loss and increased need for nutrition injury to airways and lungs within first 24-48 hrs = direct effect of heat on mouth, nose, and upper airways inhalation of heated air and noxious gases in smoke water-soluble gases can produce inflammation and swelling in upper airways, which may lead to partial or complete air obstruction lipid soluble gases are more likely to reach DEEPER airways, producing pneumonitis hypertrophic scars and itching

Answer 111

prolonged exposure to elevated temps can result in heart cramps, exhaustion, and strokes craps = loss of electrolytes via sweating, cramping of voluntary muscles usually due to vigorous exercise exhaustion = hyperthermic syndrome, dehydration causes hypovolemia and sudden collapse after period of collapse, equilibrium is re-established if person is able to rehydrate stroke = high temp, humidity, exertion, and high mortality older adults, young athletes, ppl with cardiovasc disease are at high risk thermoregl mechanisms fail, temp rises to more than 40 degrees C, leading to multiorgan dysfxn that can be rapidly fatal HYPERTHERMIA IS ACCOMPANIED BY GEN VASOCONSTRICTION hyperkalemia, tachycardia, arrhythmias sustained contractions of sk muscle can exacerbate hyperthermia and lead to muscle necrosis

Answer 112

RYR1 heat strokes deranges RYR1 function and allows Ca2+ to leak into cytoplasm stims muscle contraction and heat production inherited mutations in RYR1 occur in malignant hyperthermia which is heat-stroke like rise in body temp and muscle contractions tx = muscle relaxants

Answer 113

exposure to low temps seen in many homeless ppl high humidity, wet clothing, alc intake lowers body temp fast loss of consciousness at low body temp, followed by arrhythmia direct effects = physical disruptions within cells by high salt concs caused by crystallization of intra and extracellular water indirect effects = circulatory changes which vary depending rate and duration of temp drop - slow chilling = TRENCH FOOT --> causes gangrene that requires amputation - sudden, persistent chilling = vasc injury and edema only after rewarming and gangrene of foot or toes

Answer 114

nonionizing = UV and infrared light, microwave, and sound waves, can vibrate ATONS in a molecule ionizing = MOVES ELECTRONS and leads to electron cascade at equivalent amts of energy, alpha particles induce heavy damage in a restricted area, whereas x-rays and gamma rays dissipate energy over a longer, deeper course, and produce considerably less damage per unit of tissue altho effect of radiant energy is cumulative, divided doses allow cells to repair some damage between exposures smaller doses delivered to larger fields may be fatal but vice versa is tolerable in dividing cells (gonads, bone marrow, lymphoid tissue, and GI mucosa), DNA damage causes upreg of p53 which will upreg expression of genes that lead to cell cycle arrest or cell death

Answer 115

from most to least susceptible to radiation lymphoid system - lymphopenia and shrinkage of lymph nodes and spleen within hrs hematopoietic system - acute dose dependent marrow aplasia = first reduced neutrophils, platelets, and RBCs - high doses = aplastic anemia GI system CNS common sites for fibrosis after radiation = lung, salivary glands after radiation for head and neck cancer, and colorectal and pelvic areas after treatment for cancer of prostate, rectum, or cervix

Answer 116

primary = one or all essentials are missing from diet secondary = conditions like malabsorption, impaired utilization or storage, excess loss, or increased needs for nutrients

Answer 117

thiamine, pyridoxine, folate, and vit A

Answer 118

if weight falls below 3 SD or normal is considered malnourished may be determined according to BMI = weight in kg/height in m^2

Answer 119

small bowel - in KWASHIORKOR, rarely in marasmus - mucosal atrophy and loss of villi and microvilli - DISACCHARIDASE deficiency which impairs digestion so infants initially may not reponse well to full-strength, milk based diets bone marrow - BOTH kwashiorkor and marasmus - hypoplastic, mainly result of decrease number of red cell precursors - mild to mod anemia due to deficiencies of iron, folate, and protein suppressive effects of infection depending on predom factor, red cells may be microcytic, normocytic, or macrocytic brain - infants who are born to malnourished mothers - and who suffer PEM during first or 2nd years of life (cerebral atrophy) thymic and lymphoid atrophy - more marked in KWASHIORKOR than marasmus

Answer 120

vit D from precursor steroids vit K from biotin by intestinal microflora niacin from tryptophan

Answer 121

maintenance of norm vision reg of cell growth and differentiation plays an important role in orderly differentiation of mucus-secreting epi when deficiency state exists, epi undergoes SQUAMOUS METAPLASIA to KERATINIZING EPI reg of lipids FA metabolism and drug metabolism most important is beta-carotene fxn as photoprotective and antioxidant agents tx of skin disorders like severe acne and psoriasis 13-cis retinoic acid has been used in tx of childhood neuroblastoma host resistance to infections ex - can reduce morbidity and mortality from some forms of diarrhea - in preschool children with measles, supplementation can improve the clinical outcome

Answer 122

maintenance of adequate plasma levels of calcium and phosphorus to support - metabolic fxns - bone mineralization like rickets (in children whose epiphyses have not already closed) and osteomalacia (in adults) - norm neuromuscular transmission (hypocalcemia tetany) major soruce = cholecalciferol (vit D3) from 7-dehydrocholesterol indvs with dark skin have lower level of vit D production because of melanin pigmentation deep-sea fish, plants, and grains contribute small fraction of required vit synthesis of vit D from 7-dehydrocholesterol in skin and absoprtion from foods and supplements in gut conversion of vit D into 25-hydroxycholecalciferol in liver via 25-HYDROXYLASE 25-OH-D into 1,25-dihydroxy vit D, most active form of vit D, by 1 ALPHA HYDROXYLASE LOW Ca2+, LOW PHOSPHATE, and high PTH induces 1 alpha hydroxylase kidney failure leads to decreased 1 alpha hydroxylase and vit D3 1,25-dihydroxy vit D binds to high-affinity nuclear receptor which associates with vit A receptor --> immunomodulary and antiproliferative effects

Answer 123

stim intestinal absorption in duodenum stim reabsorption in DISTAL TUBULES of kidney reg blood Ca2+ thru bone resorption both 1,25-dihydroxy vit D and PTH induce release of calcium and phsophorus into circulation effects of vit D on bone depend on plasma levels of Ca hypocalcemia = Ca resorption normocalcemia = Ca deposition mineralization of bone mineralization of osteoid matrix and epiphyseal cartilage in both flat and long bones stims osteoblasts to induce deposition of calcium during bone developlment FLAT bones develop by INTRAMEMBRANOUS bone formation = mesenchymal cells differentiate into osteoblasts which synthesize collagenous osteoid matrix on which calcium is deposited LONG bones develop by ENDOCHONDRAL OSSIFICATION = growing cartilage at epiphyseal plates is mineralized and progressively resorbed and replaced by osteoid matrix that is mineralized to create bone

Answer 124

deficiency leads to development of scurvy - bone disease in children - hemorrhages and healing defects in both children and adults dependent on diet for this vit - milk, liver, fish, fruits, and veggies hydroxylation and amidation rxns activation of prolyl and lysyl hydroxylases from inactive precurors, providing hydroxylation of procollagen collagen is most affected, particularly in bvs, accounting for predisposition to hemorrhages in scurvy antioxidant --> scavenge free radicals

Answer 125

peripheral or afferent system gens signals from various sites main components are LEPTIN and ADIPONECTIN produced by fat cells, GHRELIN from stomach, PEPTIDE YY (PYY) from ileum and colon, INSULIN and AMYLIN form pancreas arcuate nucleus in hypothal processes these peripheral signals and gens efferent signals contain 2 subsets of 1st order neurons - orexigenic path (increase appetite and decrease metabolism, weight gain) - anorexigenic path (decrease appetite, increase metabolism, weight loss) efferent system is organized along the 2 paths

Answer 126

anorexigenic = leptin, adiponectin, PYY, insulin, and amylin orexigenic = ghrelin

Answer 127

leptin - synthesized by FAT CELLS regs weight by stimulating physical activity and reg food intake PYY - secreted from endocrine cells in ILEUM and COLON levels of PYY decrease in pxs with PWS (hyperphagia and obesity) using PYYS for tx of obesity amylin - alpha peptide secreted with insulin from pancreatic beta cells that reduces food intake and weight gain adiponectin - fat burning molecule, guardian angel against obesity produced by FAT CELLS at high levels lower in obese than lean indvs ghrelin - produced in STOMACH only gut hormone that increases food intake

Answer 128

central obesity increases risk for - T2DM and cardiovasc disease - metabolic syndrome = visceral or intrab adiposity, insulin resistance/hyperinsulinemia/glucose intolerance, HTN, hypertriglyceridemia, low HDL - fatty liver disease --> can progress to fibrosis and cirrhosis - cholelithiasis (gallstones) - sleep apnea - degen joint disease - cancer hyperinsulinemia inhibits production of IGF-binding proteins IGFBP-1 and 2 - causing rise in levels of IGF-1 which binds to IGFR-1 and activates oncogene paths increases synthesis of estrogen in adipose tissue

Answer 129

content of exogenous carcinogens aflatoxin --> exposure causes MUTATION in TP53 gene, when found in hepatocellular carcinomas, this mutation serves as a molecular signature for aflatoxin exposure endogenous synthesis of carcinogens from dietary components - HIGH ANIMAL FAT INTAKE combined with low fiber intake (carcinogens in colon) - NITROSAMINES and NITROSAMIDES from proteins, veggies, and food preservatives lack or protective factors high fiber diet = protective because increased stool bulk and decreased transit time, which decreases exposure of mucosa to putative offenders capacity of certain fibers to bind carcinogens and protect mucosa

path exam 6 Flashcards

(155 cards)