Exam 1 Flashcards

Question

How can cancers spread

Answer 1

- direct seeding of body cavities or surfaces: most often in peritoneal cavity; particularly characteristic of ovaries (can fill cavity with pseudomyxoma peritonei: gelatinous neoplastic mass) - lymphatic spread: most common for carcinomas but sarcomas can also use this route; sentinel LN = first node in regional lymphatic basin that receives lymph flow from primary tumor; - hematogenous spread: typical of sarcomas, but also seen with carcinomas; veins more easily penetrated; liver and lungs most frequently involved; vertebral Mets associated with carcinomas of prostate and thyroid

Answer 2

Renal cell carcinoma: renal vein -> IVC sometimes to right side of heart Hepatocellular carcinomas: portal and hepatic radicles

Answer 3

Brain and adrenals

Answer 4

Liver and bones

Answer 5

Prostate, lung and colon/rectum

Answer 6

Breast, lung, and colon/rectum

Answer 7

Stomach, liver, uterine cervix, and gallbladder, and certain leukemia’s

Answer 8

Carcinomas of oropharynx (except lip), larynx, esophagus, and hepatocellular carcinoma

Answer 9

Prostate, breast, and colorectal carcinomas

Answer 10

No - extremely rare

Answer 11

Small round blue cell tumors: neuroblastoma, wilms tumor, retinoblastoma, acute leukemia’s, and rhabdomyosarcomas

Answer 12

Chronic inflammations, precursor lesions, immunodeficiency states

Answer 13

Carcinomas

Answer 14

``` Arsenic: lung and skin carcinoma Asbestos: Lung, esophageal, gastric, colon carcinoma, mesothelioma Benzene: AML Beryllium: lung carcinoma Cadmium: prostate carcinoma Chromium: Lung carcinoma Nickel: lung and oropharyngeal carcinoma Radon: lung carcinoma Vinyl chloride: hepatic angiosarcoma ```

Answer 15

Asbestosis/silicosis: mesothelioma, lung carcinoma IBD: colorectal carcinoma Lichen sclerosis: Vulvar squamous cell carcinoma Pancreatitis: pancreatic carcinoma Chronic cholecystitis: GB cancer Reflux esophagitis: esophageal carcinoma Sjogren, hashimoto: MALT lymphoma Gastritis/ulcers: cholangiocarcinoma/ colon carcinoma Hepatitis: hepatocellular carcinoma Osteomyelitis: carcinoma in draining sinuses Chronic cystitis: bladder carcinoma

Answer 16

Inflammatory precursor lesions: Barrets esophagus, bronchial squamous metaplasia, colonic metaplasia of stomach (pernicious anemia nad chronic atrophic gastritis) Non-inflammatory: endometrial hyperplasia, leukoplakia (thickening of squamous epithelium in oral cavity or penis/vulva -> squamous carcinoma) Benign neoplasms: colonic follows adenoma

Answer 17

- initiation: exposure to carcinogenic agent; alters cell making it potentially capable of giving rise to a tumor; *initiation alone NOT significant for tumor formation - initiation causes permanent DNA damage; rapid and irreversible and has memory; tumors are produced even if promoting agent is delayed for several months - promoters induce tumors to arise from initiated cells, but they are nontumorigenic by themselves; promoter affects are reversible

Answer 18

Highly reactive electrophiles that react with nucleophilic sites in the cell

Answer 19

Do not require conversion to become carcinogenic; chemotherapeutic drugs are example

Answer 20

Product of metabolism of indirect acting carcinogen; *tobacco

Answer 21

Lung cancer; variations in P-450 gene help determine susceptibility to cancer due to indirect carcinogens

Answer 22

Spots in the genome with specific DNA sequences that carcinogens target; ie: aflatoxin B (produced by aspergillosis) -> associated with hepatocellular carcinoma causes G:C ->T:A transversion in codon 249

Answer 23

Chemical agents that are not mutagenic but instead stimulate cell proliferation

Answer 24

Nonmelanoma: associated with total UV exposure Melanoma: associated with intense intermittent exposure (sunbathing)

Answer 25

UVB (280-320_

Answer 26

Myeloid leukemia’s, then cancer of the thyroid (but only in the young)

Answer 27

Human T cell leukemia virus type I; causes adult T cell leukemia/lymphoma; T cells major target of virus; requires trasmission via bodily fluid; high fraction of tumors express FOXP3 -> opportunistic infections often cause of death; HTVL does not contain an oncogene and does not integrate next to a proto oncogene

Answer 28

Tax: essential for viral replication, and alters transcription of host cell genes *impt for development of cancer hallmarks -> increased pro-growth signaling and cell survival (stimulates AKT and NFkB and upregulates cyclin D2); increased genomic instability: interferes with DNA-repair functions and inhibits cell cycle checkpoints

Answer 29

HPV, EBV, Hep B, Merkel cell polyoma, kaposi sarcoma herpesvirus

Answer 30

16 and 18 -> integrated into genome; interrupts viral DNA within E1/E2 open reading farm, leading to loss of E2 viral repressive and overexpression of E6 and E7 which are oncoproteins

Answer 31

Binds to and mediated degredation of p53 and stimulates expression of TERT whic his a subunit of telomerase ; *p53 Arg72 is much more likely to develop cervical carcinomas

Answer 32

Binds RB and displaces the E2F, promoting progression through cell cycle; also inactivates CDK inhibitors p21 and 27; also activate cyclins E and A

Answer 33

Need to be co-transferred with a mutated RAS gene

Answer 34

- LMP-1: behaves Iike active CD40 receptor, activates NFkB and JAK.STAT t hat promote B cell survival and proliferation; prevents apoptosis by activating BCL2 - EBNA-2: mimic active notch receptor; activates cyclin D and SRC family of protooncogenes - vIL-10: prevents macrophages from activating T cells

Answer 35

8:14 (MYC)

Answer 36

No; sets stage for acquisition of 8:14 translocation

Answer 37

They express LMP-1 and EBNA2; also usually lack MYC translocations

Answer 38

EBV infection; develop IgA abs before tumor; LMP-1 expressed and activated NFkB (upregulates VEGF, FGF-2, MMP9 and COX2)

Answer 39

No; mechanism for HBV thought to be virus causing damage and constant repair leading to genomic damage

Answer 40

Gastric adenocarcinomas and gastric lymphomas

Answer 41

Causes increased epithelial proliferation in setting of chronic inflammation

Answer 42

Cytotoxin associated A (CagA); penetrates into gastric epithelial cells

Answer 43

Antibiotic therapy to h pylori (removes stimulation of T cells); causes MALT lymphomas -> B cell lymphomas

Answer 44

Equal loss of fat and lean m, elevated basal metabolic rate, systemic inflammation (increased acute phase proteins)

Answer 45

Cancer-bearing individuals who develop signs and symptoms not explained by the anatomic distribution of their cancer

Answer 46

Can be earliest manifestation of neoplasm, can cause significant clinical problems, can mimic metastatic disease and confound treatment

Answer 47

Ie: Cushing syndrome; common in persons with carcinoma of the lung (small cell) -> have elevated serum pro-opiomelanocortin and corticotropin (former is not found in serum of patients with excess corticotropin produced by pituitary)

Answer 48

Hypercalcemia; causes osteoclasts and production of calcemic humoral substances by extraosseous neoplasms (only later is paraneoplastic)

Answer 49

Parathyroid hormone related protein: resembles PTH and share a GPCR; produced in small amounts by keratinocytes, m, bone, and ovary; regulates calcium transport into a rating breast and across placenta; *most associated with CA of breast, lung (squamous cell carcinoma), kidney, and ovary -IL-1, TGF alpha, TNF, dihydroxyvitamin D also play a role

Answer 50

Gray-black patches of thickened hyperkeratotic skin with a velvety appearance; in ppl over 40, associated with cancer; associated with gastric, lung, and uterine carcinoma

Answer 51

Associated with lung carcinoma; characterized by periosteal. New bone formation (distal ends of long bones, metatarsals/carpals, and prox phalanges), arthritis of adjacent joints and clubbing of digits

Answer 52

Lung and pancreas

Answer 53

Acute promyelocytic eukemia and prostatic adenocarcinoma

Answer 54

Nonbacterial fibrinous vegetations on cardiac valve (more on left) found in individuals with mucin secreting adenocarcinomas

Answer 55

Degree of differentiation of tumor cells and sometimes the number of mitoses or architectural features

Answer 56

Size of primary lesion, extent of its spread to regional LN, and presence or absence of blood born Mets; uses TNM system; primary lesion T1-T4 based on increasing size (T0 is in situ), N0-N3 for involvement of LN in increasing number and range, and MO-M2 indicating presence of Mets and number

Answer 57

Endometrial carcinoma, lung carcinoma, bladder and prostatic tumor, gastric carcinomas

Answer 58

Hard to determine tumor type especially of poorly differentiated tumors

Answer 59

- categorize undifferentiated malignant tumors: use abs to intermediate filaments - cytokeratins for epithelial (carcinoma), desmin for m - determines site of origin of met tumors: ie: PSA and thyroglobulin - Detects molecules that have prognostic or therapeutic significance: ie: hormone receptors in tumors (better breast CA prognosis); can also stain for products of oncogene (HER2 -> poor prognosis)

Answer 60

To identify antigens expressed by blood forming tissues (B and T cell lymphomas and leukemia’s, and myeloid neoplasms); *multiple antigens can be assessed simultaneously

Answer 61

11;22 q24;q12

Answer 62

Acute promyelocytic leukemia

Answer 63

Melanoma, hairy cell leukemia’s, colon cancers, papillary thyroid carcinoma, langerhans cell histiocytes is

Answer 64

- hCG: trophoblastic or nonseminomatous testicular tumors - calcitonin: medullary carcinoma of thyroid - catecholamine: pheochromocytoma

Answer 65

- alpha fetoprotein: liver cell cancer, nonseminomatous germ cell tumors of testis - carcinoembryonic antigen: carcinomas of the colon, pancreas, lung, stomach, and heart

Answer 66

- prostatic acid phosphatase: prostate cancer | - neuron specific enolase: small cell cancer of lung, neuroblastoma

Answer 67

Multiple myeloma

Answer 68

- CA-125: ovarian cancer - CA-19-9: colon cancer, pancreatic cancer - CA-15-3: breast cancer

Answer 69

- TP53, APC, RAS mutants in stool and serum: colon cancer - TP53, RAS mutants in stool and serum: pancreatic cancer - TP53, RAS mutants in sputum and serum: lung cancer - TP53 mutants in urine: bladder cancer

Answer 70

Disability adjusted life year: sums of years of life lost due to premature mortality and the years of life lost to disability in a population

Answer 71

Men: 58.3 Women: 61.8

Answer 72

Undernutrition

Answer 73

Ischemic heart disease and CV disease; risks are smoking, high BP, obesity, high cholesterol and alcohol abuse

Answer 74

Infections diseases

Answer 75

Pneumonia, diarrheal diseases, and malaria

Answer 76

- diseases caused by newly evolved strains or organisms - diseases caused by pathogens endemic in other species that jumped to human populations *HIV - diseases caused by pathogens that have been present in human populations but show a recent increase in incidence (dengue fever)

Answer 77

Exogenous chemicals in air, water, food, and soil that may be absorbed via inhalation, ingestion, or skin contact; almost always lipophilic and metabolized to water soluble substances or are activated to form toxic metabolites

Answer 78

I: undergo hydrolysis, oxidation or reduction II: products from phase I are metabolized into water soluble products via glucoronidation, sulfation, methylation and conjugation with glutathione

Answer 79

Cytochrome P 450 (in ER of liver mostly); they are heme containing enzymes

Answer 80

Starvation or fasting

Answer 81

Bind to nuclear receptors which heterodimerize with retinoic X receptor to form transcriptional activation complex that associates with promoter elements of CYP gene; example of receptor is style hydrocarbon receptor, peroxisome proliferator activated receptor, constitutive androstane receptor and pregnane x receptor

Answer 82

Sulfur dioxide, lead, carbon monoxide, ozone, nitrogen dioxide, and particulate matter

Answer 83

Gas formed by reaction of nitrogen oxides and volatile organic compounds in presence of sunlight; produces free radicals which injure epithelial cells in respiratory tract and type I alveolar cells

Answer 84

Burning sensation in nose and throat, difficulty breathing, and asthma attacks in susceptible individuals

Answer 85

Aka particulate matter; pulmonary inflammation nad secondary CV effects; fine or ultra fine particles less than 10 micrometers are most harmful -> phagocytosed -> inflammation

Answer 86

Systemic asphyxiant; nonirritating, colorless, odorless produced from incomplete oxidation of hydrocarbons (engines, furnaces, cigs); chronic poisoning can occur in ppl working underground, in tunnels, and highway toll booths

Answer 87

CNS depression (especially in basal ganglia and lenticular nuclei) and systemic hypoxia (occurs when Hbg is 20-30% saturated with CO) unconsciousness and death likely with 60-70% saturation; diagnosis made by measuring carboxyhemoglobin levels in blood

Answer 88

In light skinned individuals, present with cherry red color of skin and mucous membranes; with longer exposure, brain can become edematous with punctuate hemorrhage’s and hypoxia-induced neuronal changes

Answer 89

Cigarette smoke, NO, CO - wood smoke: contains oxides of N and C pollutants; irritant that can cause lung infections and contain polycyclic hydrocarbons (carcinogens) - Bioaerosols: can cause legionnaires, viral pneumonia, or common cold, OR allergens from pet dander, dust mites, and fungi - Radon: derived from uranium present in soil and homes can cause lung CA in miners; low level exposure not a risk - formaldehyde: problem in refugees from environmental disasters living in poorly ventilated trailers-> carcinogen

Answer 90

Binds to sulfhydryl groups in proteins and interferes with calcium metabolism which leads to hematologic, skeletal, neuro, GI, and renal toxicities

Answer 91

When blood lead levels exceed 45 micrograms/dL; but subclinical lead poisoning can occur below this level (includes subtle deficits in intellectual capacity, hyperactivity, and poor organizational skills)

Answer 92

Into bones and teeth where it competes for calcium

Answer 93

Peripheral neuropathy we

Answer 94

Children; the higher absorption and more permeable BBB creates high susceptibility to brain damage in children; causes inhibition of NT caused by disruption of calcium homeostasis

Answer 95

10: developmental toxicity 20: decreased nerve conduction velocity 40: decreased hemoglobin synthesis 100: encephalopathy 150: death

Answer 96

Brain: headache, memory loss Gingiva: lead line Blood: anemia, red cell basophilic stippling Peripheral nerves: demyelination Kidney: chronic tubulointerstitial disease GI: Ab pain

Answer 97

Brain: encephalopathy, mental deterioration Bones: radiodense deposits in epiphyses; inhibits healing of fractures by increasing chondrogenesis and delaying cartilage mineralization

Answer 98

Aminolevulinic acid DH and ferrochelatase: both involved in heme synthesis; latter catalyze incorporation of iron into protoporphyrin; causes microcytic hypochromic anemia stemming from suppression of hemoglobin synthesis

Answer 99

Elevated Levels of lead in blood or free red cell protoporhyrin

Answer 100

Inhibition of ferrochelatase causes appearance of ring sideroblasts, which are red cell precursors with iron laden mitochondria that are detected with Prussian blue stain; causes brain edema and demyelination and necrosis of cortical neurons accompanied by diffuse astrocytic proliferation

Answer 101

Extensor mm of wrist and fingers (causes wrist drop) followed by perineal mm causing foot drop

Answer 102

Binds to sulfhydryl groups in proteins leading to damage in CNS and kidney; *contaminated fish, metallic mercury released from dental amalgams

Answer 103

Developing brain

Answer 104

Lipid solubility

Answer 105

Intracellular glutathione

Answer 106

Toxicities in GI tract, nervous system, skin and heart; present in Chinese and Indian herbal medicine; arsenic trioxide is treatment for acute promyelocytic leukemia

Answer 107

Arsenic trioxide, sodium arsenide, and arsenic trichloride; causes acute GI, CV an CNS toxicities that are often fatal; attributed to interference with ox phos

Answer 108

- neur effects 2-8 weeks after exposure consisting of sensorimotor neuropathy that causes paresthesias, numbness, and pain - chronic exposure causes skin changes consistent of hyperpigmentation and hyperkeratosis - increased risk for development of CA, particularly of lungs, bladder and skin

Answer 109

Often multiple and usually appear on palms and soles

Answer 110

Preferentially toxic to kidneys and lungs *relatively modern problem; mining and batteries; food is most important source of exposure

Answer 111

Transporters such as ZIP8 (normally transports zinc)

Answer 112

Obstructive lung disease caused by necrosis of alveolar epithelial cells and renal tubular damage that can progress to ESRD; can also cause skeletal abnormalities associated with calcium loss *in japan causes disease of osteomalacia and osteoporosis with renal disease; also have elevated risk of lung CA

Answer 113

Exposure of fetus to high levels of mercury -> leads to CP, deafness and blindness

Answer 114

Ie: chloroform and carbon tetrachloride; used in degreasing and dry cleaning; causes dizziness and confusion, leading to CNS depression and even coma; lower levels toxic to kidneys and liver; *exposure to benzene increases risk of leukemia (oxidized to toxic metabolites by CYP2E1 that disrupt differentiation of hematopoietic cells in BM leading to risk of acute myeloid leukemia)

Answer 115

Released during combustion of fossil fuels; present in tar and soot; most potent carcinogens -> lung and bladder CA

Answer 116

Synthetic lipophilic products that resist degredation; used as pesticides (DDT-used as insecticide in malaria areas), dioxin also an example; disrupts hormonal balance

Answer 117

Skin disorders such as folliculitis and dermatosis known as chloracne -> acne, cyst formation, hyperpigmentation, and hyperkeratosis generally on face and behind ears; can also cause abnormalities in liver and CNS; PCBs induce CYPs -> abnormal drug metabolism

Answer 118

Chronic, nonneoplastic lung disease known as pneumoconioses, most commonly from exposure to coal dust, silica, asbestos, and beryllium *exposure of asbestos extends to family members of those exposed

Answer 119

Angiosarcoma of liver, uncommon type of liver CA

Answer 120

*lines water bottles; causes endocrine disruption; linked to heart disease

Answer 121

Causes inflammation and increased mucus production (bronchitis); also causes recruitment of leukocytes with increased elastase production leading to emphysema

Answer 122

Polycyclic hydrocarbons and nitrosamines; CYPs metabolize these carcinogens, some intermediates of which can form DNA adducts which can cause mutations in oncogenes and tumor suppressors

Answer 123

Lungs and larynx: polycyclic hydrocarbons, NNK, polonium 210 Esophagus: NNN Pancreas: NNK Bladder: 4-aminobiphenyl, 2-naphthylamine Oral (smoking):polycyclic aromatic hydrocarbons, NNK, NNN Oral (snuff): NNK, NNN, polonium 210

Answer 124

Tar, polycyclic aromatic hydrocarbons, benzopyrene, nitrosamines

Answer 125

Nitrogen oxides, formaldehyde

Answer 126

Phenol, and nicotine

Answer 127

- esophageal, pancreatic, bladder, kidney, cervical and bone marrow cancer - nonmalignant conditions -> emphysema, chronic bronchitis, COPD - atherosclerosis, MI (due to increased platelet aggregation, decreased myocardial oxygen supply accompanied by increased demand) - spontaneous abortions and preterm birthday and intrauterine growth retardation

Answer 128

Blood levels of cotinine (metabolite of nicotine)

Answer 129

Oxidized to acetaldehyde in liver by alcohol DH, ethanol oxidizing system (at high BAC levels) and catalase (very minor importance); acetaldehyde then metabolized. To acetate by acetaldehyde DH, which is then used in mit respiratory chain

Answer 130

Mitochondria

Answer 131

CYPs (particularly CYP2E1) located in SER; alcohol induces CYPs -> when alcohol high in the blood, delays other drug metabolism

Answer 132

Oral cancers; also Asians have very low acetaldehyde DH activity due to substitution of lysine for glutamine at residue 487; even one deficient copy renders activity ineffective because dominant negative -> causes nausea, flushing, tachycardia, and hyperventilation

Answer 133

Reduces NAD to NADH; NAD is required for FA oxidation in liver and conversion of lactate into pyruvate -> deficiency causes fatty liver in alcoholics and lactic acidosis (increases NADH/NAD ratio)

Answer 134

Endotoxins from gran negative bacteria in intestinal flora -> stimulates production of TNF and other cytokines leading to hepatic injury

Answer 135

CNS, can induce reversible hepatic and gastric changes (acute gastritis/ulceration)

Answer 136

- liver: alcoholic hepatitis and cirrhosis -> portal HTN and increased risk of hepatocellular carcinoma - GI: massive bleeding from gastritis, gastric ulcer, esophageal varices - thiamine (B1) deficiency: causes peripheral neuropathies and wernicke’s korsakoff syndnrome, cerebral atrophy, cerebellar degeneration and optic neuropathy - CV: dilated congestive cardiomyopathy, increased risk of HTN and decreased HDL (increasing coronary heart disease) - acute and chronic pancreatitis - CA of oral cavity, esophagus, liver and in women, breast

Answer 137

Microcephaly, growth retardation, facial abnormalities in newborn and reduction in mental functions and child grows older *first trimester particularly harmful

Answer 138

Acetaldehyde

Answer 139

Individuals with one copy of ALDH2*2 allele

Answer 140

Increase HDL, inhibit platelet aggregation, lower fibrinogen levels (lowers risk of coronary heart disease)

Answer 141

Discoloration of the skin due to the antibiotic minocycline -> causes deposition of drug metabolites/iron/melanin in the dermis

Answer 142

Warfarin and dabigatran (anti-coagulants) latter is direct inhibitor of thrombin (used in a fib patients); complications include bleeding, thrombotic implications such as embolic stroke stemming from under treatment

Answer 143

Increased risk of breast CA, stroke, and venous thromboembolism; no effect on incidence of coronary heart disease

Answer 144

- combo estrogen-progestin increases risk of breast CA; estrogen alone in women who had a hysterectomy is associated with decreased risk of breast CA - protective effect on development of atherosclerosis and coronary artery disease in women < 60 but no protection that started at older age - increases risk of stroke and venous thromboembolism

Answer 145

Protective

Answer 146

Increases risk to women who have been infected with HPV

Answer 147

Does not increase risk in women younger than 30 or in older women who are nonsmokers; but risk does double in women older than 35 who smoke

Answer 148

Hepatic adenoma; rare benign hepatic tumor especially in older women who have used OCPs for prolonged periods

Answer 149

Inhibits production and release of LH and FSH and increases estrogens; stunted growth, acne, gynecomastia, testicular atrophy, growth of facial hair and menstrual changes; psychiatric disturbances and increased risk of MI

Answer 150

In the liver by phase II enzymes -> excreted in urine as glucuronate or sulfate conjugated; very small amount metabolized by CYPs to NAPQI which is a highly reactive metabolite (accumulates when taken in large doses and causes hepatocellular injury leading to centrilobular necrosis and liver failure)

Answer 151

- covalent binding to hepatic proteins which causes damage to cellular membranes and mit dysfunction - depletion of GSH (NAPQI is conjugated to it), which makes hepatocytes more susceptible to ROS injury * *toxicity can occur in low doses when drinking alcohol

Answer 152

Starts with N/V, diarrhea, shock, jaundice; can be treated within 12 hours by administration of N-acetylcystein which restores GSH levels

Answer 153

Methyl salicylate -> aspirin

Answer 154

Alkalosis as a consequence of stimulation of respiratory center of medulla, this is followed by acidosis and accumulation of pyruvate and lactate caused by uncoupling of oxphos and inhibition of keens cycle; acidosis enhances formation of non-ionized forms of salicylate which diffuse into brain and cause nausea or coma

Answer 155

Salicylism; may develop in persons who take 3 gm or more daily for long periods of time for treatment of chronic pain; manifested by HA, dizziness, ringing in ears (tinnitus), hearing impairment, mental confusion, drowsiness, N/V/D; CNS changes can progress to convulsions and coma; acute erosive gastritis

Answer 156

Tubulointerstitial nephritis with renal papillary necrosis -> called analgesic nephropathy

Answer 157

Blocks reuptake of dopamine in CNS and blocks reuptake of epi/norepi at adrenergic nerve endings while stimulating release of norepi -> leads to tachycardia, HTN, peripheral vasoconstriction; can also induce myocardial ischemia b y causing coronary artery vasoconstriction and enhancing platelet aggregation and thrombus formation; can also cause lethal arrythmias by disrupting normal ion transport

Answer 158

Hyperpyrexia and seizures

Answer 159

Acute decreases in blood flow to placenta resulting in fetal hypoxia and spontaneous abortion; neuro development can be impaired in fetus

Answer 160

Oxycodon and heroin

Answer 161

Euphoria, hallucinations, somnlolence and sedation

Answer 162

Neuro, renal and auditory

Answer 163

- sudden death: drug purity usually unknown -> respiratory depression, arrhythmia, cardiac arrest and pulm edema - pulmonary injury: edema, septic embolism from endocarditis, lung abscess, opportunistic infections, foreign-body granuloma (from talc; usually lung but also found in spleen, liver, and LN that drain UE) - infections: skin, heart valves, liver, lungs; *endocarditis (usually tricuspid) most caused by S aureus; viral hep most common infection - cutaneous lesions (abscesses, cellulitis, ulcerations) - kidney disease: amyloidosis secondary to skin infections and glomerulosclerosis (induce protein and nephrotic sydrome)

Answer 164

Released dopamine in the brain which inhibits presynaptic NT at corticostriatal synapses, slowing glutamate release; long term use leads to violent behaviors, confusion, and psychotic features

Answer 165

Ecstasy; causes increase of serotonin release in CNS; as it wears off causes a drop in serotonin; also reduces number of serotonergic axon terminals in striatum and cortex and increases peripheral effects of dopamine

Answer 166

Nausea and pain

Answer 167

Distorts sensory perception and impairs motor coordination; increases heart rate and can cause angina in someone with coronary artery disease

Answer 168

Tranquilizers

Answer 169

- superficial: first degree burns; confined to epidermis - partial thickness burns: second degree burns; involve injury to dermis - full thickness burns: third degree burns; extend to subcutaneous tissue; can also involve m (4th degree burns)

Answer 170

Shock, sepsis, and respiratory insufficiency

Answer 171

Development of hyper metabolic state associated with heat loss and increased need for nutritional support

Answer 172

Psudomonas aeurginosa

Answer 173

Pneumonia or septic shock with renal failure or acute respiratory distress syndrome

Answer 174

- direct effect of heat to mouth, nose and upper airways - inhalation of heated air and gases - chlorine, sulfur oxides, ammonia can react with water to form acids or alkalis producing inflammation in upper airways; lipid soluble gases such as NO are more likely to. Reach deeper airways producing pneumonitis

Answer 175

White or charred, dry and painless because of destruction of nerve endings

Answer 176

Pink or mottled with blisters and painful

Answer 177

Area undergoes coagulation necrosis with adjacent skin has accumulation of inflammatory cells and exudation

Answer 178

Cramps: results from loss of electrolytes via sweating; cramping of voluntary mm; able to maintain normal body temp Exhaustion: most common; sudden onset with prostration and collapse; results from failure of CV system to compensate for hypovolemia Stroke: associated with high temperatures, humidity and exertion; older adults, ppl undergoing intense physical stress, and ppl with CV disease are at risk; thermoreg. Fails, sweating ceases, and body temp rises -> multiorgan dysfunction

Answer 179

Vasodilation with peripheral pooling of blood and decreased effective circulating blood volume; hyperkalemia, tachycardia, Arrhythmias common; *sustained m contractions that exacerbate hyperthermia and lead to m necrosis (rhabdomyolysis); stems from nitrosylation of ryanodine receptor 1 -> allows Ca to leak into cytoplasm (mutated RYR1 in malignant hyperthermia -> heat stroke like in response to anesthetics)

Answer 180

High humidity, wet clothes, dilation of superficial blood vessles from ingestion of alcohol

Answer 181

Loss of consciousness followed by bradycardia and a fib

Answer 182

Mediated by physical disruption within cells by high salt concentrations caused by crystallization of intra and extracellular water

Answer 183

Results from circulatory changes which vary depending on rate of temp drop; slow chilling can induce vasoconstriction and increase vascular permeability (edema and hypoxia) ie: trench foot; with sudden persistent chilling, vasoconstriction and increased viscosity of blood can cause ischemic injury and degeneration of nerves (vascular injury only evident after temp returns to normal_

Answer 184

Burns or ventricular fibrillation/cardiac respiratory center failure resulting from disruption of normal electrical pulses

Answer 185

Induces tetanic m spasm so irreversible clutching is likely to occur ; can cause spasm of chest wall and asphyxia

Answer 186

UV, infrared light, microwave, sound waves -> can move atoms in molecule but not sufficient. To displace bound electrons

Answer 187

Sufficient energy to remove electrons; x rays and gamma rays (dispersed damage; less damage per area), high energy neutrons, alpha particles (damage to restricted area), beta particles

Answer 188

Fibrosis, mutagenesis, carcinogenesis, and teratogenesis

Answer 189

Curie: amount of radiation emitted by source Gray: energy absorbed by target Sievert:

Answer 190

- rate of delivery - field size: can sustain high doses when delivered to small fields; smaller doses to large fields can be lethal - cell proliferation: rapidly dividing cells more vulnerable; nondividing cells are not killed except at extremely high doses - oxygen effects and hypoxia: ROS main mechanism that causes DNA damage; poorly vascularized tissues less sensitive to radiation therapy (ie: center of tumors) - vascular damage: endothelial cells moderately sensitive to radiation can cause narrowing of BV leading to impaired healing and fibrosis

Answer 191

Structural changes in chromosomes that are related to ds DNA breaks; nuclear swelling and condensation and clumping of chromatin; giant cells can persist for years; at high doses, pyknosis and lysis

Answer 192

Cytoplasmic swelling, mitochondrial distortion, degeneration of ER; plasma membrane breaks; *can closely resemble cancer cells which poses problem to pathologist when examining for remaining tumor

Answer 193

During immediate post radiation, vessels show dilation; with time or higher doses, endothelial cell swelling and vacuolation, necrosis of walls; can rupture or thrombosis; later, endothelial cell proliferation and collagenous hyalinization and thickening of intima -> scarring

Answer 194

- Brain: adult -> resistant; embryonic -> destruction of neurons and glial cells - Skin: erythema and edema (early); dyspigmentation (wks-months); atrophy, cancer (months to years) - lungs: edema, ARDS, interstitial fibrosis (months to years) - LN:acute tissue loss, atrophy and fibrosis (late) - GI: mucosal injury and ulceration (early); fibrosis of wall (late) - Gonads:testis and ovaries destruction (early); atrophy and fibrosis (late) - bone marrow: thrombocytopenia, granulocytopenia, anemia, lymphopenia (early)

Answer 195

Cause marrow aplasia; very high doses cause aplastic anemia which is marked by failure of blood count recovery

Answer 196

Ds breaks; repaired by homologous recombination and non homologous end joining -> often produces mutation; *also have bystander effect -? Effect behavior of nonirradiated surrounding cells via growth factors and cytokines

Answer 197

Primary: one or all of components of healthy diet are missing Secondary:malnutrition results from malabsorption, impaired utilization or storage, excess loss, or increased need for nutrients

Answer 198

- poverty - infections - acute and chronic illnesses (ie: HIV) increase metabolic demand - chronic alcoholism (thiamine, pyridoxine, folate, and vit A) - ignorance of diet supplementation (ie: iron deficiency in infants fed artificial milk)

Answer 199

*weight/height BMI <16 is malnutrition BMI 18.5-25 is normal

Answer 200

Look at fat sores (thickness of skin folds), muscle mass (reduced circumference of mid-arm), and serum proteins (albumin and transferrin provide measure of adequacy of visceral protein compartment

Answer 201

When weight falls to 60% of normal for sex, height, and age; suffers growth retardation and loss of m, resulting from catabolism and depletion of somatic protein compartment (provides body with aa as source of energy); serum albumin are normal or only slightly reduced; production of leptin is low which causes cortisol production and lipolysis; *Extremities emaciated, head too large for body; anemia, immune deficiency

Answer 202

Occurs when protein deprivation is more severe than deficit in total calories; *most common in African children who are weaned too early and fed exclusively carb diet; can also occur in chronic diarrheal states b/c not absorbing protein or nephrotic syndrome or after extensive burns; associated with severe depletion of visceral protein compartment and results in hypoalbuminemia which causes edema; subcutaneous and m mass spared; *characteristic skin lesions w/ alternating zones of hyperpigmentation, desquamation and hypopigmentation “flaky paint appearance”; loss of hair color; enlarged fatty liver (reduced synth of carrier protein of lipoproteins); development of apathy, listlessness and loss of appetite; immune defects

Answer 203

Depletion of subcutaneous fat in arms, chest wall, shoulders, or metacarpal regions, wasting of quadriceps and deltoid mm, and ankle or sacral edema

Answer 204

Decrease in mitotic index in crypts of the glands associated with mucosal atrophy and loss of villi and microvilli; loss of SI enzymes most often manifested as disaccharides deficiency; thus, may not respond to full strength milk based diets

Answer 205

May be hypoplastic b/c of decreased blood cell precursors; red cells can be micro normo or macrocytic

Answer 206

Shown to have cerebral atrophy, reduced number of neurons, and impaired myelinization of white matter

Answer 207

- proteolytisis inducing factor: glycosyated polypeptide excreted in urine of weight losing patients with pancreatic, breast, colon and o ther cancers - lipid-mobilizing factor: increases FA oxidation and proinflammatory cytokines such as TNF and IL-6 * both of these cause skeletal m breakdown via NFkB activation of ubiquitin protease pathway

Answer 208

Similar to PEM; amenorrhea due to decreased gonadotropin releasing hormone and decreased secretion of LH and FSH, decreased thyroid hormone release leading to cold intolerance, bradycardia, constipation and changes in skin and hair, bone density decreased b/c low estrogen, anemia, lymphopenia, and hypoalbuminemia; *increased susceptibility to cardiac arrhythmia and sudden death resulting from hypokalemia

Answer 209

Hypokalemia (cardiac Arrhythmias), pulmonary aspiration of gastric contents, esophageal and gastric rupture

Answer 210

Fat: more readily stored in body, but may be poorly absorbed in fat malabsorption disorders

Answer 211

Vit D from steroids, vit K and biotin from intestinal micro flora and niacin from tryptophan

Answer 212

Maintenance of normal vision, regulation of cell growth and differentiation, and regulation of lipid metabolism

Answer 213

Retinol; also storage form

Answer 214

Liver, fish, eggs, milk, butter; yellow and leafy green. Vegetables such as carrots, squash and spinach provide carotenoids that can be met to vitamin A

Answer 215

Bile, pancreatic enzymes, antioxidant activity in food; stored in liver

Answer 216

Retinol binds to retinol binding protein and binds to RBP receptor in peripheral tissues; then binds to cellular RBP and RBP release into blood

Answer 217

Oxidation of retinol to all trans retinal, isomerization to 11 cis retinal and covalent association with opsin to form rhodopsin; photon of light isomerizes 11 cis to 11 trans retinol which dissociated from rhodopsin to generate signal

Answer 218

Play a role in orderly diff of mucus secreting epithelium; when deficient, undergo squamous metaplasia, differentiating into keratinizing epithelium; activation of retinoic acid receptors causes release of corepressors and formation of heterodimers with another retinoic receptor (RXR) -> bind to retinoic acid response element located in reg regions of gens that encode receptors for growth factors, tumor suppressors *all trans retinoic acid has highest affinity for RARs

Answer 219

RXR binds to 9 cis retinoic acid and can form heterodimers with other receptors such as nuclear receptors involved in drug met, peroxisome proliferator activated receptors (regulators of FA met), and vit D receptors

Answer 220

Can reduce morbidity and mortality of certain diarrhea(restores epithelium in gut); in children with measles, can improve clinical outcome; infections may reduce availability of vit A b/c acute phase response blocks synthesis of retinol binding protein

Answer 221

Acne, psoriasis and acute promyelocytic leukemia

Answer 222

Bitot spots, corneal ulcer, keratomalacia (destruction of cornea), metaplasia, kidney stones, night blindness, immune deficiency, xerophthalmia caused by lacrimal epithelium being replaced by keratinized epithelium, hyperplasia and hyperkeratinization of epidermis with plugging of ducts of adnexal glands an produce follicular dermatosis

Answer 223

Headache, dizziness, vomiting, stupor, blurred vision (may be confused with brain tumor -> pseudotumor cerebri)

Answer 224

Weight loss, anorexia, nausea, vomiting, bone and joint pain; retinoic acid stimulates osteoclasts leading to increased risk of fracture

Answer 225

Maintenance of plasma levels of calcium and phosphorus, bone mineralization, and neuromuscular transmission

Answer 226

Precursor 7-dehydrocholesterol that requires UV light (UVB) -> cholecalciferol (D3); those with darker skin have lower level of vitamin D production; in plants, registering is the precursor

Answer 227

Vit D binds to plasma alpha globulin (DPB) and transports to liver -> conversion to 25 hydroxycholecalciferol in liver through 25 hydroxylase (CYP27A1) -> conversion to 1,25 dihydroxyvitamin D in kidney by 1 alpha hydroxylase

Answer 228

- hypocalcemia stimulates PTH which activates 1 alpha hydroxylase - hypophosphatemia activates 1 alpha hydroxylase directly - increased levels of 1,25 dihydroxyvitamin D down regulate is own synthesis

Answer 229

Binds to vitamin D receptor and associated with RXR

Answer 230

- stimulation of intestinal calcium absorption in duodenum through interaction of 1,25 dihydroxyvitamin D with nuclear vitamin D receptor and formation of RXR complex -> binds to vit D response elements and activates TRPV6 which encodes calcium transport channel - stimulation of calcium reabsorption in kidney in distal tubules through increased expression of TRPV5 - interaction with PTH in regulation of blood calcium: enhances expression of RANKL (activator of NFkB) on osteoblasts -> binds to preosteoclasts and causes differentiation into osteoclasts -> dissolve bone - mineralization of bone: stimulates osteoblasts to synthesize calcium binding osteocalcin involved in deposition of calcium during bone development

Answer 231

PTH is elevated causing activation of 1 alpha hydroxylase (which elevates amount of active vitamin D and calcium absorption), increased resorption of calcium f rom bone by osteoclasts, decreased renal calcium excretion, and increased renal excretion of phosphate (caused by increase in fibroblast growth factor 23 - phosphatonins that block phosphate absorption in intestine and kidney); normal calcium can be restored, but hypophosphatemia will persist, imparting mineralization of bone *FGF23 may be responsible for tumor-induced osteomalacia and hypophosphatemic rickets

Answer 232

< 20 ng/mL

Answer 233

- overgrowth of epiphyseal cartilage due to inadequate calcification and failure of cartilage cells to mature - persistence of distorted irregular masses of cartilage which project into marrow cavity - deposition of osteoid matrix on inadequately mineralized cartilaginous remnants - disruption of orderly replacement of cartilage by osteoid matrix with enlargement and lateral expansion of osteocondral junction - abnormal overgrowth of cap and fibroblasts - deformation of skeleton due to loss of structural rigidity of bones

Answer 234

During nonambulatory stage, chest and head -> occipital bones flattened, parietal bones buckle inward by pressure and snap back with release of pressure (craniotabes), frontal bossing and squared appearance of head; rachitic rosary -> metaphysical areas of ribs are subject o pull of resp mm and bend inward creating anterior protrusion of sternum (pigeon breast); during ambulation, affects spine, pelvis, tibia causing lumbar lordosis and bowed legs

Answer 235

In adults, lack of vit D deranged normal bone remodeling that occurs throughout life; newly formed osteoid matrix is inadequately mineralized producing excess of persistent osteoid (characteristic of osteomalacia); bone is weak and vulnerable to fractures (mostly vertebral body and femoral neck); appears as thickened layer of matrix (stains pink)

Answer 236

-macrophages synthesize 1,25 dihydroxyvitamin D via CYP27B in mit; induced by pathogen binding to TLRs

Answer 237

Not from sunlight; oral excess can lead to hypervitaminosis; in children, this causes metastatic calcification of soft tissues (ie: kidney); in adults, causes bone pain and hypercalcemia *potent rodenticide in high doses

Answer 238

Impaired collagen formation which can lead to poor vessel support leading to bleeding tendency, inadequate synthesis of osteoid, and impaired wound healing

Answer 239

Accelerates hydroxylation and amidation reactions; activation of prolly and lysyl hydroxylase providing hydroxylation of procollagen ; also has antioxidant properties -> can scavenge free radicals and can regenerate antioxidant form of vit E

Answer 240

Increased iron overload due to increased absorption, hemolytic anemia in those with G6PD deficiency, and calcium oxalate kidney stones; very rare

Answer 241

Spinocerebellar degeneration

Answer 242

3 D’s: diarrhea, dementia, dermatitis

Answer 243

Megaloblastic anemia, neural tube defects

Answer 244

Hypochromic microcytic anemia

Answer 245

Overweight: 25-30 Obese: >30

Answer 246

- peripheral or afferent system: leptin and adiponectin produced by fat cells, ghrelin from stomach, peptide YY from ileum and colon, and insulin from pancreas - arcuate nucleus in hypothalamus: processes and integrates neurohumoral peripheral signals and generates efferent signals; POMC and CART and NPY and AgRP; communicate with second order neurons in hypothalamus - efferent system: anabolic and catabolic pathways; control food intake and energy expenditure

Answer 247

Enhance energy expenditure and weight loss by production of anorexigenic MSH and activation of melanocrotin receptors 3 and 4 -> produce TRH and CRH that increase metabolic rate and catabolic metabolism

Answer 248

Promote food intake (orexigenic effect) and weight gain via activation of Y1/5 receptors -> release MCH and orexin which stimulate appetite

Answer 249

Decreased ability to sense fat stores, overeat and gain weight; leptin secreted when fat stores are abundant *insulin stimulated glucose metabolism is impt factor in regulation of leptin

Answer 250

Stimulates POMC/CART and inhibits NPY/AgRP

Answer 251

Obesity; sensing of anorexigenic signal is not generated and behave as if undernourished; impt downstream signaling of this receptor is brain-derived neurotrophic factor (BDNF) -> haploinsufficiency of this is seen in WAGR syndrome (wilms tumor, anorexia, GU defects, and mental retardation)

Answer 252

Stimulates FA oxidation in m, causing decrease in fat mass; lower in obese ppl; decreases FA influx to liver, and glucose production in liver, causing increase in insulin sensitivity and protection against met syndrome; binding to receptor triggers cAMP dependent protein kinas A which phosphorylates and inactivates acetyl coenzyme A carboxylase (required for FA synthesis)

Answer 253

Increases food intake; binds growth hormone secretagogue receptor in hypothalamus and pituitary; stimulates NPY/AgRP; levels rise before meals and fall between 1-2 hours after eating

Answer 254

Low during fasting and increase after food intake; reduces energy intake; increase after gastric bypass; decrease with prader willi syndrome

Answer 255

Adipocytes produce cytokines (TNF, IL-6, IL-1, IL-18); high levels of CRP

Answer 256

Visceral or intraabdominal adiposity, insulin resistance, hyperinsulinemia, glucose intolerance, HTN, hypertriglyceridemia, and low HDL cholesterol

Answer 257

Retention of sodium, expansion of blood volume, production of excess norepi and smooth m proliferation = HTN

Answer 258

Obesity; occurs often in diabetic patients and can progress to fibrosis and cirrhosis

Answer 259

Respiratory abnormalities in very obese persons; aka pickwickian syndrome

Answer 260

Seen in obese people, AP DIC pauses, polycythemia, and right sided heart failure (cor pulmonale)

Answer 261

Esophageal, pancreatic, colon, rectal, breast, endometrial, kidney, thyroid, and GB

Answer 262

- elevated insulin inhibits production of IGF-binding proteins causing a rise in IGF-1 -> mitogen who’s receptor is highly expression in CA; IGF-1 activates RAS and PI3K/AKT which pr Moore growth of normal and neoplastic cells - increases synthesis of estrogen through adipose aromatases, increased androgen synthesis in ovaries and adrenals and enhances estrogen availability by inhibiting production of sex hormone binding globulin in liver

Answer 263

Aflatoxin -> hepatocellular carcinoma (usually with hep B); causes mutation in TP53

Answer 264

Gastric cancer; formed from digested proteins (preservatives)

Answer 265

High animal fat intake with low fiber intake

Answer 266

Congenital abnormalities, prematurity, SIDS, and low birth rate

Answer 267

Results from secondary destruction of organ or body region that was previously Norma in development; arise from extrinsic disturbances in morphogenetic *malformations are intrinsic; ie: amniotic bands

Answer 268

Also extrinsic disturbance of development; localized on generalized compression of fetus by abnormal biomechanical forces; ie: uterine constraint (Factors that increase risk are first pregnancy, small uterus, bicornuate uterus, leiomyomas, oligohydramnios, multiple fetuses and abnormal fetal presentation); ie: clubfeet -> potter sequence

Answer 269

Cascade of anomalies triggered by one initiating aberration; ie: oligohydramnios (potter sequence) -> can be caused by leak in amnion, uteroplacental insufficiency from maternal HTN or severe toxemia, and renal agenesis in fetus; associated with fetal compression -> leads to flattened face, positional abnormalities of hands and feet, hips dislocated, growth of chest wall and lungs compromised (lungs hypoplastic)nodules in amnion (amnion nodosum)

Answer 270

Constellation of congenital anomalies believed to be pathologically related that cannot be explain on basis of single defect; usually caused by viral infection or chromosomal abnormality

Answer 271

Absence of organ, but one that occurs due to failure of growth of the existing primordium

Answer 272

Absence of an opening

Answer 273

Maternal hyperglycemia induced fetal hyperinsulinemia which causes fetal macrosomia (organomegaly and increased body fat and m mass), cardiac anomalies, neural tube defects and CNS malformations seen in diabetic embryopathy

Answer 274

Embryonic: first 9 weeks Fetal: rest of gestation

Answer 275

Antiepileptic that is a teratogen during pregnancy; disrupts express ion of homeobox (HOX) proteins; implicated in patterning of limbs, vertebrae, and craniofacial structures

Answer 276

Deficiency: malformations of eyes, GU, CV, diaphragm and lungs Excess: CNS, cardiac and craniofacial defects (cleft lip and palate); later can be derived from retinoic acid mediated deregulation of TGFb signaling which is involved in palate formation

Answer 277

< 37 weeks

Answer 278

- preterm premature rupture of placental membranes (PPROM): risks of this occurring are previous preterm delivery, preterm labor or vaginal bleeding during pregnancy, maternal smoking, low SES, poor maternal nutrition - intrauterine infection:chorioamniotis (inflammation of placenta), funisitis (inflammation of umbilical cord), malaria nad HIV; TLR -> prostaglandin ->preterm labor - twin pregnancy

Answer 279

Neonatal respiratory distress syndrome (hyaline membrane disease), necrotizing enterocolitis, sepsis, intraventricular and germinal matrix hemorrhage

Answer 280

Intrinsically reduce growth potential of fetus despite adequate supply of nutrients; ie: chromosomal disorders, congenital anomalies, congenital infections (should be considered in all cases of FGR) *TORCH group of infections; infants with SGA because of fetal factors usually have symetric growth restriction

Answer 281

Uteroplacental insufficiency ie: single umbilical a, abnormal cord insertion, placental hemangioma, placental abruption, placenta previa, placental thrombosis and infarction, infection or multiple generations; result in asymmetric restriction (spares brain)

Answer 282

Preeclampsia and chronic HTN, thrombophilias, narcotic abuse, alcohol, cigarette smoking, chemo, phenytoin (Dilantin), malnutrition (hypoglycemia)

Answer 283

Major handicap, cerebral dysfunction, learning disability, hearing and visual impairment

Answer 284

Sedation of mother, fetal head injury during delivery, aspiration of blood or amniotic flui, intrauterine hypoxia by coiling of umbilical cord around neck

Answer 285

Male gender, maternal diabetes, delivery by cesarean section; within 30 min, breathing becomes difficult and within few hours, cyanosis and fine rales heard in both lung fields; chest X-ray shows fine ground glass picture (reticulogranular densities)

Answer 286

Mutation in SFTPB/C genes

Answer 287

Stiff atelectatic lungs compounded by soft thoracic wall that is pulled in; progressive atelectasis and reduced lung complains lead to uneven perfusion, hypoventilation -> hypoxemia and CO2 retention -> acidosis -> pulm vasoconstriction -> pulm hypoperfusion ->endothelial/epithelial damage -> fibrin rich exudate with formation of hyaline membrane (barriers to gas exchange leading to CO2 retention and hypoxemia)

Answer 288

Cortisol, insulin, prolactin, thyroxine, TGF beta; *glucocorticoids important -> conditions associated with intrauterine stress and FGR that increase corticosteroid release lower risk of developing RDS; surfactant synthesis can be depressed by high blood levels of insulin in fetuses (diabetic mothers); labor increases surfactant synthesis (reason C section increases risk of RDS)

Answer 289

Normal size, solid, airless, reddish purple and sink in water; alveoli poorly developed and collapsed; if infant dies early, necrotic cellular debri can be seen in terminal bronchioles and alveolar ducts (incorporated into hyaline membranes made of fibrin and cell debris from type II pneumocytes); *hyaline membranes never seen in stillborn infants; in infants who live > 48 hrs, reparative change are seen (alveolar epithelium proliferates and can detach into airspace where it undergoes phagocytosis)

Answer 290

Amniotic fluid (lung secretions discharged into fluid)

Answer 291

- retrolental fibroplasia (retinopathy of prematurity) | - bronchopulmonary dysplasia

Answer 292

2 phases; 1.) hyperoxic phase: expression of VEGF is decreased causing endothelial apoptosis; VEGF returns to normal after returned to room air (relatively hypoxic), which is phase II -> leads to retinal proliferation characteristic of lesions in retina

Answer 293

Decrease in alveolar septation manifested as large simplified alveoli and dysmorphic capillary configuration; caused by reversible impairment in development of alveoli during saccular stage; *hyperoxemis, hyperventilation, prematurity, inflammatory cytokines, and vascular maldevelopment contribute to this

Answer 294

Patent ductus arteriosus, intraventricular hemorrhage, necrotizing enterocolitis

Answer 295

PAF -> increases mucosal permeability by promoting enterocye apoptosis and compromising tight junctions; onset of bloody stools, ab distention, and circulatory collapse; ab radiographs demonstrate gas within intestinal wall (pneomatosis intestinalis)

Answer 296

Involves terminal ileum, cecum, and right colon; involved segment is distended, friable, and congested; can be gangrenous; intestinal perforation may be seen; coagulative necrosis, bacterial colonization, and submucosal gas bubbles seen microscopically formation of granulation tissue and fibrosis seen after acute episode; can be treated early on but if progressed need resection

Answer 297

Transcervically (referred to as ascending) or transplaccentally (hematologic)

Answer 298

Either by inhaling infected amniotic fluid shortly before birth or by passing. Through infected birth canal; *pneumonia, sepsis and meningitis most common sequelae

Answer 299

Parasitic and viral; gain access to fetal bloodstream via chorionic villi; can occur during gestation or delivery (hep B and HIV)

Answer 300

Spontaneous abortion (usually second trimester) stillbirth, hydrops fetalis, or congenital anemia

Answer 301

Erythroid cells

Answer 302

Fever, encephalitis, chorioretinitis, hepatosplenomegaly, pneumonitis, myocarditis, hemolytic anemia, and vesicular or hemorrhagic skin lesions

Answer 303

Early: within first 7 days Late: 7 days to 3 months

Answer 304

Group B streptococcus; listeria and candid a -> late onset

Answer 305

Accumulation of edema fluid in fetus during intrauterine growth; caused by Rh blood incompatibility (immune hydrops); nonimmune hydrops more common now; hydrops fetalis is generalized edema -> usually lethal

Answer 306

Turner, trisomy 21 and 18, cystic adenomatoid malformation, diaphragmatic hernia, tachyarrhythimia, high output failure, alpha thalassemia, parvovirus B19, twin to twin transfusion, cytomegalovirus, syphilis, toxoplasmosis

Answer 307

Abs attach to RBCs -> anemia ->extramedullary hematopoiesis and cardiac decompensation -> hydrops Abs attach to RBCs-> hemoglobin degredation -> bilirubin -> jaundice and kernicterus

Answer 308

RhIg containing anti-D abs at 28 weeks and within 72 hours of delivery; this is also administered following abortions

Answer 309

Contain mostly IgM abs and neonatal RBCs express blood group antigens poorly; occurs almost exclusively in. Infants of group A or B born to group O mothers -> firstborn can be affected b/c O mother has IgG abs without prior exposure

Answer 310

- anemia -> liver and heart hypoxia -> decrease plasma protein synthesis and cardiac decompenation/failure; reduced osmotic pressure and heart failure results in generalized edema and anasarca - jaundice -> CNS damage; kernicterus

Answer 311

Both fetus and placenta are pale; liver and spleen enlarged from cardiac failure and congestion; marrow demonstrates hyperplasia (except in parvovirus infection) and extramedullary hematopoiesis is seen in liver, spleen, and LN; large number of immature red cells (erythroblastosis fetalis)

Answer 312

Scandinavian

Answer 313

Fine at birth, within a few weeks develop rising plasma phenylalanine level which impairs brain development; by 6 months, severe mental retardation; seizures, decreased pigmentation of hair and skin, and eczema often seen

Answer 314

Reach childbearing age and asymptomatic, treatment discontinued; children of these woman have a high likelyhood of being mentally retarded and microcephalic and congenital heart disease *maternal PKU

Answer 315

Can’t convert phenylalanine to tyrosine

Answer 316

Complete lack of PAH activity

Answer 317

Mutation in PAH that only results in modest elevations of blood phenylalanine levels without Neuro damage

Answer 318

Abnormalities in synthesis or recycling of cofactor tetrahydrobiopterin BH4 *impt to recognize because cannot be treated by dietary restriction of phenylalanine

Answer 319

AR disorder resulting from accumulation of galactose-1-P in tissues

Answer 320

- total lack of galactose-1-P uridyl transferase (GALT) | - deficiency of galactokinase (rare); milder -> no mental retardation

Answer 321

Liver, spleen, lens of eye, kidneys, heart, cerebral cortex, and RBCs; alternative met pathways activated leading to production of galactitol and galactonate (also accumulate in tissue)

Answer 322

Variable; *liver, eyes and brain most damage; early develop hepatomegaly due to fatty change and can lead to cirrhosis; opacification of lens (cataract) within first few weeksb/c lens absorbs water and swells as galatitol accumulates and increases osmotic pressure, loss of nerve cells, gliosis, and edema in dentate nucleus and olivary nucleus; failure to thrive, vomiting and diarrhea within a few days, jaundice during first week; mental retardation within 6-12 months *not as severe as PKU; aminoaciduria (can’t transport aa in kidney)

Answer 323

Escherichia coli septicemia because depressed neutrophil bactericidal activity

Answer 324

Speech disorder and gonadal failure and sometimes ataxia

Answer 325

Reaction 1: galactose + ATP -> galactose 1-P via galactokinase Reaction 2: Galactose 1-P + UDP glucose -> UDP galactose + glucose 1-P via galactose 1-P uridyl transferase Reaction 3: UDP-galactose ->UDP glucose via UDP galactose 4 epimerase

Answer 326

Two transmembrane domains, two cytoplasmic nucleotide binding domains (NBDs) and regulatory domain that contains PKA and C phosphorylation sites; two trasnmembrane domains forms channel through which Cl passes

Answer 327

Agonist induced increases in cAMP followed by activation of PKA that phosphorylates the R domain; ATP binding and hydrolysis occurs at NBD and is essential for opening and closing of the channel

Answer 328

Outwardly rectified Cl, inwardly rectified K, epithelial sodium (ENaC), gap junction channels, and ATP transport and mucus secretion

Answer 329

Normal CFTR inhibits ENaC; in CF, ENaC activity increased and increases sodium uptake *except in sweat where ENaC activity decreases -> sine qua non (salty sweat)

Answer 330

- sweat glands: reabsorb luminal Cl and augment sodium reabsorption - respiratory: luminal secretion of Cl; mutation leads to isotonic but low-volume surface fluid layer

Answer 331

Mediated by reciprocal interactions with family of anion exchangers called SLC26 which are co expressed with CFTR; in some mutations, CFTR is preserved but bicarbonate transport is abnormal; alkaline fluids are secreted normally, but acidic fluids are secreted by epithelial harboring mutated CFTR -> leads to increased mucin precipitation, plugging of ducts, increased bacteria binding to mucin *pancreatic insufficiency

Answer 332

Defective protein synthesis = complete lack of CFTR at apical surface of epithelial cells

Answer 333

Abnormal protein folding, processing, and trafficking; deletion of delta F 508 is most common; complete lack of CFTR at apical surface

Answer 334

Defective regulation; prevent activation of CFTR by abrogating ATP binding and hydrolysis; normal amount of CFTR on surface, but its nonfunctional

Answer 335

Decreased conductance; mutation in transmembrane domain of CFTR; normal CFTR at apical membrane, but reduced function; associated with milder phenotype

Answer 336

Reduced abundance; mutations affect intrinsic splice sites or CFTR promoter such that there are reduced amount of normal protein; milder phenotype

Answer 337

Altered function in regulation of ion channels; delta F508

Answer 338

-mannose binding lectin 2, TGF beta1, interferon related developmental regulator 1; polymorphisms in these genes regulate resistance to lung infections; reason for different pulmonary manifestations

Answer 339

Colonizes lung; concurrent viral infections predispose to colonization; static mucus creates hypoxic micro environment in airway surface fluid which favors production of alginate (mucoid polysaccharide capsule); alginate permits formation of biofilm that protects bacteria from abs and antibiotics producing chronic destructive lung disease

Answer 340

Avitaminosis A can lead to squamous metaplasia of the lining epithelium of ducts in pancreas

Answer 341

Bile canaliculi are plugged by mucus material, accompanied by ductular proliferation and portal inflammation; hepatic steatosis, focal biliary cirrhosis

Answer 342

Same as pancreas; dilation of ducts, squamous metaplasia and glandular atrophy followed by fibrosis

Answer 343

Bronchioles distended with thick mucus associated with marked hyperplasia and hypertrophy of mucus secreting cells; lung abscesses; *infection with Burkhoderia cepacia is associated with fulminant illness (cepacia syndrome), longer hospital stays and increased mortality

Answer 344

Measurement of nasal transepithlial potential difference; with CF< will have more negative potential difference

Answer 345

Sudden death of an infant under 1 year of age which remains unexplained after a thorough case investigating, including performance of complete autopsy, examination of death scene, and review of clinical history

Answer 346

One or more characteristic phenotypic features or history of CF in sibling or positive newborn screening AND increased sweat chloride concentration or two CF mutations or abnormal epithelial nasal ion transport

Answer 347

2-4 months

Answer 348

Young maternal age <20, maternal smoking during pregnancy, drug abuse in either parent (specifically paternal marijuana and maternal opiate or cocaine use),short intergestational intervals, late or no prenatal care, low SES, AA or American Indian ethnicity

Answer 349

Brain stem abnormalities, usually male sex, prematurity or low birth weight, product of multi birth, SIDS in prior sibling, antecedent resp infections, germline polymorphisms in autonomic nervous system genes

Answer 350

Prone or side sleep position, sleeping on soft surface, hyperthermia, co-sleeping for first 3 months of life

Answer 351

Infections, viral myocarditis, bronchopneumonia, congenital anomaly, congenial aortic stenosis, traumatic child abuse, intentional suffocation, long QT syndrome, FA oxidation disorders, hisiocytoid cardiomyopathy, abnormal inflammatory responsiveness

Answer 352

Multiple petechiae are most common finding usually on thymus, visceral and parietal pleura, and epicardium; lungs usually congested (represent agonal events; CNS demonstrates astrogliosis of brain stem and cerebellum

Answer 353

Delayed development of arousal and cardiorespiratory control ; abnormalities in serotonin dependent signaling

Answer 354

When stimulates, typically elicits inhibitory cardiorespiratory reflex; stimulation is augmented by resp tract infections which increase volume of secretions and by the prone position, which impairs swallowing and leading of airways

Answer 355

- Heterotopia (choristoma): microscopically normal cells or tissues that are present in abnormal locations; ie: pancreatic tissue in wall of stomach or SI, adrenal cells in kidney, lungs, ovaries; usually of little significantce but can be confused with neoplasms - Hamartoma: excessive focal overgrowth of cells and tissues native to organ in which is occurs; do not reproduce normal architecture of surrounding tissue

Answer 356

Soft tissue tumors of mesenchymal derivation

Answer 357

Most common tumors of infancy; can be cavernous and capillary (later is more cellular than in adults, feature that is deceptively worrisome); most are located in skin on face and scalp where they produce flat to elevated irregular red blue masses; some of flat, larger lesions referred to as port-wine stains; may enlarge along with growth but can spontaneously regress; can represent von Hippel-Lindau disease; subset of CNS cav hemangiomas can occur in familial setting -> mutations in cerebral cavernous malformation cornea

Answer 358

Characterized by cystic and cavernous spaces; may occur in skin but more often in deep regions of neck, axilla, mediastinum, retroperitoneal tissue; benign but increase in size after birth b.c of fluid accumulation; can encroach on vital structures

Answer 359

Presents as diffuse swelling of part or all of extremity; considerable distortion and deformation can occur; lesion is not progressive; often difficult to correct

Answer 360

Fibromatosis or congenital infantile fibrosarcomas (better prognosis than adults); the later has chromosomal translocation t 12;15 (p13;q25) which results in ETV6-NTRK3 fusion *unique to infantile fibrosarcomas; simulates signaling via RAS and PI3K/AKT

Answer 361

Once at 2 years of age and then in late adolescence or early adulthood; first peak is congenital, later may be prenatal origin but are more slow growing

Answer 362

Sacroccygeal; more common in girls; associated with defects in hindgut and cloacal region and other modeling defects; most are mature teratomas; children with malignant lesions tend to be older than 4 months

Answer 363

Leukemia (ALL), neuroblastoma, wilms tumor, hepatoblastoma, retinoblastoma, rhabdomyosarcoma, teratoma, Ewing sarcoma, and posterior fossa neoplasms (juvenile astrocytoma, medulloblastoma, and ependymoma)

Answer 364

Tumors of sympathetic ganglia and adrenal medulla derived from primordial NC cells

Answer 365

Spontaneous or therapy induced differentiation of primitive neuro lasts into mature elements, spontaneous tumor regression, and wide range of clinical behavior and prognosis

Answer 366

Hepatocellular carcinoma, soft tissue sarcoma, osteogenic sarcoma, thyroid carcinoma, Hodgkin disease

Answer 367

Anaplastic lymphoma kinase (ALK); gain of function mutuations in ALK also seen in sporadic form

Answer 368

Younger than 18 months

Answer 369

Soft, gray-tan tissue; larger tumors have areas of necrosis, cystic softening and hemorrhage; can sometimes have areas of calcification; histologically composed of small primitive appearing cells with dark nuclei, scant cytoplasm and poorly defined cell borders growing in solid sheets; mitotic activity, karyotype is and pleomorphism; neutropill (fibrillar material) *rosssettes (homer-wright pseudorosettes) can be found in which tumor cells are arranged about a central space filled with neuropil

Answer 370

*ganglioneuroma; accompanied by appearance of schwann cells -> presence associated with favorable outcome

Answer 371

Early and widely -> liver, lung, bone marrow, bones

Answer 372

1: localized tumor with complete gross excision with or without microscopic residual disease; ipsilateral nonadherent LN negative for tumor (adherent LN can be positive for tumor) 2A:localized tumor with incomplete gross resection; ipsilateral nonadherent LN negative for tumor 2B:localized tumor with or without complete gross excision; ipsilateral nonadherent LN positive for tumor; enlarged contralateral LN which are negative for tumor 3:Unresectable unilateral tumor infiltrating across middling with or without regional LN involvement or localized unilateral tumor with contralateral LN involvement 4:any primary tumor with dissemination to distant LN, bone, bone marrow, liver, skin or other organs 4S: localized primary tumor with dissemination to skin, live and or bone marrow; *limited to infants younger than 1 year

Answer 373

In children under age 2 years with large ab masses, fever, and weight loss; in older children, may not come to attention until mets produce symptoms such as bone pain, resp symptoms, GI complaints; proptosis and ecchymosis may be present due to spread to periorbital region

Answer 374

Neonates with disseminated neuroblastoma present with multiple cutaneous Mets that cause deep blue discoloration of skin

Answer 375

1,2A,2B,4S

Answer 376

Absent chromosome 1 p and 11q loss; present TRKA expression with absent TRKB expression

Answer 377

Vanillylmandelic acid and homovanillic acid

Answer 378

Correlates with outcome in children less than 2, but loses prognostic significant after that; hyper diploid -> better prognosis; near diploid has more genomic instability with complex karyotype; ie:chromothripsis (localized fragmentation of chromosome segment followed by random assembly of fragments; results in amplification of NMYC)

Answer 379

Marker for neuroblastoma, family of RTKs that regulate growth of neural cells; high expression of TRKA is favorable, TRKB unfavorablle

Answer 380

Retinoids to induce differentiation of neuroblastoma; targets of ALK mutations

Answer 381

Onset about 10 months earlier than tumors restricted to one kidney

Answer 382

* syndromic tumors - WAGR syndrome: carry deletions of 11p13; WT1 and deleted AD gene for PAX6 (aniridia) - Denys-Drassh syndrome: gonadal dysgenesis (male pseudohermaphrodism), early onset nephropathy leading to renal failure; diffuse mesangial sclerosis; abnormalities in WT1, but abnormality is dominant negative missense mutation in zinc-finger region of WT1 that affects its DNA binding ability -> GU ab but no tumor; increased risk for gonadoblastomas - Beckwith-Wiedemann syndrome: organomegaly, macroglossia, hemihypertrophy, omphalocele, ab large cells in adrenal cortex; *genomic imprinting WT2; IGF2 expressed from paternal allele -> loss of imprinting; also at risk for hepatoblastoma, pancreatoblastoma, adrenocortical tumors, and rhabdomyosarcomas

Answer 383

Putative precursor lesions of wilms tumor; seen in renal parenchyma adjacent to some unilateral tumors and all bilateral tumors; *impt to identify because then at increased risk for developing tumor in contralateral kidney

Answer 384

Well circumscribed, soft, tan to gray, coco hemorrhage, cyst formation, necrosis; *triphasic combo of blastemal, stromal, and epithelial cells observed in majority of lesions; presence of anaplasia correlates with TP53 mutation and resistance to chemo

Answer 385

Large ab mass that can be unilateral or extend across middling and down into pelvis; hematuria, pain in abdomen, intestinal obstruction, HTN; pulm met often present at time of primary diagnosis; most patients can expect to be cured

Answer 386

Anaplasia, loss of genetic material on chromosomes 11q and 16q, gain of chromosome 1q

Answer 387

Developing second primary tumors including bone and soft tissue sarcomas, leukemia, lymphomas, and breast cancers; usually from radiation treatment

Exam 1 Flashcards

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