Comprehensive Basic Science Exam (CBSE) Review Set I with correct answers

Chagas Disease - correct answersCaused by Trypanosoma cruzi parasite passed in the feces of Reduviidae/kissing bug Penetrates broken skin or intact mucous membranes forming a pseudocyst releasing inflammatory infiltrates into myocytes; stains with Giemsa & Wright Romana sign occurs when portal of entry is the conjunctiva or eyelid May resulting in: Enlarged heart- CHF, sudden cardiac arrest Enlarged esophagus- difficulty swallowing Enlarged colon- abdominal pain or constipation Treat with benznidazole or nifurtimox Monocytes - correct answerscell with half-moon shaped nucleus that participates in phagocytosis Chronic graft rejection - correct answersmultifactorial but typically involves arteriosclerosis HLA-B27 - correct answersPAIR: Psoriasis Ankylosing spondylitis- chronic synovitis destroying cartilage typically in young men Inflammatory bowel dz- Crohn's & UC Comprehensive Basic Science Exam (CBSE) Review Set I Reactive Arthritis- Reactive Arthritis - correct answersArthritis as a reaction to a bacterial infection such as Campylobacter, Chlamydia, Salmonella, Shigella, or Ureaplasma. Associated with conjunctivitis & uveitis Gaucher (Type 1) - correct answersAR Lysosomal storage disease Accumulation of sphingolipid glucocerebroside Most common Wrinkled tissue paper I Cell disease - correct answersFailure of Golgi apparatus to phosphorylate mannose 6-phosphate the marker to export enzymes to lysosomes resulting in accumulation of lysosomal enzymes in serum Nitroblue tetrazolium test - correct answersAqualitative test to determine defects in NADPH oxidase Negative: CGD Positive: Acute Hepatitis, Mono CGD (chronic granulomatous disease) - correct answersinability to produce NADPH oxidase; susceptible to Cat + organisms; elevated neutrophils w/ normal T cell Gp91 phox subunit: heme binding subunit of superoxide generating NADPH Treat with interferon gamma Clarithromycin (macrolide) - correct answersADR of metallic taste & GI Codeine - correct answersADR resp. depression, euphoria, & constipation Cyclobenzaprine - correct answersStructurally similar to TCAs w/ anticholinergic side effects used for relief of muscle spasms May exacerbate glaucoma Naproxen - correct answersADR of GI & renal (in elderly) Timolol - correct answersUsed in HTN & glaucoma; ADR of bradycardia & worsening asthma Bacterial vaginosis - correct answersSloughed mucosal cells = clue cells Trichomoniasis - correct answersCilated, motile trophozoites w/ corkscrew-like motility Autism - correct answersLack of eye contact, verbal communication, & separation anxiety; repetitious behavior Emphysema - correct answersDecreased FEV1/FVC ratio, normal FVC; TLC, FRC, & RV increase Parathyroid hormone(PTH) vs phosphate in hypercalcemia - correct answersPTH: rapid & direct Phosphate: slow & indirect ANP: - correct answersAfib, Ch-1p, NPPA gene mutation causing binding interference,- decrease cGMP Failure of development of 3rd or 4th pharyngeal pouches - correct answersDiGeorge syndrome (CATCH 22): truncus arteriosus & agenesis of parathyroid glands May also be associated w/ failure of thymus to develop -> T lymphocytes w/ CD3 marker Huntington disease - correct answersPCR is the most common method to est. # of CAGs Both the coding & template strands bind the forward & reverse primers on 3' end Pyrmidine Dimers - correct answersBRAF gain of function mutation causing covalant thymine (or Cystine) bonds normally repaired thru NER in the G1 phase by endonuclease recognition then excision (DNA polymerase then fills; ligase then reseals) Xeroderma pigmentosum - correct answersMutation of NER endonuclease from UV radiation disrupting DNA replication due to the oligonucleotides remaining damaged DNA Polymerase I - correct answersRemoval of both leading & lagging RNA primers 5' to 3' (unique) Proofreading of mismatch nucleotides via 3' to 5' exonuclease & elongation of lagging strand 5' to 3' (universal) Topoisomerase - correct answersEnzyme that functions in DNA replication, helping to relieve strain in the double helix ahead of the replication fork. Teniposide - correct answersTopoisomerase II inhibitor acting in the S phase & G2 phase: S phase: prevents proper unwinding of supercoils & reannealing of DNA G phase: Permanent breaks in both strands of DNA preventing transcription & repair inducing cell cycle arrest Cytarabine - correct answersAntimetabolite inhibiting DNA polymerase, arresting cells solely in S phase Fluoroquinolones ( -floxacin) - correct answersBactercidal: direct inhibition of topoisomerase 2 & 4 halting DNA replication as 1st line treatment of uncomplicated pyelonephritis; older for gram negative & aerobic, newer more broad spectrum Contraindicated in LQTS with ADR of torn achilles Long QT syndrome - correct answersRare inborn heart condition in which delayed repolarization of the heart following a heartbeat increases the risk of episodes of torsade de pointes and other life threatening arrhythmias. Prolongation of the QT interval is a diagnostic of the condition. KCNQ1 and KCNE1 Romano-Ward syndrome - correct answersAD inherited congenital long QT syndrome No deafness Increased risk for SCD due to Torsades (polymorphic ventiruclar tachycardia) Jervell and Lange-Nielsen syndrome - correct answersAR inherited congenital long QT syndrome with congenital sensoneural deafness Increased risk for SCD due to Torsades Telemorase - correct answersCarries its own RNA template at 3' for prevention during DNA replication Salicylate (Aspirin) toxicity - correct answersMixed acid base disorder with: Early phase respiratory alkalosis, low PaCO2 Late phase metabolic acidosis, low HCO3 Normal pH Increased conversion of acteyl-CoA to ketoacids & pyruvate to lactate Lung adenocarcinoma - correct answersPeripheral glandular tumor with mucin & papillary components; biopsy for efficacy of therapy Presents in young, female, nonsmokers, with signet ring, EML4-ALK or EGFR & KRAS Signet Ring - correct answersCell with a large vacuole, seen predominantly in carcinomas. Most frequently associated with stomach cancer, but can arise from prostate, bladder, gallbladder, breast, colon, ovarian stroma and testis Scalded Skin Syndrome - correct answersS. Aureus release of exofoliative toxin A causing desmosomal keratinocyte cleavage in S. Granulosum Causing B. Impetigo: Nikolsky positive blistering brown rash with flaccid bullae that easily slough off Pemphigus Vulgaris - correct answers Cancer Anorexia- Cachexia syndrome - correct answers3 part MOA resulting in decreased calorie intake & hypermetabolic state resulting in significant weight loss 1. Cytokines IL-1, IL-6, INF-y, & TNF-a stimulate NfKb that activates ubiquitin proteasome pathway 2. TNF-a also mediates appetite suppression 3. Lipase activation causes reduction of body fat Ubiquitin-proteasome pathway - correct answersMyosin chains undergo degradation increasing catabolism Isosorbide Mononitrate - correct answersUnlike other nitrates does NOT undergo 1st pass metabolism by the liver w/ nearly 100% bioavailability, providing means of oral treatment for preventation of angina by CAD thru dephosphorylation of myosin light chains Itraconazole (Sporanox) - correct answersAntifungal that inhibits synthesis of ergosterol; metabolized by CYP450 Has a low pKa & requires a low gastric pH for dissolution & absorption; PPIs can result in low bioavailability due to gastric pH changes not CYP450 Pantoprazole - correct answersPPI with little effect on CYP450 metabolism Medications with high pKa - correct answers- Amphetamines - Phenytoin - Allopurinol - Propylthiouracil histone deacetylation - correct answersCharged ionic attraction between positive lysine residues & negative DNA occurs thru the removal of acetyl groups by histone deacetylase; resulting in DNA histones binding more tightly, restricting transcription C. Diphtheria - correct answersProduces AB toxin that inactivates ribosomal translocation, ribosomes moving by triplets on mRNA in 3' direction, during elongation phase by adding ADP-ribose to EF-2 Presents as grayish white pseudomembranes, severe lymphadenopathy, sore throat, fever, & malaise in unvaccinated Pulmonary Artery HTN - correct answersIncreased RV afterload that can lead to cor pulmonale Harder to eject blood during systole causing delayed closure of pulmonary valve- wide/fixed S2 split Increased velocity when pulmonary valve does close from increased diastolic pressure- loud P2 Cortisol - correct answersBIG fib Increased: - BLOOD PRESSURE - INSULIN RESISTANCE - GLUCONEOGENESIS decreased: - fibroblast - immune/inflammation - bone formation Cocaine - correct answersPotential anesthetic mediated by Sodium channel blockade that binds to presynaptic monoanime transporters decreasing reuptake of norepinephrine Also works as an indirect sympathomimetic on both alpha & beta adrenergic receptors Cisplatin, carboplatin - correct answersAlkylating agent-->cross-links DNA-->decreased DNA and RNA synthesis used mostly in GI tumors ADR = nephrotoxicity, otoxicity, "plates in your ears and kidneys" Mitigate nephrotoxicity by using Amifostine (scavenger of free radicals) Clomiphene - correct answersNonsteroidal estrogen receptor blocker for the treatment of PCOS & anovulation thru continued release of FSH & LH Cyclophosphamide - correct answersalkylating agent used to treat cancers ADR: Reduce toxicity with Mesna Cyclosporine - correct answersBinds cyclophilin inhibiting calcineurin that promotes interleukin−2 synthesis, suppressing T cells reducing risk of transplant rejection (not myelosuppressant) ADR: hirsutism, gingival hyperplasia, hyperlipidemia, HTN, nephrotoxicity (dose−limiting), & seizures (overdose) Anterior Pituitary hormones - correct answersFLAT PEG FSH, LH, ACTH, TSH Prolactin, Endorphins, GH Chediask- Higashi Syndrome - correct answersDecreased phagocytosis from recessive mutation of lysosomal regulators resulting in recurrent pyogenic infections w/ albinism Carnitine Shuttle Defect - correct answersImpaired transport of LCFAs into the mitochondrial matrix, the substrate needed for B-oxidation Resulting in toxic accumulation & hypoketonemia Zellweger syndrome - correct answersDefect in peroxisome formation preventing catabolism of very long chain FA (VLCFAs) or branched-chain FAs Resulting in fat accumulation & inability to form myelin causing hypotonia, hepatomegaly, & facial grimacing MEN1 syndrome - correct answersInherited failure of tumor supressor menin resulting in parathyroid, pancreas, & pituitary tumors Zollinger-Ellison syndrome - correct answershypersecretion of gastric acid that produces peptic ulcers as a result of a non-beta-cell tumor of the pancreatic islets MEN2 - correct answersInherited variation of proto-oncogene RET (specific for neural crest & TK rec) resulting in parathyroid tumors, pheochromocytoma, & medullary thyroid cancer MEN3 - correct answersInherited variation of proto-oncogene RET resulting in marfanoid, megacolon, mucosal neuroma, & medullated cornea generalized edema (anasarca) - correct answersMediated by cytokines TNF-a and IL-6 Base Excision Repair (BER) - correct answersA DNA repair pathway that involves excision of a damaged base by DNA glycosylase Followed by cleavage of the DNA backbone adjacent to the site by an AP endonuclease Nick translation, DNA polymerization, and ligation complete the repair Daptomycin - correct answersBactericidal antibiotic that causes potassium efflux & rapid membrane depolarization inhibiting intracellular synthesis of DNA, RNA, & proteins ADR: creatine phosphokinase & rhadomyosis, especially with concurrent use of statins Vancomycin alternative for MRSA but NOT to used with concomitant S. Aureus pneumonia because inactivated by surfactant & low lung pentration Tryptophan - correct answerstRNA: 3' ACC 5' mRNA: 5' UGG 3' encoded by only 1 codon tRNA acceptor stem - correct answers5' CCA 3': ATP dependent binding of amino acid catalysed by aminoacyl-tRNA synthase Turner Syndrome - correct answersCardinal features: short stature, webbed neck, & amenorrhea 45XO: Non-lyonized- Absent barr body from inactivated X chromosome 46XX (mosaic): Postzygotic mitotic nondisjunction from failure of sister chromatids to separate Down Syndrome - correct answersMeiotic: 95% of cases due to non-disjunction of Ch21 during meiosis I or II resulting in 3 copies & 47 chromosomes Mitotic: 1% of cases wiith 2 different cell lines; one w/ 47 another w/ 46 Unbalanced Robertsonian: Inheritance of a translocated Ch21 & a normal Ch21 leading to 3 copies while maintaining 46 chromosomes & causing downs Balanced Robertsonian: Exchange of homologous chromosomes w/o changing genetic material, typically between Ch 14 & Ch21; causing increased risk of Downs in offspring Degeneracy - correct answersredundancy of the genetic code; that is, most amino acids are encoded by several codons bacterial transformation - correct answersUptake & incorporation of environmental genetic material Viral Transduction - correct answersTransfer & integration of host DNA into viral cell viral reassortment - correct answersAbility amongst segmented viruses, BOAR, to exchange segments intracellularly when coinfecting a host cell Viral complementation - correct answersUse of products from one virus (Hep B) in order for another virus to work (Hep D) Viral phenotypic mixing - correct answersOccurs with simultaneous infection of a cell with 2 viruses. Partial or complete coating of the surface proteins of 1 virus onto the other. However, material is NOT shared uniparental disomy - correct answersOffspring receives 2 copies of a chromosome from 1 parent and no copies from the other parent. Angelman: absence or loss of function of UBE3A gene of Ch15 from mother & inactivation by genomic imprinting of the father's Prader-Willi: absence or loss of various genes on Ch15 from father & inactivation by genomic imprinting of the mother's Placental mosaicism - correct answersDescrepancy between placental genotype & that of the fetus Kartagener's syndrome - correct answersImmotile cilia due to a dynein arm defect. Results in male and female infertility (sperm immotile), bronchiectasis, and recurrent sinusitis (bacteria and particles not pushed out); associated w/ situs inversus. Cystic Fibrosis - correct answersDeletion of 3 DNA base pairs that code for phenylalanine in the CFTR gene at the delta 508 position Results in protein misfolding & subsequent Chloride channel dysfunction Presents as failure to thrive, abdominal distention, steatorrhea, & anemia indicating malnutrition along w/ recurrent URIs & exocrine pancreatic insufficiency Primase - correct answersA DNA dependent RNA polymerase that creates a 5-10 nucleotide RNA sequence Because producing RNA requires uracil Does not require a free 3' -OH group to add nucleic acids Foscarnet - correct answersAntiviral, DNA polymerase inhibitor, that does not require phophorylation by viral kinase- binds pyrophosphate sites ADR: seizures due to hypocalcemia; nephrotoxicity; leukopenia; GI upset; & abnormalities in phosphate, potassium, & magnesium Used to treat CMV infections and acyclovir-resistant HSV/VZV infections Cidofovir - correct answersAntiviral, DNA polymerase inhibitor, that does not require phosphorylation by viral kinase effective against herpes simplex No contraindications due to seizures Hydroxycobalamin - correct answersTreats cyanide poisoning by bonding directly & forming cyanocobalamin which is excreted by the kidneys Sodium thiosulfate - correct answersTreats cyanide poisoning by supplying additional sulfur, facilitating the continued detoxification by rhodanese Sodium Nitrate - correct answersTreats cyanide poisoning by first oxidizing hemoglobin to methemoglobin then (indirectly) binding cyanide forming cyanmethemoglobin diverting it from cytochrome complex IV Sodium Nitroprusside - correct answersHas 5 cyanide groups that can cause cyanide poisoning by binding cytochrome complex IV blocking the electron transport chain Causes a decreased oxidative phosphoylation; anaerobic metabolism, lactic acid, & metabolic acidosis Resulting in confusion, abdominal pain, & flushing Electron Transport Chain (ETC) - correct answersA sequence of electron carrier molecules (membrane proteins) that shuttle electrons during the redox reactions that release energy used to make ATP. Group A Strep - correct answersMajor virulence is M protein, a transmembrane protein, that blocks phagocytosis by inhibiting alternative complement pathway Also shares epitopes w/ human proteins causing molecular mimicry- antibodies cross react to self antigens in myocardium, acute rheumatic fever Alternative Pathway - correct answersC3 present in the blood combines with factors B, D, and P on microbe surface without requiring antibodies C3 splits into C3a and C3b, functioning the same as in the classical pathway Neutropenia - correct answersAbsolute neutrophil count <1000; norm: 4000-11,000 ANC=total WBC x %neutrophils Causes: chemo, drug induced, hematologic disorders, autoimmune disorders, infections, & misc.- severe sepsis, bone marrow infiltration, hypersplenism, nutritional deficiencies, transfusion reaction, or hemodialysis Group B Strep - correct answersS. agalactiae Enterococcus faecalis (Group D Strep) - correct answersEnteric gram positive that is part of normal GI flora; patients w/ severe neutropenia are at increased risk of infection Listeria - correct answersFacultative anaerobic gram positive intracellular rod with tumbling motility, capable of surviving in cold temperatures in the presence or absence of oxygen Self-limiting gastritis in healthy individuals with severe effects on immunocompromised Associated w/ comsumption of dairy & deli meats; treat with ampicillin Strep Pneumo - correct answersLancet-shaped, gram-positive, facultative anaerobic bacteria Number 1 cause of MOPS: Meningitis, Otitis media, Pneumonia, & Sinusitis Vaccines: IgM for adults, IgG for children Pseudomonas - correct answersEndotoxin lipid A, part of LPS gram negative cell wall, causes inflammation by activation of macrophages & complement cascade (TNFa, IL-1, & IL-6) causing further release of inflammatory mediators nitric oxide & histamine producing hypotension due to septic shock Associated with sickle cell & cystic fibrosis N. Meningitidis - correct answersComposed of LOS, not LPS (LOS lacks O antigen), in gram negative cell wall; lipid A component still present & produces hypotension from septic shock Tay-Sachs - correct answersCaused by a frameshift mutation resulting in complete misreading of information downstream resulting in decreased protein translation of hexosaminidase A Progressive neurodegeneration, developmental delay, red spot on macula, & lysosomes filled with GM2/ gangliosidosis Neimann-Pick - correct answersDeficiency in sphingomyelinase resulting in accumulation of the lipid sphingomyelin due to mutation in SMPD1 gene Presents w/ Enlarged spleen & liver, Jaundice, intellectual deficit, "Cherry-red" spots in eyes, & Muscle weakness, Histones - correct answersAbundant lysine & arginine amino acids with positively charged side groups Linker - correct answersH1 histone Noncovalently binds to stabilize the chromatin fiber by binding to the nucleosome & DNA Nucleosome - correct answersMade up of H2A, H2B, H3, & H4 Positive charge of the nucleosome forms ionic bonds w/ negatively charged DNA Due to a high proportion of anionic phosphate molecules Fanconi Anemia - correct answersAR gene mutation, similar to BRCA1 in breast & ovarian cancer Responsible for homologous end joining repair of DNA interstand crosslinks causing bone marrow failure Anemia of chronic disease - correct answersAlso called the anemia of inflammation, Associated with cancer, infections, autoimmune & inflammatory diseases such as rheumatoid arthritis or lupus Microcytic anemia with ↓ serum iron, ↓ total iron-binding capacity (TIBC), and normal or ↑ ferritin Hepcidin - correct answersHormone produced by the liver that regulates iron by preventing its release when bound to ferritin promoting intestinal absorption Ferritin - correct answersLocated on the basolateral surface of gut enterocytes and the plasma membrane of reticuloendothelial cells that function to store iron Acute Phase Reactants - correct answersFactors produced in the liver induced by IL-6 whose serum concentrations change significantly in response to inflammation: C-reactive protein, Ferritin, & Fibrinogen Porphyria cutanea tarda - correct answersRare photosensitive bullous disease characterized by painful, blistering skin lesions; liver abnormalities may also occur Due to deficiency of uroporphyrinogen decarboxylase Acute Intermittent Porphyria (AIP) - correct answersThe most common porphyria- an AD metabolic disorder affecting the production of heme resulting from a deficiency of the porphobilinogen deaminase Causes urine to turn dark upon standing, abdominal pain, agitation, tachycardia, breathing problems, nausea, confusion, & lower extremity weakness Hemin - correct answersD- ALA synthase Inhibitor used in the treatment of AIP MRSA (methicillin-resistant Staphylococcus aureus) - correct answersStrain of S. Aureus that has gained resistant thru mutation of mecA gene Treat w/ Vancomycin or Daptomycin; NOT aminoglycosides or macrolides Dermatomyositis - correct answersPresents with proximal muscle weakness, heliotrope rash over eyelips, & Gottron papules on dorsal interphalengeal joints Diagnose by detection of anti-Mi2 & anti-Jo1 antibodies; parafascicular & perivascular infiltration w/ plasmacytoid dendritic cells & B lymphocytes Increased risk of developing malignancies associated with inflammatory myopathies- ovarian, cervix, lungs, & bladder Pompe Disease - correct answersBoth Lysosomal & Glycogen (Type II) Storage Disease Due to a-1,4 & a-1,6 glucosidase activity (acid maltase) deficiency Causes cardiomegaly/hypertrophic cardiomyopathy, leading to hypotonia, exercise intolerance & early death hypertrophic cardiomyopathy - correct answersA condition in which the heart muscle becomes abnormally thick. Methylation of cytosine - correct answersDNA methyltransferases typically within a gene promoter (CpG islands) repress gene transcription Most common epigenetic modification of human DNA involved inactivation of the X chromosome leading to formation of barr bodies Absent in Turner, Extra in Klinefelter Pyruvate dehydrogenase complex (PDHC) deficiency - correct answersFailure to convert pyruvate to acetyl Coa Presents as growth retardation & neurological defects Improves with ketogenic diet; worsens witih glucose-rich foods or glucogenic amino acids (such as valine) Results in pyruvate accumulation & shunting to lactate & alanine causing metabolic acidosis Ketogenic Amino Acids - correct answersLeucine & Lysine Glucogenic Amino Acids - correct answersCan be converted into intermediates that feed into gluconeogenesis anesthetic potency - correct answersIncreased by high lipid solubility or low minimal alveolar concentration, allowing for greater ability to cross the BBB Can also cause risk of delayed recovery due to elimination thru redistribution & accumulation in obese patients SPEED OF ANESTHETIC INDUCTION - correct answersVaries based on solubility in the blood and the difference in partial pressure between alveolar gas and venous blood Fenoldopam - correct answersNot a Benzo! D1 receptor agonist: vasodilation of coronary, renal, splanchnic, & peripheral vessels Decrease blood pressure in hypertensive emergencies & increase natriuresis Contraindicated in glaucoma Metabolic Syndrome - correct answersA cluster of conditions that increase the risk of heart disease, stroke, diabetes, & nonalcoholic steatohepatitis Conditions: high blood pressure, high blood sugar, excess body fat around the waist, and abnormal cholesterol levels nonalcoholic steatohepatitis (NASH/fatty liver) - correct answersFatty infiltration of hepatocytes independent of alcohol resulting in eventual necrosis & fibrosis of liver leading to cirrhosis or hepatocellular carcinoma Parvovirus B19 - correct answersCauses aplastic anemia by binding to blood group P antigens; measured by hemagglutination Associated with sickle cell anemia Can be treated with monoclonal antibodies to globosides, an essential component of P antigens Cytosine vs Cysteine - correct answersCytosine: Nucleic acid complement to guanine Cysteine: Amino acid with Thiol side group oxidized to cystine; cystine is site of redox & mechanical linkage for 3D structure Marfanoid habitus - correct answersPresents as tall; thin; long limbs, toes, & fingers (arachnodactly); bilateral inferomedial lens subluxation, & intellectual disability Associated with MEN2, MEN3, & Homocystinuria Pheochromocytoma - correct answersBenign tumor of the adrenal medulla that causes the gland to produce excess epinephrine Associated with MEN2, MEN3, NF1, VHL Neurofibromatosis Type 1 - correct answersPresents with: optic gliomas, hyperpigmentated café au lait spots, cutaneous neurofibromas, & bone dysplasia Alkaptonuria (ochronosis) - correct answersBenign AR deficiency of homogentisate oxidase in the degradative pathway of tyrosine to fumarate Turns urine & organs dark, calcification of heart valves, nephrolithiasis, & arthralgia Arginase deficiency - correct answersPresents w/ unsteady gait, lower extremity spasticity, poor feeding, & vomiting Increased serum arginine without hyperammonemia like deficiencies of other enzymes in the urea cycle (seen in late infancy) Deficiency causes failure of arginine to be converted to ornithine Galactosemia - correct answersLactose from breastfeeding causing hypoglycemia because when broken down to glucose & galactose, the galactose is unable to be for glycosis GALT deficiency: The most common form can cause cirrhosis, renal failure, hypogonadism, seizures, brain damage, & cataracts Galactokinase def: causes infantile cataracts only from accumulation of galactitol in lens of the eye Coenzyme A - correct answersCarrier of acyl groups such as in - acetyl CoA - succinyl CoA - methylmalonyl CoA Reactions involved in: - a ketoglutarate dehydrogenase - pyruvate dehydrogenase - citrate synthase Cofactor of pantothenic acid (Vitamin B5) Pantothenic Acid (Vitamin B5) - correct answersPrecursor to Coenzyme A that is required for the transfer of 2 acyl groups Deficiency is rare usually occurring during famine or war Presents as irritability, abdominal cramps, & burning paresthesias of the feet Urea Cycle Disorders - correct answersHyperammonemia and increased blood glutamine levels Paget's disease of the breast - correct answersinvasive ductal cancer into nipple Paget's disease of bone (Osteitis Deformans) - correct answersSkeletal disease of increase bone resorption and formation which softens, thickens, & deforms bone Caused by RANKL- RANK receptor activation triggering Nf-Kb signaling direct increase of osteoclast, & responsive increase of osteoblast Characterized by bowed long bones, sudden fractures, frontal bossing, enlarging skull, headache, vertigo, tinnitus, progressive deafness, optic atrophy & spinal cord compression Metabolic processes in the cytoplasm - correct answers- Glycolysis - Nucleotide synthesis: - Nonsecretory protein synthesis: RER - Fatty Acid synthesis: Mitochondria First step of HMP shunt - correct answersRate limiting step occuring solely in cytoplasm Glucose-6-phosphate to 6-phosphogluconolactone By enzyme glucose-6-phosphate dehydrogenase Renal ammonia - correct answersPrimarily generate from glutamine entering the PCT by apical amino acid & basolateral membrane transporters Glutamine is catabolized to glutamate & ammonium; glutamate transformed into a-ketoglutarate Therefore inhibiting glutamine uptake decreases both glucose production & NH4+ excretion; resulting in low blood sugar & positive urine anion gap w/o urine glucose increase RNA polymerase I - correct answersExclusively present in the nucleolus where it performs rRNA transcription; catalyzing all types except 5S which is transcribed by RNA polymerase III in the nucleus Lyme disease - correct answersCaused by: Presents as: Treat with doxycycline; complication to Lyme carditis causing Mobitz Type I use ceftriaxone Mobitz Type I (Wenckebach) - correct answersSecond degree block with progressively longer PR intervals before a QRS is dropped and resets the cycle Mobitz Type II - correct answers2nd degree block Prolonged PR unchanged and then drop one beat 3: 2 -> for ever 3 x atrium beats the ventricle beats 2 x Third degree AV block - correct answersThe atria and Ventricles are totally dissociated. -So, the QRSs and the P waves have no relation to each other. Tetrahydrobiopterin (THB) - correct answersConverted from dihydropterin thru reductase Precursor to: Tyrosine, deficiency leading to subsequent decreases of DOPA, dopamine, norepinephrine, & melanin Causing hypotonia, progressive neurologic deterioration, fair skin, & blue eyes Isoniazid (INH) Treatment - correct answersUsed in Tuberculosis Slow acetylators Drug Induced Lupus Vit B6 deficiency CYP450 inhibitor Acute Tubular Necrosis (ATN) - correct answersOliguria, elevated serum creatinine, granular muddy casts, proteinuria, & patchy necrosis in PCT within 2 weeks of kidney insult May be caused by use of Gentamicin Aminoglycosides - correct answersGentamycin, Kanamycin sulfate, Neomycin sulfate, & Streptomycin Sulfate ADR: ototoxicity & kidney damage (ATN) Methotrexate - correct answersCompetitive inhibitor of dihydrofolate reductase that catalyzes the synthesis of tetrahydrofolate Can cause folate deficiency leading to painful ulcers Megaloblastic Anemia - correct answersa blood disorder characterized by anemia in which the red blood cells are larger than normal Folate (Vitamin B9) - correct answersCoenzyme in the transfer & methylation of nitrogenous bases needed for DNA synthesis Deficiency can cause megaloblastic anemia & oral ulcers; may be due to treatment with Methotrexate for RA Rheumatoid Arthritis - correct answersA chronic systemic disease characterized by inflammation of the joints, stiffness, pain, and swelling that results in crippling deformities Leukocytoclastic vasculitis - correct answersUmbrella term for vasculitides such as Behcet's & HSP Behçet's: multi-system disorder presenting with uveitis, recurrent oral & genital ulceration, venous thrombosis, and skin & joint involvement HSP: Inflammation induced by IgA deposit into walls of small vessels follwoing an URI causing palpable purpura, abdominal pain, renal disease, & arthralgias; occassionally blood stools Differentiate from thrombocyptopenia by rise in platelet count Sarcoidosis - correct answersChronic inflammatory disease in which small nodules (noncaseating granulomas) develop in lungs, lymph nodes, and other organs Characterized by macrophages within the granulomas with elevated levels of 1a-hydroxylase leading to hypercalcemia PRPP synthetase - correct answersCatalyzes the production of PRPP, a substrate for de novo purine & pyrimidine synthesis Increased activity causes an overproduction of uric acid from purine degradation leading to accumulation of monosodium urate crystals- Gout Bevacizumab - correct answersMonoclonal Ab against VEGF inhibiting angiogenesis; used in solid tumors such as colorectal cancers & renal cell carcinoma and neovascular age related macular degeneration Rule out Hx of GI bleeding due to risk of increased perforations, hemorrhage, heart failure, HTN, & impaired wound healing Restoration of Central Thermoregulatory Set-point - correct answersAccomplished by NSAIDS & acetaminophen by decreasing production of prostagladin E2- antipyretics Although used to control fevers no effect on fever induced seizures Maple Syrup Urine Disease - correct answersDefect in alpha keto acid dehydrogenase, leading to an inability to degrade branched amino acids (isoleucine, leucine, valine I Love Vermont Maple Syrup) Results in poor feeding & dystonia as well as maple syrup scent of patients urine Patients may be responsive to thiamine supplementation due to a cofactor for the dehydrogenase Polymerase Chain Reaction (PCR) - correct answersTest that multiplies a specific target segment of DNA using primers & DNA polymerase enzyme Flow cytometry - correct answersTechnique used to count/sort cells after immunolabeling antigen of interest Paroxysmal nocturnal hemoglobinuria - correct answersResults from impaired synthesis of glycosylphosphatidylinositol (GPI) anchor linking CD55/CD59 to plasma membrane Can present with pancytopenia, DVT, & intermittent hemoglobinuria Lesch-Nyhan syndrome - correct answersX-linked recessive disorder is characterized by hyperuricemia, spastic cerebral palsy, mental retardation, and self-mutilation due to HGPRT deficiency Hereditary Abetalipoproteinemia - correct answersAbsence of production of apolipoprotein B (Apo B); resulting in no chylomicrons, LDL, or VLDL in serum, leading to fat malabsorption Treat with low fat soluble diet & fat soluble vitamin supplementation Bacteroides fragilis - correct answersGram negative anaerobe that is part of the normal flora of the colon; a common pathogen in diabetic ulcers Pyridoxine (B6) - correct answersActivated to pridoxal phosphate; transamination cofactor for ALT & AST Required for: - Glycogen phosphorylase reactions - Decarboxylation - Synthesis of cystathionine, heme, niacin, histamine, & neurotransmitters Adrenoleukodystrophy - correct answersX-linked neurological diseased caused by peroxisomal ATP Binding Cassette defect in β-oxidation resulting in very long chain FA accumulation affecting adrenals, testes, & white matter Amanita phalloides - correct answersWild mushroom that produces the toxin, a-amantin, that inhibits mRNA synthesis Preferrentially taken up by the liver causing severe hepatotoxicity Manifest with severe diarrhea 6-24 hours after ingestion that resolves in 24-36 hours; Multiorgan failure 2-4 days after ingestion Lynch Syndrome (HNPCC) - correct answersAD non-polyposis syndrome with high risk of CRC Acute cholangitis - correct answersThe acute disease of the bile ducts caused by an ascending bacterial infection from the small intestines and characterized by neutrophilic inflammation Brown Pigment Gallstones - correct answers-form when bacteria alters bilirubin in the gallbladder -altered bilirubin then combines w calcium & fats to form dark brown gallstones 7a-hydroxylase - correct answersreduced by fibrates, needed for conversion of cholesterol to bile acids Psoriasis - correct answerschronic recurrent dermatosis characterized by flare-ups in which red papules covered with silvery scales occur on the elbows, knees, scalp, back, or buttocks Ankylosing spondylitis - correct answersLong-term inflammation of the joints of the spine Frequently develops some of the features of restrictive lung disease because of impaired mobility of the spine & thoracic cage inflammatory bowel disease - correct answersinflammation of the colon and small intestine due to Crohns or UC Reiter's syndrome (reactive arthritis) - correct answersSeronegative spondyloarthropathy that often presents with a triad of conjunctivitis, urethritis, & oligoarthritis - "Can't see, can't pee, can't climb a tree" Usually occurs 2-8 weeks after an infection such as a STD or gastroenteritis Limited Scleroderma - correct answersAnti-centromere Calcinosis, Raynaud's, Esophageal dysmotility, Sclerodactyly, Telangiectasia DIffuse Scleroderma - correct answersAssociated with anti-Scl-70 antibody (anti-DNA topoisomerase I) & anti RNA polymerase III antibody Widespread skin involvement with rapid progression & early visceral involvement Rheumatoid factor - correct answersGroup of autoimmune, typically IgM, that target the Fc region of IgG Associated with RA but has low specificity Sonic hedgehog (Shh) - correct answersCritical role in patterning neurologic development & organizing the anterior-posterior axis of the embryo, not the craniocaudal axis Mutations result in craniofacial defects, holosencephaly, & abnormal tooth development HOX gene - correct answersCritical role in organizing the craniocaudal axis of the embryo; ensuring proper placement of limbs Mutations may result in craniofacial defects, atypical limb placement, & syndactyly Biotin (B7) deficiency - correct answersAlopecia, enteritis, dermatitis, conjunctivitis, faitgue, & parasthesias in the setting of extreme consumption of raw egg whites Biotin is a cofactor for carboxylase enzymes Hartnup disease - correct answersAR defective neutral amino acid transporters on PCTs and enterocytes leads to neutral amino aciduria, decreased gut absoprtion & conversion of tryptophan to niacin causing pellagra. Treat with high protein diet and niacin. Niacin (B3) - correct answers Pellagra - correct answers Cladribine - correct answersFirst line treatment of hairy cell leukemia Mimics adenosine & inhibits nucleotide metabolism Resistance to breakdown by adenosine deaminase during S phase Pentostatin - correct answersNot a statin! Treatment for hairy cell leukemia Inhibits adenosine deaminase-->decreased purine degradation Essential tremor - correct answersAD nerve disorder causing slowly progressive, symmetric postural tremors while moving or trying to move; not usually associated with Parkinson's Improves with alcohol; treat w/ propranolol Atracurium - correct answersSkeletal muscle relaxant that undergoes Hofmann elimination, spontaneous organ independent breakdown & elimination, along with a predictable duration of time Preferred in patients with impaired renal or hepatic function Von Gierke's Disease - correct answersType 1 glycogen storage disease (most common) due to defect in glucose 6 phosphatase used in the final steps of both glycogenolysis & gluconeogenesis Leads to periods of hypoglycemia between meals requiring continual eating to maintain blood sugar Additionally accumulation of glucose 6 phosphate builds up enlarging & damaging the liver over time Celecoxib - correct answersNSAID, COX-2/prostaglandin synthesis inhibitor Can cause vasoconstriction of afferent arterioles & subsequent renal impairment decreasing clearance, especially of lithium causing toxicity Fabry disease - correct answersFabry was a gal that liked to tri ceramix Inherited x-linked deficiency of a-galactosidase that causes accumulation of ceramide trihexoside in tissues developing into progressive renal failure Earliest manifestations are cataracts, angiokeratomas, hypohidrosis & acroparesthesia I cells - correct answersLocated in the duodenum & jejunum where they secrete CCK which increases pancreatic secretion & slows gastric emptying S cells - correct answersLocated in the duodenum & jejunum where they produce secretin which increases pancreatic bicarbonate & bile secretion causing decreased gastric acid secretion & neutralization of chyme K cells - correct answersLocated in the duodenum & jejunum where they secrete glucose-dependent insulintropic peptide (GIP) which decreases gastric acid & increases insulin secretion Ornithine transcarbamylase deficiency - correct answersMost common urea cycle disorder X-linked recessive (other urea cycle enzyme deficiencies are autosomal recessive) First few days of life, may present later Excess carbamoyl phosphate converted to orotic acid High orotic acid in blood and urine Low BUN Hyperammonemia symptoms No megaloblastic anemia (vs orotic aciduria) Hunter syndrome - correct answersX-linked recessive lysosomal storage disease similar to Hurler but not associated with corneal clouding Deficiency in iduronate sulfatase resulting in accumulation of heparin & dermatan sulfate Causes aggressive behavior, developmental delay, cognitive impairment, carpal tunnel, & hepatospenomegaly Hurler disease - correct answersAlso known as Mucopolysaccharidoses Type 1 alpha l iduronidase - MR, HSM, hernia, opacities, gargoyle like features Mycosis fungoides/Sezary syndrome - correct answersCutaneous T-cell lymphoma (most common primary cutaneous lymphoma) Can progress to Sezary syndrome, T cell leukemia, characterized by systemic symptoms & the presence of CD4+ cells with cerebriform nuclei in blood smears