NBME 26

Vitamin C (ascorbic acid) is an antioxidant and coenzyme in the synthesis of _____________ via what enzyme?

collagen prolyl hydroxylase can lead to scurvy due to impaired collagen synthesis --> weakness of blood vessel walls due to collagen and connective tissue deficiency - swollen bleeding gums - easy bleeding and bruising - petechiae - impaired wound healing - fragile curly hair *should not be confused with hemophilia

Tibial fractures are at high risk for _____________

compartment syndrome increased compartment pressure in the anterior leg can lead to muscle necrosis and rhabdo can be complicated by ATN due to nephrotoxicity of myoglobin and its byproducts

Philadelphia chromosome

created by a translocation between chromosomes 9 and 22, leading to constitutive activation of the ABL1 tyrosine kinase (places next to BCR leading to constitutive activation) activation of the ABL1 tyrosine kinase leads to subsequent activation of the JAK/STAT and Ras/MAPK/ERK pathways, with the downstream consequences of increased cellular proliferation, inhibition of normal checkpoint inhibition, and resistance to apoptosis required for diagnosis of CML but can also be found in ALL and AML

In a _______ study design, subjects receive multiple treatments in sequence with a washout period between

crossover

What is a potential adverse effect of nitroprusside infusion?

cyanide toxicity causes uncoupling of the ETC (cyanide inhibits mitochondrial enzyme cytochrome c oxidase), leading to lactic acidosis, compensatory respiratory alkalosis, hypotension, lethargy, and bradycardia

While EBV infects B lymphocytes through CD21, atypical lymphocytes seen on peripheral blood smear actually represent what cell?

cytotoxic CD8+ T lymphocytes reacting to the viral infection

Respiratory depression results in hypoventilation, which is characterized by __________ PO2, _________ PCO2, and ________ A-a gradient

decreased PO2 (hypoxemia) increased PCO2 (respiratory acidosis) normal A-a gradient

What explains why deoxygenated blood can carry more carbon dioxide for a given PCO2 than oxygenated blood?

deoxyhemoglobin is a better buffer for hydrogen ions than oxyhemoglobin this is called the HALDANE effect when hemoglobin unloads oxygen in the tissues, it is more accepting of hydrogen ions. the cytosolic increase in PH from the removal of hydrogen ions that are now bound to hemoglobin favors the formation of bicarbonate from carbon dioxide and water. bicarbonate is a highly soluble form of carbon dioxide

Overdoses of neostigmine can lead to cholinergic crisis due to ?

desensitization of the nicotinic receptors by prolonged exposure to acetylcholine treatment includes administration of atropine

Leukocyte adhesion deficiency (type 3)

due to dysfunctional integrin response to chemoattractants (such as C5a, IL8, leukotriene B4) and presents similarly to LAD type 1 recurrent bacterial infections, impaired wound healing, delayed attachment of cord after birth, complete lack of neutrophils at sites of infections with no pus

A 75 year old man with alcoholism is brought to the ED 30 minutes after he began vomiting blood. He has a history of portal HTN. Abdominal examination shows spider angiomata. What is the most likely cause of this patient's hematemesis? (be specific)

esophageal varices secondary to retrograde flow through the portosystemic anastomosis between the left gastric and azygous veins this results in esophageal varices, which are dilated submucosal blood vessels

___________ study design is an interventional study design in which combinations of a number of interventions are trialed concurrently, allowing for the investigation of interactions between these interventions as well as a more complete understanding of the treatment strategies

factorial

__________________ is a non-inflammatory and non-atherosclerotic angiopathy of medium-sized arteries that can lead to renal artery stenosis and secondary HTN, commonly in young patients with no medical comorbidities or abnormal lab findings

fibromuscular dysplasia

Meckel's diverticulum rule of 2's

- 2 feet from ileocecal valve - 2 inches in length - 2 years most common age at presentation - 2 common types of ectopic tissue (gastric or pancreatic, endometrial is rare) - 2% symptomatic - 2% population

Characteristics of bacterial vaginosis infection (4) what is the treatment?

- gray thin malodorous vaginal discharge - vaginal pH > 4.5 - fish odor (strong amine smell) upon KOH testing - clue cells on microscopy treat with metronidazole do not need to treat partners (not considered STI)

A 42 year old man has an autoimmune disorder resulting in proximal muscle weakness of the lower extremities. Arrows in the photomicrograph shown indicate membranes that contain high concentration of channels that are targeted by this condition. What is the most likely diagnosis?

choose between Myasthenia gravis and Lambert Eaton and explain

Does COPD cause an increase or decrease in hemoglobin?

increase, it causes polycythemia commonly presents with chronic hypoxemia, which triggers increased EPO production by the kidneys EPO induces the proliferation and maturation of erythroid progenitor cells in the bone marrow and results in a secondary polycythemia this is reflected by an increased hemoglobin concentration and an increased density of normochromic, normocytic erythrocytes on peripheral blood smear

Premature closure of which suture results in narrow, elongated cranium? which suture results in short, broad flattened cranium?

increased AP dimension: sagittal suture short broad (arrests the AP dimension): coronal

What effect to primary leptin deficiencies have on BMI?

increased BMI

In anemia of chronic disease, a bone marrow aspirate with Prussian blue staining for iron will reveal?

increased deposits of iron in the bone marrow

Anemia of chronic dz MOA

increased hepcidin levels decrease intestinal iron absorption and increase iron storage in bone marrow and the RES, preventing urse of iron by erythrocyte precursors, resulting in anemia

Diverticulosis is characterized by sac-like protrusions of the colonic wall, which is hypothesized to develop secondary to what?

increased intraluminal pressure that predisposes the herniation of mucosa and submucosa through the muscularis propria layers of GI wall: mucosal, submucosa, muscularis propria, serosa

Cimetidine can cause significant drug-drug interactions how?

inhibition of CYP450 metabolism results in the increased concentration of drugs typically metabolized by the CYP450 system i.e. phenytoin concentration increases --> increased risk for abnormally high phenytoin levels and associated neurotoxicity

Why are tetracyclines contraindicated in pregnancy and in children?

inhibition of bone growth discoloration of teeth

Lesions of the __________ horn of the spinal cord can interrupt the sympathetic nerve supply to the ipsilateral face and eye and cause Horner syndrome

intermediate horn, between spinal cord levels C8 and T1 aka ciliospinal center of Budge

What does the ulnar nerve innervate?

intrinsic muscles of the hand --> abduction and adduction of all fingers except thumb muscles of the forearm (flexor carpi ulnaris, flexor digitorum profundus) sensation fourth and fifth fingers

Is horner syndrome caused by ipsilateral or contralateral lesion?

ipsilateral

PPI MOA

irreversible block H/K ATPase pump in parietal cells They rapidly and effectively increase stomach PH and are first line therapy for GERD and erosive esophagitis

How does neomycin help in the treatment of hepatic encephalopathy?

killing of Gram negative gut flora that generate ammonia - works by inhibiting the 30S subunit of the bacterial ribosomes to prevent protein translation no longer a preferred therapy for HE as it is absorbed readily and has side effects including AKI and ototoxicity Rifaximin is currently the antibiotic of choice for the adjunctive treatment of HE, which also targets colonic ammoniagenic bacteria

The ____________ serves as the most appropriate location for surgical entrance to the spinal canal to access herniated disc

lamina (D) = the bony arch connecting the pedicles, transverse, and spinous processes excised to permit access to the herniated disc

The portal vein starts at the confluence of the _________ , _________ , and ___________ veins

left gastric splenic Superior mesenteric

Where do the left and right recurrent laryngeal nerves loop?

left: inferior and posterior to the aortic arch right: inferior and posterior to the right subclavian

Memory and emotional regulation are mediated by the _________________.

limbic system

Where is CRP synthesized?

liver CRP = acute phase reactant synthesized in the liver in response to pro-inflammatory cytokine IL6

Which amino acids have basic side chains?

lysine, arginine, histidine

The electrical complex labeled B in the attached rhythm strip is characteristic of what?

premature ventricular contraction (PVC) associated with a lower SV than compared to a normal beat --> when this occurs, diastolic filling time is reduced so the amount of blood in the ventricles prior to ventricular systole is less

What lab studies would you see in hypersplenism?

presence of one or more cytopenias normal or hyperproliferation of bone marrow (normal or increased reticulocyte index) normal markers of coagulation cascade activation (normal PT, aPTT, fibrin, fibrin split products)

Tetracyclines (i.e. doxy) MOA

prevents the attachment of aminoacyl-tRNA to ribosomes

The precentral gyrus of the frontal lobe contains the _____________ which controls ____________________. Laterally, the precentral gyrus controls the ________________ Medially, the precentral gyrus controls the ________________

primary motor cortex voluntary movement to the contralateral body contralateral face contralateral LE

What are characteristic signs/symptoms of Measles?

prodromal fever cough coryza conjunctivitis Koplik spots confluent maculopapular rash that starts at the head/neck and spreads to the trunk, INCLUDING the palms and soles

The higher incidence of birth defects in children born to women more than 35 years old may be the result of environmental influences on chromosomes in developmentally arrested oocytes at which stage of cell division?

prophase, meiosis I

What is cystinosis?

rare lysosomal storage dz that results in increased levels of cystine and its accumulation in tissues (crystals), which can lead to severe organ dysfunction (cystine is normally stored in lysosomes) in kidneys: dysfunction of PCT leading to Fanconi syndrome (impaired bicar reabsorption) cystine crystal deposition in tissues can result in FTT, polyuria, dehydration, myopathy, GI dysmotility, hepatomegaly, splenomegaly, visual disturbances

Chronic mesenteric ischemia is characterized by what presentation?

recurring episodes of abdominal pain after eating hypothesized to be secondary to mismatch between intestinal blood flow and metabolic demands or secondary to small intestinal hypoperfuson when blood is shunted to the stomach during meals

What causes the virulence of Histoplasma capsulatum?

residing and replicating inside nonactivated macrophages - protect the fungal cells from detection and elimination

Proteasome inhibitors (i.e. bortezomib) MOA

result in impaired proteasomal activity, especially useful in multiple myeloma cells due to the increased production of proteins by plasma cells, they depend on the ability to degrade unfolded or misfolded proteins to limit the stresses placed on the cell (this is the function of the proteasome) when the cells are unable to clear misfolded or abnormal proteins, the induction of apoptosis occurs patients should be monitored for TLS

Meckel diverticulum

results from persistence of the vitelline duct and can demonstrate ectopic, functional gastric, pancreatic, or rarely endometrial tissue can present with acute or chronic hematochezia or melena often painless but may present with abdominal pain typically presents in childhood < 2yo although because of its indolent nature, it may not be diagnosed until later in life commonly located 2 feet proximal to the ileocecal valve and is approximately 2 inches in length in children, it may serve as a potential lead-point for intussusception treat with surgical resection

How to patients with carnitine-acylcarnitine translocase deficiency present?

results in accumulation of long chain fatty acids, particularly in the muscle and liver rare AR disorder onset of symptoms in infancy or early childhood encephalopathy, vomiting, hypoketotic hypoglycemia, hyperammonemia, muscle weakness, skeletal myopathy, cardiomyopathy, ventricular dysrhythmias can be triggered by illness or fasting

What is the "respiratory burst" employed by neutrophils

results in rapid bactericidal activity describes a process by which neutrophils and phagocytes utilize oxygen to produce free radicals, hypochlorite, and peroxides, all of which are toxic to rapidly dividing bacterial cells

A parasternal heave on physical exam is most commonly associated with?

right ventricular hypertrophy parasternal heave = thrusting impulse palpable along the LSB, most prominently in the third, fourth, and fifth intercostal spaces

What enzyme is needed to activate antiviral drugs like acyclovir?

thymidine kinase acyclovir, valacyclovir, and famciclovir are guanosine analogs Guanosine analogs must be phosphorylated by thymidine kinase --> activated and can inhibit the viral DNA polymerase

Neutrophil activation as part of the innate immune response to infection involves binding of pathogen-associated molecular patterns (i.e. bacterial lipopolysaccharides) to _________ receptors on the neutrophil surface

toll-like receptors leads to NF-kB activation and production of pro-inflammatory cytokines

How do you calculate prevalence?

total # cases / total # people in the at-risk population

Granuloma formation is often a consequence of what type of hypersensitivity reaction?

type IV (delayed)

Granulosa cell tumors

type of malignant sex-cord stromal tumor generally occur in women in their 60s, but can occur at any age, including children presentation is marked by the effect of their functional production of hormones (estrogen) - in children and young women, often result in precocious puberty or premenstrual vaginal bleeding - postmenopausal bleeding if postmenopausal typically indolent and may not be detected until large or advanced

What is slipped-strand mispairing

type of mutation that may occur during DNA replication In an area of repetitive nucleotides, such as a series of 8 cytidine residues, DNA polymerase slips and either inserts one or more additional nucleotides or removes one or more additional nucleotides by mistake

Patients with phenylketonuria do not have the ability to convert phenylalanine to ____________ due to deficient/defective ________________. Accumulation of phenylalanine in this disorder leads to physical manifestations including ______________, ____________, and _____________

tyrosine phenylalanine hydroxylase impaired neurologic development, seizures, and musty odor

Broadly, what muscles do the ulnar, radial, and median nerve innervate?

ulnar: intrinsic muscles of the and (adduction and abduction of fingers except thumb) radial: extensors of the fingers and wrist, as well as abductors of the thumb median: flexors of the wrist and fingers as well as intrinsic muscles of the hypothenar eminence

In the US, __________________ carcinoma of the bladder is the more common variant, account for 90%, but in Africa and the Middle east _______________ is more common. What accounts for this difference?

urothelial (transitional) cell carcinoma squamous cell carcinoma Schistosoma haematobium is endemic to areas such as the Africa and the Middle East

__________ deficiency is associated with severe measles infection

vitamin A

What is the MOA of tretinoin and other retinoids?

vitamin A analogs; exert effects by binding to retinoic acid receptors, which are transcription factors in the nucleus in the case of dermal fibroblasts, binding to its receptor causes activation of the nuclear gene transcription of collagen mRNA

Meckel's diverticulum results from persistence of the ______________ and can demonstrate ectopic, functional _____________, ______________, and ____________ tissue

vitelline duct gastric pancreatic endometrial

Chronic lymphocytic leukemia (CLL) predisposes to the development of what kind of anemia?

warm autoimmune hemolytic anemia (because malignant CLL cells produce autoantibodies)

When does gastrulation occur?

week 3 process that generates three germ layers (ectoderm, mesoderm, endoderm)

In embryogenesis, when does the neural tube form?

week 4

Proliferative endometrium is present during the follicular phase of menstruation prior to ovulation. Histologically, what does it demonstrate?

well-developed stratum basale long straight uterine glands extension of the spiral arteries abundant stromal cells

Mutations in _______, _______, and ________ promote disordered cell growth and division, leading to malignant transformation in colorectal cancer

APC, K-ras, p53 mutations, generally in sequence APC and p53 are tumor suppressors K-ras is an oncogene

A patient has a tibial fracture and later develops increased leg pain and paresthesias. He then begins to pass dark red urine and becomes oliguric. UA is positive for blood but no erythrocytes. What is the most likely cause of renal failure?

ATN due to tibial fracture --> compartment syndrome --> rhabdo --> myoglobin its byproducts causing ATN

Vocal cord nodules in the setting of immunodeficiency are most likely caused by ____________

HPV

What metabolic disorder involves tyrosine?

alkaptonuria (AR) prevents degradation of tyrosine to fumarate via homogentisate oxidase characterized by - blue black discoloration of connective tissue, sclerae, and urine

What will histology of a molar pregnancy show?

hypertrophy of the chorionic villi with focal edema and trophoblastic hyperplasia

__________ and _________ activate the two primary cells responsible for granuloma formation in TB

IL12 and interferon gamma IL12 is an inflammatory cytokine secreted by macrophages infected with TB IL12 acts on both NK cells and cytotoxic T lymphocytes, causing them to release IFN-y (which has several roles) Collectively, the activating pathway of IL12 and IFNy allows for granuloma formation

What are main distinguishing factors between RA and OA?

1. Joint involvement - RA: MCP, PIP - OA: DIP, larger joints 2. Pain characteristics - RA improves with use throughout the day - OA worsens through the day 3. Age - RA typically presents younger since it is an autoimmune inflammatory arthritis - OA affects 60-80% of adults > 65 4. Serum - RA: high in rheumatoid factor, anti- CCP antibodies

_________________ presents with multiple skeletal deformities including frontal bossing, nodules at the costochondral junctions of the anterior chest, and delayed closure of the growth plates due to impaired bone mineralizaton

Child Vitamin D deficiency (Rickets)

What metabolic disorder involves phenylalanine?

phenylketonuria (AR inheritance) secondary to deficiency in phenylalanine hydroxylase = excess phenylalanine characterized by - intellectual disability - seizures - musty body odor - eczema

Describe the pathway by which HIV infects a cell and replicates

1. HIV binds to the surface of CD4 cells via interaction of its specific glycoproteins with CD4 receptors such as CCR5 2. Fuses with cell membrane and releases its contents into the cytoplasm 3. HIV RNA is reverse transcribed by reverse transcriptase to create HIV DNA 4. HIV DNA is integrated into the CD4 cell genome 5. HIV hijacks the cellular machinery to create HIV DNA, followed by all the prerequisite proteins to form a new HIV viral particle - new viral particles require protease activity to become mature 6. The new virus then buds off the CD4 cell and is released to infect other cells

What are the layers of the scrotum? (6, superficial to deep) List what layer of the abdominal wall each layer is derived from

1. Skin 2. dartos muscle/fascia (subcutaneous tissue) (derived from Scarpa fascia) 3. external spermatic fascia (derived from external abdominal oblique) 4. cremaster muscle/fascia (derived from internal abdominal oblique) 5. internal spermatic fascia (derived from transversalis fascia) 6. tunica vaginalis (derived from peritoneum)

What is the inheritance of Huntington disease?

AD

The rate of onset of anesthesia relies on which 3 characteristics?

1. blood solubility (low solubility increases speed) 2. cardiac output (low cardiac output decreases blood delivered to alveoli, anesthetic will more quickly equilibrate with the blood that is present) 3. minute ventilation (increased delivers more anesthetic to the alveoli, increases gas concentration)

Surfactant is critical for reducing alveolar surface tension and collapsing pressure; without it, alveolar collapse results in (3)

1. impaired gas exchange 2. decreased lung compliance 3. increased lung elastic recoil

How can the jejunum be distinguished from the ileum? (5)

1. inner mucosal folds (plicae circulares) are more prominent, more numerous, and taller --> (this leads to increased mucosal SA and associated feathered appearance after the administration of oral contrast material) 2. larger caliber, thicker muscular walls 3. longer vasa rectae 4. fewer arcades 5. the ileum is notable for the presence of Peyer patches and mucosal lymphoid follicles

What are the two primary forms of genomic instability in the pathogenesis of colon cancer?

1. microsatellite (15%) - failure of mismatch repair pathway (MMR) from mutations in MLH1, MSH2, APC, and other genes, results in the propagation of aberrant DNA and accumulation of mutations that predispose to malignant transformation - seen in familial syndromes: Lynch, FAP 2. chromosome instability (85%) - specific activating mutations of oncogenes (i.e. KRAS) or LOF mutations of tumor suppressor genes (i.e. p53) results in aberrant entry into the cell cycle (and oncogenic potential) - genomic instability occurs during chromosomal replication (S), fidelity checks of the chromosomes (G2) and during separation of the chromosomes (M phase) during cell cycle - sporadic colon cancers

What are the two medication used in a medical abortion? What order do you give them in?

1. mifepristone: progesterone antagonist - dilation of the cervix and placental separation 2. misoprostol: synthetic prostaglandin - causes uterine contractions

What is the mechanism by which oxytocin promotes uterine muscle contractions during labor?

1. oxytocin binds receptor on uterine myometrial smooth muscle cells 2. signal cascade results in activation of ligand-gated calcium channels 3. calcium influx into the uterine smooth muscle cells 4. increased calcium-calmodulin complex activation of MLCK 5. phosphorylation of myosin light chains by MLCK 6. cross-bridge formation between myosin heads and actin = contraction

During thyroid surgery, which structures are at risk of being damaged? (4)

1. parathyroid glands 2. superior and inferior thyroid arteries 3. recurrent laryngeal nerve 4. external branch of the superior laryngeal nerve

What are the 4 stages of neutrophil recruitment and the associated receptors for each stage?

1. rolling - vasculature/stroma: E selectin, P selectin - leukocyte: sialyl lewis (glycoprotein) 2. adhesion - vasculature/stroma: ICAM-1 - leukocyte: LFA-1 3. extravasation - vasculature/stroma: PECAM-1 - leukocyte: PECAM-1 4. chemotaxis/migration - vasculature: C5a, IL8, leukotriene B4, kallikrein - leukocyte: various

What are 3 complications of severe measles infection?

1. subacute sclerosing panencephalitis (neurodegenerative dz associated with intellectual regression, personality changes, motor deterioration, seizures, premature death) 2. encephalitis 3. giant cell pneumonia - rare except in patients who are immunosuppressed - often fatal - characterized by presence of inclusion bodies and multinucleated giant cells in the respiratory epithelium

TIPS to treat esophageal varices creates a shunt between the _________ and _________

portal vein hepatic vein this decreases portal pressure by shunting blood to the systemic circulation, bypassing the liver

Hereditary Hemorrhagic Telangiectasia (HHT)

AD disorder of the vasculature that is characterized by arteriovenous malformations (AVMs) and telangiectasias (small vascular malformations which appear as bright red, blanching lesions of the skin and mucous membranes) classically present with recurrent epistaxis, hematuria, and GI bleeding cerebral AVMs may cause hemorrhagic stroke Pulmonary AVMs may lead to embolic stroke and can result in pulmonary arteriovenous shunting with subsequent hypoxemia, which can lead to clubbing

What is placenta accreta?

abnormal attachment of the placenta directly to the myometrium, which most commonly presents with retained products of conception and postpartum hemorrhage

_________ addition to PRP (platelet-rich plasma) will result in rapid and irreversible aggregation

ADP (adenosine diphosphate) - critical in normal hemostasis Acts via the receptors P2Y1 and P2Y2 on the surface of platelets. Binding to these receptors results in G-protein coupled receptor signaling, with concurrent alteration of platelet shape and activation of GPllb/IIIa via the PI3K signaling pathway, which results in rapid platelet aggregation

How many half lives until steady state?

4-5

What is the function of CRP?

acute phase reactant that functions as an opsonin and aids in targeting cells for phagocytosis and in the fixation of complement

A 55 yo woman who is a physician is admitted to the hospital because of a fractured femur sustained in a MVC. Two days after admission, she develops tachycardia, restlessness, diaphoresis, and anxiety. She says that vague shapes are coming out of the walls. Which of the following is the most likely cause of the patient's current condition? A. Acute stress disorder B. Alcohol withdrawal C. Bipolar disorder D. Histrionic personality disorder E. Panic disorder

B. Alcohol withdrawal c/f delirium tremens

______________ is a malaria-like illness that can be recognized by the presence of intra-erythrocytic ring forms or a tetrad formation on peripheral blood smear

Babesiosis caused by protozoa Babesia microti classically presents with fevers, chills, myalgias, weakness, headache, an associated hemolytic anemia asplenia is a RF for severe dz

Patients with painless hematuria should be evaluated for ____________

Bladder cancer with UA, cytology, and cystoscopy

Vitamin ___________ deficiency is common in persons having diets poor in fruits and vegetables

C

How does cystic fibrosis affect coagulation factors?

CF is an AR disorder due to defect in CFTR gene, leading to deficiency in the chloride channel that secretes chloride in lungs and GI tract (and reabsorb chloride in sweat glands) abnormal Cl- transport leads to abnormally viscous mucous in lungs and GI tract thick mucous in GI tract contributes to pancreatic insufficiency, steatorrhea, and malabsorption malabsorption leads to deficiency in fat soluble vitamins ADEK Vitamin K plays a critical role in synthesis of hepatic coagulation factors II, VII, IX, and X, and protein C and S

What disease process is the Philadelphia chromosome associated with?

CML (required for diagnosis) however you can also see it in ALL and AML

What torch infection is commonly associated with intracranial calcifications? also: jaundice, hepatomegaly, petechial rash, seizures

CMV

_____________ is an opportunistic infection that commonly occurs in immunocompromised patients in the setting of solid-organ or allogeneic stem cell transplantation, severe UC, or HIV/AIDs

CMV can present with pneumonitis with diffuse alveolar damage (picture), colitis, retinitis, esophagitis, encephalitis infected cells typically demonstrate a large, atypical appearance and feature the presence of basophilic nuclear inclusions

____________ presents with sudden, painless monocular vision loss, relative APD, retinal whitening with a cherry red spot, and retinal arteriolar narrowing with boxcarring

CRAO central retinal artery occlusion

12 yo boy admitted with lethargy, hip pain, a temp of 103, has been hospitalized several other times because of PNA. Neonatal period normal. CBC counts wnl, HIV negative. Blood cultures grow Staph aureus. Serum electrophoresis is likely to show what?

D: deficiency in immune globulins A: narrow monoclonal spike in the gamma region - multiple myeloma - Waldenstrom macroglobulinemia - monoclonal gammopathy of undetermined significance - amyloidosis B: blurring of the beta-2 and gamma regions (beta/gamma fusion) - increased CRP or increased IgA (severe respiratory infections, RA, cirrhosis) C: large but wide gamma region consistent with hypergammaglobulinemia - nonspecific hypergammaglobulinemia (chronic liver dz, CT dz, inflammatory conditions) E: normal first peak = albumin alpha = alpha 1 antitrypsin, thyroid-binding globulin, transcortin beta: transferrin and B-lipoproteins, complement y: immunoglobulins

A 65 yo woman has ascites. Which of the following additional findings indicates a diagnosis of constrictive pericarditis rather than cirrhosis? A. LE edema B. Esophageal varices C. Hypoalbuminemia D. Hyponatremia E. Increased JVP F. Splenomegaly

E. Increased JVP Cirrhosis can lead to hypervolemia, often manifested by peripheral edema, pulmonary edema, pleural effusions, or ascites, rarely increased JVP pressure unless concomitant RHF

What are 2 virulence factors associate with measles virus?

F (fusion) protein - aids in viral fusion to host cells - can result in formation of multinucleated giant cells Hemagglutinin (HA) protein - viral binding to host cells

Correct splicing is dependent on the spliceosome recognizing a splice site at the start of an intron, which typically consists of base pairs ____________. A point mutation in this has what effect?

G-U-A-A-G A point mutation in DNA (i.e. changing a guanine to an adenine) may mask a splice site and either cause an intron to remain in the final mRNA product erroneously or cause a larger region of pre-mRNA to be spliced, leading to removal of an exon

What is the MOA of baclofen

GABA (y-aminobutyric acid) analogue acts as an agonist at the GABA-B receptors GABA-B receptors are metabotropic G protein receptors that increase the efflux of K+ (thus hyperpolarize skeletal muscle cells and decreased AP frequency)

Describe the affect of acetylation of histones and transcription

Histones are proteinaceous cores, rich in lysine and arginine (+ charge). Without modification, the + charge attracts the - charged DNA, which loops around it Condensed heterochromatin is transcriptionally inactive because the binding sites for RNA polymerase II is occupied by the histone acetylation of the histone (by histone acetyltransferases, adds acetyl groups to lysine residues) decreases affinity of histones for DNA the unpacked (euchromatin) DNA can be bound by transcriptional enzymes, promoting gene transcription

What is the only widely accepted indication for aspirin use in febrile children due to the risk of Reye syndrome?

Kawasaki

The genetic disorder leukocyte adhesion deficiency type 1 is caused by a defect in ___________

LFA-1 (lymphocyte function-associated antigen 1)

Why are varicoceles more common on the left?

Left gonadal vein drains to left renal vein obstruction of the left renal vein, such as local invasion of a renal tumor, causes pressure to mount behind the obstruction which is transmitted through the left gonadal vein to the pampiniform plexus surrounding the testicle

________________ syndrome presents with intellectual disability, aggressive behavior, self-mutilation, gout, and dystonia What causes this syndrome?

Lesch-Nyhan syndrome inactivating mutations of the hypoxanthine-guanine phosphoribosyltransferase (HGPRT), a key enzyme in the purine salvage pathway = unable to salvage guanine and hypoxanthine = develop elevated levels of xanthine and uric acid hyperuricemia is treated with xanthine oxidase inhibitors like allopurinol inherited X linked recessive

______________ are found at each of the 5' and 3' ends of retroviral DNA and transposons and are used to integrate the viral genome into the host genome. Mutations in these regions may prevent integration.

Long terminal repeats (LTRs)

What metabolic disorder involves leucine?

Maple syrup urine disease caused by abnormal degradation of leucine, isoleucine, and valine characterized by: - neurologic defects - intellectual disability - vomiting - poor feeding - urine with odor similar to maple syrup

Chronic granulomatous disease results from a defect or deficiency in the ________________. What does this impair?

NADPH oxidase complex impairs the production of ROS and the respiratory burst in neutrophils, increasing a patient's susceptibility to catalase positive pathogens diagnosis is made by dihydrorhodamine test, or a nitroblue tetrazolium reduction test

Ammoniagenesis takes places in the ___________ of the nephron and uses _______ as the primary substrate.

PCT glutamine

How does the administration of PGE2 lead to decreased smooth muscle tension?

Prostaglandin E2 stimulates adenylyl cyclase in smooth muscle cells, which leads to an increase in cAMP cAMP inhibits the activity of myosin light chain kinase (MLCK), resulting in decreased phosphorylation of myosin light chains --> decreased smooth muscle tension *remember that smooth muscle contraction occurs when myosin light chains are phosphorylated, leading to cross-bridge formations between myosin and actin filaments. this reaction is performed by myosin light chain kinase (MLCK). this process is opposed by myosin light chain phosphatase, which dephosphorylates the myosin light chain --> decreased muscle tone

The ________ is the most anterior and inferior part of the heart. A penetrating object through the inferior sternum would affect this

RV

Chronic mesenteric ischemia is caused by chronic atherosclerotic stenosis of the celiac or mesenteric arteries, with the _______________ artery the most commonly affected

SMA

_______________ is a self-limited thyroiditis that follows an acute viral illness and presents with symptoms of hyperthyroidism. A painful, tender thyroid is highly suggestive of this.

Subacute granulomatous thyroiditis (de Quervain)

_______________ is a superficial infection of the epidermis characterized by hypo or hyperpigmented patches on the chest and back, which are more conspicuous after sun exposure. What is the causal organism? How do you treat?

Tinea versicolor Malassezia furfur treat with antifungals (topical ketoconazole or selenium sulfide)

How do you calculate relative risk?

[a/(a+b)]/[c/(c+d)] describes the difference in likelihood of occurrence of a particular disease outcome between two groups of patients with or without a particular exposure

Hardy-Weinberg equilibrium principle

allele frequencies will remain constant across generations in the absence of evolutionary change - natural selection does not occur - no random mutations - no movement in or out of population - mating is completely random p^2 + 2pq + q^2 = 1 p is the frequency of the dominant allele q is the frequency of the recessive allele 2pq is the probability of heterozygosity p^2 is the probability of the dominant homozygote q^2 is the probability of recessive homozygote

When does cooperative play develop?

around age 4

Which amino acids have acidic side chains?

aspartate, glutamate

heparin MOA

binds and potentiates action of anti-thrombin III (inhibits thrombin and Xa)

A male newborn is found to have a defect in anchoring fibrils. What skin finding is most likely to occur in this patient?

blisters anchoring fibrils are made of type VII collagen and are a component of the hemidesmosome hemidesmosome: anchors basal keratinocytes of the epidermis to the dermis at the dermal-epidermal junction any impairment of the hemidesmosome will cause the basal keratinocytes to separate from the dermis, causing blisters to form Because the hemidesmosomes of neighboring skin are still intact, these will be tense blisters examples: bullous pemphigoid, epidermolysis bullosa (in contrast, pemphigus vulgaris is caused by antibodies to desmosomes, the protein complex which maintains cell-to-cell adhesion in the epidermis, so this is more superficial, in the epidermis, and the blisters are fragile and flaccid)

What is the difference between Smith and Colles fractures?

both distal radius fractures Smith: volar displacement Colles: dorsal displacement common complications: acute carpal tunnel syndrome, delayed tendon rupture

Long chain and very long chain FA require ____________ to enter the mitochondrial matrix for beta-oxidation

carnitine-acylcarnitine translocase

What are hydatidiform moles?

caused by: - fertilization of an empty egg by a single sperm, followed by duplication of the paternal DNA resulting in 46 chromosomes (complete) - dual fertilization of a normal ovum resulting in 69 chromosomes (partial) complete moles contain no fetal tissue partial moles contain some fetal tissue neither are viable labs will reveal abnormally increased b-hcg levels u/s will show bilateral multilocular ovarian cysts (theca lutein cysts)

donepezil MOA

cholinesterase inhibitor

In a patient with megaloblastic anemia - how to differentiate between folate vs B12 deficiency?

folate: elevated homocysteine, normal methylmalonic acid B12: elevated homocysteine, elevated methylmalonic acid since folate and B12 are needed for the conversion of homocysteine to methionine, deficiency in either is associated with elevated homocysteine vitamin B12 also acts as a cofactor for the conversion of methylmalonyl-CoA to succinyl CoA and its deficiency is associated with increased methylmalonic acid levels

What substance is associated with excitotoxicity?

glutamate also NMDA

____________ is a primary hepatic antioxidant and neutralizes oxidizing compounds by absorbing electrons at its sulfur atom

glutathione this reaction oxidizes two molecules of reduced glutathione (GSH) to glutathione disulfide (GSSG) hepatic oxidizing stress is most directly reflected by a depletion of GSH, leading to a reduction in the ratio of GSH to GSSG

Which metabolic disorder involves glycine?

glycine accumulation can result from glycine encephalopathy (AR inheritance) characterized by: - intellectual disability - lethargy - hypotonia

What are the nonpolar amino acids?

glycine, alanine, valine, leucine, isoleucine, methionine, phenylalanine, tryptophan, proline Grandma Always Visits London In May For Winston's Party (G, A, V, L, I, M, F, W, P)

MacConkey agar is used to selectively grow _______________ and differentiate between _______________ and _______________. What is an example of a bacteria that grows poorly on MacConkey agar?

gram negative bacilli lactose fermenting from non lactose fermenting fastidious anaerobic bacteria such as b. frag

What is the most likely explanation for the feathery appearance in the portion of the GI tract indicated by X when compared to the portion indicated by Y?

greater mucosal surface area (more prominent and numerous plicae circularis)

______________ is a benign, disorganized overgrowth of histologically normal tissue in its native location within the body

hamartoma

What is a potential complication of heparin therapy? What is its mechanism?

heparin induced thrombocytopenia (HIT) antibody-mediated reaction to heparin-platelet factor 4 complexes that results in abnormal activation of platelets, with subsequent thrombocytopenia and arterial or venous thromboembolic dz

What are the parts of the limbic system?

hippocampus, parahippocampal gyrus amygdala mammillary bodies ventral tegmentum prefrontal cortex cingulate gyrus entorhinal cortex

Risk factors for ______________ include exposure to bird or bat droppings

histoplasmosis

What metabolic disorder involves homocysteine?

homocystinuria (AR inheritance) characterized by: - increased levels of homocysteine in urine - intellectual disability - lens subluxation or dislocation (typically downward) - osteoporosis - marfanoid habitus - thrombosis - atherosclerosis (increased risk PAD, stroke, CAD)

______________ is defined as the presence of one or more cytopenias in the setting of splenomegaly

hypersplenism common complication of cirrhosis and portal hypertension

What are (5) causes of high output cardiac failure?

hyperthyroidism chronic lung dz sepsis cirrhosis large AV fistulas AV fistulas lead to significant shunting of blood directly from the arterial to venous system --> increased venous return to right side of heart --> increase in HR and SV --> increase in CO eventually, due to the persistent increased myocardial oxygen demand of the heart in the setting of high-output, patients will decompensate and present with signs and symptoms of HF

Chondrosarcoma

malignant neoplasm that arises from the mesenchymal cells that produce cartilage; commonly arises in the axial skeleton, particularly in the pelvis presents in 50s, slow growing and initially asymptomatic, permitting extensive growth before detection will often present with pelvic pain and compression of adjacent structures such as the lumbosacral plexus, leading to neurologic symptoms in the ipsilateral lower extremity on histology, the tumor will show lobules of hyaline-like cartilage and nests of malignancy chondrocyte-like cells

_______________ is caused by widening of a lactiferous duct with concomitant fibrosis and inflammation, often near the nipple., commonly in perimenopausal and postmenopausal women

mamillary duct ectasia

_________________ often occurs in perimenopausal women when a lactiferous duct becomes blocked and accumulating lipid and debris cause dilation to occur

mammary duct ectasia

The hippocampus, parahippocampal gyrus, and amygdala are located in the ______________________. ____________________ commonly damages these structures, leading to emotional dysregulation and the development of short-term memory loss

medial temporal lobe cancer-related radiation/chemo

___________ is commonly used as paint thinner or as an additive to paint thinner and can cause an anion gap metabolic acidosis.

methanol once absorbed, methanol can be converted by alcohol dehydrogenase to formaldehyde, which is then converted by aldehyde dehydrogenase to formic acid, a toxic metabolite that can cause visual disturbances (i.e. retinal edema, optic disc hyperemia), GI distress, putaminal hemorrhage, and neurologic depression (i.e. confusion, ataxia) formic acid causes the anion gap metabolic acidosis treatment is fomepizole - inhibits alcohol dehydrogenase

One is one commons side effect of TIPS, which is a drawback of this procedure?

more frequent and severe episodes of HE

____________ is an indolent form of cutaneous T cell lymphoma. It is characterized by infiltration of malignant _________ cells into the epidermis

mycosis fungoides T cells characterized by erythematous, wrinkled, scaly patches if left untrated, will thicken to plaques and then tumors classically involve places protected from the sun like the axillae and butt

Melanocytes are dendritic cells located in the epidermis basal layer and are derived from ____________

neural crest

Lymphocyte function-associated antigen 1 (LFA-1) is an integrin protein involved in _____________

neutrophil adhesion to the endothelium

Myasthenia gravis is an autoimmune disorder in which the body makes antibodies against what?

nicotinic acetylcholine receptors at the postsynaptic membrane of the NMJ

AIHA (autoimmune hemolytic anemia)

occurs due to production of antibodies targeting circulating rbc surface antigens either mark them for removal via reticuloendothelial system (RES) (IgG, warm) or fix complement (IgM, cold) lab findings demonstrate - normocytic anemia - increased reticulocyte count (indicates hematopoiesis) - unconjugated hyperbilirubinemia - low haptoglobin - spherocytes on peripheral blood smear - positive coombs

Damage to the ___________ can affect both bladder contraction and internal urethral sphincter relaxation, leading to overflow incontinence

pelvic nerve plexus pelvic parasympathetic nerves of the pelvic plexus function to excite and contract the detrusor muscle of the bladder via muscarinic ACh receptors sympathetic nerves mediate relaxation of the internal urethral sphincter via alpha 1 adrenergic receptors, leading to normal urination

How is acetaminophen metabolized?

safely metabolized through phase II conjugations, including glucuronidation and sulfation when at high doses, saturation of the phase II metabolic pathways leads to excess acetaminophen being metabolized by cytochrome P450-mediated reactions to N-acetyl-p-benzoquinoneimine (NAPQI), which has strong oxidizing properties and is directly hepatotoxic chronic ethanol ingestion leads to the induction of cytochrome P450. Therefore chronic alcoholics are at increased risk of hepatotoxicity when consuming high doses of acetaminophen due to the increased production of NAPQI

What are the polar amino acids?

serine, threonine, cysteine, asparagine, glutamine, tyrosine Santa's Team Crafts New Quilts Yearly (S, T, C, N, Q, Y)

the splice acceptor site resides between an intron and an exon on pre-mRNA and functions to recruit _____________

snRRPs (small nuclear ribonucleoproteins) snRRPS remove introns, with subsequent connection of exons via the spliceosome, forming fully mature mRNA

What does the pudendal nerve innervate?

somatic sensory and motor innervation to the genitals and the pelvic floor musculature, including the levator ani muscle and external anal and urethral sphincters

Hereditary spherocytosis is caused by mutations in _________ or __________.

spectrin or ankyrin (cytoskeletal anchoring genes) leads to fragile rbc membranes and poor distensibility

What are the two most common subtypes of esophageal cancer?

squamous cell carcinoma - tend to produce foci of keratin (differentiates them from adenocarcinoma) adenocarcinoma

Damaged muscle is often replaced by fibrotic scar, which leads to ________, __________, and ____________

stiffness reduced passive stretching joint contractures

What is attributable risk?

the risk of developing disease that can be attributed to the exposure as compared to the risk that exists without the exposure calculated as the difference between disease incidence among those with the exposure and those without the exposure

Malignant hyperthermia is caused by a genetic defect in _________________.

the ryanodine receptor