Random Flashcards
What are the major toxicities of acyclovir?
crystal nephropathy and neurotoxicity
What are the major toxicities of Cidofovir (CMV retinitis)?
nephrotoxicity–> proteinuria or increased creatinine
What are the major toxicities of lamivudine?
peripheral neuropathy, lactic acidosis
What are the major toxicities of sofosbuvir?
fatigue, nausea
What are the major toxicities of gancyclovir?
severe neutropenia
Where is ribosomal RNA transcribed?
The nucleolus
Which vitamins are deficient in breast milk?
Vitamin D & K
What is defective in xeroderma pigmentosum?
Nucleotide excision repair- thymine dimers repaired by UV specific endonuclease
What symptoms are seen in vitamin A deficiency?
night blindness, corneal ulceration and severe eye dryness, hyperkeratosis, growth retardation
What does secretin stimulate?
release of bicarb from pancreatic ductal cells
What is the form of dendritic cell most commonly found in the skin and mucous membranes?
Langerhans cell- racquet-shaped, derived from the myeloid cell line
Which geniculate body is auditory and which is visual?
Lateral: visual
Medial: auditory
What are the steps in base excision repair?
- recognition of abnormal bases by glycosylases, which cleave the base, leaving an empty site
- Endonuclease cleaves the 5’ site
- Lyase completes extraction
- DNA Polymerase fills in
- Ligase seals the final nick
What mediates DIC in pregnancy?
tissue factor released from sites of placental injury, initiating the clotting cascade. Most commonly caused by a placental abruption that leads to fetal demise.
Why does hyperventilation cause neurological symptoms?
decrease in pCO2 causes a decrease in cerebral blood flow, because CO2 is a potent vasodilator
Which cephalosporins have action against Pseudomonas?
Ceftazidime, cefepime
What virulence factor does Staph A have in its cell wall?
Protein A- binds the Fc portion of IgG and prevents complement binding, leading to impaired opsonization and phagocytosis.
How do you differentiate roseola from measles/rubella?
Roseola has high fever or 3-5 that goes away before the rash. The rash starts on the trunk then spreads, whereas with rubella/measles it starts on the face then spreads
What is a complication associated with APML?
DIC
What is the most common location of anterior nosebleeds?
Nasal septum- Kiesselbach plexus (anastamosis of anterior ethmoidal a, sphenopalatine a, and superior labial a.
What is the treatment for 21-hydroxylase deficiency?
physiologic doses of exogenous corticosteroids
Where are bile acids normally reabsorbed?
Terminal ileum- resection can lead to wasting of bile acids and poor absorption of fat and Vitamins ADEK
What are the teratogenic effects of ACEi and ARBs?
Low Ang II leads to renal maldevelopment and oligohydramnios, leading to pulm hypoplasia and skeletal defects
What are the teratogenic effects of tobacco?
impaired O2 delivery leads to growth restriction and preterm labor
What are the symptoms of polymyositis? Pathologic features?
Proximal muscle weakness
endomysial mononuclear infiltrate with patchy necrosis
Anti-Jo-1
Over-expression of MHC I on sarcolemma, leading to CD8 myocyte damage
How do Cyclosporine and Tacrolimus inhibit T-cells?
Inhibit calcineurin activation
normally, calcineurin–>NFAT–>IL-2–>growth and differentiation of T-cells
What is crest syndrome?
Calcinosis Raynaud's Esophageal dysmotility Sclerodactyly Telangiectasias
What should be supplemented in a pt with orotic aciduria?
Uridine
What are the symptoms of orotic aciduria?
physical and mental retardation, megaloblastic anemia, and elevated urinary orotic acid
Where in the cell is collagen synthesized?
Rough endoplasmic reticulum
How is Vit C involved in collagen synthesis?
required cofactor for hydroxylation of collagen alpha chain proline and lysine in the RER
Where do type B aortic dissections usually arise?
Close to the origin of the left subclavian artery
Where do type A aortic dissections usually arise?
in the sinotubular junction
How do nitrites cause poisoning?
Oxidize Fe2+ to Fe3+ –> formation of methemoglobin that cannot bind O2. Also, allosteric effects such that affinity of the other Hgbs in the tetramer is increased, shifting the dissociation curve to the left
How is oral bioavailability determined?
area under the oral curve divided by area under the ive curve (graph of plasma concentration over time)
How does prostate cancer to the lumbrosacral spine?
via the vertebral venous plexus, which communicates with the prostatic venous plexus (prostate, penis, and bladder). This can also lead to brain metastases, because it runs straight to the brain
What is the most frequent cause of malignant otitis externa?
Pseudomonas
How are particles in the respiratory bronchioles and alveolar ducts cleared?
Macrophages- This leads to release of cytokines, platelet-derived GF, and insulin-like GF –> stimulate fibroblasts–>progressive interstitial lung fibrosis
Which lung cancer causes SIADH? What are the tumor cell markers?
Small cell lung cancer
Neuroendocrine markers: Neural cell adhesion molecule, neuron-specific enolase, chromogranin, and synaptophysin.
What is the most common cause of death in TCA overdose? Why?
Cardiac arrhythmia- TCAs inhibit fast sodium channel conduction, leading to slow myocardial depolarization. Can also lead to refractory hypotension and peripheral vasodilation (alpha 1 adrenergic receptor antagonism)
What are the first line treatments or bipolar disorder?
Valproate, Quetiapine, and lithium
Which enzyme is absent in criggler najjar and which step of bilirubin conjugation does this disrupt?
UGT (uridine diphosphate glucuronyltransferase), which conjugates bilirubin with glucuronic acid.
What is kernicterus?
bilirubin encephalopathy- potentially fatal, severe jaundice, neurologic impairment
What determines the ventricular contraction rate in atrial fibrillation?
AV node refractory period
What is the difference between junctional, compound, and intradermal nevi?
junctional nevi- limited to the dermoepidermal junction. Flat pigmented macules
compound nevi- nevus extends into dermis. Raised papules
Intradermal- older. lost the epidermal nests. skin to tan colored dome-shaped
What is a serious complication of untreated IBD? How should it be diagnosed?
Toxic Megacolon
Abdominal x-ray
What are the symptoms of toxic megacolon?
ab pain/distention, fever, bloody diarrhea, signs of shock
What causes gallstones in pts with TPN?
Decreased cholecystokinin release due to lack of enteral stimulation leads to reduced biliary contraction and biliary stasis.
Where are parietal cells located and what do they secrete?
upper glandular layer of the gastric body and fundus.
They secrete gastric acid and intrinsic factor
What defects would be expected in Patau syndrome?
Midline defects: holoprosencephaly, microcephaly, micropthalmia, cleft palate, omphalocele, polydactyly, and cutis aplasia
Which prokaryotic polymerase has both 3’ to 5’ and 5’ to 3’ exonuclease activity?
DNA Pol I
What are the two types of Hyperimmunoglobulin M syndrome deficiencies?
CD40L: XLR Most common
CD40: AR
What activates trypsin? Which other pancreatic enzymes does trypsin activate? Where?
Trypsinogen is activated to trypsin by enteropeptidases in the brush border of the duodenum. Trypsin then activates chymotrypsinogen, procarboxypeptidase, and proelastase.
What issues are seen in patients with enteropeptidase deficiency?
Protein and fat malabsorption –> diarrhea, failure to thrive, edema
What deficiency causes porphyria cutanea tarda?
uroporphyrinogen decarboxylase
What enzyme deficiencies result in photosensitivity?
uroporphyrinogen decarboxylase, coprophyrinogen oxidase, protoporphyrinogen oxidase, or ferrochelatase
What is the defect in lynch syndrome (hereditary nonpolyposis colon cancer)? What are the most common mutations?
Defective DNA mismatch repair
MSH (MutS) & MLH1 (MutL)
What does overlying skin retraction signal in invasive breast carcinoma?
involvement of the suspensory ligaments of the breast.
How does invasive breast carcinoma usually present?
As an irregularly shaped adherent breast mass
What causes spinal stenosis?
degenerative arthritis of the spine results in narrowing of the spinal canal due to intervertebral disc herniation, ligamentum flavum hypertorphy, and osteophyte formation
What are the symptoms of spinal stenosis?
posture-dependent lower extremity pain, numbness/paresthesia, and weakness. Worse with standing up, better with leaning or walking uphill
What topical drug used for psoriasis activates Vitamin D receptors? Why is that therapeutic?
Vit D analogs- calcipotriol, calcitriol, and tacalcitol
Vit D receptor is a nuclear transcription factor that causes inhibition of keratinocyte proliferation and stimulation of keratinocyte differentiation
What are the symptoms associated with dengue fever? Dengue hemorrhagic fever?
flu-like febrile illness with MARKED MYALGIAS and JOINT PAIN, retro-orbital pain, rash
Hemorrhagic: thrombocytopenia, spontaneous bleeding- shock
What causes dengue hemorrhagic fever?
Exposure to a different serotype after primary exposure. May be due to Ab dependent enhancement of infection, enhanced immune complex formation, and/or accelerated Tcell response
What organs are most commonly affected by GVHD? What are the symptoms?
Skin, liver, GI
Usually starts with maculopapular rash on the soles and palms
Abnormal LFTs
diarrhea, intestinal bleeding, ab pain
Which bacteria are most commonly involved in cholecystitis?
E Coli, Enterococcus, Klebsiella, Enterobacter
What illnesses does the H flu vaccine protect against?
H flu type b- MENINGITIS, pneumonia, epiglottitis, and sepsis
What are the signs associated with hypocalcemia?
Chvostek: muscle contraction elicited by tapping on the facial nerve.
Trousseau: Carpopedal spasm with polonged inflation of a blood pressure cuff around the arm
What is the most common cause of hypocalcemia?
injury to the parathyroids during thyroid surgery
What does rituximab target?
monoclonal Ab against the CD 20 surface Ig on B cells (lymphoma)
What does Infliximab target?
chimeric IgG1 against TNF-alpha (RA, Ankylosing spondylitis, fistulizing Crohn’s)
Why is IL-2 used for treatment of renal cell carcinoma and melanoma?
It regulates activation and differentiation of t cells to aid in tumor destruction
What test can be used to diagnose strep pyogenes?
Pyrrolidonyl arylamidase test (PYR +)
Which malignancies cause osteoblastic (sclerotic) cancers?
More indolent
Prostate cancer
small cell lung
Hodkin lymphoma
Which malignancies cause osteolytic (lucent) cancers?
Aggressive Multiple myelome non-small cell lung non-Hodgkin lymphoma renal cell carcinoma melanoma
Which malignancies cause mixed osteolytic and osteoblastic cancers?
GI
Breast
Why are nitrates dosed to have a long gap overnight?
Nitrate-free interval is to prevent tolerance
What is a very bad long term risk associated with PCOS? Why?
Endometrial carcinoma- imbalance of estrogen and progesterone, because there isn’t a monthly dominant follicle to produce progesterone
What proteins are involved in gap junctions?
Connexins
What proteins are involved in Tight Junctions?
Claudins, occludin
What proteins are involved in Adherens junctions?
cadherin
What proteins are involved in Desmosomes?
Cadherins (desmogleins, desmoplakin)
What proteins are involved in Hemidesmosomes?
Integrins
What are the derivative of the 3rd branchial pouch?
dorsal: inferior parathyroids
ventral: thymus
What are the derivative of the 1st branchial pouch?
Middle ear cavity, eustachian tube, mastoid air cells
What are the derivative of the 2nd branchial pouch?
Epithelial lining of the palatine tonsil
What are the derivative of the 4th branchial pouch?
Dorsal: superior parathyroid
Ventral: ultimobranchial body and Thyroid parafollicular (C) cells
What hormone causes increase in insulin resistance during pregnancy?
human placental lactogen
Why do high levels of aflatoxin cause hepatocellular carcinoma?
G:C –> T:A transversion in codon 249 of the p53 gene
In third degree heart block, what is responsible for ventricular pacing?
AV nodal cells
What nerve provides innervation to the suprapubic region?
iliohypogastric
What nerve provides sensory innervation to the upper thigh and inner leg and motor innervation to muscles that extend the knee?
femoral
What nerve provides sensory innervation to the upper anterior thigh and motor innervation to parts of the genitalia?
genitofemoral
What nerve provides sensory innervation to the upper and medial thigh and parts of the external genitalia?
ilioinguinal
What nerve provides sensory innervation to the lateral thigh
Lateral femoral cutaneous
What nerve provides sensory innervation to the medial thigh and motor innervation to the adductor muscles of the lower extremity?
Obturator nerve
What are the signs and symptoms of gallstone ileus? What causes it?
Bowel obstruction with ab pain/distention, N/V, there may be gas in the gallbladder and biliary tree
A large gallstone causes formation of a cholecystenteric fistula b/w gallbladder and small intestine. Gallstone travels freely until it gets stuck in the ileum
What are amatoxins? where are they found? what do they do? What are the symptoms?
Amatoxins are in poisonous mushrooms and get concentrated in the liver where they bind DNA-dependent RNA pol II and halt mRNA synthesis, ultimately resulting in apoptosis
Symptoms: ab pain, vomiting, sever, cholera-like diarrhea- can lead to acute hepatic and renal failure
NAD+ is necessary for which step of the TCA cycle? How does it get converted back from NADH in aerobic and anaerobic conditions?
Necessary for G3P–>1,3 BPG
Aerobic: during TCA cycle
Anaerobic: Conversion of pyruvate to lactate by lactate dehydrogenase
Without recovery of NADH, glycolysis cannot continue
How can GI bleeding lead to hepatic encephalopathy?
Bleeding in the gut leads to breakdown of Hgb, which produces ammonia that is absorbed into the blood stream. If the patient has impaired liver function, they will not be able to detoxify this ammonia to urea
What are the 3 causes of HIV-associated esophagitis and what are the endoscopic findings?
Candida Albicans: patches of adherent, grey/white pseudomembranes on erythematous mucosa
HSV-1: Small vesicles–> punched out ulcers
CMV: Linear ulcerations
What artery provides blood supply to the pelvic organs and should ligated during postpartum hemorrhage? Is the patient infertile after this procedure?
Internal iliac arteries
No, because there is collateral blood supply to the uterus from the ovarian arteries
What is the mechanism of resistance to aminoglycosides?
Bacterial production of aminoglycoside modifying enzymes
Acquired from transposon or plasmid
Which adrenoreceptors are activated by norepi?
Alpha 1&2, and Beta 1
NOT Beta 2 (No bronchodilation or vasodilation)
What usually causes hepatic abscess in developed countries? Undeveloped countries?
developed countries: Bacterial infection (Staph A)- Can gain access via biliary tract infection, portal vein pyemia, hepatic artery, Direct invasion from adjacent source, or penetrating trauma
Undeveloped countries: Parasitic infection (Entamoeba histolytica, echinoccocal)
What is the most common cause of bloody nipple discharge?
intraductal papilloma- proliferation o papillary cells in a duct or cyst with fibrovascular core
How can rasburicase help to prevent tumor lysis syndrome?
Rasburicase is a recombinant version of urate oxidase, which converts uric acid into allontoin. Allantoin is 5-10x more soluble in urine than uric acid
Describethe gram stain and media used to grow cholera
oxidase +, gram -, comma-shaped organism that grows on high-alkaline selective media
Which diarrheal bacteria causes fecal mononuclear leukocytes?
Salmonella Typhi
What is the main source of protection from reinfection with a similar strain of flu virus?
antibodies to hemagglutinin
What cell is important for prevention of superficial candida infection? Hematogenous spread?
superficial candida infection: T-cells
Hematogenous spread: Neutrophils
What are the dysmorphic features associated with Edwards (trisomy 18) syndrome?
micrognathia, low-set ears, prominent occiput, hypertonia, clenched fists with overlapping fingers, Cardiac, genitourinary, and GI anomalies
Where are aspiration pneumonias in supine individuals?
dependent locations:
Superior regions of the lower lobe and posterior regions of the upper lobes
What are the complications that can occur with congenital CMV infection?
chorioretinitis, sensorineural deafness, seizures, jaundice, hepatomegaly, splenomegaly, and microcephaly
Which branch of the trigeminal nerve controls the muscles of mastication?
Mandibular
Which cells produce IFN-gamma? What does it do
Produced by activated Tcells and NK cells in response to IL-12 from macrophages, IFN-gamma stimulates macrophages to kill phagocytosed pathogens
How do interferon gamma release assays test for TB?
Measure response of Tcells when exposed to TB antigens
Which familial cancer genes are associated with pheochromocytoma?
VHL, RET (MEN2), NF1
Form which cells does a pheochromocytoma arise?
The chromaffin cells of the adrenal medulla
How many half-lives does it take to reach steady state of a drug?
4-5
What cardiac issue associated with a murmur can cause head bobbing and nocturnal palpitations?
Aortic regurgitation:
head bobbing from widened pulse pressure
nocturnal palpitations from forceful ventricular contractions ejecting large stroke volumes
What is the effect of sun exposure on vitamin D?
Converts 7-dehydrocholesterol (provitamin D3) to cholecalciferol (D3)
What is the pathogenesis of preeclampsia?
abnormal placental vasculature–> hypoxic placenta–> release of antiangiogenic factors–> endothelial injury–> increased permeability (proteinuria) and dysregulation of vascular tone (hypertension)
What is Rett syndrome?
X-linked de novo mutation in the MECP2 gene
Normal development until 5-18 months followed by a loss of motor and language skills, stereotypic hand movements, deceleration of head growth, seizures, ID
What is adenomyosis and how does it present?
Presence of endometrial glandular tissue in the myometrium, usually in middle-aged parous females
Presents with heavy menstrual bleeding, dysmenorrhea, and uniformly enlarged uterus
What is the most common congenital anomaly of the small intestine?
Meckel diverticulum due to incomplete obliteration of the omphalomesenteric duct that connects the midgut lumen and yolk sac cavity (rule of 2s). Can contain ectopic tissue- most often gastric epithelium producing acid that ulcerates neighboring tissue and causes painless melena
What are the pathologic findings in Primary Biliary cirrhosis and graft versus host disease?
lymphocytic inflammation with destruction of intrahepatic bile ducts
What are the pathologic findings in serious acetaminophen overdose?
liver failure with centrilobular necrosis that can extend to the entire lobe
What are the pathologic findings in Alcoholic hepatitis?
hepatocellular swelling and necrosis, mallory bodies, neutrophilic infiltration, and fibrosis
What are the pathologic findings in Budd-Chiari syndrome?
Clot at the junction of hepatic vein and IVC causes increased intrahepatic pressure–> reddish-purple parenchyma with severe centrilobular congestion and necrosis
What are the adverse effects associated with erythropoiesis-stimulating agents?
thromboembolic events, hypertension
What are the primary effector cells in urushiol-induced contact dermatitis?
CD8 cells
Why do fibrates lead to gallstones?
In addition to upregulating PPAR alpha, they inhibit cholesterol 7 alpha hydroxylase, which catalyzes the last step in bile acid formation. The reduced bile acid production results in decreased cholesterol solubility.
What are the 5 cofactors required for Branched chain alpha ketoacid dehydrogenase (Deficient in MSUD)?
Thiamine, Lipoate, Coenzyme A, FAD, NAD
High dose thiamine can help improve MSUD
If a patient has been stabbed and bleeding does not stop with Pringle maneuver (occlusion of the hepatoduodenal ligament- portal triad), which vessel is likely injured?
Inferior vena cava or hepatic veins
What are the two primary sources of alkaline secretions to the duodenum?
Brunner glands
Epithelial cells of the pancreatic ductules and ducts produce water secretions containing high concentrates of bicarbonate ions
When do patients exhibit Cheyne-Stokes breathing?
Advanced congestive heart failure
Which organisms are resistant to cephalosporin?
Resistant PBPs: -Listeria -MRSA -Enterococci No cell wall -Atypicals (mycoplasma, chlamydia)
What monoclonal antibody is used in the management of HER2 positive breast cancer?
Trastuzumab- binds HER2 and prevents activation of a transmembrane tyrosine kinase
What is chlordiazepoxide?
a benzo
Which bacteria are found in soil and able to survive high temp, dessication, and chemical agents by forming spores?
Members of the Bacillus and Clostridium genuses
Why are E6 and E7 viral proteins oncogenic?
E6 binds p53, leading to ubiquitination–> can’t halt cell cycle
E7 binds Rb and displaces bound transcription factors, promoting unregulated DNA replication and cylcin-mediated cell cycling
Why do patients with normal pressure hydrocephalus have urinary incontinence?
Cortical fibers that run in the periventricular pathways get distended, leading to disruption of impulses from the cortex to the sacral micturition center
Which HLA allele is associated with Ankylosing spondylitis?
HLA B27
How does copper move through the body?
60% of ingested Cu is absorbed in the stomach and duodenum. It is made into ceruloplasmin in the liver, which is secreted into the plasma. Senescent ceruloplasmin and the unabsorbed Cu (40%) are secreted into bile and excreted in stool. About 5-15% of daily Cu excretion is from the kidney
What is the gram stain for H. Flu? What factors does it need to grow?
X factor (hematin) and V factor (NAD+)
What are some examples of disorders with multifactorial inheritance?
Spina Bifida, cleft lip and palate, DM, coronary artery disease, and HTN
Why do corticosteroids acutely increase the neutrophil count?
Demargination of neutrophils previously attached to the vessel wall
What will an mutation that Increases the amount of PRPP synthetase cause?
Gout, because there will be increased purine and pyrimidine production, leading to increased degradation and hyperuricemia
What are the primary cells responsible for the intense inflammatory response seen in patients with gout?
Neutrophils
What artery provides blood supply to the proximal ureter?
Renal artery
What artery provides blood supply to the distal ureter? Middle ureter?
Superior vesical artery.
Circulation to the middle ureter is anastomotic and variable
What are the symptoms of cat scratch fever? What is the presentation of Bartonella henselae in immunocompromised patients?
primary erythematous lesion followed by tender regional lymphadenopathy
Bacilliary Angiomatosis- red-purple papular skin lesions that may also be found within the viscera. Can be fatal if left untreated.
What are the parts of LPS? Which part causes sepsis?
O antigen, core polysaccharide, and lipid A
Lipid A induces shock by activation of macrophages and granulocytes
Where does lymph from the testes drain to?
para-aortic lymph nodes
What is the most common cause of fatal sporadic encephalitis?
HSV 1
What is the most common cause of bronchiolitis? In what age group does it occur?
RSV
less than 2 y/o
Which benzos can be given for anxiety without causing daytime sleepiness?
Short-acting: triazolam, oxazepam, midazolam
Intermediate-acting: lorazepam, alprazolam
From which amino acid is nitric oxide synthesized? What is the enzyme?
Arginine (+NADPH and O2)
eNOS (epithelial nitric oxide synthase)
How does NO cause vasodilation?
Activates Guanylyl cyclase–> increased cGMP, which activates protein kinase G and leads to a reduction in cytosolic Ca level
How does testosterone cause acne?
promotes follicular epidermal hyperproliferation and excessive sebum production
What do oxalate crystals in the renal tubules suggest?
Ethylene glycol poisoning causing toxic renal injury and acute tubular necrosis
What is the renal morphology on light microscopy in ethylene glycol poisoning?
Normal glomeruli, but proximal tubular necrosis with cell ballooning and vacuolar degeneration
What is the most common secondary tumor in patients with hereditary retinoblastoma?
Osteosarcoma,
They also are at high risk for other types of sarcoma
What is the action of the Rb gene on chromosome 13?
Tumor suppressor, active when dephosphorylated, does not allow cell to proceed from G1 to S
Phosphorylation of Rb permits cell division
Which patients are at higher risk of developing ALL?
Down Syndrome, Ataxia Telangiectasia, and NF1
What are the risks to children of secondhand smoke?
Prematurity, low birth weight SIDS Middle ear disease Asthma Respiratory tract infections
What is the most common benign tumor in the lung?
hamartoma: well-defined coin lesion with “popcorn calcifications”
What are the epithelia associated with: ovary, fallopian tube, uterus, cervix, and vagina?
ovary: Simple cuboidal
fallopian tube: Simple columnar- ciliated cells transport egg/embryo
uterus: Simple columnar- prolonged estrogen prevents shedding–> hyperplasia/malignancy
Endocervix: Simple columnar
Ectocervix: Stratified squamous non-keratinized
vagina: Stratified squamous non-keratinized- maintains acidic environment
What are the symptoms of primary carnitine deficiency?
myopathy, cardiomyopathy, hypoketotic hypoglycemia, decreased muscle carnitine content
Why s carnitine necessary?
Needed to shuttle fatty acids from the cytoplasm into the mitochondria during fatty acid oxidation. Therefore muscles can’t use fats for ATP generation, and liver can’t synthesize ketone bodies (acetoacetate) when glucose levels are low
What causes X linked agammaglobulinemia?
Failure of bone marrow pre-B cells to mature, leading to low or absent B cell levels and pan hypoglobulinemia
What causes sarcoidosis?
dyregulated cell-mediated immune response to unknown antigen driven by macrophages and Th1: IL-2 and IFN-gamma. Promote formation of non-caseating granulomas
Which hormone is responsible for gallbladder contraction? Where is it made?
Cholecystokinin- made in duodenum and jejunum in response to fatty acids and amino acids
What does RT-PCR detect and measure?
mRNA (produce complementary cDNA with the exons nad 5’ and 3’ untranslated regions)
What causes brown pigmented stones?
Typically arise secondary to bacterial or helminthic infections that result in the release of beta-glucuronidase from injured hepatocytes and bacteria. The beta-glucuronidase hydrolyzes bilirubin glucuronides and leads to increased unconjugated bilirubin
What are the pathological findings in HPV?
Koilocytes- immature squamous cell with dense, irregularly staining cytoplasm and perinuclear clearing, resulting in a halo. “raisinoid” appearance of the the enlarged pyknotic nucleus
Which nerve supplies innervation to the perineum?
Pudendal
Which nerve supplies sympathetic and parasympathetic innervation to the internal pelvic viscera?
inferior hypogastric plexus
Which nerve supplies parasympathetic (only) innervation to the pelvic and genital organs?
Pelvic splanchnic nerve (S2-4)
What does the inferior gluteal nerve supply?
Motor function to the gluteus maximus
What test should be used to check for fat malabsorption?
Sudan III stain of the the stool to check for fat
What is the appearance of the liver on autopsy in Inhaled anesthetic hepatotoxicity? What anesthetic is most commonly associated?
Shrunken due to rapid atrophy with widespread centrilobular necrosis and inflammation to the portal tracts and parenchyma (same as fulminant hepatitis)
Halothane, but also enflurane, isoflurane, desflurane, and sevoflurane
What are the symptoms and lab findings in inhaled anesthetic hepatotoxicity?
fever, anorexia, nausea, myalgia, tender hepatomegaly, and jaundice
Elevated LFTs, Prolonged PT, leukocytosis, and eosinophilia
What are the symptoms of meniere’s disease?
low frequency tinnitus with a feeling of fullness
Vertigo
Sensorineural hearing loss
What causes meniere’s disease?
Defective resorption of endolymph and resultant increase in volume and pressure of endolymph, causing damage to the vestibular and cochlear components of the inner ear
What is the primary pathophysiologic mechanism responsible for GERD?
Gastroesophageal junction incompetence
What are characteristic histological findings in GERD?
Distal esophagus with basal zone hyperplasia, elongation of the lamina propria papillae, and scattered eosinophils and neutrophils
What happens when a muscle contracts too hard?
It pulls the golgi tendon organ, which uses 1b sensory axons to contact inhibitory interneurons that synapse with the alpha motor neurons from that group–> relaxation
What happens when a muscle is stretched?
Activates the intrafusal fibers of the muscle spindle, leading to contraction–> deep tendon reflex
How do shiga and shiga-like toxins work?
inactivate 60s ribosomal subunit in human cells
What are some common medical conditions with polygenic inheritance?
androgenetic alopecia epilepsy glaucoma HTN Ischemic hrt dz schizophrenia T2DM
Describe the findings in hirschsprung disease
fail to pass meconium within 48 hours
bilious vomiting, ab distention
empty rectal vault
increased anal sphincter tone
What can be used to treat lyme disease?
doxycycline
penicillin-type antibodies (ceftriaxone)
Why is HbA1C falsely low in people with beta thalassemia?
High RBC turnover rate means there is a shorter period of exposure to high glucose levels
Look for elevated HbA2 to diagnose beta thalassemia
What is the exotoxin involved in staph scalded skin syndrome? How does it present?
Exfoliatin- cleaves desmoglein in desmosomes (only in epidermis)
Skin slips off with gentle pressure, epidermal necrolysis, fever, and pain
(bullous impetigo is a more localized form of SSSS)
What type of epithelium is HPV most likely to infect? Where is it located?
Stratified squamous epithelium
anal canal, vagina, cervix, and the true vocal cords in the respiratory tract
What conditions are associated with osteonecrosis of the femoral head?
Sickle cell dz–> thrombotic occlusion
Vasculitis–> impaired blood supply
Corticosteroids and alcohol–> unknown mechanism
What are the s/s associated with glucagonoma (rare tumor of the alpha cells of the pancreatic islets of Langerhans)?
DM
Necrolytic migratory erythema: Erythematous papules/plaques on face, perineum, extremities. The lesions enlarge and coalesce, leaving a bronze-colored, central indurated area with peripheral blisters and scaling
What is the order of fastest to slowest conduction in the heart?
Purkinje>Atrial>Ventricular>AV node
Which Biochemical processes take place in the cytosol?
glycolysis, fatty acid synthesis, and the pentose phosphate pathway
Which Biochemical processes take place in the mitochondria?
beta-oxidation of fatty acids, TCA cycle, and carboxylation of pyruvate
What does hormone sensitive lipase do and where is it found?
Stress hormone induces release of hormone sensitive lipase in adipose tissue, which catalyzaes the mobilization of TGs into FFAs and glycerol.
Glycerol is a source of Cs for gluconeogenesis and FAs are used to make Acetyl CoA for the TCA cycle or further metabolized into ketone bodies
What structure is most vulnerable to injury during a hysterectomy?
Ureter, because it is just deep to the where the uterine vessels are ligated and the closure of the lateral aspect of the vaginal cuff–> can be sutured shut by accident
What is the most common GI abnormality associated with Down Syndrome? How does it present?
Duodenal atresia (failure of the recanalization of the duodenum in early gestation)
Double bubble sign and bilious emesis
Other GI issues: imperforate anus, Hirschsprung dz, TE fistula, and celiac dz
What is Buspirone used to treat? How?
Generalized anxiety disorder
partial agonist of the 5HT1A receptor
Slow onset of action
What is the difference between the ulcers in HSV, Haemophilus ducreyi, Klebsiella granulomatis, and chlamydia trachomatis?
HSV: shallow ulcerations with erythematous base Haemophilus ducreyi (chancroid): deep, purulent, painful ulcers with suppurative lymphadenitis Klebsiella granulomatis (granuloma inguinale): painless, progressive, red serpiginous ulcerative lesions without lymphadenopathy Chlamydia trachomatis (lymphogranuloma venereum): Initially painless small and shallow ulcers, followed by large painful coalesced lymph nodes, intracytoplasmic chlamydial inclusion bodies in epithelia cells and leukocytes
What causes uncomplicated umbilical hernia?
incomplete closure of the umbilical ring–> linea alba not formed. Most resolve spontaneously. Associated with Downs, Hypothyroidism, and Beckwith-Wiedemann syndrome
What are the most common microbes involved in nec fasc?
S. Pyogenes, S. Aureus, C. perfringens, and polymicrobial
What are the major virulence factors involved in S. Pyogenes necrotizing fasciitis?
Hyaluronidase- spread through skin and fascia
M protein- evades phagocytosis by preventing activation of the alternative complement pathway
Hemolysins O and S- hemolysis
Pyrogenic exotoxin: superantigen–> tissue injury and septic shock
Where are lesions that cause homonymous hemianopia with macular sparing? Why is the macula spared?
Occipital cortex - posterior cerebral artery
The macula is spared because there is collateral blood flow from the middle cerebral artery to the occipital pole, which processes central visual info
What causes reactive arthritis? What does joint aspirate show?
Reactive arthritis is caused by immune complex deposition with bacterial antigens, though it is not a disseminated infection- taps are sterile. It most commonly follows infection with campylobacter, shigella, salmonella, Yersinia, CT, or Bartonella
What are the extraarticular sx associated with reactive arthritis? What is the associated HLA type?
conjunctivitis, urethritis, and keratoderma blennorrhagicum
HLA-B27
What should be monitored in a patient taking olanzapine?
BMI, fasting glucose and lipids, BP, waist circumference
What is the action of colchicine? Why is it given?
binds intracellular tubulin and inhibits its polymerization- This disrupts functions such as chemotaxis, phagocytosis, and degranulation.
Colchicine also reduces formation of LTB4
Used during gout flare when NSAIDs are contraindication
What are the pathologic features of the two types of hydatidiform mole?
Complete: diffuse trophoblastic proliferation and edematous chorionic villi (bunch of grapes)- no fetal tissue. p57-negative
Partial: Some enlarge villi with focal trophoblastic proliferation. p57-positive
Why does galactosemia cauase cataracts?
Galactokinase deficiency prevents galactose from being converted into galactose 1 phosphate. Instead, it is converted by aldose reductase into galactitol that is an osmotic agent and causes cataracts
How can Galactokinase deficiency show up in urine tests?
excess galactose spills into urine, causing it to test positive for a reducing substance
How does Galactokinase deficiency compare to deficiency of galactose-1-phosphate uridyl transferase?
GALT is much more severe due to buildup of toxic galactose-1-phosphate, which causes hepatic and renal dysfunction. It presents in neonates as vomiting, lethargy, and failure to thrive.
Where is the most common site of intussusception? How is it diagnosed and treated?
ileocecal junction
Barium enema is used for diagnosis, but can also be the treatment- if it doesn’t work, then surgery
What ratio is important for determining whether there will be increased bone turnover?
Osteoprotegerin to RANK-L
Low ratio means more bone being resorbed
How does prolonged NSAID use lead to chronic interstitial nephritis?
NSAIDs uncouple oxidative phosphorylation and deplete glutathione, leading to lipid peroxidation–> damage to tubular and vascular endothelial cells
Also leads to ischemic papillary necrosis via constriction of the medullary vasa recta
What are the pathological findings in chronic interstitial nephritis?
patchy interstitial inflammation–> fibrosis, tubular atrophy, papillary necrosis and scarring, and caliceal architecture destruction
What pathway does IFN gamma activate in macrophages?
Jak-STAT
How do you tell the difference between 21-hydroxylase deficiency and aromatase deficiency in a female newborn with clitoromegaly?
With aromatase deficiency, the mom will undergo virilization (hirsutism) during the pregnancy
Which tumor most typically metastasizes to the ovaries?
GI tumor
What is it called when gastric cancer metastasizes to the ovaries? How does it present?
Krukenberg tumor
unintentional weight loss, epigastric pain, and adnexal masses
What is the pathologic finding in gastric cancer with krukenberg tumor?
Signet ring cell- large amount of mucin displacing the nucleus
How does gastric signet ring cell cancer spread to the ovaries?
lymphatic invasion and peritoneal seeding
When would you see acute renal after initiation of ACEi?
In patients with bilateral renal artery stenosis- they depend on the vasoconstriction from Ang II to maintain GFR
Where in the nephron is urine most dilute?
Distal convoluted tubule, because solutes are still being reabsorbed, but it is relatively impermeable to water, so the water can’t be reabsorbed
What is the rate-limiting step in the synthesis of catecholamines?
Conversion of tyrosine to DOPA by tyrosine hydroxylase
What converts DOPA to dopamine?
DOPA decarboxylase
What converts dopamine to norepinephrine?
Dopamine beta-hydroxylase
What converts norepinephrine to epinephrine? Where? What upregulates expression of this enzyme?
Phenylethanolamine-N-Methyltransferase (PNMT) in the adrenal medulla. Upregulated by cortisol, so decreased cortisol/ACTH can lead to decreased conversion of Norepi to Epi
What are the three phases of paget’s disease of the bone?
- Osteolytic (osteoclast)
- Mixed Osteoclastic-Osteoblastic: abnormal bone formation with areas of disorganized lamella and woven bone
- Osteosclerotic (Osteoblast): remodeling–> dense, hypovascular mosaic pattern of lamellar bone with prominent cement lines
What are the downstream effects of Gq activation?
Alpha subunit exposes a Phospholipase C site theat hydrolyzes PIP2 into DAG and IP3. DAG stimulates PKC and IP3 releases intracellular Ca stores leading to even more PKC stimulation
How can temporomandibular disorder present? Why?
Can present with both otologic symptoms and jaw pain, because the mandibular division of CN V innervates the middle ear and the muscles of mastication
What is the blood supply to the femoral head? What can damage to it?
Medial circumflex artery
Damage from fracures of the femoral neck
How does blood from the spleen return to circulation?
Splenic vein to the portal circulation rather than going straight back to systemic circulation
What type of poisoning is caused by ingestion of pesticides? What are the symptoms?
Arsenic poisoning
ab pain, vomiting, severe watery diarrhea, delirium, and hypotension
Prolonged QTc–> Torsades de Pointes
Garlic odor on patient’s breath or stool
What damage does arsenic do when ingested? What is the treatment?
Binds sulfhydryl groups, impairing cellular respiration via inhibition of pyruvate dehydrogenase and diruption of gluconeogensis and glutathione metabolism.
Tx: Dimercaprol- chelating agent increases urinary excretion
What is a pancreatic pseudocyst? What causes it? What lines the walls of the pseudocyst?
Common complication of acute pancreatitis with collection of fluid rich in enzymes and inflammatory debris. The walls are lined by granulation tissue and fibrosis (unlike true cysts, which are lined by epithelium)
What are the most important opsonins?
C3b and IgG
mannose-binding lectin and CRP can also opsonize
With which other rheumatological disease is Giant cell arteritis associated?
Polymyalgia Rheumatica
What are the histological findings in Giant cell arteritis (temporal arteries) and Takayasu’s arteritis (aortic arch)?
scattered, focal granulomatous inflammation centered on the media with intimal thickening, elastic lamina fragmentation, and giant cell formation
What are the symptoms and histological findings in Polyarteritis Nodosa?
Sx: intermittent episodes of ab pain, peripheral neuropathy, renal insufficiency, and severe HTN
Histology: Transmural inflammation of the arterial wall with fibrinoid necrosis
What are the symptoms associated with acute HBV infection?
serum-sickness like syndrome with joint pain, lymphadenopathy, and a puriritic urticarial rash
Can also have RUQ pain, hepatomegaly, and elevated LFTs
Which organ passes between the SMA and the Aorta and is squished with a loss of mesenteric fat (low body weight, recent weight loss)?
Transverse portion of the duodenum
Why does metronidazole cause adverse reaction to alcohol?
disulfiram-like inhibition of acetaldehyde dehydrogenase causes buildup of acetaldehyde
What does tyrosinase deficiency cause?
Albinism, because tyrosinase is necessary to synthesize melanin from tyrosine
What two deficiencies can cause phenylketonuria? Which is worse?
Phenylalanine Hydroxylase
Dihydrobiopterin reductase: worse, because also can’t convert tyrosine into dopa, so can’t form NE, EPI,DA, or 5HT
What causes alcohol induced hepatic steatosis?
Decrease in fatty acid oxidation due to excess nADH production by alcohol dehydrogenase and aldehyde dehydrogenase
What is the difference between schizophrenia, brief psychotic disorder, and schizophreniform disorder?
Brief: >1 day and <1 month
Schizophreniform: >1 month and <6 months- doesn’t require functional decline
Schizophrenia: >6 months requires functional decline
What is the treatment for SCID?
Stem cell transplant
Which immune cells are responsible for type 4 hypersensitivity reaction?
Macrophages, CD4 and CD8 tcells. Macrophages present to CD4, which recruit CD8 to produce the characteristic signs of induration and edema
With which dyes does diptheria stain?
Aniline dyes (methylene blue)
What is the mutation in Hartnup disease? Why does this cause symptoms of niacin deficiency?
AR inactivating mutation of the neutral amino acid transporter in the small intestine and kidney.
This leads to tryptophan (essential a.a.) deficiency. Tryptophan is a precursor for Niacin, serotonin, and melatonin
How is hartnup disease diagnosed and treated?
Excessive neutral amino acids in urine
Treated with a high protein diet and daily niacin or nicotinamide supplementation
What is the effect of Nitrates and phosphodiesterase inhibitors on a cell?
Increased cGMP- Nitrates enhance synthesis and PDEs prevent degradation
From where to where is a midline episiotomy made?
From the posterior vaginal opening to the perineal body
What exits the skull through the jugular foramen?
CN IX, X, XI, and jugular vein
What does the uterus look like during ectopic pregnancy?
Decidualization- dilated, coiled endometrial glands and vascularized edematous stroma, prepared for implantation
NO embryonic or trophoblastic tissue
Which cells produce inhibin?
Sertoli cells produce inhibin in response FSH. Inhibin then has negative feedback on FSH
Which bacteria cause a mouse-like odor after a dog bite?
Pasteurella
What are symptoms associated with significant hypokalemia?
muscle weakness, cramps, paresthesias and possible rhabdomyolysis
Which organs/cells have insulin-independent glucose transporters (GLUT 1, 2, 3, 5)?
Brain, Kidney, Intestine, Liver, RBCs
Which organs/cells have insulin-dependent glucose transporters (GLUT 4)?
Muscle cells, adipocytes
What are the most common organisms involved in Parotitis? What causes parotitis?
S. Aureus or mixed oral aerobes/anaerobes
Risk factors: dehydration, intubation, anticholinergics (decrease salivary flow), salivary flow obstruction, intense teeth cleaning
What are the symptoms of parotitis? How is it diagnosed?
firm and erythematous pre/postauricular swelling that extends to the mandible
Elevated amylase without pancreatitis
How does mifepristone end a pregnancy?
Acts as a progesterone antagonist that binds progesterone receptors with greater affinity. Progesterone blockade results in apoptosis and necrosis of the uterine decidua
What hormones produced by sertoli cells are necessary for internal sex differentiation?
AMH and Androgen binding protein
What are the histological findings in sarcoidosis?
non-caseating granuloma: aggregates of epithelioid cells (activated macrophages) and multinucleated giant cells
What correlates with the severity of temporal arteritis?
IL-6- antibody against IL-6 (tocilizumab) is effective in treating GCA
What nerve plexus can be injured during prostatecomy? What are the consequences? How is this avoided?
Prostatic plexus
Erectile dysfunction
Preserve the integrity of the prostatic fascial shell during surgery
What are the characteristic s/s of eosinophilic granulomatosis with polyangiitis (churg-strauss)?
small to medium vessel vasculitis with late-onset asthma, rhinosinusitis, and eosinophilia
Mononeuritis multiplex due to involvement of the epineural vessels of peripheral nerves is common
What symptoms are associated with acute viral hepatitis?
low-grade fever, anorexia/nausea, dark-colored urine RUQ pain
What are the hallmark histologic findings in acute viral hepatitis?
Hepatocyte necrosis characterized by cellular swelling and cytoplasmic emptying
Hepatocyte apoptosis characterized by cellular shrinkage and nuclear fragmentation with intense eosinophilia
How do osteocytes communicate with one another within the bone matrix?
They extend cytoplasmic processes through the canaliculi to create gap junctions
What is damaged in noise-induced hearing loss?
The stereociliated hair cells in the organ of corti
Which muscles usually contract to dampen loud noises?
stapedius (facial nerve) and tensor tympani
What are the hearing abnormalities in vestibular schwannoma?
Unilateral high-frequency sensorineural hearing loss
What are the hearing abnormalities in defects of the middle ear ossicles (stenosis)?
Only affects air conduction across all frequencies
What are the hearing abnormalities in rupture of the tympanic membrane?
unilateral conductive hearing loss
What do the ovaries look like in Turner Syndrome?
Streak ovaries primarily composed of connective tissue with no follicles (usually lost by age 2)
What is the first line treatment for trigeminal neuralgia? How does it work?
Carbamazepine
reduces the ability of sodium channels to recover from inactivation
What is the most concerning side effect of carbamazepine?
Bone marrow suppression- monitor CBC
What mutation is associated with Crohn disease? How does it cause pathology?
NOD2 mutation- reduces NF-KB pathway activity –>reduced cytokine activation–> decreased mucosal defenses, so bacteria can invade further and cause a more robust inflammatory response from the adaptive immune system
What are some extraskeletal complications of Ankylosing Spondylitis?
Respiratory due to limited chest wall expansion
Ascending aortitis–> dilation of the aortic ring and aortic insufficiency
Anterior uveitis: pain, blurred vision, photophobi
Facial abscess following dental extraction? Notable feature?
Actinomyces israelii
“sulfur granules”- yellow aggregations of organisms bound together by proteins
Which nerve causes eversion of the foot? Which nerve is needed for dorsiflexion of the foot and toes?
Superficial peroneal
Deep peroneal
Is Ehlers-Danlos a collagen or elastin defect?
Collagen
How does pompe disease present?
In infancy, with marked cardiomegaly, hypotonia, macroglossia, hepatomegaly, and normal glucose levels
What causes Pompe disease?
Deficiency of acid alpha glucosidase. Can’t break down the small amount of glycogen that ends up in the lysosome–> pathologic accumulation of glycogen within liver and muscle lysosomes
What serum marker is used to monitor for recurrence of colorectal cancer?
Carcinoembryonic antigen
Explain the dose based effect of dopamine
Low dose: D1 receptors on renal vasculature–> ^GFR, ^RBF, ^Na excretion
Medium: Stimulates Beta-1 in the heart–> ^cardiac contractility, pulse pressure, and systolic BP
High: Stimulates alpha-1 in systemic vasculature–> vasoconstriction –> v Cardiac output due to the increased afterload
What is the most common benign tumor? What is the histology?
Cavernous hemangioma
Enlargement caused by ectasia, cavernous, blood-filled spaces of various size lined by a single epithelial layer
DO NOT BIOPSY- can cause fatal hemorrhage
What are typical features of Paget’s disease of bone?
pain and deformity of long bones, hearing loss due to bony deformity of the skull
What are osteoclasts like in Paget’s disease?
Very large and can have up to 100 nuclei
What is the pathogenesis of dermatitis herpetiformis?
IgA antibodies against gliadin cross-react with epidermal transglutaminase, causing microabscesses containing fibrin and neutrophils at the dermal papillae tips
What is the characteristic histology associated with celiad disease?
increased intraepithelial lymphocytes, variable loss of villus height, and crypt hyperplasia
Which antidepressant carries the risk of priapism (persistent erection)?
Trazodone
What are the two mechanisms by which the lac operon is regulated?
- Negatively by binding of the repressor protein to the operator locus
- Positively by cAMP-CAP binding upstream from the promoter region
What does light microscopy of a VZV vesicle base show? Skin biopsy?
intranuclear inclusions in both keratinocytes and multinucleated giant cells
Acantholysis (loss of intracellular connections) of keratinocytes and intraepidermal vesicles
What is lateral epicondylitis? What movement does it restrict?
Tennis elbow- due to repetitive microtrauma to the extensor carpi radialis brevis
Restricts wrist extension
What are the symptoms associated with CN 3 palsy?
ptosis (levator palpebrae)
down and out gaze
fixed, dilated pupil
What are the fundoscopic findings in central retinal artery occlusion?
pale retina and a cherry-red macula
What medium is commonly used to isolate Neisseria from clinical specimens?
Thayer-Martin: a chocolate agar based medium with various antibiotics- vancomycin to kill gram +, Colistin to kill gram -, nystatin to kill yeast, and TMP to inhibit the proteus species
What are the effects of Henoch Schonlein on various organs?
GI: bloody diarrhea, risk for intussusception
Kidney: same as IgA nephropathy- mesangial proliferation and crescent formation
Skin: purpura on butt and lower extremities
Joints: migratory arthralgias- mostly LE
What does BCR ABL code for?
a fusion protein with constitutive protein kinase activity
How does intestinal malrotation present?
intestinal obstruction- due to compression by the adhesive bands
Midgut volvulus-twisting around blood vessels–>ischemia
How do alcohols disinfect?
disruption of cell membranes
Denaturation of protein
How does chlorhexidine disinfect?
disruption of cell membranes
coagulation of cytoplasm
How does iodine disinfect?
halogenation of proteins and nucleic acids
What are the JONES criteria for rheumatic fever
Joint pain O- Endocarditis Nodules, subcutaneous Erythema marginatum Sydenham Chorea
What type of receptors are used by the parathyroids to sense calcium? What does a defect cause?
Calcium-sensing receptors- transmembrane G-protein-coupled receptors
Familial hypocalciuric hypercalcemia
How do beta lactams work?
irreversibly bind to penicillin-binding proteins that normally act as transpeptidases and cross-link peptidoglycan in the cell wall
Compare the characteristic histology of villous and tubular adenomas
Villous: large and sessile with cauliflower-like projections, more malignant transformation
Tubular: form tubes, smaller, and pedunculated
What are the symptoms associated with villous adenomas
secretory diarrhea, hypovolemia, electrolyte abnormalities
What treatments are available for C. Diff? Which one is preferred for recurrent infections?
Metronidazole, vancomycin, or fidaxomicin
Recurrent: Fidaxomicin- lower recurrence rate, lesser effect on normal colonic flora. Macrocyclic antibiotic that inhibits RNA pol
What causes cystic hygroma (neck mass) and lymphedema in Turner’s?
abnormalities of lymphatic outflow- swelling decreases with age
WHAT CAUSES MINIMAL CHANGE DISEASE?
Immune dysregulation leading to overproduction of glomerular permeability factor, a cytokine which damages podocytes and decreases the anionic (negative) properties of the basement membrane
What pathway is activated by growth hormone? What does this lead to in the liver
JAK-STAT
Release of IGF-1 which binds to receptor kinase and stimulates growth of bone, cartilage, muscle, and other tissues
What are homeobox genes? How long are they?
transcription factors that bing to regulatory regions on DNA, altering the expression of genes involved in segmental organization of the embryo
180 nucleotides
What are the symptoms of CJD?
rapidly progressive dementia and myoclonic jerks
What areas in the colon are most affected by nonocclusive ischemic colitis?
Watershed areas: splenic flexure and rectosigmoid junction
What is caudal regression syndrome? What is a common etiologic factor?
Agenesis of the sacrum and occasionally lumbar spine- flaccid paralysis of legs and urinary incontinence.
Maternal Diabetes
What causes hypercalcemia in sarcoidosis?
Activated macrophages express 1 alpha hydroxylase, which is used in the conversion to active vitamin D–> increased intestinal absorption of Ca, independent of PTH
What vessels must be ligated during a cesarean involving a horizontal transection of the rectus abdominis muscle?
Inferior epigastric arteries, because there is supporting posterior rectus sheath
What effect does myasthenia gravis have on motor end plate potential?
decreases end plate potential
Why would scopolamine be helpful in a patient already being treated for myasthenia gravis?
TX for MG is cholinesterase inhibitor–> excessive activation of both nicotinic and muscarinic acetylcholine receptors
Scopolamine selectively antagonizes the muscarinic receptors
Which two enzymes in the prophyria pathway are blocked by lead poisoning?
Ferrochelatase and d-aminolevulonic acid dehydratase
What two diagnoses should be considered for a bluish neoplasm underneath the nail bed? Function?
- Melanoma- pigmentation
2. Glomus tumor- modified smooth muscle cells of the glomus body, which shunts blood from skin surface in cold temps
Where are the majority of anal fissures?
posterior midline of the anal verge due to the poor perfusion of the posterior anal canal
What medications should you give to a lady with PCOS who is trying to get pregnant?
If weight loss doesn’t work, give her an estrogen receptor modulator to induce ovulation- clomiphene or letrozole
What symptoms are associated with Galactokinase deficiency?
cataracts, rarely pseudotumor cerebri
What is the deficiency in essential galactosemia? What gets built up? What are s/s?
Galactose-1-PO4 uridyl transferase
Galactose-1-PO4
jaundic, vomiting, hepatomegaly, E Coli sepsis, cataract, hemolytic anemia
How do most cases of sporadic colorectal carcinoma arise?
- APC - responsible for regulating cell growth/adhesion
2. K-RAS (unregulated proliferation), DCC (avoidance of apoptosis), p53 (regulates cell cycle)
What are the characteristic mutations in Lynch syndrome (HNPCC)?
DNA mismatch repair gene mutation–> microsatellite instability pathway
What are the key features of paranoid personality disorder?
Suspicious, distrustful, hypervigilant
What are the key features of schizoid personality disorder?
prefers to be a loner, detached, unemotional
What are the key features of schizotypal personality disorder?
eccentric, odd thoughts, perceptions, and behaviors- superstitions
What are the key features of Antisocial personality disorder?
Disregard and violation of the rights of others
What are the key features of borderline personality disorder?
chaotic relationships, sensitivity to abandonment, labile mood, impulsivity, inner emptiness, self-harm
What are the key features of histrionic personality disorder?
Dramatic, superficial, attention-seeking
What are the key features of Narcissitic personality disorder?
grandiosity, lack of sympathy
What are the key features of avoidant personality disorder?
avoidance due to fears of criticism an rejection
What are the key features of dependent personality disorder?
submissive, clingy, needs to be taken care of
What are the key features of obsessive compulsive personality disorder?
rigid, controlling, perfectionistic
Why is raloxifene a better choice than tamoxifen for treatment of osteoporosis?
Raloxifene is an estrogen agonist in the breast and uterus
Tamoxifen is an agonist in bone and uterus–> increased risk for endometrial cancer
Which receptor on a cell drives apoptosis via cytotoxic T cell extrinsic pathway?
FasR- can have transmembrane portion spliced out in some cancers to evade apoptosis
What E Coli virulence factor is associated with UTI? How?
P Fimbriae (fimbrial antigen)- allows adhesion to uroepithelium
What E Coli virulence factor is associated with BACTEREMIA AND SEPTIC SHOCK? How?
LPS- macrophage activation–> widespread release of IL-1, IL-6, and TNF-alpha
What E Coli virulence factor is associated with neonatal meningitis? How?
K1 capsular polysaccharide- prevents phagocytosis and complement-mediated lysis
What E Coli virulence factors are associated with gastroenteritis? How?
Verotoxin (shiga-like): inactivates 60s ribosomal subunit
Heat stable/labile enterotoxins: promote fluid electrolyte secretion from intestinal epithelial cells
Where do the ovarian veins drain?
Left: Left Renal vein
Right: IVC
What should you suspect in a postpartum patient with a fever that is unresponsive to antibiotics?
postpartum ovarian vein thrombosis- an example of septic pelvic thrombophlebitis
What is the difference between low and high grade cervical intraepithelial neoplasia?
low: atypical cells only in the lower 1/3rd of the cervical epithelium
high: atypical cells beyond the lower 1/3rd of the cervical epithelium
What marker significantly increases the risk of vertical transmission of HBV?
HBeAg- marker of viral replication and increased infectivity
What in the intestine can precipitate hepatic encephalitis?
GI bleeding
Excess dietary protein intake
How does Rifaximin treat hepatic encephalitis?
alters GI flora to decrease intestinal production and absorption of ammonia
What is the protein defect in familial chylomicronemia? Major manifestation?
LPL and ApoC-II
Acute pancreatitis
What is the protein defect in familial hypercholesterolemia? Major manifestation?
LDL receptor, ApoB-100
Premature coronary artery dz
What is the protein defect in familial dysbetalipoproteinemia? Major manifestation?
ApoE–> chylomicron and VLDL remnants
Premature coronary artery dz
What is the protein defect in familial hypertriglyceridemia? Major manifestation?
ApoA-V–> VLDL
increased pancreatitis risk
What are the findings in a patient with Peutz-Jeghers syndrome?
pigmented mucocutaneous macules and multiple hamartomatous polyps in the gastrointestinal tract. Progressive growth of hamartomas can lead to ab pain and GI bleeding
How can you tell the difference between a lipoma and a liposarcoma?
liposarcomas are pleiomorphic causing scalloping of the nuclear membrane
What does direct immunofluorescence of pemphigus vulgaris show?
epidermal, intercellular IgG and C3 depositis in a netlike or chickenwire pattern
Which parts of the brain are atrophied as a result of chronic alcoholism?
anterior lobes and cerebellar vermis–> gait ataxia, truncal instability, intention tremor
What renal issue does lithium cause?
causes nephrogenic diabetes insipidus- Interferes with the action of vasopressin on the renal collecting ducts
Brisk but painless lower GI bleeding in a child…
Meckel’s diverticulum with heterotopic mucosa–> gastric mucosa can release H+ and eat through the intestine- BLEEDING
What causes a wide split S2?
lengthening of right ventricular ejection time- right bundle branch block, pulmonary stenosis, and PAH
What are the two calcineurin inhibitors? What effect do they have on the kidneys?
Cyclosporine and tacrolimus
Afferent and efferent arteriolar vasoconstriction leading to a dose-dependent rise in BUN, Creatinine, and HTN. Long term use can eventually lead to obliterative vasculopathy
What drug used for vomiting or gastroparesis should not be used in a patient with Parkinsons?
Metoclopramide- dopamine receptor antagonism can cause de novo parkinsonian symptom and extrapyramidal reaction
What is the deficient enzyme in alkaptonuria?
homogentisic acid dioxygenase- part of the degradation pathway for phenylalanine ad tyrosine
What are the clinical features of alkaptonuria
urine that turns black on exposure to air
blue-black pigment deposition- nose, eyes, ears
Ochronotic osteoathropathies
Where is the substantia nigra located?
In the midbrain just deep to the corticobulbar tract in the cerebral peduncle
What gets built up in the substantia nigra in Parkinsons?
alpha synuclein filaments (eosinophilic inclusions)
What is the foam stability index?
Amniotic fluid is added to several wells with different concentrations of ethanol and shaken. The foam stability index is the highest value well that contains a ring of foam
What causes amenorrhea in thin female athletes?
Serum levels of LH and GnRH decline, leading to an estrogen deficiency–> infertility, vaginal atrophy, breast atrophy, osteopenia
How do you tell the difference between Marfans and Homocystinuria?
Homocystinuria has INTELLECTUAL DISABILITY, HYPERCOAGULABILITY, and downwardly displace lens
Marfans is upwardly displaced
What is the deficiency in homocystinuria? What gets built up?
Cystathione-beta-synthase
Builds up methionine and homocysteine
What does gonorrhea need to establish infection? Why can you get infected multiple times?
pili that bind to host epithelia cells and undergo phase and antigenic variation
What is the deficiency in McArdle dz?
muscle glycogen phosphorylase (myophosphoyrylase)
What causes proptosis and exopthalmos in Graves disease?
Lymphocytes infiltrate the orbital tissues and secrete cytokines–> fibroblast secrete increasing amounts of glycosaminoglycans (hyaluronic acid)–> extraocular muscle edema
What is the function of the pineal gland?
modulates circadian rhythms, secreting melatonin in response to darkness or sympathetic stimulation
What are the effects of a pinealoma?
- HA, N/V due to obstruction of cerebral aqueduct
2. Parinaud syndrome- upward gaze palsy, absent pupillary reflex, impaired convergence
Where are the stem cells of the intestine located?
crypts of lieberkuhn
Whata significatnly increases the risk for Thyroid cancer later in life?
external radiation to the head and neck
What part of the brain is affected in Kluver Bucy syndrome? What are the symptoms? What is it associated with?
Amygdalae
Inappropriate sexual acivity, oral fixation, hyperphagia, placidity, amnesia
Associated with HSV-1 encephalitis
How do calcineurin inhibitors prevent graft rejection?
Activated calcineurin dephosphorylates NFAT, which binds to an IL-2 promoter
How do patients with dopamine beta hydroxylase present?
Can’t make NE or Epinephrine–> postural hypotension, exercise intolerance, nasal congestion, and ejaculatory difficulties
What type of virus is adenovirus?
dsDNA
What are the pathognomonic findings in rabies?
eosinophilic cytoplasmic inclusions in hippocampal neurons(negri bodies)
also causes pharyngeal muscle spasms, hydrophobia, and ascending paralysis
What is the action of orlistat? What is it prescribed for? What are the side effects?
Inhibits intestinal lipase, leading to decreased fat absorption and modest weight loss
Side fx: ab discomfort, flatulence, diarrhea
What is seen on LM with Jones Methenamine silver stain in membranous nephropathy?
thickening of the glomerular basement membrane with pale non-staining spikes of immune complex deposits
Discuss anorectal venous drainage- think hemorrhoids
Above dentate line: superior rectal vein–> inferior mesenteric vein–> portal venous system
Below dentate line: middle and inferior rectal veins–> internal iliac vein–> systemic circulation
What is the effect of insulin on the conversion of F6P to F1,6BP?
Insulin upregulates PFK2, which converts F6P to F2,6BP. F2,6BP then upregulates PFK1, which is the enzyme needed for the conversion of F6P to F1,6BP–> glycolysis
What is the effect of glucagon on the conversion of F1,6BP to F6P?
Glucagon activates F2,6BPase, which downregulates F2,6BP, leading to conversion of F1,6BP to F6P–> gluconeogenesis
What are the nonpolar amino acids?
alanine, valine, leucine, isoleucine, phenylalanine, tryptophan, methionine, proline, and glycine
What nerves travel through the cavernous sinus? Where is it?
III, IV, V1, V2, VI
On each side of the sella turcica
How do facial infections spread to the cavernous sinus? What infection does this to patients with DKA?
Mucormycosis- spreads through the valveless facial venous system to the cavernous sinus, where it can cause infection or thrombosis
How do you calculate a 95% standard error?
mean +/- 1.96xSD/(n^.5)
How can anaphylaxis be diagnosed after a patient is stable?
Elevated tryptase levels- tryptase is relatively specific to mast cells
What triggers mast and basophil degranulation?
Multivalent antigen crosslinks multiple IgE antibodies, resulting in aggregation and activation of non-receptor tyrosine kinases
What is the TATA box a promoter for?
gene transcription- located ~25 bases upstream
What is anti-Jo-1?
anti-histidyl-tRNA synthetase
Where is superior gluteal nerve located (L4-S1)?
in the superomedial quadrant of the buttock
What is the predominant form of hemoglobin in a term infant?
Fetal hemoglobin- mostly replaced by Hb A within the first 6 months
What is the best way to know that someone is on PCP?
Look for nystagmus
What is the superficial inguinal ring?
opening in the abdominal oblique aponeurosis
What is the deep inguinal ring?
opening in the transversalis fascia
What is the treatment for daytime sleepiness in patients with narcolepsy?
stimulants- modafinil (1st line), amphetamines (2nd line)
scheduled naps
What antibiotics are usually used for aspiration pneumonia?
clindamycin or beta-lactam and beta lactamase inhibitor
How can Hirschsprung disease be diagnosed?
rectal biopsy of the submucosa to look for ganglion cells (meissner)
What type of ulcers can be related to physiologic stress?
Curling’s ulcers: arise in the proximal duodenum- associated with severe trauma/burns
Cushing’s ulcer: arise in the esophagus, stomach or duodenum with intracreanial injury due to direct vagus nerve stimulation by the increased ICP–> Ach release–> hypersecretion of gastric acid
Why does sepsis cause ARDS?
cytokines circulate in resopnse to infection, promote inflammatory response by netrophils–> capillary damage and leakage of protein and fluid into the alveolar space
What medications are associated with osteoporotic fractures?
Anticonvulsants that induce CYP450 Aromatase inhibitors Medroxyprogesterone GnRH agonists PPIs (decrease Ca absorption) Glucocorticoids Unfractionated heparin Thiazolidenediones
Where do M. TB bacteria proliferate?
inside macrophages
How is concentration assessed?
say the months of the year backwards
What is the histology of amniotic fluid embolism?
fetal squamous cells and mucin in the maternal pulmonary arteries
What is the cause of duodenal atresia?
failure of recanalization, associated with Downs
What is the cause of jejunum/ileum atresia
Vascular occlusion in utero leading to ischemia with subsequent narrowing (stenosis) or obliteration (atresia). The terminal ileum spirals around an ileocolic vessel
What does sorbitol get converted to? By what enzyme? Which tissues have lower concentrations of this enzyme?
Fructose
Sorbitol dehydrogenase
retina, lens, kidney, and peripheral nerves
What are the histological features of clear cell renal cell carcinoma? From which tissue does it arise?
cuboidal or polygonal cells with clear abundant cytoplasm eccentric nuclei. Grossly yellow due to high glycogen and lipid content
Arises from proximal renal tubules
What happens after alpha 1 adrenergic receptor (Gq) is bound?
GDP is exchange for GTP on alpha subunit and it dissociates and activates Phospholipase C, which breaks PIP2 into IP3 and DAG. DAG directly activates Protein Kinase C, IP3 activates it by increasing intracellular Ca
Where are the two promoters of transcription? What binds to them?
TATA box: 25 bases upstream
CAAT box: 70-80 bases upstream
promote initiation of transcription by acting as binding sites for transcription factors and RNA pol II
What are the most common pathogen associated with septic abortion?
Gram neg. bacilli (E Coli)
S. Aureus
Why can succinylcholine cause hyperkalemia? Who is at risk?
Opening the nAChR allows influx of sodium and Potassium release. Those with burns, myopathies, crush injuries, and denervating injuries or disease upregulate the number of muscle nACHRs, resulting in release of large amounts of K
What lab values indicate a poor prognosis in a patient with liver cirrhosis?
Elevated PT or bilirubin levels, hypoalbuminemia
What are the teratogenic effects of phenytoin?
neural tube defects, orofacial clefts, microcephaly, nail or digit hypoplasia
What are the teratogenic effects of lithium?
Ebstein anomaly, nephrogenic DI, hypothyroidism
What are the teratogenic effects of Valproate?
Neural tube defects
What are the teratogenic effects of Isotretinoin?
microcephaly, thymic hypoplasia, small ears, hydrocephalus
What are the teratogenic effects of Methotrexate?
limb and craniofacial abnormalities, neural tube defects
What are the teratogenic effects of ACEi?
Renal dysgenesis, oligohydramnios
What are the teratogenic effects of warfarin?
nasal hypoplasia, stippled epiphysis
What signifies irreversible injury in the mitochondria?
appearance of vacuoles and phospholipid-containing amorphous densities
What is seen on light microscopy in PSGN? Electron Microscopy? Immunofluorescence?
hypercellular glomeruli
Electron dense deposits on the epithelial side of the basement membrane
Coarse granular deposits of IgG and C3- “starry sky”
What are the lab findings in PSGN?
elevated anti-strep titers (anti-SLO, Anti-DNase B, anti-cationic proteinase)
Low C3
Possibly cryoglobulins
How does Leuprolide treat prostate cancer?
GnRH agonist- constitutive activation–> downregulation
How does Ketoconazole reduce testosterone levels?
decreases synthesis of steroid hormones in the gonads and adrenals
How do flutamide, cyproterone, and spironolactone treat prostate cancer?
Competitive testosterone receptor inhibitor
What are the s/s of renal vein thrombosis?
flank pain, gross hematuria, elevated LDH, left-sided varicocele
What is one of the more severe toxicities of osmotic diuresis?
pulmonary edema
What are the pathologic liver findings in alpha 1 antitrypsin deficiency?
In the periportal granulocytes, there will be intracellular granules of unsecreted AAT that stain reddish-pink with PAS and resist digestion by diastase
What do you give a patient with both tonic-clonic and absence seizures?
Valproate
How does pre-mRNA get spliced?
Removal of introns by spliceosome, which consists of snRNPs (target of anti-smith) and other proteins
Under hypoxic conditions, what enzyme is downregulated? What downregulates it? What gets built up?
Pyruvate dehydrogenase (pyruvate–>acetyl coA)
NADH, can’t be converted back to NAD by electron transport chain
Lactate, because lactate dehydrogenase can regenerate NAD
What causes X-linked agammaglobulinemia?
Mutation in the bruton tyrosine kinase gene cause failure of bone marrow pre-B to mature
What are the three points of insertion of the sternocleidomastoid muscle? Where does it move the clavicle after fracture?
The sternum, clavicle, and mastoid
superiorly and posteriorly
Which way does the pectoralis major pull a clavicular fracture?
inferiorly and laterally
What are the signs and symptoms of a psoas abscess?
fever, back or flank pain, inguinal mass, difficulty walking
Pain with psoas muscle stretch (extension of hip)
Will position for minimum discomfort- hip flexion and lumbar lordosis
Why does increased intracranial pressure lead to papilledema?
CSF in the subarachnoid space is continuous with the optic nerve sheath and the external pressure compresses the nerve externally, leading to impaired axoplasmic flow within the optic nerve
What is the characteristic histopathology of ductal carcinoma in situ?
ducts distended by pleomorphic cells with prominent central necrosis that does not extend through he basement membrane
What can be used for nonoperative management of gallstones?
administration of hydrophilic bile acids to make cholesterol more soluble and promote gallstone dissolution
What is the most frequent CNS tumor in immunosuppressed patients?
primary CNS lymphoma- dense, cellular aggregates of uniform, atypical lymphoid cells
Associated with EBV
What protein is found outside of the core of the nucleosome and helps to promote chromatin compaction?
Histone 1- binds the linker segments of DNA that lie between the nucleosomes
(nucleosome composed of 2 each of Histone 2A, 2B, 3, 4)
What are the s/s associated with tabes dorsalis?
Lancinating pains, loss of vibratory and position sensation, areflexia, and a neurogenic bladder with overflow incontinence
Argyll Robertson pupils: small pupils that don’t constrict to light, but do for accomodation
What is the difference between a gastric erosion and a gastric ulcer?
Erosions do not fully extend through the muscularis mucosa, whereas ulcers extend through and into the submucosa
What are the arteries that are most heavily involved in atherosclerosis?
Abdominal aorta>coronary arteries>popliteal arteries>internal carotids>circle of willis
What are the biochemical effects of C1 inhibitor deficiency? How does this lead to sx?
Increased cleavage of C2 and C4–> inappropriate activation of the complement cascade
Increased conversion of kininogen to Bradykinin–> potent vasodilation asscoiated with angioedema
Which parts of the body can’t use ketone bodies for energy? Why?
Erythrocytes: don’t have mitochondria
Liver: Lacks succinyl CoA-acetoacetate CoA tranferase (thiophorase)
Which of the non-glucose monosaccharides can bypass the major regulatory step in glycolysis?
Fructose- metabolized by the lier fastest and rapidly cleared from the serum
What is the role of CYP450 in the treatment of estrogen receptor-positive breast cancer?
Tamoxifen is a prodrug metabolized to endoxifen by CYP2D
How can an appendix be located during an appendectomy if it cannot be palpated?
Look for where the 3 ribbons of the teniae coli converge at the root of the vermiform appendix
Where is the locus ceruleus? What neurotransmitter is produced there?
In the posterior rostral pons near the lateral floor of the fourth ventricle
Norepinephrine
What correlates with severity of mitral regurgitation?
S3- high regurgitant volume and left ventricular volume overload
What does the dorsal pancreatic bud give rise to?
pancreatic tail, body, most of the head, and the small accessory pancreatic duct
What does the ventral pancreatic bud give rise to?
uncinate process, proximal portion of the main pancreatic duct
Why does HDV require HBV to be infectious?
Hepatocytes must be coated in the hep B surface antigen before it can infect hepatocytes and multiply
What is the appearance of gardnerella vaginosis under light microscopy?
Clue cells- epithelial cells covered with gram variable rods
How long does it usually take to compensate for respiratory alkalosis in people with altitude sickness?
Renal compensation with loss of bicarb takes 24-48 hrs
What is the treatment for diphtheria?
diphtheria antitoxin (passive immunization)
PCN or erythromycin
DPT vaccine
What are the classic lab abnormalities in multiple myeloma?
erythrocyte rouleaux formation, bence-jones proteins in the urine, and an M peak showing excessive monoclonal immunoglobulin
What are the classic s/s in multiple myeloma?
normochromic, normocytic anemia
lytic bone lesion
hypercalcemia
AL amyloidosis
What are the two codons at the beginning and end of each intron?
5’: GU
3’: AG
What supplementation do CF kids require for digestion?
pancreatic lipase
Which beta blockers are contraindicated in patients with COPD? Why?
propanolol, nadolol
Non-cardioselective beta blockers- can trigger bronchospasm
Which are the cardioselective beta blockers? Which receptor?
Beta 1
metoprolol, atenolol, bisoprolol, nebivolol
What beta blockers can be used in patients with COPD
Beta 1 cardioselective (metoprolol, atenolol, bisoprolol, nebivolol)
Combined beta and alpha (carvedilol, labetalol)
Why do some people get glomerulonephritis with infective endocarditis?
Circulating immune complexes deposit in the glomerular capillary wall- looks similar to PSGN
What are the histological findings in IgA nephropathy?
mesangial hypercellularity with mesangial IgA deposits on immunohistochemical staining
What causes acute morbidity in rheumatic fever?
pancarditis
Severe mitral regurgitation and/or myocarditis can lead to hrt failure and death in some pts
What are the s/s of I-cell disease?
failure to thrive, cognitive defects, coarse facial features, corneal clouding- typically fatal in childhood
What causes I-cell disease?
Defective phosphotransferase enzyme in the golgi body- there is no phosphorylation of mannose residues on lysosome bound proteins–> extracellular secretion of these proteins and accumulation of cellular debris in the lysosome
What are the bone structure changes in osteoporosis?
trabecular thinning with fewer interconnections
What are the bone structure changes in Vit D deficiency?
unmineralized osteoid
What are the bone structure changes in Hyperparathyroidism?
increased resorption of cortical bones and subperiosteal thinning
What are the bone structure changes in Paget’s disease of the bone?
mosaic pattern of lamellar bone connected by cement lines
What are the bone structure changes in osteopetrosis?
persistence of primary, unmineralized spongiosa in the medullary canals
What is targeted by Kegels?
Strengthening of the pelvic floor muscles- levator ani
What causes spastic rigidity in upper motor nerve injury?
Loss of upper motor neuron inhibition of spinal stretch reflex arc
What is a sequela of rubella in adults?
polyarthralgias
What are the retroperitoneal organs?
Suprarenal glands Aorta and IVC Duodenum (not 1st part) Pancreas (head and body) Ureters and bladder Colon (ascending and descending) Kidneys Esophagus Rectum
What is a distinct histopathologic manifestation of chronic hep b?
Accumulation of hep B surface antigen within infected hepatocytes, giving a finely granular, diffusely homogenous, pale eosinophilic cytoplasm
Why are pregnant women and those on COCs at greater risk of gallstones?
Estrogen increases cholesterol synthesis
Progesterone reduces bile acid secretion and slows gallbladder emptying
What color are gout crystals in parallel light?
Yellow- negatively birefringent
What is the target of anti-Smith antibodies?
snRNPs
Which tumors are associated with PTHrp production?
Squamous cell cancers
Renal and Bladder
Ovarian and endometrial
Breast cancer
Which tumors are associated with Vit D production?
All Lymphomas
What is the RPR test?
nonspecific nontreponemal serologic test in which pt serum is mixed with cardiolipin, lecithin, and cholesterol to look for aggregation.
What is a diagnostic test for meckel’s diverticulum?
Tc-pertechnetate scan
What would cause a person with Meckel diverticulum to have currant jelly stools
At higher risk for intussusception
Where does parvovirus B19 replicate? What is the cellular receptor?
in erythrocyte precursors in the bone marrow
blood group P antigen (gloroside)
Where types of proteins are made in the RER?
Secretory proteins, integral membrane proteins (nucleus and cell membrane), proteins within the ER, golgi network and lysosome
What substance is involved in the majority of overdose deaths in the US?
Opioids- either in isolation or with co-ingestants
What are the characteristic findings in abusive head trauma (shaken baby)?
subdural hemorrhages due to tearing of the bridging veins, retinal hemorrhages due to rupture of congested retinal veins, posterior rib fractures
What is associated with left-sided frontal lobe lesions?
apathy and depression
What is associated with right-sided frontal lobe lesions?
disinhibited behavior
How do ADHD drugs work?
stimulant drugs (methylphenidate, amphetamines) increase NE and DA release from vesicular storage sites and block their reuptake at synapses in the prefrontal cortex
What are the s/s of retinal hemorrhage? What causes it?
unilateral visual disturbances
severe hypertension–> fibrinous necrosis
In what types of monocular vision loss is a cherry red spot seen at the macula?
atherosclerosis, cardioembolic disease, or vasculitis (giant cell arteritis)
What malignancies are associated with acanthosis nigricans?
GI and GU, most commonly gastric adenocarcinoma
Why does allopurinol increase the effect of azathioprine?
The two major inactivation pathways for azathioprine and 6-MP are thiopurine methyltransferase and xanthine oxidase- allopurinol blocks xanthine oxidase, causing more to be converted to active 6-thioguanine
What drug can be used to reduce craving for alcohol?
Naltrexone blocks the mu opiod receptor- alcohol becomes less rewarding
What is seen on light microscopy of a liver with Reye’s syndrome?
microvesicular steatosis- the presence of small fat vacuoles in the cytoplasm of hepatocytes. No necrosis or inflammation
EM- swelling and a decreased number of mitochondria and glycogen depletion
How does cocaine cause intoxication?
Inhibits presynaptic reuptake of monoamines (NE, DA, 5HT)
What are the lab findings in antiphospholipid antibody syndrome?
Paradoxical aPTT prolongation
Anticardiolipin ab
anti-beta2-glycoprotein-I ab
What causes open-angle glaucoma? How is it treated?
Increased production or decreased outflow of aqueous humor–> elevated intraocular pressure
Timolol and other nonselective beta blockers diminish secretion of aqueous humor by the ciliary epithelium
What causes scarlet fever?
pyrogenic exotoxins from group A strep. Usually associated with strep pharyngitis
What are the symptoms of serum sickness?
pruritic skin rash and arthralgias 7-14 days after exposure to an antigen.
Histology: small vessel vasculitis with fibrinoid necrosis and intense neutrophil infiltration
What type of hypersensitivity rxn causes serum sickness? What antigen are involved?
Type III –> hypocomplementemia
antigenic heterologous proteins such as chimeric monoclonal abs or nonhuman immunoglobulins
What causes Waterhouse-Friderichson syndrome?
Meningococcal septicemia causes bilateral hemorrhagic infarction of the adrenal glands
Which receptors block insulin secretion by the beta cells?
Alpha-2 adrenergic and somatostatin 2
Which receptors increase insulin secretion by the beta cells?
M3, Beta-2 adrenergic receptor, and Glucagon-like peptide-1
What are the symptoms of debranching enzyme deficiency (Cori)?
hypoglycemia, hepatomegaly, ketoacidosis, muscle weakness, hypotonia
In which ligament can the ovarian artery and vein be found?
Infundibulopelvic (suspensory) ligament
What is the first step in gluconeogenesis?
Conversion of pyruvate to oxaloacetate by pyruvate carboxylase (biotin-dependent)
Why are you concerned about a patient being treated for Graves disease with signs of infection?
Thionamides (propylthiouracil and methimazole) can cause agranulocytosis
Get WBC with differential
What are the most frequent causes of lung abscess?
Peptostreptococcus, prevotella, bacteroides, and fusobacterium- orral anaerobe involved in aspiration pneumonia
What is the prodrome for measles?
Koplik spots, conjunctivitis, fever, cough, rinorrhea
What causes congenital achalasia? Achalasia secondary to T. Cruzi?
Congenital: dysfunction of ganglion cells of the myenteric plexus
T. Cruzi: Neurotoxin destroys myenteric plexus and causes parasympathetic denervation of smooth muscle
How can non-segmented viruses acquire new trains during coinfection?
Recombination- gene exchange through the crossing over two dsDNA molecules
What causes wound contractures?
Excessive matrix metalloproteinase activity and myofibroblast accumulation in the wound margins
what medication can be used for serotonin syndrome?
cyproheptadine- a 5HT1A and 5HT2A antagonist
What type of receptor does PTH bind?
Gs
What are the characteristics of a drug that is limited to the plasma compartment (Vd~3-5)?
high molecular weight, high plasma protein binding, high charge, and hydrophilicity
What is the mechanism of action of daptomycin?
Depolarizes cellular membrane by creating transmembrane channels
What are the adverse effects associated with daptomycin?
Myopathy and CPK elevation
What are the adverse effects of vancomycin?
red man syndrome
nephrotoxicity
What drug can be used to reduce the formation of adenomatous polyps?
Cox-2 inhibitors such as aspirin
Why would someone get abdominal pain after administration of an opioid?
Can cause contraction of smooth muscle cells in the sphincter of oddi–> increased pressure in the common bile duct–> biliary colic
What cancers are associate with MEN type 1?
Primary hyperparathyroidism
Pituitary tumors
Pancreatic Tumors
What cancers are associate with MEN type 2A?
Medullary thyroid carcinoma
Pheochromocytoma
Parathyroid hyperplasia
What cancers are associate with MEN type 2B?
Medullary Thyroid Carcinoma
Pheochromocytoma
Mucosal Neuromas/Marfanoid habitus
What tests assess liver functionality?
PT, bilirubin, albumin, cholesterol
What tests assess liver structural integrity and intadtness of the liver?
transaminases
What tests assess the biliary tract?
alkaline phosphatase, gamma-glutamyl transpeptidase- need both to determine if elevated alk phos is from hepatic or bony origin
What happens when the processus vaginalis is not obliterated?
persisten connection between the scrotum and the peritoneal cavity through the inguinal canal-
Small opening- only liquid can get through–>hydrocele
Large- indirect inguinal hernia
What are the s/s of VIPoma?
watery diarrhea, hypokalemia, and achlorhydria
What does VIP do?
stimulates pancreatic bicarbonate and chloride secretion.
Also, binds epithelial cells–> ^cAMP–> Na, Cl, and H2O secretion into the bowel
What gastrointestinal hormone secretion does somatostatin decrease?
VIP
Gastrin
Glucagon
Cholecystokinin
What is the most common of the galactosemic disorders?
Classic galactosemia- AR absence of galactose-1-phosphate uridyl transferase
Very severe- presents within days with jaundice, vomiting, and hepatomegaly
What do cytoplasmic P bodies do?
play an important role in mRNA translation regulation and mRNA degradation
What enzymes are needed for glycerol to be used in gluconeogenesis?
Glycerol kinase to get to glycerol 3-phosphate, then glycerol 3-phosphate dehydrogenase to get to DHAP which can be used for gluconeogenesis
Which patients are at greatest risk for PDA?
premature or those with cyanotic congenital hrt dz
Absorption of what type of sugar is unaffected by loss of pancreatic enzymes ?
monosaccharides
What causes a direct inguinal hernia? Where is it in relation to the inferior epigastric vessels
Weakness of the transversalis fascia
Medial to the inferior epigastric vessels
What are the symptoms of patellar fracture?
swollen knee, focal patella tenderness, and inability to extend the knee against gravity (quads insert on the superior pole of the patella)
What are the most common pathogens in secondary (flu) bacterial pneumonia?
strep pneumo, S aureus, and H flu
What is deficient in leukocyte adhesion deficiency?
absence of CD 18 antigens–> recurrent infections that lack purulence, leukocytosis, late separation of umbilical cord
Name a couple alpha 1 blockers
phentolamine, phenoxybenzamine (non-selective alpha)
What drugs can be used to treat both HTN and BPH? How?
alpha 1-blockers: doxazosin, prazosin, and terazosin
relaxation of smooth muscle in the vasculature and in the bladder neck and prostate
When should you suspect multiple myeloma?
Elderly person with one or more of the following:
- Fatigability (anemia)
- Constipation (hypercalcemia)
- Bone pain
- Elevated serum protein
- Renal failure
What causes myeloma cast nephropathy? Histology?
Excess excretion of free light chains (Bence Jones proteins) exceed reabsorptive capacity and precipitate to form casts that cause tubular obstruction and epithelial injury.
light Microscopy: glassy casts that stain eosinophilic
What should you be concerned about in a patient with sudden onset headache in the setting of chronic pituitary tumor symptoms?
Pituitary hemorrhage- can be differentiated from SAH by the presence of bitemporal hemianopsia
What can cause death in pituitary apoplexy? what is the treatment?
Cardiovascular collapse due to ACTH deficiency
Give glucocorticoids and consult neurosurgery urgently
What is acute acalculous cholecystitis?
Acute inflammation of the gallbladder in the absence of gallstones- usually in critically ill pts due to gallbladder stasis and ischemia
Where are the receptors for thyroid hormone, Vit A, and Vit D located?
They are DNA binding receptors located in the nucleus
Where are steroid receptors located?
They are DNA binding receptors located in the cytoplasm that go to the nucleus after binding
What receptor do PTH and glucagon act on?
Gs
How does the growth hormone receptor work?
It interacts with the JAK-STAT pathway (no intrinsic tyrosine kinase activity)
How do insulin and IGF-1 receptors work?
located on the cell membrane- have intrinsic tyrosine kinase activity, so ligand binding leads to autophosphorylation
What is dry age-related macular degeneration?
Dry: chronic oxidative damage to retinal pigment epithelium and choriocapillaris –>drusen deposits
What is wet age-related macular degeneration?
Wet: Excessive extracellular matrix accumulation–> retinal hypoxia–> ^VEGF–> neovascularization with leaky vessels–>fundoscopy showing gray-green subretinal discoloration with adjacent fluid/hemorrhage
What is the treatment for dry and wet age-related macular degeneration?
Dry and wet: antioxidant vits and zinc, smoking cessation
Wet only: VEGF inhibitor
What are the 3 most important factors for hypoglycemia in T1DM?
Excessive insulin dose
Inadequate food intake
Exercise
What should you be concerned about in a patient with migratory thrombophlebitis?
Visceral adenocarcinoma of the pancreas, colon, or lung
Hypercoagulability due to tumor production of a thromboplastin-like substance that can cause chronic intravascular coagulations
What is the most common enzyme deficiency that leads to defects in fatty acid beta oxidation? What are the clinical s/s?
Acyl CoA dehydrogenase deficiency
hypoketotic hypoglycemia- need to break down FAs to make ketone bodies- can be asymptomatic until a significant fast
How does Hepatitis B cause damage to the liver?
It has no direct cytotoxic effect. Instead, it induces cytotoxic T cells to destroy the infected hepatocytes
The antigen-Ab ICs can lead to extrahepatic damage- arthralgias, urticaria, glomerulonephritis, cryoglobulinemia, vasculitis
What is diphenoxylate?
An antidiarrheal agent similar to meperidine that binds to mu opiate receptors in the GI tract and slows motility
Overuse can lead to euphoria, so it is often combined with atropine to induce adverse effect if taken in high doses
Where does CN V exit the brainstem?
The pons at the level of the middle cerebellar peduncle
What tracts are disrupted by anterior pons infarct?
corticospinal tract (contralateral hemiparesis) Corticobulbar tract (contralateral lower facial palsy)
How do triamterene and amiloride function?
Block ENaCs on the apical side of the principal cells- potassium sparing
What is the characteristic histology in acute Hep A?
spotty necrosis with ballooning degeneration, councilman bodies (eosinophilic apoptotic hepatocytes), and mononuclear cell infiltrates
What are the two forms of hereditary pancreatitis?
- SPINK1 deficiency: normally secreted by pancreatic acinar cells- trypsin inhibitor
- Formation of abnormal trypsin that is not susceptible to inactivating cleavage by trypsin
Why would a person with lung cancer develop left shoulder pain, persistent hiccups, and dyspnea?
phrenic nerve (C3-C5) irritation and palsy.
Why do patients get amyloid deposition in multiple myeloma?
Accumulation of monoclonal immunoglobulin light chains- seen as eosinophilic extracellular deposit in H&E
Apple-green birefringence with congo red under polarized light
What is the most common pediatric malignancy?
ALL
Which type of ALL is more likely to present with an anterior mediastinal mass? What are the effects?
T cell
SVC syndrome, dysphagia (esophageal compression), dyspnea and stridor (trachea compression)
What causes cleft lip? cleft palate?
lip: failure of fusion of the maxillary prominence with the intermaxillary segment
palate: failure of fusion of the palatine shelves with one another or with the primary palate
What is defective in Dubin-Johnson?
Defective hepatic secretion of bilirubin glucuronides across the canalicular membrane, resulting in direct (conjugated) hyperbilirubinemia and jaundice
Why does hyperammonemia cause neurologic symptoms?
Excess NH3 in the blood is absorbed by astrocytes, which combine it with glutamate to make glutamine–> This builds up, causing astrocyte hyperosmolarity and cellular swelling–> decreased release of glutamine that can be converted to glutamate in the neurons
What is the effect of higher tissue solubility in an inhaled anesthetic?
Slow onset of action, because it takes more anesthetic to saturate the blood and then the brain
Which structure should be cut to help with carpal tunnel syndrome?
transverse carpal ligament (flexor retinaculum)
What is citalopram?
an SSRI
What makes up the cellular component of an atherosclerotic plaque? What provides stimulus for proliferation?
Vascular smooth muscle
Platelet-derived growth factor from locally adherent platelets, dysfunctional endothelial cells, and infiltrating macrophages stimulates VSMC migration and proliferation
What is reduced in Gilbert syndrome?
Production of UDP glucuronyl transferase
What are the characteristic features of silicosis?
calcification of the rim of the hilar nodes and birefringent silica particles surrounded by fibrous tissue on histology
Which amino acids are exclusively ketogenic?
lysine and leucine
What supplement should be given to measles patients why?
Vitamin A
Measles can deplete vitamin A, causing keratitis and corneal ulceration
What kind of toxicity does nitroprusside cause? What are the s/s?
Cyanide toxicity
altered mental status, seizures, CV collapse, lactic acidosis, bright red venous blood
Why is cyanide toxic?
Binds to Fe3+ in cytochrome c oxidase and halts electron transport chain in the mitochondria
What are the treatments for cyanide toxicity?
Sodium nitrite–> methemoglobin formation, which binds the cyanide
Sodium thiosulfate–> donates sulfur to convert cyanide to thiocyanate, which can be excreted in urine
Hydroxocobalamin–> cobalt binds cyanide and forms cyanocoblamin–> excreted in urine
What normally metabolizes cyanide?
Rhodanese- donates a sulfur molecule to convert it to thiocyanate that can be excreted in the urine
Why is the H flu B capsule virulent?
The capsule prevents phagocytosis and intracellular killing by neutrophils
What are the symptoms of lead poisoning?
cognitive impairment, irritability
constipation, abdominal pain
interstitial nephritis
anemia
What marker is elevated in epithelial ovarian cancer?
CA-125 (psamomma bodies)
What marker is elevated in dysgerminoma?
b-hCG (fried egg cells)
What marker is elevated in endodermal sinus tumor?
AFP (Schiller-Duval bodies: look like glomeruli)
What marker is elevated in granulosa cell tumors?
Increased estrogen and inhibin (call-exner bodies, coffee bean nuclei)
What marker is elevated in sertoli-leydig cell tumor?
increased androgen
What is the most common mutation in melanoma? What is the treatment?
BRAF- V600E (valine–> glutamic acid)
protein kinase involved in activation of signaling pathways for melanocyte growth, survival, and metastasis
TX: Vemurafenib
Why do Fas and FasL mutations lead to autoimmune disorders?
Mutations inhibit the extrinsic pathway of apoptosis of autoreactive lymphocytes
Why do Crohn’s patients get kidney stones?
Normally, Ca and oxalate bind in the intestine and are released in fecal matter. In Crohn’s bile acids are not recycled so there is excess fat, which binds the Ca, so more oxalate is absorbed and turned to stone
What is the mechanism of action of shiga toxin?
disables 60s ribosomal subunit and halts protein synthesis
What are the symptoms of scurvy?
perifollicular hemorrhages, myalgias, subperiosteal hematoma, and gingivitis
How do beta blockers lower blood pressure?
- reduce myocardial contractility and HR
2. Decrease renin release by kidney
What are the histopathologic changes in acute neuronal injury?
Shrinkage of the cell body
Pyknosis of the nucleus
Loss of Nissl Substance
Eosinophilic cytoplasm
What are the histopathologic changes in Axonal rxn?
Enlargement of the cell body
Eccentric nucleus
Enlargement of the nucleolus
Dispersion of the Nissl substance
What are the histopathologic changes in neuronal atrophy?
Loss of neurons and functional groups of neurons
Reactive gliosis
Which heart issue causes head bobbing?
Aortic regurgitation
In a patient with hypoglycemia that induces unconsciousness, what is the best method of normalizing the patient’s blood glucose?
Intramuscular glucagon
What would case gastric varices only in the fundus?
Clot within the splenic vein (pancreatitis, pancreatic cancer)
What does the dominant coronary artery supply blood to?
Posterior Descending artery which supplies blood to the AV node via the AV nodal artery
What is a developmental field defect?
initial embryonic disturbance leads to multiple malformations
Where are androgens and progesterones synthesized from cholesterol? Where are they turned into estradiol?
Theca cells stimulated by LH
Granulosa cells stimulated by FSH
What is a choleastoma?
collection of squamous cell debris that forms a pearly mass behind the tympanic membrane. Can lead to otorrhea and eventually conductive hearing loss due to erosion of the ossicles
Into which part of the duodenum does the ampulla of Vater drain? Which part is in close association with the uncinate process and the SMA?
The 2nd part
The 3rd part
What is the best drug for treatment-resistant schizophrenia?
clozapine
Which is an irreversible competitive alpha adrenergic agonist- phentolamine or phenoxybenzamine?
phenoxybenzamine
What structures are cut during a cricothyrotomy?
skin
Superficial cervical fascia (including platysma)
investing and pretracheal layers of the deep cervical fascia
Cricothyroid membrane
What is the formula for half life
t1/2= (0.7 x Vd)/CL
What are the major adverse effects of theophylline intoxication?
Seizures and Tachyarrhythmias
What lab test can differentiate between leukemoid reaction and CML?
Leukocyte alkaline phospatase- normal or elevtaed in leukemoid reaction, but decreased in CML
What are the histological findings in acute allergic contact dermatitis?
spongiosis: an accumulation of edema fluid in the intercellular spaces of the epidermis
What tissues are affected by Wilson’s disease? What are the treatments?
cornea and basal ganglia
d-Penicillamine and trientine- chelators
What is the gross appearance of lungs with septic pulmonary emboli?
multiple wedge-shaped hemorrhagic lesions in the periphery of the lung. Hemorrhagic due to the dual blood supply
In which reactions is biotin a cofactor?
Gluconeogenesis: Pyruvate to ocaloacetate (pyruvate carboxylase)
FA synthesis: Acetyl-CoA to Malonyl CoA (acetyl-CoA carboxylase)
FA oxidation: Propionyl CoA to methylmalonyl CoA (Propionyl-CoA carboxylase)
What can actinic keratosis be a precursor to?
Invasive squamous cell carcinoma
What are the classic s/s of parathyroid adenoma?
bone pain, renal stones, GI issues (peptic ulcer dz), and psychiatric disorders
What are the characteristic features of bone issues with excess PTH?
Subperiosteal thinning with subperiosteal erosions in the phalanges on radiography and osteolytic cysts in the long bones
Whatdetermines whether a patient will develop lepromatous leprosy or tuberculoid leprosy?
Tuberculoid: appropriate cell mediated response by Th1
Lepromatous: Humoral response by Th2
Which substances predominantly drive angiogenesis
VEGF and FGF
When do class Ib antiarrhythmics ted to bind?
When sodium channels are in their inactiated state. Because ischemic myocardium is at a higher resting potential, they are inactivated for longer, so class Ib is more selective for ischemic myocardium than normal myocardium
What is the major component of the adaptive immunity against giardia?
Secretory IgA- impairs adherence
What is characteristic of the liver destruction in primary biliary cirrhosis? What are the s/s?
intrahepatic, interlobular ducts destroyed by granulomatous inflammation.
pruritis, fatigue –> jaundice, pale stools, dark urine, hypercholesterolemia
How is propofol rapidly cleared from the plasma, leading to rapid recovery?
At first, it is distributed to organs that receive high blood flow, like the brain. After time, it is redistributed to other organs, so the effect on the brain is terminated
What are the characteristic biopsy findings in polyarteritis nodosa?
segmental, transmural inflammation of the arterial wall with fibrinoid necrosis
What organs does Polyarteritis nodosa affect?
Most commonly- kidney, heart, GI, and liver, but can affect any organ other than the lungs
With what issue is polyarteritis nodosa associated?
Hep B
In which direction are mismatched nucleotides removed? RNA primer?
Mismatched: 3’ to 5’ exonuclease
RNA Primers: 5’ to 3’ exonuclease
What are the actions of the latissimus dorsi muscle? What innervates it?
Extension, adduction, and internal rotation of the humerus
Thoracodorsal
What are the characteristics of atrophy on a cellular level?
reduction in mitochondria and RER
Which cofactor is necessary for transamination reactions?
B6
Why does chronic diarrhea cause uric acid stone formation?
Patients with chronic diarrhea have reduced absorption of bicarb from the gut. This leads to metabolic acidosis and increased renal H+ excretion, causing conversion of soluble urate salts into insoluble uric acid
What is the most common organism causing bacteremia in sickle cell patients?
Strep pneumo
