UWorld QBank - 2nd Round - part 1 Flashcards
What effect does intracellular hyperglycemia have on peripheral nerves?
glucose –> sorbitol by aldose reductase
Increased cell osmolarity –> water influx –> osmotic damage to schwann cells
In a positively skewed bell curve, where are the mean, median and mode located?
Bell curved is shifted towards left
Therefore, Mode is highest peak of curve (lowest number), median is middle of curve (middle number) and the mean is at far right of curve (highest number).
What is propriomelanocortin (POMC)?
A polypeptide precursor that is cleaved enzymatically to give rise to beta-endorphins, ACTH and MSH
What is somatomedin C?
peptide that is structurally similar to insulin (insulin like growth hormone)
Released in response to growth hormone –> stimulates growth in target cells
What predisposes someone to malignant hyperthermia, and what is involved in this reaction? Treatment?
Autosomal dominant defect of Ryanodine receptors in sarcoplasmic reticulum of muscles
Results in large releases of calcium after anesthetic use
Tx: Dantrolene - prevents further release of Ca from Ryanodine-Rs
What is the MoA and main side effects of Thiazolidinediones (TDZs) like pioglitazone?
MoA: Reducing insulin resistance by binding PPAR-gamma
SE: Weight game, edema, and can precipitate congestive heart failure
What diabetic medications predispose patients to hypoglycemia?
Insulin and sulfonylureas
Which structure runs perpendicular to the 3rd part of the duodenmum?
SUPERIOR MESENTERIC ARTERY
What is the course of the gastroduodenal artery?
Arises from common hepatic artery, coursing inferiorly posterior to the fist part of duodenum
Where does the protein that inhibits the lac operon bind? What is the purpose of catabolite activator protein (CAP)?
Repressor protein binds at OPERATOR LOCUS when low levels of lactose present. increased allolactose binds repressor protein –> increased expression of lac operon
CAP binds upstream to promoter region when cAMP concentration is high (i.e. low glucose)
Which tissue layers must be incised in an emergent cricothyrotomy?
Superficial cervical fascia and cricothyroid membrane
What is the disease process that leads to Maple Syrup Urine disease (MSUD)? Symptoms that result?
defective breakdown of branched chain amino acids (leucine, isoleucine and valine)
Normally degradation occurs by transamination of respective alpha-ketoacids and metabolism by branch-chain-alpha-ketoacid dehydrogenase (any mutation in this complex leads to disease)
Neurotoxicity from increase leucine in serum/tissues
Sweet urine odor from isoleucine in urine
What are the 5 cofactors required for branch-chain alpha-ketoacid dehydrogenase, pyruvate dehydrogenase, and alpha-ketoglutarate dehydrogenase?
Tender Loving Care For Nancy -
Thiamine pyrophosphate, Lipoate, Coenzyme A, FAD, NAD
What compounds can constrict efferent arteriole? How can you override this and what effect would it have?
Angiotensin II
ACE-I would decrease ATII and cause dilation –> decreased GFR
What is a key immune factor necessary for eliminating mycobacterial infections?
Interferon-gamma (macrophage and Th1 cell crosstalk)
-Deficiency –> recurrent mycobacterial infections
What results from defects in leukocyte adhesion?
delayed umbilical cord separation, recurrent CUTANEOUS infections, no pus formation and poor wound healing
What type of vaccine would you give to a patient with a suspected bite from a bat?
Rabies immune globulin and rabies vaccine (an INACTIVATED VACCINE)
What is the main side effect of bupropion and what can exacerbate these effects?
SEIZURES - increased risk in epileptics, bullemics and anorexics
Which psychiatric medications are associated with increased weight gain?
Atypical antipsychotics like Olanzapine
What organism is highly likely to have coinfected someone with gonorrhea and how would you treat?
Chlamydia!
Tx: Ceftriaxone for gonococcal and azithromycin for chlmaydia (or multi-day regimen of doxycycline)
When does contraction band necrosis occur in infarcted cardiac myocardium? Neutrophilic infiltration?
12-24 hrs post MI - coagulative and contraction band necrosis
1-5 days post MI - PMNs
What do renal uric acid crystals look like?
Yellow/Red-Brown diamond/rhombus
What is a common cause of osteomyelitis in patients with sickle cell disease?
Salmonella
What is positive predictive value? What factors influence this rate?
The number of true positives, over all total positive test results
Disease prevalence can change PPV
What are the two main enzymatic pathways necessary for RBC survival?
Glycolysis –> to generate energy via anaerobic ATP production
HMP Shunt –> Provide reducing agent NADPH to prevent oxidative damage
What are key enzymes involved in the oxidative reactions of the HMP shunt? And what is their purpose?
G6PD and glutathione reductase regenerate NADPH, and deficiencies lead to pathophysiologically similar susceptibility to oxidative damage
What is the purpose of transketolase and transaldolase in RBCs?
Catalyze NON-oxidative reactions of HMP shunt - generate ribose-6P and glyceraldehyde-3P
(note: No NADPH produced)
What general effects do -azole antifungal drugs have? Which drugs would lower serum concentrations of azoles?
inhibit cell colony growth by altering fungal cell membrane composition –> inhibit demethylation of lanosterol to ergosterol
inhibit activity of human P450 cytochrome oxidase system
Cytochrome oxidase inducers increase azole metabolism –> rifampin, phenytoin, carbamazepine and phenobarbital
What is the MoA of caspofungin? Amphotericin B? Flucytosine?
block 1,3-beta-D-glucan synthesis (a major component of fungal CELL WALL, not membrane)
Binds ergosterol in fungal cell membrane –> pore formation and lysis
inhibits synthesis of DNA and RNA in fungal cells
What are the key serum metabolic changes that occur in diabetic ketoacidosis and how does the body attempt to make up for this?
Decreased serum pH and bicarb –> compensatory decrease in pCO2
Kidney attempts to correct by:
- Increase bicarb reabsorption –> decreased urine biacrb
- Increased H+ excretion –> decreased urine pH
- Increase acid buffer (ammonia and phosphate) excretion to maintain H+ excretion –> increased urine NH4+ and H2PO4 -
A patient presents with chronic hemolytic anemia, splenomegaly and poor exercise tolerance, what is most likely deficient?
Pyruvate kinase
What reaction maintains blood glucose levels after 18 hrs of fasting? What allosterically activates this?
Gluconeogenesis - activated by acetyl CoA
What is the main role of fructose-2,6-BP in metabolism regulation?
regulates glycolysis and gluconeogenesis via inverse regulation of phosphofructokinase 1 and fructose 1,6-bisphosphatase
DECREASED f26BP –> gluconeogenesis (via fructose6P)
increased f26BP –> glycolysis
What may increased nests of mast cells in the mucosa of small bowel indicate?
Systemic Mastocytosis - increased mast cell proliferation in bone marrow and systemic organs –> increased histamine –> 1) gastric hypersecretion 2) Syncope 3) flushing 4) Hypotension and Tachycardia 5) bronchospasm
Which three factors increase gastric acid secretion and which is the most potent of these?
Histamine, Acetylcholine and Gastrin (strongest via increased histamine release by enterochromaffin like cells)
Which microorganism’s virulence depends on binding of cellular integrins?
CMV
What are the gross specimen characteristics of craniopharyngiomas?
Calcified masses with cystic spaces filled with thick brownish fluid rich in cholesterol
Why doesn’t blood become saturated with CO2 during V/Q mismatch as with pulmonary embolism?
Well ventilated regions compensate for low ventilated regions and hyperventilation blows off excess CO2
What could lead to retinal damage in neonates with treated respiratory distress?
Oxygen supplementation
What are the complications of surfactant treatment in neonates with respiratory distress?
Transient hypoxia and hypotension, blockage of endotracheal tube, and pulmonary hemorrhage
What drug would cause mycobacteria to lose acid-fastness and stop proliferating, and why?
Isoniazid – which inhibits mycolic acid synthesis. without mycolic acid, division would not occur properly because proper cell walls cannot be generated, and mycolic acid is what gives mycobacteria acid fast staining
What are the MoAs of rifampin, ethambutol and streptomycin?
Rifampin - inhibits bacterial RNA polymerase (preventing transcription of DNA –> mRNA)
Ethambutol - inhibits mycobacterial cell wall synthesis, but no effect on creation of mycolic acid
Streptomycin - aminoglycoside that inhibits 30S ribosome unit, halting protein synthesis
MoAs of Macrolides vs. aminoglycosides and how to distinguish their names:
Macrolides - inhibit 50s ribosome subunit by blocking translocation (binding of 23S rRNA) so bacteriostatic- they all end with “-THROMYCIN”
Aminoglycosides - bactericidal; irreversible inhibition of initiation complex by binding 30S subunit; all end with “-CIN” and start with letters in word GNATS
What is linkage disequilibrium?
when a pair of alleles from the same loci are inherited together in the same gamete, more or less frequently than expected based on the individual frequencies of the alleles
i.e. 2pq does not equal the value it is supposed to
What is pleiotropy?
Multiple phenotypic manifestations in different organs which result from ONE single GENE
e.g. PKU
What is the difference between phentolamine and phenoxybenzamine, and what would be the effects of norepinephrine when pretreated with either of these drugs?
Phenoxybenzamine - noncompetitive IRREVERSIBLE alpha1 and alpha 2 receptor antagonist - higher doses of NE would not overcome this drugs effects (i.e. maximum effect by NE is decreased)
Phentolamine - competitive, reversible, and nonspecific adrenergic antagonist - higher doses of NE would overcome this drugs effects
A patient presents with fever, anorexia and nausea following isoniazid therapy, what is the cause?
HEPATOTOXICITY - Isoniazid is hepatotoxic in 10-20% of patients
What is the purpose of haptoglobin?
Serum protein that binds free hemoglobin and promotes its uptake by reticuloendothelial system –> decreased levels in hemolytic anemias
Low hemoglobin + jaundice should make you think…
what gross organ feature is associated with this?
HEMOLYTIC ANEMIA
-Pigmented gallstones
What does a positive osmotic fragility test signify?
HEREDITARY SPHEROCYTOSIS
Where is bile reabsorbed in the digestive tract? What potential problems could arise here?
Terminal Ileum - in Crohn’s ileocolitis you could have decreased absorption –> Increased bile acid wasting –> gallstones
What does valproate treatment in the pregnant mother put the child at risk of and why?
Neural tube defects (e.g. meningocele) b/c valproate inhibits intestinal folic acid absorption
What may lead to renal agenesis in a fetus?
Potter Syndrome - oligohydramnios + facial dysmorphism
What happens to FEV1 and FVC in obstructive lung disorder?
Both decrease so FEV1/FVC ratio stays the same
What is the medicine of choice for gestational diabetes mellitus and why?
First diet/lifestyle modification and if this fails –> INSULIN
Oral hypoglycemic medication should be avoided because of the risk of fetal hyperinsulinemia and resultant hypoglycemia
What are the purposes of Dexrazoxane and Amifostine?
Dex - iron chelator that can prevent anthracycline induced cardiotoxicity
Amif - cytoprotective free radical scavenger used to decrease cumulative nephrotoxicity of platinum-containing and alkylating chemotx and to decrease xerostomia (dry mouth)
A patient who suffered extensive blood loss is given packed red blood cells and develops paresthesias, what is the cause?
Hypocalcemia - before packaging whole blood cells are treated with citrate anticoagulant, infused citrate can chelate serum calcium in the blood recipient
What structure needs to be ligated during ovary resection? Which structure needs to be ligated in radical hysterectomy?
Suspensory ligament - contains nerve, vessels, and lymphatics of ovary
Transverse ligament - extends from cervix to lateral pelvic walls and carries the uterine artery
What is the mesosalpinx?
region of broad ligament of uterus that lies between uterine tube and ovary
Which vessels are on the lesser and greater curvature of the stomach?
Lesser- Left and right gastric
Greater - Left/right gastroepiploic
Which electrolyte is most likely to be lost by packed RBCs during storage and what may result?
Intracellular potassium lost to surrounding solution
May cause hyperkalemia in patient
What effect does UV radiation have on DNA? What results from this process?
Formation of PYRIMIDINE dimers
Nucleotide excision repair –> endonuclease NICKING on either side of damaged DNA –> removal –> ligation of repaired region
What is necessary for drugs like valacyclovir and famciclovir to function? How can you circumvent this issue?
These drugs (including acyclovir and ganciclovir) are nucleoSIDES thus they require viral phosphorylating enzymes to turn them into activated nucleotide analogs so they can function.
AIDS w/ Varicella zoster often are thymidine kinase deficient strains
Nucleotide drugs (cidofovir and tenofovir) circumvent this problem by only requiring cellular kinases to turn into active triphosphate. Foscarnet can also be used.
What is the initial immunoglobulin synthesized by all B-lymphocytes before class switching?
IgM - first coding region of Ig gene (IgM -> D -> G -> E -> A)
e.g. if B-cell signaled to synthesize IgE, IgM-G coding regions excised and B-cell will only make IgE, or IgA if induced to do that
6 year old with recurrent infections and failure to thrive, defective immunoglobulin isotype switching, large tonsils and palpable lymph nodes…
Hyper-IgM Syndrome - genetic deficiency in enzymes responsible for isotype switching or CD40 T-lymphcyte ligand essential for inducing B-Cell to switch classes
Recurrent airway/sinus infections very common because of lack of IgA
How can you distinguish AML from poliomyelitis?
Polio is exclusively LMN signs
What is the MoA and key side effects of Indinavir?
Protease inhibitor used in HAART (never as monotx)
SE: lipodystrophy, hyperglycemia, inhibition of P450 (do not use with rifampin) –> ALL protease inhibitors
Nephrotoxicity + nephrolithiasis –> specific to Indinavir
What is the MoA and SEs of Foscarnet?
Pyrophosphate analog, viral DNA polymerase inhibitor Tx of CMV and varicella zoster in HIV patients
SE: Nephrotox, electrolyte disturbance (low Ca, Mg, K)
What is the main side effect of Zidovudine?
Bone marrow toxicity –> anemia in 40% of patients
Increased AFP and amniotic fluid in the amniotic fluid…
NEURAL TUBE DEFECT
Which compound forms NO in endothelium mediated vasodilation?
ARGININE
What is a pathophysiological sign of diastolic left ventricular dysfunction and what could cause this?
Elevated LV pressure with low LV volume - Restricted Cardiomyopathy, which can occur from amyloidosis, sarcoidosis, metastatic cancers, inborn metabolic errors or idiopathic myocardial change
What sort of diseases can lead to systolic dysfunction with dilated cardiomyopathy?
Infectious myocarditis or cardiotoxic agents (e.g. alcohol, Doxorubicin)
What are the symptoms of serotonin syndrome? What drug most likely would cause this in a patient with depression who was treated for a bacterial infection?
- Neuromuscular excitation - hyperreflexia, clonus, myoclonus and rigidity
- Autonomic stimulation - hyperthermia, tachycardia, diaphoresis, and tremor
- Altered mental status - agitation and confusion
SSRI/MAOI/TCA + LINEZOLID
What is the alteration that occurs in familial erythrocytosis? What is this result similar to?
beta-globin mutation (lysine -> methionine) that leads to reduced binding of 2,3-BPG –> this leads to increased affinity for O2 (since normally 2,3BPG would bind the beta-globin and decrease O2 affin)
This increased affinity for O2 is most similar to fetal hemoglobin
What is the murmur heard in a L->R atrial septal defect? What can be a major risk with this condition?
WIDE and FIXED splitting (no change with respiration) of S2
Upon straining/Defecation/coughing the shunt can revere R->L and cause paradoxic embolism in those susceptible (e.g. DVT)
Presystolic murmur that disappears with atrial fibrillation?
Mitral/Tricuspid valve stenosis (will have presystolic accentuation due to atrial contraction)
What causes hand-foot and mouth disease? Scarlet fever? Erythema infectiosum?
Coxsackievirus A
Strep pyogenes –> Rheumatic fever
Parvovirus B19 -> Fifth disease
How do penicillins and cephalosporins function? (give specific example) How can bacteria gain resistance
IRREVERSIBLE binding to penicillin binding proteins (various bacterial strains produce many PBPs)
e.g. Transpeptidases - type of PBP that crosslinks peptidoglycan in bacterial cell wall
What antibiotic binds cell wall glycoproteins?
Vancomycin, binds to D-ala-D-ala terminal residues
How does carotid stretch maneuver improve elevated heart rate and low BP?
Prolonging AV node refractory period (via PANS)
What is necessary for an RNA molecule purified from a virus to be infectious (i.e. induce viral protein synthesis and genome replication)?
positive sense, single-stranded
What cellular protein mutation can lead to polycythemia vera?
Janus Kinase 2 (JAK2) a cytoplasmic tyrosine kinase –> abnormal transduction of erythropoietin growth signals
A patient being treated for cancer develops tingling of the hands, what is the cause of this?
Vincristine chemotherapy –> bind beta-tubulin preventing polymerization of microtubules –> inhibits M phase (mitosis) of cell cycle and as side effect can inhibit transport of neurotransmitters down axons
Patient with injury receives opioid analgesic in the ER, later develops RUQ pain, what is the cause?
Opioids like morphine can cause SMOOTH MUSCLE CONTRACTION especially in sphincter of Oddi which leads to constriction and spasm. This can increase common bile duct pressure and possibly gallbladder pressure -> biliary colic
Switch patient to NSAIDs
Which portions of the kidney are most susceptible to ischemic injury?
OUTER MEDULLA or CORTEX - PCT and thick ascending loop of Henle
What situations lead to ischemic injury in renal papillae? (also where is this portion located)
Inner part of kidney
Diabetes mellitus, analgesic (NSAID) nephropathy, and sickle cell disease
Which drugs are selective vasodilators of coronary vessels?
Adenosine and dipyridamole
What is PaO2 usually at someone who just climbed to a high altitude? What about pH, PaCO2 and bicarb?
60mmHg or less –> low O2 stimulates baroreceptors which cause a compensatory increase in respiratory drive
This results in hyperventilation (very low PaCO2) and respiratory alkalosis (high pH), at which point the kidney attempts to compensate by excreting biacrb (low serum bicarb)
What is the presentation and treatment of a patient in adrenal crisis?
Hypotensive, tachycardic, hypoglycemic and adrenal insufficiency (vomiting, ab pain, weight loss, and hyperpigmentation)
Tx: with corticosteroids immediately
What is the final step in collagen synthesis?
Covalent cross links formed by lysyl oxidase
What is a key mutation that can occur in melanomas? How can you combat this?
BRAF glu600val –> uncontrolled BRAF activation –> increased nuclear DNA replication
Tx: Vemurafenib - potent inhibitor of mutated BRAF
What type of drug is phenelzine? Name others within this group and MoA + clinical uses.
MAOI (like trancyclopromine and isocarboxazid)
Use in atypical depression when 1st line tx fail. e.g. MOOD REACTIVITY, rejection sensitivity, increased sleep and appetite
Which drugs are SSRIs? SNRIs?
Fluoxetine, paroxetine, sertraline, citalopram
Venlafaxine, duloxetine
What is the purpose of gag, pol, and env genes in HIV?
gag = group specific antigens in virion core like nucleocapsid proteins p24 and p7
pol = many proteins like reverse transcriptase
env = envelope glycoproteins gp120 and gp41
How can you monitor fetal lung development over the course of pregnancy?
Lecithin to sphingomyelin (L/S) ratio
Lecithin = phosphatidylcholine which increases sharply at 30 weeks gestation when type II pneumocytes begin secreting surfactant while sphingomyelin remains relatively stable with just a slight increase 30 weeks onward
What is sensitivity?
True positive rate, it equals the true positives divided by all people who have disease
Which drugs should be avoided with benzodiazepines?
Other CNS depressants that cause sedation
e.g. Alcohol, other benzos, barbiturates, and 1st generation antihistamines (chlorpheniramine)
What type of drugs are loratadine and ranitidine?
Lor = 2nd gen antihistamine, blocks peripheral H1-R does not enter CNS
Ran = H2-R antagonist that inhibits gastric secretion with slight affinity for CYP450 (but okay with diazepam)
Which nitrate compound has the highest first pass metabolism?
Isosorbide MONOnitrate
-dinitrate form is parent compound and not the one that is absorbed
What are some key symptoms that can be associated with endometriosus?
- Dysmenorrhea - with pain during menstrual period
- Dyspareunia - painful intercourse (from retroversion of the uterus and endometrial implants on uterosacral ligaments)
- Dyschezia - painful defication (pelvic adhesions)
What symptoms are associated with malposition of uterus?
None–> usually ASYMPTOMATIC
What is released from mast cell and basophil degranulation?
Histamine and TRYPTASE (unclear function, but it is a serine protease highly associated with MAST cells)
What are the treponemal and non-treponemal tests and how are they used?
Non-trep = VDRL & RPR which look for cardiolipin (a byproduct of infection) - used for screening and ARE affected by treatment -> monitor to see Tx response
Trep = FTA-ABS & MHA-TP which are specific treponemal antigens and remain for life regardless of treatment (used if Non-trep are negative and suspicion is high or just to confirm a positive Non-trep test)
Which cells in the body cannot use ketones for energy?
RBCs!!! obviously…. because they rely on glucose for glycolysis and you need MITOCHONDRIA to metabolize ketones
Which viruses have segmented genomes?
RNA (-)
Influenza virus (orthomyxoviruses), Reovirus (rotavirus, coltivirus), Arenaviruses, Bunyavirus
A patient with cystic fibrosis passes out during a workout, what is the cause of this?
Chloride is reabsorbed by mutated CFTR as it travels through eccrine duct to the skin surface. Naturally Na+ will follow and poor H2O is left by itself on the surface –> HYPOTONIC SWEAT –> Dehydration :(((
An HIV patient presents with multiple ring enhancing lesions in the brain. Toxoplasmosis is ruled out, and patient is found to be +EBV, what is the cause?
Primary CNS lymphoma - diffuse large-cell non-hodgkin B-CELL lympoma
Which kidney structures develop from the ureteric bud? Metanephric blastema?
Ureteric bud -> Collecting system: collecting tubules/ducts, major and minor calyces, renal pelvis, ureters
Met - glomeruli, bowman’s space, PCT, loop of henle, and DCT
What effects do inhaled anesthetics have on the kidneys?
What are some unique effects of fluorinated anesthetics?
Decrease GFR, decrease renal vascular resistance, and decreased RPF
Fluor - decrease vascular resistance -> increase Cerebral blood flow -> increased ICP (bad)
also decrease hepatic blood flow and cause hypotension (from decreased Cardiac output)
All except NO2 cause respiratory depression
What is an autoimmune disorder associated with Celiac disease and what would be revealed on microscopy and IF?
Dermatitis Herpetiformis - Neutrophils and fibrins at the tips of dermal papilla forming microabscesses; IgA depostis also at the tips on IF
A patient presents with signs of heart attack, with ST elevations in the inferior leads. She also has low heart rate and blood pressure. What is the appropriate treatment for her bradycardia and what are risks involved?
Atropine - anticholinergic that will decrease vagal influences of AV/SA node (the ones that are currently effected since it is an inferior MI - RCA distribution)
But it will also cause mydriasis of eye diminishing outflow of aqueous humor -> can precipitate angle closure glaucoma in susceptible patients (sx = unilateral severe eye pain and halos)
What is one treatment for cirrhosis related hepatic encephalopathy and how does it work?
Lactulose - osmotic diuretic; not absorbed by gut so causes retention of water. Also acidifies colon contents trapping ammonia as NH4+ which decreases serum ammonia concentrations
What is deferoxamine used for?
Iron chelating agent used to treat hemachromatosis
Multiple round lesions are found in the lung that have metastasized from a primary source. biopsy shows round and polygonal cells with abundant clear cytoplasm. What is the origin for this tumor?
Renal Cell Carcinoma - Clear cell subtype
From what aortic arch does the carotid artery develop from? Arch of the aorta?
3rd - common and proximal internal carotid arteries
4th - part of true aortic arch and subclavian
6th - small part of true arch and pulmonary arteries and ductus arteriosus
What are 3 significant purposes of the oxidative reactions of the HMP shunt?
- NADPH produced -> reducing glutathione -> repairing oxidative damage in RBCs
- NADPH necessary as an electron donor for ANABOLIC reactions (e.g. Cholesterol/Fatty Acid synthesis)
- Forms Ribulose-5-P from 6-phosphogluconate to provide substrates for nucleotide synthesis
What is the defect that leads to Lynch syndrome?
Hereditary nonpolyposis colon cancer (HNPCC) - Autosomal dominant disease with defect in NUCLEOTIDE MISMATCH REPAIR (MSH2 and MLH1 gene mutations in 90%)
What does delta agent or hepatitis delta virus rely on to cause hepatitis?
Replication defective b/c it must be coated by the external coat antigen HBsAg of the hepatitis B virus
How can you quickly calculate PAO2 and what is the normal value for A-a gradient?
PAO2 = 150 - (PaCO2/0.8)
A-a gradient should not exceed 10-15 mmHg
What effect does CHF have on the lungs?
Decreased lung compliance - because of the presence of fluid in pulmonary interstitium
What leads to Patau syndrome and what characteristic features will be seen on the fetus/neonate?
Trisomy 13 -> early defect on precordal mesoderm -> Midface, eye and forebrain most markedly affected
- severe cleft lip/palate, microphthalmia, deafness, scalp defects
- CNS: severe mental retard, microcephaly, holoprosencephaly, neural tube defects
- Polydactyly, rockerbottom feet
- PDA, ASD, VSD
- PCKD
- Ab wall defects -> omphalocele, umbilical hernia, pyloric stenosis
What are the key features of Edward syndrome?
Prominent occiput, micrognathia, small mouth, low set and malformed ears, rocker bottom feet, overriding fingers,
GI- meckel’s diverticulum and malrotation
What are the key features associated with cardiac tamponade and tension pneumothorax and how can you differentiate?
Acute CVP elevation (indicated by increased JVD), Hypotension and tachycardia
Can check lung sounds to rule out PNTx; and muffled heart sounds, pulsus paradoxus and history of viral infection (causing significant pericardial effusion) are some things that can rule in Tamponade
What are some presenting signs indicating acute fibrinous pericarditis?
-May follow URI
-pleuritic chest pain
-Pericardial friction rub
(No increase JVD, hypotension, muffled sounds which are more likely to be tamponade)
A 56 year old woman gets a vertebral compression fracture and is started on hormone replacement therapy. What was the cause of this, what is she receiving and what effects will this have on other hormones in the body?
Osteoporosis -> receiving Estrogen +progesterone therapy
-Estrogen causes a decrease in thyroid binding globulin (TBG) catabolism -> TBG levels increase -> more bound T3/T4 so total levels of hormone increase -> but free hormone levels remain normal and patient is euthyroid
What is the main first line treatment for Rheumatoid Arthritis and key side effects that may result? How can you prevent some of these?
Methotrexate - inhibits dihydrofolate reductase
SE: stomatitis (painful mouth ulcers) and hepatotoxicity (hepatitis, fibrosis and cirrhosis) -> increased AST/ALT
Co-administration of Folic acid may prevent stomatisis
What else can induce asthma in patients with exercise-induced asthma subtype? What about in a patient with intermittent respiratory symptoms, decreased FEV1, and occasional sputum eosinophils?
Exercise induced = cold air
These sx are characteristic of allergen induced asthma therefore animal dander, feathers, dust mites, pollen and mold should be avoided
How does serosal inflammation manifest in SLE?
Pleuritis and Pericarditis
What are actin and myosin filaments bound to in the sarcomere?
Actin - Z-line (A to Z actin) - I-band
Myosin - M-line (myosin in the middle) - H-Band
What is the MoA of omalizumab?
Anit-IgE Abs given as subQ injection for moderate to severe asthma with incomplete response to steroids
What is chloride transport in the RBCs dependent on?
Carbonic anhydrase - as CO2 builds up in post capillary venules, it is converted into bicarb which then diffuses out of the RBC. Chloride ions diffuse in to take their place and maintain neutrality - “chloride shift”
Which compounds are freely filtered into the glomerulus and NOT secreted? Filtered and secreted?
Inulin, mannitol, and glucose (but of these only glucose is reabsorbed back in) - analogous to filtration rate
PAH and Creatinine (to a lesser degree) - analogous to excretion rate
Which nerve roots make up the sciatic nerve and which are usually involved in sciatica?
Nerve = L4-S3
Sciatica = L5 or S1
What is the usual presentation in homocystinuria and how can it be treated?
Cystathionine synthetase enzyme deficiency
Causes dislocated lenses, intellectual disability, marfanoid habitus, osteoporosis, high risk for thromboembolic events which usually cause death
Tx: Pyridoxine (V. B6) which is a cofactor for that enzyme and results in dramatic improvement by increasing enzyme activity; also RESTRICT METHIONINE as this can increase homocystine and make patient worse
Which enzyme is deficient in Lesch-Nyhan syndrome and which enzyme activity would increase?
HGPRT def. (X-linked recessive) -> failure of purine slavage
PRPP is a substrate which accumulates -> downstream enzyme activity increases (PRPP amidotransferase)
What is the treatment option for a non-hodgkin’s lymphoma expressing cell surface marker CD20?
Rituximab (tu-x = 2 times 10 = 20)
What is the purpose of IL2 treatment?
Increase activation of T-cells to kill TUMOR cells
What is Abciximab?
Chimeric mouse/human monoclonal antibody against platelet GP iib/iiia receptor. Blocks final step in platelet activation
Given during angioplasty in patients with acute coronary syndrome
What happens to V/Q as you go from the base of the lung to the apex?
exponential increase
A patient experiences dysphagia, nocturnal cough and sore throat. What do they most likely have and what can you see on microscopy?
Silent GERD
Basal zone hyperplasia, elongated lamina propria papillae, and inflammatory cells (eosinophils, neutrophils and lymphocytes)
Which drugs given in pill form can cause esophagitis?
TCAs, potassium chloride, and bisphosphates
What is the principle behind zero order kinetics?
Metabolizing enzymes become fully saturated, and drug metabolism continues at a constant rate regardless of the concentration/dose of the drug - aka capacity-limited (saturable) enzyme kinetics
What is the MoA of Raltegravir?
Integrase inhibitor for Tx of HIV - inhibits integration of viral DNA into host genome
What can result from increased alkaline secretions of the vagina?
Bacterial vaginosis or Trichomonas vaginitis
What are histological/radiological findings of silicosis? Berylliosis?
Silic - nodular interstitial densities on CXR, eggshell calcifications of hilar nodes, birefringent silica particles surrounded by fibrous tissue
Beryll - Ill-defined nodular/irreuglar opacities on CXR, hilar adenopathy in 40%, noncaseating epitheliod granulomas (similar to sarcoid) without obvious particles present
What is significant about HBV infection in prodromal period? HCV?
B - Serum-sickness like syndrome (fever, fatigue, joint pain, urticaria-type skin rash) + surge of AST/ALTs
C - usually asymptomatic, some may have malaise, nausea or RUQ pain
What are characteristics of idiopathic pulmonary fibrosis?
Exertional dyspnea with increased FEV1/FVC and biopsy -> dense fibrosis, fibroblast proliferation, and cyst formation, most prominent in subpleural regions
How do you calculate number needed to treat (NNT)?
NNT = 1/ARR
ARR = absolute risk reduction which is event rate in control group minus event rate in treated group
How do you calculate number needed to harm (NNH)?
NNH = 1/AR
AR = attributable risk which is incidence with exposure minus incidence without exposure
What effect does goodpasture syndrome have on the glomerulus and what deposits are made?
Rapidly Progressive Glomerular Nephritis (w/ Crescent formation)
IgG and C3 deposits on GBM
What mediates the effects of Insulin in the cell?
Insulin binds Tyroskine Kinase membrane protein -> these phosphorylate insulin receptor substrates -> which leads to activation of PROTEIN PHOSPHATASE 1 -> dephosphorylates glycogen synthase thereby activating this protein and promoting glycogen synthesis
What is fever, pruritic skin rash, and arthralgias 7-14 days after exposure to an antigen indicative of?
Acute serum sickness (type III hypersensitivity reaction) -> immune complex formation and decrease C3
What is TNF-alpha?
A cytokine acute phase reactant that mediates inflammation -> #1 role to regulate immune cells -> able to induce fever, apoptotic cell death, cachexia, tumor cell death, inhibit tumorogenesis and viral replication, respond to sepsis via IL1 and IL6
Implicated in many autoimmune diseases -> inhibited by infliximab
What is a very high alveolar pO2 and and very low alveolar pCO2 indicative of?
Very high PO2 means it is about the same as tracheal pO2, which means that the ventilated air is not equilibrating properly with the blood perfusing the alveolar capillaries. This means that there is poor alveolar perfusion which could result from a PE.
What alveolar pO2 and pCO2 levels be like in a situation with poor alveolar ventilation?
Similar to venous blood, because of the extended time the gas is left to equilibrate with capillaries
What nerve courses through the popliteal fossa and what does it innervate?
Tibial nerve -> muscles for plantar flexion and inversion of the foot (damage would cause unopposed dorsiflexion and eversion)
What nerve courses around the neck of the fibula and what does it innervate?
Common peroneal nerve -> splits into superficial branches which innervate muscles of lateral compartment of foot (eversion) and deep peroneal nerve which innervates anterior compartment of leg (dorsiflexors of foot and toes)
Superficial peroneal also provides sensation to most of foot
What does permissive effects indicate in pharmacology?
e. g. A drug may not ordinarily have any effect on vasoconstriction (cortisol) but when given with another drug which has vasoconstrictive effects (NE), the vasoconstriction is significantly augmented (vs. if NE was given alone)
i. e. Cortisol allows for NEs full force to be unleashed
What is the #1 brain tumor in the pediatric population and where is it usually located? #2 and #3? Give descriptions of appearance on imaging.
- Pilocytic astrocytoma in cerebellum - mass with solid AND CYSTIC regions; pilocytic astrocytes and rosenthal fibers on biopsy
- Medulloblastomas (#1 malignant) - exclusively in the cerebellum but it is a SOLID mass; biopsy-> made of sheets of small blue cells with hyperchromatic nuclei and scant cytoplasm
- Ependymomas - from ependymal lining of brain stem and can obstruct CSF flow (hydrocephalus); biopsy -> gland like structures, rosettes
What effect do Neuraminidase inhibitors have?
Viral release from cell
What is the intermediate of the catabolism of branched chain amino acids, and what enzyme def. can lead to the build up of this compound?
Propionic acid - Propionyl CoA carboxylase deficiency will prevent formation of methylmalonyl CoA and propionic acid will build up
What substance recruits and activates eosinophils?
IL5 release by Th2 helper T-cells
What is the most effective agent to reveal ischemia and acidity in tissues (such as a cord, hard, pale region of skin where NE is being infused)?
This ischemia is caused by NE extravasation into the tissues causing alpha-1 mediated vasoconstriction and local tissue necrosis
Tx: immediately infuse an alpha 1 blocker into the area (thin syringe with 10-15 cc saline and 5-10 mg of phentolamine)
What effect does Nitrite exposure have on a human?
Converts the reduced ferrous iron in hemeoglobin (Fe2+) and oxidizes to ferric state (Fe3+) -> Methemoglobin forms which cannot carry oxygen, binds tightly to cyanide, and causes dusky colored skin (cyanosis which will not improve with O2 supplementation)
PaO2 in arterial blood will remain same because the amount of O2 diffused in plasma does not change.
Which carries a worse prognosis in a colon tumor, poorly differentiated cells or invasion of muscularis propria?
Invasion of muscularis propria (stage always has bigger effect on prognosis than grade)
Which areas of the respiratory tract are lined by pseudostratified columnar mucus secreting epithelium? Stratified squamous epithelium?
Pseudo Colum - nose, paranisal sinus, nasopharynx, most of larynx, and tracheobronchial tree
Stratified Squam - oropharynx, laryngopharynx, anterior epiglottis, upper half of posterior epiglottis, and vocal folds (true vocal cords)
Which microorganism can cause warty growths on the true vocal cords?
HPV - small naked DNA virus type 11 - causing papillomas which can cause hoarseness and stridor
Antibodies produced by which blood type can cross the placenta?
Type O makes IgG Abs to A and B antigens which can cross and kill fetus
A and B blood types make IgM which does not cross
Which part of the nephron is impermeable to water?
Thick and Thin ascending limbs of the loop of Henle
What is conversion disorder? How does it differ with hypochondriasis?
Symptoms of motor/sensory deficits that seem neurological in nature, but all tests of a neurological cause are negative.
Associated with young women and emotional stress
Hypochon is more of a fear of getting disease (small gassy pains in abdomen make patient convinced that they have cancer)
What effect does demyelination have on time constant and length constant?
TC - is time it takes for change in membrane potential to achieve 63% of new value -> so it will increase with demeylination because more time needed for changes
LC - measure of how far along an axon an electrical impulse will propagate -> so it will decrease with demeylination because charge can’t travel as far
A patient presents with signs of septic shock and labs reveal decreased bicarb and increased lactic acid levels. What is the cause of this?
In septic shock there is impaired tissue oxygenation which results in decreased oxidative phosphorylation. This leads to shunting of pyruvate to lactate formation. Hepatic hypoperfusion also contributes to lactic acidosis.
Decreased bicarb and increased anion gap identify this as anion gap metabolic acidosis
What may result from inability to form methylcobalamin?
Homocystinuria because homocysteine can’t get converted back into methionine. Also cannot form THF leading to folate trap and megaloblastic anemia
Which antiviral drug can inhibit DNA polymerase and reverse transcriptases and does not require intracellular activation to function? What about same characteristics but act on reverse transcriptases?
Foscarnet
NNRTIs - Delavirdine, Efavirenz, Nevirapine
What is necessary for NRTIs to function?
Must be phosphorylated in the cell to get activated
What is impaired in patients lacking ApoE3 and ApoE4 in circulating lipoproteins?
Chylomicron remnant uptake by liver -> elevated cholesterol and Triglycerides (Type III hyperlipoproteinemia)
What is the best option for post-meal hyperglycemia in diabetics?
Short acting - Lispro, Aspart, Glulisine - before the meal (peaks 45-75 min)
Note: regular insulin does not mean it is like the insulin in your body, it is just the first insulin that was developed and requires 2-4 hrs to peak
When should regular insulin be used?
IV for diabetic ketoacidosis (peeks 2-4 hrs)
What are key findings associated with Acute promyelocytic leukemia?
Subtype of AML - Many Auer rods, peroxidase +, t(15;17); young patients and DIC is common (recurrent gum bleeding etc.)
What are the most common primary cardiac neoplasms and how do they present?
Signs of Cachexia, SOB (worsening when sitting), low pitched mid diastolic rumble, large pedunculated mass on echo
Histo: Scattered cells within mucopolysaccharide stroma
How do you differentiate CML and AML?
CML - Leukocyte count >50k and often >100k; peripheral smear with complete spectrum of granulocytic cells, with myelocytes, and neutrophils predominantly, blasts less than 10% - t(9; 22)
AML - Increased number of myeloblasts (>20% of total nucleated cells), Auer Rods may be present
Which cancers present with Auer rods?
AML with maturation t(8; 21)
Acute promyelocytic leukemia t(15;17)
What is the MoA of buspirone?
Selective 5HT1A-R agonist - generalized anxiety
How is digoxin metabolized from the body and what can lead to increased levels? Where is digoxin stored in the body and how is this important?
Renal Clearance - with increased age renal activity decreases and renally cleared drugs like digoxin build up
Lean muscle mass - must factor this weight into account as high levels will concurrently increase digoxin via increased storage
What are two similar features between secondary syphillis and chlamydia and how can they be differentiated?
Rash on palms and soles - hyperkeratotic vesicles in chlamydia v.s maculopapular/pustular rash in 2nd Syph
How do you calculate the attributable risk of a particular exposure, in the exposed population?
ARP = 100 x [(RR - 1)/RR)] where RR = Risk in exposed/risk unexposed
e.g. if RR for esoph. cancer in smokers vs. non-smokers is 5 then the % of esoph attributable to smoking is:
100 x [(5-1)/5)] = 80%
What is the most common cause of congenital adrenal hyperplasia? Will male or females present earlier?
21-hydroxylase deficiency
increased androgen doesn’t effect males until 2-4 years old (salt wasting and precocious puberty); females at 1-2 weeks with virilization
What is the most crucial gene activated by PPAR-gamma?
Adiponectin (an adipocytokine that is low in T2DM) which TZD drugs activating PPAR-gam increase
What can result from a defect in DNA mismatch repair?
HNPCC - Lynch syndrome (AD predisposition to colon cancer
What are the features of pituitary apoplexy and what should it be distinguished from? Treatment?
- Acute pituitary hemorrhage (often in preexisting adenoma)
- Severe headache, bitemp hemianopsia, opthalmoplegia, panhypopit
- Can present months before with headaches and decreased libido (this differentiates from ruptured berry aneurysm)
Tx: glucocorticoids
How can you differentiate strep pyogenes from other gram + cocci that are cat - and coag - ?
Pyrrolidonyl arylamidase (PYR +)
Wide zone of beta hemolysis
Bacitracin sensitive
What are the overall effects of a strong non-selective muscarinic agonist?
M1 - PANS activity in CNS and enteric nervous system
M2 - decrease HR and contractility of ATRIA
M3 - Increase exocrine gland secretions (lacrimal, salivary, gastric acid), increase gut peristalsis, increase bladder contraction, bronchoconstriction, miosis, ciliary muscle contraction (accomodation)
M-R on endothelial cells -> release of NO (EDRF) -> vascular smooth muscle relaxation
What occurs in the heart (volume-pressure loop) if there is an AV shunt?
Increased pressure of Arterial blood into venous system increases preload -> increased volume into ventricles
Arterial blood lost to venous system decreases TPR which decreased afterload -> decrease pressure of ventricles
Which drugs can cause SIADH?
Carbamazepine, Cyclophosphamide, SSRIs
Which class of diseases frequently result in hypercalcemia and hypercalciuria?
Granulomatous disorders - Sarcoidosis, TB, Hodgkin’s disease and Non-Hodg Lymphoma
How can you estimate Renal plasma flow (RPF)? RBF?
RPF = Urine concentration of PAH x V(urine flow rate) divided by Plasma concentration of PAH
This equals the clearance of PAH
RBF = RPF / (1-Hct)
Which amino acid gets converted to niacin? What can result from deficiency of this process and what disease is it associated with?
Tryptophan -> Niacin
Hartnup disease is AR deficiency of neutral amino acid transporters in PCT, so tryptophan is lost to urine and patient develops pellagra like symptoms
How would an adult with lead poisoning present?
Weakness, ab pain, constipation, blue lines at junction of teeth and gingiva
- > blood smear: coarse basophilic stippling on a background of hypochromic microcytic anemia
- > previous history as industrial worker (battery) or miners
How does a patient with acute intermittent porphyria present and what would you see on blood smear?
Sx: Abdominal pain attacks
Blood smear = NORMAL
What effect does vasopressin administration have on the medullary collecting duct?
V2 - Receptor mediated increase in permeability to H2O and UREA at the luminal membrane
With increased reabsorption to inner medullary interstitium -> fractional excretion of Urea decreases
What is the process of Calcium reabsorption in the nephron?
50-60% reabsorbed in PCT
Further reabsorption in DCT depends on PTH
What process leads to keloid formation? Can foreign bodies lead to this?
Excess collagen formation during tissue repaire (2 weeks post injury)
No foreign bodies do not lead to keloids
What is the presentation and cause for McArdle’s syndrome?
Type V glycogen storage disease -> strictly affects muscles -> poor exercise tolerance, muscle cramps, and urine discoloration after exercise
Caused by deficiency of Myophosphorylase, an isoenzyme of glycogen phosphorylase present in muscle tissue
What is the progression acute salicylate intoxication?
- Respiratory alkalosis - from direct stimulation of medullary centers -> increase ventilation -> increase CO2 lost
- Anion gap metabolic acidosis - salicylates increase lipolysis, uncouple ox phos, and inhibit TCA -> organic acid accumulation in blood
Patient can present with mixed respiratory alkalosis/metabolic acidosis
What does this ABG indicate: pH - 7.42, pCO2 - 40mmHg, bicarb- 26 mEq/L
NORMAL
How is resistance calculated in a parallel system?
1/R of Total = 1/R1 + 1/R2 + 1/R3 +….1/Rn
In which location are GI ulcers least likely to be from a malignant cause?
Duodenum - 95% are in first part of duodenum and majority are from H. Pylori and NSAIDs
What are the features of a highly soluble anesthetic gas?
blood saturates slowly -> delayed rise in partial pressure -> slowed brain saturation -> increased onset time
increased blood/gas partition coefficient and more potent (if it works at low partial pressures)
What does antibodies to PLA2R transmembrane receptor lead to?
Membranous nephropathy (this receptor is in high concentrations in glomerular podocytes)
In what form must Rb be in to allow for progression into S stage?
Cyclin D, E and CDKs cause Rb to be hyperphosphorylated, which inactivates the protein and causes it to release E2F, and allows for cell cycle progression
What is E. Coli’s virulence factor that leads to neonatal meningitis?
K1 Capsular Polysaccharide antigen
What are the effects of Lipid A and what organisms produce it?
Lipid A in lipopolysaccharides is similar for all enterics
-> activates Macrophages -> widespread release of IL1 and TNFalpha -> SEPTIC SHOCK
Name all of the features of Turner syndrome:
- 45XO
- Low set ears, low hairline, narrow high arched palate, broad chest, webbed neck, wide nipples, short stature
- Coarctation of aorta, bicuspid aortic valve
- Horseshoe kidney
- Streak (atrophic) ovaries, amenorrhea, infertility
What is the indication for giving blood or other invasive treatments to an unconscious Jehova witness if contact with family is not possible?
Unless there is an identifying Jehova witness card on the patient or next of kin explicitly states they are of that religion and cannot be treated -> GIVE TREATMENT
What is the murmur heard with VSDs? ASDs?
VSD - Loud holosystolic murmur at left sternal border, from turbulent flow into the RV
ASD - wide fixed splitting of S2
What allows for strep viridans to colonize heart valves?
Fibrin and platelets deposited at sites of endothelial trauma -> forms valvular vegitation
What happens from exposure of subendothelial collagen?
Potent activation of platelets -> rapid thrombus formation -> MI, stroke, other ischemia depending on location of damage
What allows non-pathogenic C. Diphtheriae to acquire pathogenecity and cause severe pseudomembranous pharyngitis?
Acquired virulence via bacteriophage-mediated infection with Tox gene -> this codes for diphtheriae AB exotoxin
Cornyphage-beta is bacteriophage that causes this
What happens upon G-protein activation in the IP3 DAG cell messenger pathway?
G-protein activates phospholipase C which cleaves phosphatidylinositol-4,5-BP into IP3 and DAG -> IP3 causes intracellular calcium release and both Calcium and DAG activate PROTEIN KINASE C
A young teen presents 1 year after menarche complaining of heavy bleeding lasting 7-9 days and spotting in between periods. Her last period was 6 weeks ago. What is the cause of this?
Immature hypothalamic-pituitary-ovarian axis leads to longer periods and irregular bleeding patterns this is caused by ANOVULATORY CYCLE
Without ovulation the ovarian follicle does not degenerate and becomes corpus luteum -> no progesterone is produced, estrogen remains persistently high -> endometrium remains in proliferative phase
What are the main drugs used to treat MRSA, their MoAs and major side effects?
- Vancomycin - blocks glycopeptide polymerization -> red man syndrome, nephrotoxicity
- Daptomycin - depolarization of cell membrane (only use vs. g+ organisms) -> Myopathy and CPK elevation, inactivated by pulm. surfactant
- Linezolid -> blocks 50s subunit inhibiting protein synthesis -> Thrombocytopenia, optic neuritis, serotonin syndrome
What is the purpose of lipoic acid, and what can result if lipoic acid is not functioning in key enzymes?
Lipoic acid involved in decarboxylation of alpha ketoacids and transfer of alkyl groups
It is essential in pyruvate dehydrogenase which transfers alkyl groups from pyruvate to CoA -> TCA
If lipoic acid doesn’t work pyruvate is shuttled into lactic acid fermentation -> LACTIC ACIDOSIS
What is pemphigus vulgaris a disorder of?
DESMOSOMES!!!!! -> leads to flaccid bullae and erosions of skin and mucosal membranes
Bullae spread laterally with pressure and new ones form from skin traction
What is FSH responsible for in the male? LH?
FSH -> produce inhibin B and cause spermatogenesis. also produce androgen binding protein locally which increases testosterone levels in the seminiferous tubules
LH -> produce testosterone
What is the MoA of bupropion and what is it used to treat?
Mixed NE/Dop reuptake inhibitor for depression and smoking cessation
What will cause NPV to vary?
High pretest possibility of disease will result in a lower NPV (e.g. a patient with thyroid nodule negative for cancer, but is young and had radiation exposure)
Low pretest possibility of disease will result in higher NPV (e.g. a patient with negative HIV test who has only had 1 sexual partner, and does not use drugs)
Which drug prevents viral uncoating?
Amantadine
What leads to the pathogenesis of pulmonary hypertension in a young female and how do you manage/treat it?
inactivating mutation of pro-apoptotic BMPR2 gene –> increased endothelial and smooth muscle cell proliferation -> vascular remodeling -> elevated pulmonary vascular resistant -> pulm HTN
Bosentan is an endothelial receptor antagonist that blocks the potent vasoconstrictor endothelin and Bosentan also stimulates endothelial proliferation
Definitive treatment is lung transplant
What sensations does the phrenic nerve carry?
Pleuritic chest pain that sharpens on inspiration and may be referred to the shoulder because of the nerve roots (C3-5) that make up the phrenic nerve
What is the main function of the vagus nerve?
PANS innervation of viscera of chest wall and foregut
What is the effect of elevated prolactin in a man with pituitary tumor?
Decrease GnRH -> decrease LH and Testosterone
A cancer cell is found with a large nuclei that contain prominent round basophilic bodies. What enzyme activity is elevated in this structure?
RNA polymerase I -> makes rRNA
What is dry/wet beri beri and how does it arise?
Adult deficiency in Thiamine (V. B1)
Dry = symmetrical peripheral neuropathy w/ sensory/motor impairments
wet = neuropathy + cardiac involvement (cardiomegaly, cardiomyopathy, CHF, peripheral edema and tachycardia)
infantile beri beri = cardiac syndrome w/ cyanosis, vomiting and tachypnea
What happens to bone density as BMI decreases?
LOWER BONE DENSITY
Which race is less predisposed to osteoporosis?
African Americans
How do you calculate maintenance dose?
MD = Cp55 x CL / [bioavailability fraction]
IV medication bioavailability fraction = 1
Cp55 = therapeutic steady state concentration (mg/min)
CL = clearance (L/min)
What predisposes someone to warfarin induced skin necrosis?
inhibition of anticoagulation activity of protein C
Risk increased in predisposed patients who already have congenital deficiency of protein C/S
What occurs if an XY male fetus is deficient in sertoli cells?
SRY gene on chrom. Y -> activates Testes differentiating factor (TDF) -> Leydig cells + testosterone increase make male internal and external genitalia
-> sertoli cells release mullerian inhibitory factor -> involution of paramesonephric ducts (female structure)
So if sertoli cells are not functioning the child will have male external genitalia + male/female internal genitalia
How would a patient with a glucagonoma present?
Tumor from alpha cells pancreatic islets of langerhans
1. Necrolytic migratory erythema (face, extremities, groin) -> can form large lesions with bronze induration
2. Hyperglycemia -> diabetes mellitus + GI symptoms
3. Normocytic, normochromic anemia
Dx: from elevated serum glucagon levels
What skin condition is strongly associated with celiac disease?
Dermatitis herpetiformis (bilaterally and symmetrically on extensor surfaces, upper back and butt) - papules, vesicles and bullae
What nerve innervates the posterior arm and forearm?
Radial Nerve
What is administered to treat Acetaminophen toxicity?
N-acetyl-cysteine (sulfahydryl group mediates
What is the mechanism of fibrate drugs?
Gemfibrozil or fenofibrate -> activate PPAR-alpha which increases lipoprotein lipase activity
What hormone changes lead to ovulation? How can you simulate this process in a patient with infertility?
FSH stimulates formation of dominant follicle and estrogen production from ovaries -> increase in serum estrodiol have positive feedback on LH -> LH surge -> rupture of dominant follicle -> extrusion of ovum
infertility -> Menotropin acts like FSH and ovulation induced by large dose of beta-hCG which simulates LH surge
Which factors can precipitate increase load of nitrogenous substances absorbed by the gut, and how can you treat this?
GI bleeds can cause increase nitrogen delivery to the gut in the form of hemoglobin which gets converted to ammonia and absorbed (normally NH3 in gut produced by enterocytic catabolism of glutamine and colonic bacteria catabolism of dietary proteins)
Tx: Disaccharide administration (lactulose) -> bacterial breakdown of sugar -> acidification of colonic contents -> NH3 converted to non-absorbable NH4+
What is the function of thyroid peroxidase? What disease interferes with this enzyme>?
Iodination and coupling of thyroglobulin
Hashimoto’s thyroiditis -> antibodies against thyroid peroxidase
What is an essential pathological step in the development of rapidly progressive glomerular nephritis? How can you detect this specifically?
Crescent formation -> fibrin deposition and macrophages in bowman’s space (inflammatory debris)
Will show up on H&E but can also do IF of fibrin
What type of patients does staph aureus infect in endocarditis?
IV drug users -> Tricuspid vegetations
causes damage on previously undamaged valves
What is the most sensitive marker for diagnosing hypothyroidism?
Serum TSH -> in primary hypothyroidism TSH rise is seen well before low thyroid levels
What are key features that will distinguish cushing syndrome from hypothyroidism?
Central obesity, skin striae, proximal muscle weakness (more pronounced in cushings)
What drug class should be avoided in C1 esterase inhibitor deficiency, and why?
Hereditary angioedema, resulting from low C1 esterase inhibitor -> kallikrein and bradykinin levels increased -> these will mediate worsening angioedema
ACE inhibitors will further increase bradykinin, worsening angioedema (pulmonary and GI symptoms/discomfort)
Which bowel segment is always involved in Hirschsprung disease and why?
Neural crest cells migrate along vagal nerve fibers, caudally from proximal colon (8 weeks) to rectum by 12 weeks. Since rectum is last stop, if there is an arrest in migration, RECTUM is always involved. If arrest occurs sooner, sigmoid may also be involved
What is the most common cause of adrenal insufficiency and what disease is associated with it?
Autoimmune adrenitis (destroys all 3 layers of adrenal cortex) -> increased in type I DM (because already has an autoimmune disorder; destruction of pancreatic beta cells)
What does decrease serum levels of cortisol and unresponsiveness to ACTH indicate?
Defect of cortisol (or mineralocorticoid/androgen) secretion is in adrenal gland
e.g. could be a primary adrenal insufficiency like autoimmune adrenitis
How will patients with adrenal insufficiency present and why?
Decreased cortisol -> increased MSH and ACTH (hyperpigmentation and decreased requirement for insulin)
Decreased aldosterone -> decrease sodium reabsorption and increase K+ and H+ retention -> compensatory drop in bicarb to bind H+ (metabolic acidosis) -> compensatory rise in Cl- (to maintain electroneutrality
Lack of aldosterone also causes hypotension so Vasopressin is released -> increases free water absorption and worsens hyponatremia
Which drug classes increase endogenous insulin secretion and how do they do this? How can this be distinguished from excessive exogenous insulin use?
Sulfonylureas and meglitinides bind ATP dependant K+ channels on beta-cells, inhibit the hyperpolarizing K+ current and cause depolarization -> opens Ca2+ channels -> increased release of INSULIN, C-PEPTIDE, and some excess PRO-INSULIN
Exogenous insulin use will not show high C-peptide and proinsulin levels
What are the presenting features of Kallmann syndrome, and how does this disorder arise?
Delayed puberty and anosmia, from failure of GnRH secreting cells to migrate from olfactory centers into the hypothalamus
What is a key product of anaerobic glycolysis in RBCs and what is its function?
generate 2,3-BPG via enzyme bisphosphoglycerate mutase -> this production will increase in low oxygen tissues which will facilitate even more unloading of O2 by allosterically inhibiting Hemoglobin affinity for oxygen
What are the side effects caused by clindamycin? Gentamicin? Metronidazole?
Clinda = pseudomembranous colitis
Genta = vestibular/cochlear ototoxicity, nephrotoxicity, and neuromuscular paralysis (w/ large dose/intrapleural)
Metro = GI (ab pain, vomiting, nausea) and Neuro (paresthesias/dizzy). Disulfiram like reaction w/ ETOH
What is the MoA of donepezil? What are other MoAs that are useful in treating the same disorder this drug is used for?
Donep = Ach-esterase inhibitor -> enhancing cholinergic neurotransmission
Others = Neuroprotection via antioxidants (Vit. E) or NMDA receptor antagonism (Memantine)
What is the key difference between finasteride and the other drugs used in BPH?
Finasterid lowers prostate volume
Terazosin/Tamulosin improves urination and Tolterodine (anti-musc) helps with low post-void volume and overactive bladder, but these don’t affect prostate size
What are the two main anti-inflammatory cytokines?
IL10 (inhibits all but IL4/5 production by Th2) and TGF-beta (inhibits everything)
What do, severe hypertension, low plasma renin and weakness/paresthesias indicate?
Primary meralocorticoid excess (Hyperaldosteronism)
What will result from excess aldosteronism?
Increased Na reabsorption (+H2O) -> this induces ANP release and increased pressure naturesis to counteract -> mild increase in extracell fluid with hypertension and no edema/hypernatremia
Increased urinary K+ and H+ release -> hypokalemia and metabolic alkalosis
What is a serious complication that can arise from PID?
endometritis, salpingitis, tubo-ovarian abcess, or pelvic peritonitis -> can cause Permanent damage to reproductive system -> INFERTILITY
What can lead to endometrial hyperplasia?
Excess estrogen
How can you prevent recurrence of HSV2 (genital HSV)?
Continuous daily valcyclovir
What finding is suggestive of Strongyloides stercoralis infection?
Rhabditiform larvae in stool
What characteristic abnormality may you see in a patient presenting with acute pancreatitis from alcoholic hepatitis?
Macrocytosis (MCV > 100fL) -> possibly from vitamin deficiency (folate/B12) from chronic alcohol abuse
How does TNF-alpha facilitate decreased uptake of glucose (insulin resistance)?
Serine residue phosphorylation on Insulin Receptor Substrate 1 (IRS 1) which inhibits IRS1 tyrosine phosphorylation by insulin
Phosphorylation of serine residues on beta subunit of insulin receptor also hinders downstream signalling that would normally occur from insulin binding
What are the dopamine agonist compounds?
Ergots: Bromocriptine, and pergolide
Nonergots: Prampipexole and ropinirole
Where are VIPomas located and how would a patient present? Treatment?
Pancreatic islet cell tumor -> excess VIP secretion -> pancreatic cholera or WDHA syndrome (Watery Diarrhea, Hypokalemia, Achlorydia
Somatostatin (Octreotide) -> decreases production of ALL GI hormones
What is the mechanism of nitroprusside and what effects would it have on the pressure volume loop?
Short acting balanced venous/artery vasodilator -> increases direct release of NO -> increased cGMP -> V/A vasodilation -> decreases LV preload (less volume) and afterload (less pressure)
Treats severe hypertension
Which drugs can be used with levdopa to increase dopamine availability to the brain?
COMT inhibitors - Entacapone (inhibits peripheral methylation of levdopa only) and Tolcapone (inhibits peripheral AND central methylation, but causes hepatotoxicity)
MAOB inhibitor - Selegeline (decreases metabolism of Dop in brain)
DOPA Decarboxylase inhibitors - Carbidopa (decreases conversion of L-DOPA -> dopamine in periphery)
Amantadine - increases dopamine release and decreases dopamine reuptake in axons
How do you reverse the effects of severe atropine poisoning?
Physostigmine (interacts in periphery and centrally - unlike edrophonium and neostigmine which have quatrenary ammonimum structure, can’t pass BBB and act only in NMJct)
What is the purpose of primaquine treatment in a patient with P. vivax/ovale infection who has already been treated with chloraquine?
Chloraquine eradicates sensitive plasmodium from the blood stream but has no effect on the latent hepatic infection caused by hypnozoites
Primaquine is introduced to completely eradicate the infection from the body and PREVENT RELAPSE
What is the difference between sensitivity and PPV and how do you calculate each?
Sensitivity is the true positive rate among all who actually have disease
SN = TP / (TP + FN)
PPV is the true positives among all with a positive test
PPV = TP / (TP + FP) -> PPV is all P’s
What is the difference between specificity and NPV, and how do you calculate each?
Specificity is the true negative rate among all who don’t have disease
SP = TN / (TN + FP)
NPV is the true negatives among all with a negative test
NPV = TN / (TN + FN) -> NPV is all N’s
What is the order for cardiac tissue conduction velocity?
(Fastest) Purkinje -> Atrial Muscle -> Ventricular Muscle -> AV node (Slowest)
“Park At VENTura AVenue”
What systemic routes are preferred in Aspergillus infections (especially in immunocompromised)? How would this fungus appear?
First infects lungs forming granulomas,fevere, hemoptysis and pleuritic chest pain
Predilection for blood vessels and can spread hematogenously causing infection and infarcts along skin, PARANASAL SINUSES, Kidneys, endocardium and brain.
Thins spetate hyphae with acute V-shaped branching
What type of infections is nafcillin preferably used to treat?
Skin and soft tissue infections (e.g folliculitis, abscesses) for which S. Aureus is the usual cause
What is the most common cause of tubal infertility in females? What situation would put a patient at risk for infertility despite treatment?
PID -> usually from Gonorrhea and Chlamydia which often co-infect
If patient is inappropriately treated for only one microbe, (e.g. given only Ceftriaxone monotherapy vs. Cef+Azithromycin-or doxy-) co-infection may cause progression of PID -> infertility
What factors may be toxic to the ovaries? What is a common drug that IS NOT?
Toxic - smoking, chemo, radiation
non-toxic - OCP therapy
What is the MoA of buspirone, and what is it used for? Main side effects?
selective 5HT1A-R agonist, best for generalized anxiety disorders
SE: dizzy/lightheadedness
What deposition is associated with Henoch Schonlein Purpura (HSP)?
Small vessel leukocytoclastic angiitis with IgA and C3 deposition
What must be administered in patients who are susceptible to increased NMJ blockade by succinylcholine to reverse the paralysis, and at what time?
Neostigmine, during Phase 2 blockade where you see a fading train of 4 depolarizing response (in slow metabolizers or continuous dosing)
injection of Neo during phase 1 would cause increased paralysis vs. reversal
What are the 3 phases that stimulate acid secretion in the stomach, and how does acid secretion decrease?
- Cephalic phase - site, smell of food (cholinergic/vagal mechanisms)
- Gastric phase - Gastrin secretion onto ECL cells -> release histamine onto parietel cells -> acid release
- Intestinal phase - protein containing food enters duodenum (only a very minor role)
Intestinal influences downregulate gastric acid secretion by releasing PEPTIDE YY which binds receptors on ECL cells
What is the difference between dystonias and myoclonus?
Dystonias are prolonged, repetitive muscle contractions that can be painful
Myoclonus - sudden, brief and sometimes severe shock-like jerk (like a hiccup)
What is ustekinumab? Calcipotriene?
human monoclonal antibody used in psoriasis to target IL12 and IL23 -> inhibits differentiation and activation of CD4+ Th1 and Th17 cells
Calcipotriene = vitamin D analog that can activate nuclear transcription factors, inhibiting keratinocyte proliferation and stimulating keratin. differentiation (may also inhibit T-cell proliferation and inflammatory mdiators)
What damage is caused by long-term noise induced hearing loss?
Damage to hair cells on organ of corti
What can cause damage to the tympanic membrane?
Infection, trauma, pressure changes (when eustachian tube is blocked), or sudden very loud noises
What is the most common emergent complication faced by IV drug users?
Right heart endocarditis (S. Aureus) which can lead to sepsis, and septic embolization to lungs causing pulmonary infarct
What is the disease presentation for Fabry disease, and what can this progress to? How can you avoid fatal complications?
- Hypohydrosis- diminished sweathing
- Acroparasthesia - episodic and debilitating neuropathic pain in extremeties
- Angiokeratomas - punctuate non blanching macules and papules between umbilicus and knees
- Renal insufficiency -> Renal failure
Tx: Enzyme replacement therapy
What is the MoA and use of Mifepristone? How effective is this drug?
Progesterone antagonist (w/ 5x greater affinity for progesterone receptor) - progesterone is necessary for implantation and maintenance of pregnancy, therefor this drug would cause decidual necrosis and expulsion of the products of conception
80% effective -> but higher success when combined with prostaglandin analog misprostol
Why is ceftriaxone ineffective against chlamydia? What organism that can cause similar symptoms is also resistant to this drug?
C. trachomatis has no cell wall peptidolgycan - LACKS MURAMIC ACID
Ureaplasma urealyticum, which lacks a cell wall entireley
How do you calculate the half life of a drug?
T1/2 = (Vd x ln2) / CL
Vd = volume of distribution ln2 = log2 = rounded to 0.7 CL = clearance (in L/h)
What cell feature is last to disappear as you continue distally along the bronchi from pseudostratified epithelium to the alveoli?
Cilia - present at terminal bronchioles, distal to goblet cells, mucous and serous glands so that it can sweep any mucous or fluid away from alveoli and out
How is cyanide normally metabolized in tissues? How do you treat toxicity?
Rhodanese - an enzyme that transfers sulfur molecules to make thiocynate (a less toxic form that is excreted in urine)
Toxicity: Sodium thiosulfate (additional SULFUR groups), sodium nitrite (methemoglobin which binds cyanide) , hydroxycobalamin (forms cyanocobalamin, excreted in urine)
Which medications have negative chronotropic effects?
- Beta blockers (metoprolol, atenolol)
- Non-dihydropyridine Calcium channel blockers (verapamil, diltiazem)
- Cardiac glycosides (digoxin)
- Amiodarone and sotalol
- Cholinergic agonists (pilocarpine, rivastigmine)
What can occur if drugs that are negatively chronotropic are given together? Give an example of such a combination.
Atenolol + Verapamil
Additive negative effects on heart rate, AV node conduction, and myocardial contractility -> significant sinus bradycardia and hypotension may occur
What effect do fibrates have on cholesterol metabolism>
Inhibit enzyme cholesterol 7alpha-hydroxylase activity -> reduces conversion of cholesterol into bile acids -> increased insoluble cholesterol in bile -> precipitate stone formation
What is the most important mechanism for mediating lead toxicity, and what compounds would be elevated?
Lead has a strong affinity for sulfhydryl groups -> inhibition of enzymes that incorporate iron into heme molecule (Delta-aminolevulinic acid dehydratase, and ferrochetalase) -> if this enzyme is inhibited the substrate delta-aminolevulinic acid builds up
What is delta-aminolevelulinc acid and how is it produced?
One of the first substrate’s for heme synthesis
Succinyl-CoA and glycine combine in presence of cofactor pyridoxal phosphate
What is pyridoxal phosphate (PLP) used for?
V. B6, pyridoxine is converted into PLP which is a cofactor for transamination reactions (ALT, AST), decarboxylation, glycogen phosphorylase, and synthesis of cystathionine, heme, niacin, histamine and neurotransmitters
What happens if progesterone is withdrawn?
Apoptosis of endometrial cells
What are the main findings in Wiskott-Aldrich syndrome?
Eczema, recurrent infections and thrombocytopenia
Which compounds mediate neutrophil chemotaxis?
Leukotriene B4, IL8, C5a, bacterial products
What effect is caused by carcinoid syndrome?
Diarrhea and flushing from seratonin secretion
What does a ghon complex signify?
Primary infection with TB -> the organism is inspired by respiratory droplets and walled off in a fibrous capsule by macrophages, langerhans cells and fibroblasts (Th1 mediated)
95% of time there is elimination, but in some cases dormant bacilli remain!
What is the afferent nerve involved in carotid stretch reflex? Aortic stretch?
Carotid baroreceptor impuleses carried to brainstem by GLOSSOPHARYNGEAL NERVE (CN IX)
Aortic arch baroreceptor by VAGUS NERVE (CN X)
Both synapse onto solitary nucleus
What protects against the various types of UV radiation?
PABA sunscreens -> UVB only
Avobenzone - UVAI and UVAII
Zinc-oxides - UVB, UVAI, and UVAII
A newborn presents with absence of thymic shadow on XRay and narrowing of the aortic arch, what embryonic derivatives failed to develop?
Di George Syndrome -> 3 pharyngeal pouch
What do the 3rd and 4th branchial arches give rise to?
3rd - tissues innervated by CN IX -> stylopharyngeus muscle, part of hyoid bone, posterior 1/3 of tongue
4th - tissues innervated by superior laryngeal branch of CN X -> most other muscles of soft palate + posterior 1/3 of tongue
What is the effect of hyperventilation?
DECREASED pCO2!!!! (hypocapnia) -> decreased cerebral perfusion (hence why patients with ICP are hyperventilated)
(note: increase in pCO2 would cause linear increase in cerebral perfusion)
How would a patient with Berger disease present?
IgA nephropathy -> hematuria 2-3 days post URI
EM shows prominent IgA deposits in mesangium (dispersed electron dense materials, a slightly darker gray than the rest of the light colored mesangium)
What distinct abnormality can myasthenia gravis sometimes present with?
Thymic abnormalities (Thymoma, thymic hyperplasia)
How can cystic fibrosis lead to infertility?
absent vas deferens bilaterally -> azoospermia
How much sodium and urea are excreted per amount that is filtered?
N= amount Na+ filtered/min -> excretion = 0.01 x N
U= amount urea filtered/min -> excretion = 0.55 x U
Which disorders involve a JAK 2 mutation? How can you treat?
Chronic myeloproliferative disorders (except CML)
-Essential thrombocytosis, Polycythemia vera, and primary myelofibrosis
Tx = JAK2 inhibitor (ruxolitinib)
What are the possible sequelae of ankylosing spondylitis (asside from bamboo spine and low back pain)?
MRCE MRCE (mercy), my back hurts!
- Musculoskeletal - Peripheral enthesitis, or inflammation at tendon insertion site to bone
- Respiratory - Enthesopathies at costovertebral/sternal junctions -> limit chest expansion -> hypoventilation (should be monitored frequently)
- CV - ascending aortitis -> dilation of aortic ring and aortic insufficiency
- Eye - Anterior uveitis
What pharmacological treatment should be used in severe cases of seratonin syndrome?
- Cyproheptadine - first generation histamine antagonist that has nonspecific antagonism of 5HT1 and 5HT2 receptors
- Short acting antihypertensives (esmolol or nitroprusside) can be used for hypertension, but DO NOT use antihypertensives with long half lives (propranolol) which may cause hypotension and shock
What is p-ANCA?
Ab against neutrophil myeloperoxidase
How do platelets provide proliferative stimuli to the cells within an atherosclerotic plaque?
Release PDGF -> promote smooth muscle cell migration from media to intima and SMC proliferation
TGF-beta is also released -> chemotactic for SMCs and induces interstitial collagen production
What is the volume of distribution of a drug?
Vd = amount of drug in the body/plasma drug concentration
How do you calculate loading and maintenance doses?
Loading dose = Cp x Vd / F
Maintenance dose = Cp x CL x t / F
Cp = target plasma concentration at steady state Vd = Volume distribution F = bioavailability (100% or 1.0 for IV dosage) t = time between doses, if not given continuously CL = Clearance = Rate of elimination of drug/plasma drug concentration = Vd x Ke (elimination constant
What are the two phases of drug metabolism?
Phase 1 - reduction, oxidation, hydrolysis w/ cytP450 -> yeils slightly polar metabolites (still active) - lost first in geriatrics
Phase 2 - Conjugation (GAS - glucoronidation, acetylation, sulfation) -> yield very polar, inactive metabolites -> renally excreted
note: slow acetylators have increased side effects from some drugs because decreased phase 2 metabolism
How do you calculate the therapeutic index of a drug?
TITE -> Therapeutic Index = TD50/ED50 -> safer drugs have higher TI values
TD50 = median toxic dose ED50 = median effective dose
How may a patient with HIT present and how can you treat this?
Heparin induced thrombocytopenia –> severe foot pain, toe paleness (could also be hand) and low platelet count
Use direct thrombin inhibitors (hirudin, lepirudin, argatroban) and stop all forms of heparin -> this will keep patient anticoagulated
What are the key characteristics of hereditary spherocytosis?
- AD inheritance
- Hemolytic anemia -> jaundice + splenomegaly
- INCREASED mean corpuscular HEMOGLOBIN (MCHC)
- increased osmotic fragility (acidified glycerol lysis test)
- Abnormal eosin-5-maleimide binding test
What are Howell Jolly bodies and Pappenheimer bodies associated with?
HJB -> DNA inclusions -> Splenectomy
PHB -> Fe inclusions -> Sideroblastic anemia
Occasionally present in hemolytic anemias
What are brown pigmented gallstones associated with and how may they arise?
Secondary to infection of biliary tract (cholecystitis) -> Injured hepatocytes and bacteria -> release of BETA-GLUCURONIDASE -> hydrolysis of bilirubin glucoronides -> increased insoluble unconjugated BR
Which enzymes would contribute to cholesterol stone formation?
increased HBG-CoA reductase activity, deficiency of 7-alpha hydroxylase (converts cholesterol into bile acids), Aromatase (converts androgens -> estrogen, increase cholesterol)
What are the structures of the retroperitoneum?
- Vessels - abdominal aorta, IVC, and their branchs
- Solid organs - Head/body of pancreas, kidneys, adrenal glands
- Hollow organs - Duodenum (2,3, part of 4), Ascending/descending colon, rectum, ureters, bladder
- Vertebral column and pelvic muscles
What is one possible major cause of the hyperuricemia seen in gout?
Increased purine metabolism -> Phosphoribosyl pyrophosphate (PRPP) synthetase is enzyme responsible for activation of ribose necessary for de novo purine/pyrimidine nucleotide synthesis
Mutation increasing activity of this enzyme would subsequently result in excess degradation of purines -> hyperuricemia
What is excretion of a substance defined as? Can this process be saturated, why or why not?
Excretion = (filtration + secretion) - reabsorption
Carrier mediated Secretion and reabsorption rates can get saturated, but filtration is not enzyme or protein mediated, so it cannot get saturated (i.e. at any given moment a constant proportion of a substance will get filtered) -> therefore excretion cannot be saturated either
How is PAH excreted?
Proportion if filtered through glomerulus at a constant rate, while some portion can be taken up by proximal tubular epithelial cells and secreted into tubular fluid by a carrier enzyme mediated process
What is Cheyne-stokes respiration and when do you see it?
Cyclic breathing in which apnea is followed by gradual increase then decrease of tidal volumes until next apneic episode
-Seen in Cardiac disease (advanced CHF) and neuro disease (Stroke, brain tumors, TBI) -> it is a poor prognostic indicator
Which drugs inhibit thyroid peroxidase?
Propylthiouracil (PTU) and methimazole
PTU also decreases peripheral conversion of T4 -> T3 (note methimazole does not have that function)
What affects iodine uptake by the thyroid?
TSH will increase uptake
Perchlorate and thiocyanate will compete for uptake
What is primarily responsible for the intense inflammatory response in patients with gout? How can you specifically inhibit this?
Neutrophils -> which phagocytose urate crystals -> release cytokines and chemotactic agents for more neutrophils to come
Note: Colchicine inhibits both PMN chemotaxis and decreases tyrosine phosphorlylation in response to MSU crystals -> decreased PMN activation
What is akathisia, and how may it arise?
Subjective restlessness and inability to sit still (antipsychotic medication side effect)
What drug acting on the heart may cause severe constipation?
Verapamil
Which factors increase activity of ALA synthase? How is this inhibited?
Alcohol, hypoxia and barbiturates increase ALA synthesis
Heme inhibits via reverse negative feedback inhibition
What other important effects does desmopressin (DDAVP) have aside from its anti-diuretic action?
DDAVP increases vWF release from endothelial cells
(transient increase over 30-60 minutes) and stabilizes clotting factor VIII (good for VonWillebrand’s disease and hemophilia)
What is the most common factor predisposing patients to bacterial endocarditis of a native valve?
Mitral Valve Prolapse (rheumatic mitral valve deformity less likely because of decrease incidence of disease)
What will result from a metyrapone stimulation test in a healthy HPA axis?
Metyrapone will block cortisol synthesis by inhibiting 11-beta-hydroxylase (which normally converts 11-hydroxycortisol -> cortisol in Zona F.) -> decrease in cortisol will stimulate CRH -> increased ACTH from pituitary -> ACTH will increase levels of 11-hydroxycortisol -> 11-OH-cort gets metabolized by liver into 17-hydroxycorticosteroids which is excreted into the urine
What are pol genes and how may mutations occur in HIV infected individuals?
Pol genes code for the Proteins of HIV -> reverse transcriptase, protease, integrase
Mutations can occur with prolonged HAART developing strains that are resistant to protease inhibitors and have reverse transcriptase resistant to standard NRTIs or NNRTIs
What HIV mutations may lead to viral evasion of humoral immunity?
Env genes which code for viral envelope glycoproteins
What are the characteristics of melanomas and what is the origin of these tumors?
ABCDEs - Asymmetry, Border irregularities, Color variation, Diameter increased, Evolving shape, color etc.
Melanocytes originate from neural crest cells
What are the derivations of surface ectoderm, neural crest cells and neuroectoderm?
Surface ect- epidermis and appendages, mamillary glands, lens of eye, adenohypophysis
Neural crest - Melanocytes and PNS
Neuroect - CNS, preganglionic autonomic neurons, retina, posterior pituitary
What drug given with an opioid or to patients dependent on opioids would cause withdrawal symptoms?
Pentazocine - opioid narcotic with partial analgesic activity and weak antagonist activity at mu receptor. Can competitively inhibit mu receptors, producing antagonist effect and reducing opioid analgesia
When is pulmonary vascular resistance the lowest?
Near the functional residual capacity (FRC) - PVR forms a U-shaped curve with highest resistance at maximal expiration and inspiration
What is statistical power?
1 - beta
beta is the probability of committing type II error, which is not recognizing when a true relationship exists
What are the characteristics seen in Whipple disease?
Tropheryma Whippelii -> systemic disease of small intestine, joints and CNS
Intestinal Biopsy-> Multiple foamy macrophages loaded with PAS+ granules, in the lamina propria
-Middle aged white men get diarrhea and malabsorption
Which drugs can improve the muscarinic side effects of acetylcholinesterase inhibitor drugs (neostigmine) without affecting Ach conduction in the NMJ?
Scopolamine and Hyoscyamine
What is the MoA of Cilostazol?
Inhibits phosphodiesterases that breakdown cAMP -> increased cAMP decrease platelet conformational changes that cause aggregation and cause direct vasodilation
What specific defect leads to cystic fibrosis?
70% of the time the mutation is a 3 base pair deletion that removes Phe at position 508 -> this impairs posttranslational modification -> impaired folding and glycosylation -> targets protein for proteosomal degradation preventing transmembrane insertion
Which how would increased preload change the pressure volume curve? Ejection fraction? Afterload?
Preload - would extend the curve along the X-axis to the right
EF - Would extend the curve along x-axis to the left
Afterload - Would shift increase pressure (up on Yaxis) and decrease SV (decrease X-axis length)
What is the morphology of cryptococcus?
Yeast form only, w/ round/oval encapsulated cells with narrow-based buds
Which fungus forms spherules?
Spherules = round structures containing endospores -> Coccidioides
What are some manifestations of riboflavin deficiency?
Main ones -> Cheilosis (inflammation of lips, scaling and fissures at corners), Corneal vascularization.
-Also glossitis, seborrheic dermatitis, and anemia
(alcoholics and severely malnourished)
What is the most common disorder of porphyrin synthesis?
Porphyria Cutanea Tarda - deficiency of Uroporphyrinogen Decarboxylase -> induces photosensitivity and presents with elevated serum plasma protoporphyrins
What leads to morphine tolerance?
Glutamate activates NMDA-Rs -> increased phosphorylation of opioid receptors by protein kinase and increased NO and cAMP which lead to chronic morphine tolerance
What is a good way to evaluate toxic megacolon, and what can lead to this?
Flat plain X-ray
Can be a major complication of Ulcerative colitis
