Miscellaneous - UWorld Flashcards
Elastic resistance in the lungs increases WOB with regards to tidal volume so you increase RR to optimize whereas airflow resistance (COPD, emphysema, alpha-1 anti-trypsin, anxiety) is characterized by needed to take few, deep breaths - meaning reduce RR.
Repeat
Attributable risk percent
ARP(exposed) = 100 x [(Risk exposed - risk unexposed)/(risk exposed)]
How is filtration fraction calculated?
FF = GFR/RPF. Normally 0.15-0.2 because GFR is 125 and RPF is 600-700.
What is the mechanism of Fragile X?
The additional CGG repeats (that present as Fragile X when they are over 200) cause methylation of the FMR (fragile X mental retardation gene) on the X chromosome that renders the gene inactive. This gene is usually required for proper neural development.
Presentation: Mental retardation, dysmorphic face, large testes.
If the superior thyroid artery is ligated, what nerve and associated muscle and sensory supply is likely to be ligated with it?
The superior thyroid artery runs with the superior laryngeal nerve (vagus origin) which ONLY supplies cricothyroid muscle (external branch of the superior laryngeal nerve) and supplies ALL sensory innervation above the vocal chords (internal branch of the superior laryngeal nerve).
What are the cells that following an ischemic injury to the brain could be expected to be filled with lipid contents?
Microglia - these cells appear from 3-5 days after ischemic injury in the brain (CNS) onward and phagocytize myelin, dead neurons (red neurons - occur 48 hrs in, sign of irreversible damage), and debris. The first cells to appear in the setting of ischemic injury in the brain are neutrophils (recall these are NOT phagocytes).
Note, astrocyes form glial scar around cystic space about 2 weeks after injury.
What E. Coli virulence factor is responsible for its infectivity in UTIs?
fimbria - pili.
E.Coli’s capsule - neonatal meningitis - prevents phagocytosis
Lipopolysaccharide - bacteremia and septic shock - causes macrophage activation.
What is the significance of increased acetylcholinesterase in amniotic fluid?
Suggests neural tube defects (failure of fusion of the neuropores). Synonymous with increased AFP.
Rapidly developing cutaneous flushing, tachypnea, headache, and tachycardia are concerning for…
What is treatment?
Cyanite poisoning which can cause quick death by binding to the cytochrome a-a3 complex (critical for electron transport in oxidative phosphorylation).
Treatment: Nitrites or sodium thiosulfate. These nitrites are used to induce methemoglobinemia and convert iron to Fe3+ which more strongly binds cyanide and thereby spares the mitochondrial enzymes from cyanide’s toxic effects.
Hepatitis D relies on Hepatitis B for…. To be effective
Viral coat (HBSAg).
Neisseria meningitidis and Neisseria gonorrhea have an effective mechanism against an immunoglobulin to assist with mucosal penetration.
IgA protease that cleaves IgA hinge region. Normally IgA binds to pili and fimbria of organisms to prevent mucosal penetration.
Leptin inhibits production of ________ and increases production of ____
Inhibits neuropeptide Y. Increases alpha-MSH. Leptin is produced by adipocytes and acts on the Arcuate nucleus of the hypothalamus.
What does the ventral pancreatic bud give rise to?
It gives rise to the uncinate process, inferior/posterior portions of the pancreatic head, and the MAIN pancreatic duct.
In pancreas divisum where there is failure of fusion of the two buds, the accessory duct drains dorsal bud derived structures which are the majority of pancreas. The fusion should occur around week 8. (Foregut)
What cancer is associated with Auer rods?
What is the chromosomal abnormality associated with it?
Acute myeloblastic leukemia (M3 variant) specifically acute promyelocytic leukemia.
Chromosome t(15;17). The M2 variant which also has Auer rods is t(8;21).
A study that measures exposure and outcome AT ONE TIME is a…
Cross-sectional study.
Where are the cell bodies of cholinergic neurons in the brain?
In what common disease are these cell bodies affected?
Nucleus Basalis of Meynert
Alzheimer’s disease
Where in the brain does the progressive neurological disease associated with Wilson’s disease cause copper deposition?
Putamen
In what type of muscle is myosin light chain kinase found?
Smooth muscle.
Red neurons means at least 48 hrs after the injury. Do not forget that after the Nissl substance disappears the nuclei of these neurons becomes DEEPLY basophilic. These are NOT neutrophils. You are still 48 hrs out of the injury. Look for Mickey Mouse ears for neutrophils.
Repeat
How far out of an ischemic injury does liquefactive necrosis and reactive gliosis begin to occur?
1-2 weeks.
What enzyme is deficient in Tay-Sachs?
What metabolite accumulates?
Beta-hexoaminidase A is missing.
GM2 ganglioside is the metabolite that accumulates.
There is NO hepatosplenomegaly in Tay-Sachs.
If a patient has an advance directive, it is the physician who should make the decision and they should ALWAYS follow it.
Repeat.
What is metacholine’s effect on airways
It is a CHOLINERGIC agonist. It causes bronchoconstriction (>20% is asthma) and increased secretions.
What does folate deficiency do?
What agent if added can mitigate its effects?
Folate deficiency limits DNA synthesis and promotes megaloblastosis and increases erythroid apoptosis.
To mitigate its effects, you can supplement with thymidine. (dTMP).
Rheumatic heart disease tends to present as ________ murmur when patients are younger and ______ murmur when they are middle aged.
Mitral regurgitation when patients are younger.
Mitral stenosis when they are middle aged.
When they are older, you can see a mixed presentation.
What are the proteins associated with the following HIV genes?
gag -
Env -
Which proteins are REQUIRED for replication of HIV?
gag - nucleocapsid - p24, p7
Envelope - gp 120, gp 41
Required for viral replication? Tat, rev
What does crescent formation in the glomerulus usually indicate? Which do the crescents consist of?
Crescents usually indicate rapidly progressing glomerulonephritis (weeks to months).
The crescents include abundant fibrin, glomerular parietal cells, monocytes, macrophages. These crescents disrupt renal function.
Around when should the Vitelline duct disappear in embryonal development?
7th week
How can methylmalonic acid acidemia result?
It can result from failure of isomerization of methylmalonic acid CoA to succinyl CoA which then enters the citric acid cycle (TCA).
Joint pain and pruiritic rash shortly after starting a monoclonal antibody is concerning for_______
What is the pathophysiology?
Serum sickness
Pathophysiology: Type III hypersensitivity reaction (immune complex) with immune complex deposition which involves neutrophil and complement activitation. Expect to see low complement levels (C3, C4) and neutropenia (all the neutrophils are being attracted to site of injury). Small vessel vasculitis with fibrinoid necrosis is also common.
What is the role of Sertoli cells?
They secrete inhibin B, promote spermatogenesis and release Mullerian inhibiting hormone.
If alveolar oxygen and tracheal oxygen equilibrate AT REST, what kind of defect do you have? This defect is true especially if pCO2 in the alveolus is LOWER than expected.
Were oxygen to equilibrate during exercise or in a disease state AND pCO2 levels in the alveolus were normal, the defect would be?
Perfusion defect. Normally, alveolar oxygen should be 104mmHg while tracheal oxygen should be 140mmHg.
If pCO2 levels were normal and oxygen equilibrate you would have a diffusion exchange defect as is the case in emphysema, pulmonary fibrosis, or high exercise state.
If someone notices diplopia especially when walking down stairs or reading the newspaper they have what nerve injury?
Trochlear nerve - vertical diplopia.
Where are Peyer’s patches located? What kind of tissue are they?
Ileum. Lymphoid tissue.
Primary amenorrhea is defined as absence of menses by age 15 if you have secondary sex characteristics or absence of amenorrhea by age 13 if NO secondary sex characteristics are present.
Repeat
What process do endometrial cells undergo in response to withdrawing progesterone?
Apoptosis
In a bicornuate uterus, which ducts fail to fuse?
Paramesonephric ducts.
What is the function of smooth ER?
Smooth ER contains enzymes for steroid and phospholipid biosynthesis. Thus, well-developed smooth ER present in the adrenals, gonads, and liver.
What is the significance of S4?
It is the sound of blood hitting a stiff left ventricle.
What are the ST DEV benchmarks
1 SD is 68%
2 SD is 95%
3 SD is 99.7%
Between diet control and smoking cessation which is best to reduce mortality?
Smoking cessation.
When is pulmonary vascular resistance lowest?
PVR is lowest at functional residual capacity which is the volume left after regular exhalation.
What are the stop codons? What do they encode?
UAA, UAG, and UGA. They code for releasing factors.
What is the start codon?
AUG - encodes methionine.
What reaction does glucose 6 phosphate dehydrogenase catalyze?
What is its inheritance pattern?
Glucose 6 phosphate dehydrogenase catalyzes the conversion of glucose-6-phosphate to 6-phosphogluconate. One NADPH (reducing equivalent) is formed in this irreversible reaction.
It is inherited in an X-linked pattern.
If a mom experiences virilization during pregnancy and her baby is born with ambiguous genitalia and increased levels of testosterone and androstenedione, what deficiency is occurring? Where is this enzyme active during pregnancy?
Aromatics deficiency. It is active in the placenta.
If a baby is born with ambiguous genitalia (if female) and has hypotension and salt-wasting, what hormone is decreased?
Aldosterone. This is 21 hydroxylase deficiency. Also low levels of cortisol. Due to the deficiency, more things are routed to androgens.
If you are born with ambiguous genitalia (if male) and increased mineralocorticoid activity (hypertension and salt retention), you have
17 alpha hydroxylase activity.
How do you calculate number needed to treat if there is a control group and a treatment group
NTT = 1/(Control Rate - Treatment Rate).
What immune complexes are deposited on the epithelial side of the GBM in post-strep GN?
Where in the nephron structure are these deposits found?
What are other common laboratory findings?
IgG, IgM, C3
Location: mesangium and basement membrane. “starry sky” appearance.
Common findings: elevated anti-streptolysin O, elevated DNA-ase B, decreased C3, presence of cryoglobulins
What common signals use the JAK/STAT pathway?
Growth hormone, prolactin, cytokines, colony-stimulating factors. For these signals, the receptor is ASSOCIATED with a tyrosine kinase pathway. The receptor itself is not a tyrosine kinase.
This pathway is NOT used by INSULIN.
What structures does the metanephric mesoderm give rise to?
Glomeruli, Bowman’s space, PCT, loop of Henle, DCT.
NOT the collecting duct.
What happens to C-peptide after it is cleaved off pro-insulin in the Golgi apparatus (making insulin and C-peptide)
c-peptide is packaged into islet cell secretory granules along with insulin. They are then released in equal concentration into the extracellular space.
If a patient with history of recurrent infection (GI or sinopulmonary) has an Anaphylactoid reaction to a blood transfusion, he/she has….
IgA deficiency. These patients often have IgG antibodies directed against IgA which is transfused along with blood.
What vitamin is an essential co-factor in transamination reactions where an amino acid is being generated?
Pyridoxine (B6)
What enzymes require thiamine (Vitamin B1) as a co-factor?
Pyruvate dehydrogenase, alpha-keto glutarate dehydrogenase and transketolase.
Patients with cystinuria who may present with cystine hexagonal stones which are pathognomonic will also have problems transporting..
Lysine, arginine, ornithine.
What disease (of young people) that occurs 2-3 days after a flu-like illness is associated with mesangial deposits?
IgA nephropathy. Patients have recurrent bouts of painless hematuria. In half of patients can progress to chronic renal failure.
What is the embryologic origin of the following congenital heart defects: Tetralogy of Fallot, truncus arteriosus, and transposition of great arteries?
Failure of septations between the aorta and pulmonary artery due to abnormal migration of NEURAL crest cells through the primitive truncus arteriosus and bulbus cordis.
What is the term for trinucleotide repeats expanding with paternal transmission so that subsequent generations have earlier onset as is the case with Huntington’s Dusease?
Anticipation.
What portion of an mRNA is NOT transcribed from a DNA template?
The portion following the AAUAAA on the 3 prime end of an mRNA tarnscript was not TRANSCRIBED from a DNA template as it represents the poly A tail. The poly A tail is a POST-TRANSCRIPTIONAL modification that protects the mRNA transcript from degradation.
What is the impact of disrupting t-tubules?
Disrupting the coordinated contraction of myofibrils. I.e. Getting uncoordinated myofibrils contractions because the t-tubules are invaginations of the sarcolemma (plasma membrane) that extend into each muscle fiber.
Extra medullary hematopoiesis, anemia, jaundice, generalized edema, uncleared erythrocytes in a newborn are concerning for…
Hemolytic disease of the newborn (erythroblastosis fetalis) which occurs due to maternal sensitization to a prior pregnancy with an RhD+ve baby. Maternal IgG antibodies cross the placenta.
Besides the deltoid, what other muscle does the axillary nerve innervate? What is the most common way the axillary nerve is injured?
Anterior shoulder dislocation due to forced external rotation and abduction.
Other muscle: Teres minor.
What substance secreted by inflammatory macrophages in artherosclerotic plaque compromises the integrity of the plaque?
Metalloproteinases which degrade collagen.
Membranoproliferative glomerulonephritis associated with ____ virus and ____ complement.
Hepatitis C virus
C1q complement.
At what stages of meiosis are primary oocytes arrested? What promotes their development? Secondary oocytes are ovulated at what arrested stage?
Primary oocytes at birth are in prophase of meiosis I. Ovarian cycle hormones help them complete their development. Secondary oocytes are then ovulated in metaphase of meiosis II.
Women who have just delivered babies with neural tube defects are asked about acetaminophen use in pregnancy. Women who delivered healthy babies are also asked about acetaminophen use in pregnancy. What measure of association are you likely to report?
Odds ratio (the example is of a case control study. You are looking for the odds of exposure in ALREADY diseased people as opposed to following them over time).
With what autosomal dominant disease are bilateral renal angiomyolipomas (fat, muscle, blood vessels) seen?
Tuberous sclerosis.
What is the policy on parental notification or consent for elective termination?
Two-thirds of states require parental consent.
What phases stimulate gastric acid secretion? What phase(s) inhibit it?
The cephalic phase (acetylcholine and vagal) and gastric phase (promoted by gastrin secretion which stimulates histamine which then stimulates acid) promote gastric acid secretion. The gastric phase is stimulated by the physical and chemical presence of food. Pls, note that when protein rich food enters the duodenum, the intestinal PHASE plays a minimal role in also stimulating gastric acid secretion.
The intestinal INFLUENCES inhibits it. These include peptide YY released by the ileum and colon that inhibits the ECL cells release of histamine. Also, somatostatin and prostaglandins similarly are intestinal influences that inhibit gastric acid secretion.
In what location in the GI tract is an ulcer LEAST likely to be malignant?
Duodenum. These ulcers are usually due to H.Pylori or NSAIDs.
Most common PEPTIC ulcer locations: Proximal duodenum, antral stomach, and gastro-esophageal junction
What type of CD4 Tcells help macrophages in the clearance of TB?
Th1
What drugs are most likely to cause drug-induced lupus?
SHIPP-E. Sulfa drugs, hydralazine, INH, Procainamide, Phenytoin, Etanercept.
Which ducts are affected in primary biliary cirrhosis and what immunologic marker is usually associated?
Intrahepatic. Anti-mitochondrial antibodies.
When a study’s unit of analysis is populations and NOT individuals, what kind of study is it?
Ecological study.
What structure do the common cardinal veins drain into? What do they develop into?
Develop into SVC - superior vena cava and other veins. Drained embryologically into the sinus venosus.
What does the delta-F508 mutation result in terms of the CFTR?
It result in a problem with post-translational processing of CFTR that directs the protein to the proteasome so that it is completely absent from the apical surface of the cell.
How does the required immune cell for processing Candida change depending on the nature of the infection (I.e. Local vs systemic)? Systemic infection is considered synonymous with hematogenous spread.
For local infections (as is the case in HIV), T-cells are required but for systemic infection, neutrophils are required. Thus neutropenic patients tend to get systemic infection while HIV patients tend to get local infection.
What pediatric cardiac abnormality increases in sound with a handrip (an exercise that increases afterload)
VSD
What cells in the stomach secrete intrinsic factor and where are they located?
Parietal cells secrete HCl and intrinsic factor and they are located in the glandular layer. This is the cell layer affected in pernicious anemia leading to chronic Atrophic gastritis.
What do the chief cells in the stomach secrete?
Pepsinogen and are in the deeper glandular layer.
How does Ca2+ dramatically increase energy consumption in contracting muscles?
Ca2+ mediates the increased activity of myophosphorylase by allosterically activating phosphoryl kinase which then activates (phosphorylates) muscle phosphorylase.
When is chi-squared appropriate to analyze a test?
It is appropriate to analyze a test when your variables are recorded in a non-numerical way like the number of people with the variable as high or low. For z or t tests, you need variables that are recorded in a detailed numerical manner so you can calculate means (averages) for each variable.
What kind of effect does cortisol have on the normal effect of catecholamines?
Permissive - this means that on its own, cortisol has NO effect but when administered along with catecholamines, it increases their natural effect.
Other effect concepts:
Additive - if the combined effect of the two drugs is equal to the sum of each of their actions when used independently.
Synergistic - if the combined effect of the two drugs supersedes or is more than each of their individual effects added together.
What does tachyphylaxis refer to?
It refers to decreased effect to a drug with repeated exposure to it.
An infant with bilateral cleft lip, microcephaly, and microphthlamos, with an omphalocele is most concerning for…
Trisomy 13! Patau syndrome. MUST know. Non disjunction usually occurs in meiosis I.
Edwards syndrome, Trisomy 18, is associated with clenched hands, prominent occiput, low set malformed ears, small chin, small mouth.
Repeat.
What disease does primary biliary cirrhosis have findings similar to?
PBC has findings similar to graft vs hist including: granulomatous bile duct destruction and heavy lymphocyte-predominant portal tract infiltrate.
Fever, oral ulcers, and cervical lymphadenopathy in a patient aged 5 years is most concerning for…
Primary infection with HSV.
How does carbon dioxide exert its effect on Hemoglobin?
It competitively inhibits it — meaning it competitively binds to heme (in terms of oxygen binding).
A dispropionate loss of a certain group to follow-up in a study is a form of what type of bias?
Selection bias – specifically attrition bias.
What is lead time bias?
Lead time bias occurs when a screening test diagnoses a disease earlier than it would have otherwise been detected so that the time from diagnosis to death appears to be increasing even when there is no true change in survival.
When two viruses that independently would not have infected a cell create cytopathic effects when introduced together, what phenomenon has occured?
What type of viruses do these usually have to be?
Genome recombination has occured.
Occurs through crossing over of two Double stranded DNA molecules.
When two or more segmented viruses infect the same cell and mix their genetic informatics what is this called?
Reassortment
Where in the nephron is the most dilute concentration (~100mOsm) found?
Thick ascending loop of Henle and distal convoluted tubule, but especially DCT. DCT is impermeable to water.
Where does angiotensin II normally affect the kidney
EFFERENT arteriole - vasoconstricts the EFFERENT arteriole to increase GFR.
What are the most common metastases to the brain?
Lung cancer, renal cancer, melanoma.
How does nitroprusside work in the setting of heart failure?
Nitroprusside is an equal venous and arterial vasodilator. It REDUCES BOTH afterload and preload allowing similar cardiac output to be obtained at a lower left ventricular end diastolic PRESSURE. As a result the pressure-volume loop on nitroprusside is reduced in both directions. Shifted down and left but the cardiac contractility curve stays the same. You are just further down on the same curve. This means STROKE VOLUME is MAINTAINED.
When you match controls to your study population, you are correcting for what type of bias?
Confounding.
What causes cleft lip?
Failure of the maxillary prominences to properly fuse with the intermaxillary segment. The intermaxillary segment becomes the philtrum.
What causes cleft palate?
When the palatine shelves of the maxillary prominence fail to fuse with one another or with the primary plate.
When there is improper fusion of the maxillary prominence with the medial nasal prominence, what is the result?
Cleft lip
What immunologic deficiency predisposes to recurrent infections with Neisseria?
Failure of MAC complex C5b-C9.
What kind of protein is Ras which is involved in the RAS-MAP kinase pathway where a growth factor ligand binds to a tyrosine kinase that auto phosphorylates, interacts with SOS protein which then activates Ras.
RAS is a G-protein. When it is bound to GDP it is inactive. At the end of the cascade, MAP kinase alters gene transcription when it enters the nucleus.
Be careful when calculating the likelihood of a child acquiring autosomal recessive disease based on frequencies of allele in parent populations. Remember to multiply the frequency of each parent being a carrier by 1/2 for autosomal recessive disease because each parent has a 1 in 2 chance of passing the carrier allele to the child.
Repeat
What is the order of neutrophil movement?
Margination - vascular leakage in the microvasculature leads to hemoconcentration and decreased wall shear stress.
Rolling - neutrophils bind weakly to selectins
Activation - slow rolling allows neutrophils to sample chemokines being released which causes them to upregulate certain molecules (integrins).
Tight adhesion - neutrophils become firmly attached by CD 18 beta 2 integrins (Mac-1, LFA-1) binding ICAM on endothelial cells.
Transmigration - neutrophils then leave the vasculature by binding PECAM-1 molecules with their integrins. These PECAM molecules are at the peripheral intercellular junctions of endothelial cells.
Where is stratified squamous epithelium found?
Stratified squamous epithelium is ONLY found on the true vocal chords (vocal folds), Oropharynx, laryngopharynx, anterior epiglottis, upper half of posterior epiglottis.
All the other tissue in the respiratory tract is pseudostratified, columnar, mucus-secreting epithelium.
What co-factors does alpha keto acid dehydrogenase need?
What two other similar enzymes require the same co-factors?
Tender Loving Care For Nancy - Thiamine, Lipoate, Coenzyme A, FAD, NAD.
Pyruvate dehydrogenase, alpha keto-glutamate dehydrogenase.
What is often seen with imperforate anus?
Urinary tract abnormalities.
What kind of junctions connect osteocytes in different lacuna?
Gap junctions
What directly dictates OSTEOCYTE activity? What indirectly?
Directly- plasma calcium concentration. Indirectly - PTH, calcitonin
In the setting of mechanical stresses, osteocytes can send signals and regulate the activity of surface osteoblasts I.e. Help regulate bone remodeling.
What are the less common genetic abnormalities that can lead to Down syndrome?
Unbalanced Robertsonian translocation - an extra arm of chromosome 21 is attached to another chromosome.
Mosaicism - patients have 2 lines - one with normal number of chromosomes and one with Trisomy 21.
What is the embryologic origin of the anterior pituitary? Inner ear?
Pineal gland?
Middle ear?
Anterior pituitary - Rathke’s pouch - Surface ectoderm. Inner ear sensory organs has similar origin.
Pineal gland - neural tube (ectoderm)
Middle ear - endoderm
Look to Feb 25 test 1 Q2 for more info.
What structure does the notochord become in the adult?
Nucleus pulposus.
What does Nissl substance in neurons correspond to?
Rough endoplasmic reticulum.
What type of polymer are microvilli on intestinal cells made of?
ACTIN!!!!
A patient with dysarthria and contralateral ataxic hemiparesis is concerning for infarction of the … Especially if facial weakness occurs in addition to hemiparesis.
Anterior portion of the medial pons - this is around the origin of the Trigeminal nerve. The middle cerebellar peduncles are also a great landmark for this region.
What drug works by competitive inhibition of iodide transport in the thyroid?
Potassium perchlorate. Pertechnetate ions also work through a similar pathway through the sodium-iodide SYMPORTER. This is used in hyperthyroidism
How do methimazole and PTU work?
Methimazole and PTU exert their action by blocking THYROID PEROXIDASE which converts Iodide TO IODINE. This class of drugs is called anti-thyroid thionamides.
What is important to remember about the lab values in polycythemia Vera?
In PV, ALL the cell lines are elevated.
What is the main defense against Giardia? How/where does Giardia exert its effect?
Diagnostic work-up:
IgA is the main defense against Giardia as Giardia causes injury to the mucosa in the duodenum and jejunum by ADHERING to the brush border and releasing molecules that induce mucosal inflammatory response. IgA interferes with adherence. Thus, if someone is IgA deficient for any reason, they are more likely to get Giardia.
Work up for diagnosis: Stool ova and parasites.
What is the central issue in CVID?
Decrease in plasma cells causes decrease in immunoglobulins. It is a defect in B-cell differentiation.
What is the pathogenesis of the less common, brown pigment stone
They arise typically secondary to infection of the biliary tract that results in the release of Beta-glucoronidase from injured hepatocytes and bacteria. The presence of beta-glucoronidase contributes to hydrolysis of bile glucoronides that results in INCREASE in amount of UNCONJUNGATED BILIRUBIN in BILE.
What values of the pulmonary function test does COPD increase? Decrease?
COPD decreases elastic recoil and FEV1 and/or FVC.
It INCREASES residual volume, functional residual capacity and total lung capacity.
Where is Anserine bursal located?
It is located along the medial aspect of the knee and is usually overused by athletes or chronic trauma in people with large body habitus.
What does prolonged kneeling put someone at risk for that develops as pain, erythema, swelling, and inability to kneel on the affected side.
Pre-patellar bursa.
If a patient presents with hypoglycemia and high NADH in liver what does this suggest?
An alternate fuel other than glucose is being used. E.g. Alcohol which increases the NADH/NAD ratio and inhibits gluconeogenesis.
This (high NADH) promotes the conversion of Pyruvate to lactate and the conversion of oxalateacetate to malate. Pyruvate and oxaloacetate are both required for gluconeogenesis.
What is the most helpful sign in distinguishing common peroneal nerve injury from superficial peroneal nerve injury?
In common peroneal nerve injury, loss of dorsiflexion, I.e. Foot drop is present because the deep peroneal nerve innervates the dorsiflexors of the foot.
In what pharyngeal pouch does the thymus develop? What is the only other anatomical structure that develops in the same pouch?
Pharyngeal pouch 3. INFERIOR parathyroid glands.
See 2/25 Test 3, Q2 for other pharyngeal pouch origins.
What gives rise to the thyroid gland embryologically?
The floor of the FOREGUT!!! The thyroid migrates downward from the mouth but remains connected by the thyroglossal duct.
What is the main substance in the cytoplasmic granules of eosinophils that is though to target helminths?
What is the interleukin signal for IgE production?
Major basic protein
IL-4
Why is duodenal enteropeptidase important?
It activates trypsinogen to trypsin.
Trypsin is essential for degrading complex peptides into dipeptides and amino acids. It is also important for activating other peptidases like carboxypeptidase, elastase, and chemotrypsin.
What is the most common cause of FETAL hydronephrosis?
Failure of recanalization at the ureteropelvic junction, the junction between the kidney and the ureter.
What is the appropriate control group in a case-control study.
Individuals without the disease, regardless of their exposure status.
Blood flow per minute must be equivalent AT ALL times between the pulmonary and systemic circuits
Repeat
What does absence of surfactant, neonatal resp distress, show up as on CXR?
Patchy alveolar atelectasis.
In the eat, what structure is close to place where you hear high frequency sound? Low frequency?
High frequency - basilar membrane. Low frequency - helicotrema is large and flexible for low frequency.
Bone pain, Salt and pepper skull, and sub-periosteal erosions affecting the phalanges of the hand, and brown tumor cysts are suggestive of
Primary hyperparathyroidism. Osteitis fibrosa cystica.
What does IL-12 do?
It stimulates naive T-cells to become T-helper 1 cells. Patients who are IL-12 receptor deficient on their T-cells are susceptible to MYCOBACTERIAL infections due to their inability to mount string granulomatous response. Treat with IFN-gamma.
Is LPS secreted by bacteria?
NOOOO. Gram-negative bacteria can release LPS during lysis or during division but they do not secrete it. Lipid A is the toxic so pinene of LPS. It causes activation of macrophages leading to widespread release of IL-1 and TNF-alpha which are associated with symptoms of shock.
Remember to be careful when trying to distinguish between bipolar disease with psychotics features and schizoaffective disorder.
In schizoaffective disorder, psychosis MUST occur in the absence of major mood episodes but mood symptoms have to be present for most of the illness. There must be at least 2 weeks of psychosis in the absence of mood symptoms.
Whereas in major depressive or bipolar disorder with psychotic features, psychosis has to always occur in the setting of mood symptoms.
In DNA base excision repair, which is used to correct defects in single bases, what enzyme initiates the process? What are the next steps?
Glucosylase removes the defective base first. Then, the corresponding sugar-phosphate bond is cleaved and removed by endonuclease.
Lyase follows.
Then DNA polymerase. Then ligase.
What type of collagen is found in scar tissue? What other types of collagen is it similar to? In what disease is there a defect in this type of collagen.
What is the inheritance pattern of this disease?
Scar tissue contains Type 1 collagen. It is also present in tendons, bone, dentin, ligaments.
Type 1 collagen is defective in osteogenesis imperfecta. Autosomal dominant.
A patient who does not agree with his doctor and then begins coming to subsequent appointments late or canceling them is exhibiting ehat defense mechanism?
Passive aggressiveness. It is carrying out hostile feelings in a non-conformational manner.
A pro-thrombotic state in a young (under 50) Caucasian female which has a normal PTT and is resistant to activated Protein C is suggestive of …
Factor V Leiden disease which accounts for Factor Va resistance to being inactivated by (activated) Protein C.
What is the pathophysiology of Toxic Shock?
Superantigens activate a large number of T-helper cells which go on to release IL-2.
These T-cells activate macrophages which release IL-1 and TNF-alpha.
What is path of Cloristidium tetani in order to cause an infection?
It goes from the wound to motor neurons (retrograde transport) to the spinal cord and prevents inhibitory neurons firing. tetanus presents primarily with rigidity of the face, neck, and trunk.
What nerve is injured in Trendenlenberg?
Superior gluteal nerve! It innervates gluteus minimus and medius. Also innervates TFL ( tensor fascia lata).
What is clinical presentation is associated with inferior gluteal nerve injury?
Difficulty arising from a seated position (or climbing chairs). The. Inferior gluteal nerve innervates gluteus Maximus which is responsible for extension and external rotation of the thigh at the hip.
A child holding an injured arm in a fully extended and pronated position likely has what kind of injury?
Radial head subluxation at the elbow or annular ligament tear/displacement. This injury (nursemaid’s elbow) usually occurs due to sudden traction of an outstretched and pronated arm.
D-xylose is what kind of carbohydrate – monomer or polymer?
It is a monosaccharide. It DOES NOT require pancreatic enzymes so it is used to distinguish malabsorption due to pancreatic disease from GI absorption disease.
What is responsible for cleaving the di-sulfide rich terminal extensions of the pro-collagen molecule?
Extracellular transpeptidases. The cleaving by these peptidases allows the formation of troopcollagen which is less soluble and can then assemble into collagen fibrils.
The final crosslinking of these collagen fibrils is accomplished by Lysyl oxidase.
What is the treatment for Enterobius (pinworm) in the peri-anal area?
Albendazole
What is dietylcarbamazine used for?
Loa Loa and wucheria (lymphatic filariasis)
What is ivermectin used for?
Stronglyoides and Onchocerca
What is nifurtimox used for?
Chagas - trypanosome.
Amyloid deposition confined or a single organ is usually due to a protein specific to that organ. What are some common ones?
Cardiac atria: atrial natriuretic peptide Pancreas: amylin (islet amyloid protein) Thyroid gland: calcitonin Cerebrum/cerebellum: beta-amyloid Pituitary: prolactin
Note that immune globulin deposition causes primary SYSTEMIC amyloidosis not a local amyloid deposition.
What equation does 21 hydroxylase catalyze?
It catalyzes the conversion of progesterone to 11 deoxycorticosterone.
How do nitrates exert their effect?
They are converted to NO (endothelial derived relaxing factor) and increase cGMP, decrease intracellular calcium and result in myosin dephosporylation.
A pale retina and a cherry red macula are concerning for…
Central retinal artery occlusion. Another clue is that this results in permanent prolonged loss of vision.
Amaurosis fugax is a painless, TRANSIENT loss in vision. Usually does not last more than a few seconds.
Repeat.
A patient with orotic acid in her urine has a defect in ______ synthesis
PYRIMIDINE. They will present with hypo chromic megaloblastic anemia, neurologic abnormalities, growth retardation, and orotic acid in urine.
Supplements with uridine which will block the activity of carbamoyl phosphate synthetase II.
Muscle fibers with a blotchy red appearance on GOMORI TRI-CHROME stain are suggestive of what kind of disease?
Mitochondrial myopathies.
I.e. They have no likelihood of being passed from a father and 100% for being passed on by a mother.
When a person is standing upright, perfusion is greatest at the base of the lungs as is ventilation but perfusion is increased far greater than ventilation meaning that as you go from Apex to base, V/Q reduces dramatically.
Repeat
What drug can chelate calcium and promote nephrotoxic renal magnesium wasting leading to hypocalcemia and hypomagnesemia?
Foscarnet
How does Flutamide exert its effect in prostate cancer?
Flutamide is a non-steroid anti-androgen that competes with testosterone and DHT for testosterone receptors. If used as monotherapy, as a result of negative feedback it can result in gradual increase of serum testosterone so simultaneous GnRH inhibition with GnRH agonist.
Flutamide by itself can shrink the size both of the primary tumor and its metastases.
Where does CO2 increase in aerobic exercise?
CO2 content increases in mixed venous blood because exercise causes oxidative metabolism of glucose and fatty acids. There ARE no changes in arterial pH and blood gas due to homeostatic regulation.
How do your treat slow-growing cervicofacial Actinomyces infection that usually occurs in setting of oral or dental trauma?
Long course of penicillin treatment and debridement.
MAC of anesthetic corresponds to?
The dose (concentration) of anesthetic in alveoli at which 50% of patients were non-responsive to painful stimuli. MAC is inversely proportional to potency. The lower the MAC, the more potent the anesthetic.
What do enolase, chronogranin, and synaptophysin share in common?
They are neuroendocrine markers. Chronogranin for example, can be seen in small cell carcinoma of the lung.
What is vimentin?
Vimentin is an intermediate filament used to diagnose sarcomas.
What is tetrahydrobiopterin?
It is a cofactor for phenylalanine hydroxylase (PAH)
Where in the urea cycle is N-acetylglutamate needed?
It serves as a cofactor for carbamoyl phosphate I in the addition of CO2 to NH3.
N-acetylglutamate is formed by N-acetylglutamate synthetase from acetyl-CoA and glutamate.
What do Rb, p53, APC/Beta-catenin, and BRCA genes have in common?
They are all tumor suppressor genes. They need to be inactivated in cancer.
What drugs will increase levels of warfarin in the blood by inhibiting its metabolism?
Cimetidine, Bactrim, Amiodarone.
What drugs can lead to sub-therapeutic warfarin levels by speeding up the Cytochrome P-450 system?
Phenytoin, phenobarbital, and RIFAMPICIN/Rifampin.
Metabolism of 1g of protein or carbs gives you ___ cal.
Metabolism of 1g of fat gives you ___ cal.
1g of protein or carb is 4cal.
1g of fat is 9 cal.
When after ischemia does the myocardium stop contracting? When is the point of irreversibility?
Myocardial contractility stops contracting within 60 seconds of ischemia. Lactate begins building up immediately.
The point of irreversible damage even if blood flow is restored is 30 minutes.
What is the meningitis vaccine made of? How about the conjugate vaccines?
Meningitis vaccine is made of the polysaccharide capsule. The conjugate vaccines are attached to diphtheria toxoid protein.
Note the capsule in Neisseria meningitidis is what normally impairs phagocytosis.
In the renal proximal tubules, what is secreted?
What is absorbed?
Secreted:
Freely filtered and secreted:
creatinine (20% of the amount in the post-glomerular capillaries is secreted by PCT).
PAH (at low concentrations, up to 90% is secreted by PCT).
Not absorbed: inulin - though inulin is not secreted, it’s relative concentration in PCT increases.
Freely filtered, Poorly absorbed: Urea.
Similar line for chloride. Far less so but similar line for potassium.
——- at about the same throughout the length of the PCT is SODIUM!
Decreasing concentration along PCT.
Bicarbonate - actively reabsorbed due to activity of carbonic anhydrase.
Glucose
Amino acids
What term refers to the amount of oxygen dissolved in the plasma?
What is oxygen saturation?
Percent saturation is amount of oxygen per gram of hemoglobin. Should be unchanged in anemia and polycythemia. Should be decreased in carbon dioxide poisoning.
What interleukin is thought to downregulate the immune system along with TGF-beta?
IL-10
What does hyperventilation do?
It decreases the arterial partial CO2 tension.
Regardless of the topic of discussion, general medical or otherwise, a parent who is taking over the visit with an adolescent patient should be asked to step out.
Repeat
Fatigability, weight gain, and focal mounding of muscle on percussion (myoedema) and elevated CK are suggestive of… Myalgia and proximal muscle weakness are also present.
HYPOthyroid induced myopathy. This form of myopathy can precede other signs of hypothyroidism by several years.
The myoedema is cause by slow uptake of the Ca2+ by the sarcoplasmic reticulum.
In gluco-corticoid induced myopathy with progressive proximal muscle weakness and atrophy without pain, the CK is…
Normal!
In statin induced myopathy, patients experience proximal muscle weakness and pain within months of starting a statin and the creatinine kinase is…
ELEVATED!
What is the mechanism of intestinal atresia depending on its location???
Beyond/Distal to duodenum e.g. Involving the ileum spiraling around a vessel - it is due to VASCULAR OCCLUSION in utero. If the “Apple core lesion” with the ileum wrapping around and ileocolic vessel is seen, it usually means there was occlusion of the Superior mesenteric artery.
Duodenal atresia - due to failure of recanalization
What might explain vomiting in a 3 month old that involves pancreatic tissue encircling his duodenum.
Annular pancreas - abnormal migration of the ventral bud.
A young child with hypertension and mild Hypokalemia early in life is concerning for…
11 beta hydroxylase deficiency. They have high levels of deoxycorticosterone (weak mineralocorticoid) and androgens.
If you need a short-acting benzodiazepine that is good for insomnia due to its short-term effects use…
Triazolam or
Alprazolam.
Streptococcus pneumoniae is optochin ________ (sensitive/resistant) and bile _______soluble/min soluble
Strep pneumonia is alpha hemolytic (green, incomplete hemolysis) optochin sensitive and bile soluble.
Trendenlenberg suggests injury to the CONTRALATERAL superior gluteal nerve which traverses on the…
SUPEROMEDIAL side of the buttock (again on the side CONTRALATERAL to the side that drops). If the right hip drops when the patient walks, it is a left superior gluteal nerve issue.
What two important metabolites does hyperammonemia deplete?
Alpha keto-glutarate AND GLUTAMATE. Don’t be fooled, hyperammonemia makes glutamine. It does not deplete it. Hyperammonemia causes increased conversion of glutamATE to glutaMINE in the astrocytes.
Note that glutaMATE is the excitatory neurotransmitter.
Angiokeratomas (non-blanching between the umbilicus and the knees), acroparasthesias (burning or numbing sensation on awakening or following nerve compression), and hypohidrosis (sweating too little) in the setting of excess ceramide trihexose del is concerning for…
What is the end result of this disease?
fabry’s disease.
Progressive Renal failure is the end result of Fabry’s disease. The missing enzyme is alpha-galactosidase A.
Anosmia and Hypogonadism in a male suggest…
Kallmann syndrome, which results in absence of GnRH secretory neurons in the hypothalamus. They fail to migrate from olfactory placode.
Where are the nerves and blood vessels that supply the ovary?
Suspensory ligament.
Note, the ovarian ligament has NO blood supply.
Berkson bias is picking hospital patients.
Hawthorne effect is study participant changing their behavior once they know they are being studied.
Pygmalion effect is if a researcher’s beliefs in the efficacy of treatment affect the outcome.
Repeat
What is the cardiac auscultation finding associated with atrial septal defects that can contribute to paradoxical embolism?
Fixed split S2. Does not change with respiration. Paradoxical embolism occurs when you have a cerebral event in the setting of DVT.
Circulating copper does so in the plasma as ceruloplasmin. Excess Copper is secreted into bile. Senescent ceruloplasmin has the same fate.
Repeat
Embryology
Aortic arches
What aortic arch gives rise to the common carotid and internal carotid?
What aortic arch gives rise to the subclavian?
What aortic arch gives rise to the true aortic arch?
3rd aortic arch associated with glossopharyngeal nerve gives rise to internal and common carotid arteries
4th aortic arch associated with superior laryngeal branch of the vagus nerve gives rise to the TRUE aortic arch and the subclavian arteries.
Note the 5th arch is obliterated in fetal development.
The 6th arch is associated with recurrent laryngeal nerve and pulmonary arteries/ductus arteriosus.
What does histone DE-acetylation do?
In what inherited, autosomal dominant, genetic disease is this thought to play a role?
What are the repeats in Huntington’s?
Histone deacetylation allows the histones to interact MORE closely with the DNA causing reduced transcription of genes.
Hungtinton’s disease (autosomal dominant)
Repeats are CAG repeats.
What is the primary nerve that innervates the dorsum of the foot with the exception of a little patch between big toe and second toe?
Superficial peroneal nerve.
How do you calculate renal clearance?
How do you go from this or calculation filtration fraction?
Clearance = (urine concentration x urine flow rate)/plasma concentration
You calculate filtration fraction by using the clearance of Creatinine or Inulin to calculate GFR and
you use the clearance of PAH to calculate renal plasma flow.
What is Starling’s equation for calculating GFR?
GFR = Kf [(Pg - Pb) - (Oncotic pressure glomerulus - Oncotic pressure Bowman’s)]
The P stands for hydrostatic pressure.
Kf is the filtration coefficient.
What is the core pathophysiology of Kartagener’s syndrome?
Failure of DYNEIN arms to develop that connect the microtubules that form the cilia.
This results in recurrent respiratory infections. Also associated with DEXTROCARDIA and infertility in men and women.
If a test comes up with a different result each time it is used on the same sample, what is the issue?
What time of error is associated with this?
The test is not RELIABLE. This is due to random error.
When a test is not accurate, what does that mean?
What kind of error is associated with accuracy?
How is the accuracy of a test be evaluated?
It is not valid – the trueness of the test’s measurements are being called into question.
Accuracy (validity) – associated with systematic error.
The accuracy of a test is evaluated by comparing it to the gold standard.
What is the genetic origin of a COMPLETE mole (46, XX or 46, XY)?
A COMPLETE mole is COMPLETELY of paternal origin. This results when sperm fertilizes an ovum that has lost its maternal chromosomes and the sperm genetic information is duplicated.
High malignant potential.
What is the genetic origin of a partial mole (69, XXX or 69, XXY)?
Fertilization of one ovum by 2 or more sperm.
Partial moles have LOW potential for malignancy.
In an emergency situation, if the patient is unable to consent, and the physician is able to in his/her reasonable judgement determine that the patient’s family is who they say they are (I.e. No ID) and it serves in the patient’s best interest, the physician may provide the family with general information regarding the patient’s status.
Repeat
What is the effect of anterior cerebral artery occlusion?
CONTRALATERAL motor and sensory deficits of the lower extremities, behavioral changes, and urinary incontinence.
If a medical error has occured, the right thing to do is to: (pick one of the following): tell the patient or involve risk management?
TELL the patient. Forget risk management. Ethical duty as physician is to tell the patient.
Why is the amount of oxygen in the blood in left atrium a little lower than the amount of oxygen in pulmonary capillaries?
It is lower because the oxygenated blood in the pulmonary veins mixes with deoxygenated blood in the bronchial circulation.
Note that while the actual bronchial veins send deoxygenated blood to the azygous vein and hemiazygous vein, the vast majority of the deoxygenated blood that was supplied to the lungs via the oxygenated bronchial arteries, returns through the pulmonary veins.
Gifts. What is the policy?
Express appreciation but DO NOT accept them ever. Even of they cost the patient no monetary value or very little. Unconscious favoritism must be avoided.
A man with tall stature, small firm testes, and absent body hair with bilateral breast enlargement is concerning for…
Klinefelter’s (XXY), he is likely to have an increased FSH level and low testosterone.
E.Coli stop fermenting lactose in the presence of glucose by what mechanism?
Glucose inhibits adenyl cyclase so that reduces intracellular cAMP levels and that causes poor binding of the CAP-DNA binding domain leading to decreased expression of the structural genes of the lac operon.
Note that the repressor of the lac operon in the presence of lactose, binds to the OPERATOR region of the gene.
Clinical botulism by blocking the release of _____ neurotransmitter results in a _____ type of paralysis.
Acetylcholine
Results in flaccid paralysis.
The presence of clenched fists in a neonate is most consistent with: Edwards (18) or Patau (13)?
18 – Edwards syndrome.
What is the sign of chronic infection in Hepatitis?
HepBsAg. If this persists, chronic infection is present with low infectivity.
Any presence of E antigen suggests high infectivity.
Once someone has anti-HepBsAg antibodies along with anti-core, they are considered to have cleared the infection.
The difference between minute ventilation and alveolar ventilation is that minute ventilation is all the air that enters the lung in one minute and alveolar ventilation is the about the air that enters in a given minute that participates in GAS EXCHANGE. Alveolar ventilation has DEAD SPACE subtracted.
Repeat.
The posterior cruciate ligament connects where?
The PCL connects to the medial epicondyle of the femur and prevents anterior displacement of the knee. It also connects to the posterior portion of the intercondylar area of the tibia.
Along with conjunctival injection, marijuana is also associated with:
Tachycardia.
Sweating, gigantism are associated with
Gigantism; which is associated with increased release of IGF-1 from the liver upon stimulation by Growth Hormone.
IGF-1 stimulates the Intrinsic tyrosine kinase (MAP kinase) pathway while growth hormone stimulates JAK-STAT.
Twinning - when does the split of the zygote have to occur for different options?
Monozygotic twins After 13 days -- conjoined Days 8-12 -- 1 chorion, 1 amnion Days 4-8 -- 1 chorion, 2 amnions Days 0-4 -- 2 chorions, 2 amnions
Tetrahydrobiopterin is important in the synthesis of what compounds? Especially which neurotransmitter?
Tetrahydrobiopterin (BH4) is important co-factor in the synthesis of dopa, tyrosine, serotonin, as well as nitric oxide.
Tryptophan is the precursor for serotonin. Tetrahydrobiopterin reductase is important because some cases of PKU are due to its absence.
How does PTH act on osteoclasts?
PTH acts on osteoclasts indirectly. It causes osteoblasts to increase the secretion of RANK-ligand and monocyte colony stimulating factor. This two factors stimulate OSTEOCLASTS.
PTH increases serum Calcium and decreases serum phosphate.
What is vascular, fibrinoid necrosis and neutrophil infiltration suggestive of in a transplanted organ?
Hyperpacute rejection.
What are the 2 signals from OSTEOBLaSTS that stimulate osteoclasts precursors to become mature, multinucleated osteoclasts?
How does estrogen fit in here?
What is the decoy receptor released by osteoBLASTS that negates this effect?
Rank-ligand and monocyte colony stimulating factor are signals from the OSTEOBLASTS to the osteoclasts to increase bone resorption. These signals are increased in the presence of PTH. Low ESTROGEN is associated with increased expression of RANK by osteoCLASTS leading to increased bone resorption.
Decoy receptor is Osteoprotegrin and it reduces bone resorption.
What is the correlate of CHRONIC (greater than 6 months to years) rejection of a kidney transplant? (Suggested by worsening hypertension and rising creatinine).
Obliterative vascular fibrosis. Vascular wall thickening and luminal narrowing. Interstitial fibrosis. Parenchyma atrophy.
What is the path of PAH in the nephron?
PAH’s concentration is lowest in Bowman’s space because it is similar to its concentration in the plasma there. PAH is freely filtered and NOT ABSORBED by any part of the nephron. It is secreted by CARRIER-MEDIATED ACTIVE TRANSPORT in the proximal tubule.
In a positively skewed distribution, what is the relationship of the mean, median, and mode?
If a distribution is positively skewed, it means it has a long positive tail the most affected value is the mean which will be greater than the median. The median will be greater than the mode.
What part of the intestine is ALWAYS involved in Hirschsprung’s disease due to the migration pattern of neural crest cells?
Rectum. Note that tone of the anal sphincter is usually increased.
Which embryologic structures FAIL to develop in DiGeorge syndrome
3rd and 4th pharyngeal pouch.
Loss of contraction of the anal sphincter in response to pinprick (anocutaneous reflex), saddle anesthesia, low back pain, bowel and bladder dysfunction, and loss of ankle-jerk reflex are suggestive of…
What nerve roots are affected???*
Cauda equina syndrome!
Nerve roots - S2-S4. Pudendal nerve is included here.
Flaccid paralysis of the bladder and rectum, impotence, and saddle anesthesia (S3-S5) corresponds to what syndrome? At what level is the injury?
Conus medullaris syndrome - at L2. Note that L2 also innervates the gluteal region inferior to the iliac crests and anteriorly the thigh inferior to the femoral triangle and inguinal ligament.
L3, L4 contribute to the femoral nerve and knee-jerk reflex.
What are associations between common drugs of abuse and their most commonly associated causes of death?
PCP - violence and trauma lead to death.
Cocaine - myocardial infarction and stroke
Opioids - respiratory depression
What glands are responsible for body odor?
What glands are responsible for secreting most of the sodium chloride in sweat?
Apocrine glands. They release an ODORLESS substance that acquires an odor upon bacterial decomposition of the substance.
The eccrine/merocrine glands secrete the watery fluid of sweat.
Holocrine - associated with sebaceous glands.
If someone has high aldosterone, Conn’s syndrome, what will be his/her symptoms?
Hypertension (due to increased Sodium retention), HYPOkalemia, and METABOLIC ALKALOSIS. The Hypokalemia results in muscle weakness and the hypokalemic alkalosis results in paresthesias.
There is NOOO weight gain in the above syndrome which is called Conn’s syndrome. Weight gain is associated with Cushing’s which is a result of GLUCOCORTICOID excess.
What syndrome are diarrhea and flushing associated with?
Carcinoid syndrome which is associated with release of serotonin from neuroendocrine cells in the GI tract.
When looking at a drug dose vs response graph,
A shift up or down corresponds to _____
A shift to the right or left corresponds to _____
What is the effect of adding a non-competitive antagonist? (I.e. Binds to allosteric site)
A shift up or down corresponds to a change in efficacy. A non-competitive antagonist will decrease efficacy and shift the curve DOWN.
A shift left or right corresponds to a change in potency.
If a man is able to achieve morning tumescence, that suggests that the physiologic machinery to achieve an erection is intact and his erectile dysfunction made be due to psychologic cause.
Repeat.
What is bromocriptine?
It is a dopamine AGONIST.
What is reserpine?
Reserpine is an anti-hypertensive medication – can cause severe depression.
Recall that of the benzodiazepines, the LOT ones are SAFE to use in liver disease. Chlordiazepoxide is not safe to use in liver disease.
Repeat.
If a 46 XY fetus has normally functioning Leydig cells and no Sertoli cells, what structures will develop?
Male and female internal genitalia and make external genitalia.
Note that testosterone is what causes persistence of the Wolffian ducts (male internal genitalia). Muellerian inhibiting factor which would have been secreted by Sertoli cells causes involution of the paramesonephric ducts which become the female structures.
What is the pattern of resistance along the airways?
The upper airway (everything pre-trachea) accounts for half of airflow resistance. From the trachea onwards, airway resistance in the first 10 generations of bronchi contributes most to total airway resistance of the lower respiratory tract. The medium sized bronchi have MORE airway resistance than the trachea due to turbulent airflow and then the smallest airways have the least resistance contributing less than 20% of airway resistance.
In the process of INFORMED consent when a foreign language is spoken, the appropriate course of action even in the presence of a translating family member is to use…
A PROFESSIONAL foreign language interpreter. Use a family member only in an EMERGENCY.
Uric acid, cystine, and calcium oxalate stones are promoted in ______ pH.
Acidic pH.
Only calcium phosphate and struvite stones like alkaline pH.
Galactose enzyme defects – explain what enzymes are involved and what builds up. If you have a child with only clouding of the lens, what enzyme is affected?
Only lens (cataracts) - you have galactitol formed by ALDOSE REDUCTASE from the excess galactose – the galactitol is deposited in the lens. This is due to Galactokinase deficiency which would have made galactose - 1 - phosphate were it functional.
If you have systemic symptoms (HSM, cataracts, failure to thrive, inability to tolerate breast milk, hyperchloremic metabolic acidosis) then uridyl transferase is the deficiency and what is building up is galactose 1 phosphate. This is classic galactosemia. The treatment to limit LACTOSE and breast milk. The common sepsis associated is E.Coli sepsis.
Osmotic damage is the mechanism of the cataracts forming.
What is the role of CFTR in the creation if sweat?
The role of CFTR is to facilitate the creation of HYPOTONIC sweat from the eccrine glands. It resorbs chloride as the fluid makes its way through the eccrine glands and sodium follows the chloride back in to the cells so that sweat ends up being hypotonic.
However, in patients with cystic fibrosis, CFTR is defective so their SWEAT is full of SODIUM and CHLORIDE.
CFTR does not play any role in the kidneys.
What is streptomycin?
Streptomycin is an Aminoglycoside. It binds to the 30S subunit and prevents initiation. The other Aminoglycoside to keep in mind is Tobramycin.
Tetracyclines block amino-acyl tRNA at the A site.
Chloramphenicol blocks peptidyltransferase.
What is the primary site of entry of cryptoccoccus neoformans into the body?
LUNGS!!! It only exists as a yeast.
It is not the nasopharynx.
What is number needed to harm?
It is 1/(attributable risk) meaning 1/(adverse event treatment - adverse event placebo).
It is important to correctly identify the adverse event. Is it death, disability etc? Makes the math easier to set up.
What are neurophysins?
Neurophysins are the carrier proteins that are each unique to vasopressin and oxytocin. They carry these hormone from their site of production in the paraventricular and supraoptic nuclei to their site of release in the posterior pituitary.
MHC Class II in an antigen presenting cell is loaded in an acidified lysosome after the cell has endocytosed or phagocytosed the protein of interest.
Repeat.
MHC Class I on the other hand, takes an internal route involving proteins being degraded in the proteasome, then going to rough ER then Golgi.
Repeat.
How do fibrates work and how does their use promote developing gallstones?
Fibrates block 7 alpha hydroxylase which reduces conversion of cholesterol to bile acids causing build up of cholesterol in bile leading to excess secretion of cholesterol in bile.
A neonate has swelling of the hands and a posterior neck mass composed of cystic spaces separated by connective tissue rich in lymphoid aggregates.
What is the neck mass?
What genetic syndrome is associated?
The neck mass is a cystic hygroma
It is common in TURNER’s syndrome. Where there are no secondary sexual characteristics (due to no estrogen).
What is adrenogenital syndrome?
Congenital adrenal hyperplasia
What is testicular feminization syndrome?
It is androgen insensitivity syndrome. There is a defect in testosterone receptors. 46, XY babies appear phenotypically as female but there is a blind ended vaginal pouch (lower portion of vagina) with no uterus.
What is the mechanism of macrolides like erythromycin? It is the same mechanism of related drug clindamycin.
They block TRANSLOCATION during the elongation phase at the 50s subunit. It inhibits ribosome from moving along the mRNA that is being translated to a protein.
The site on the immunoglobulin just above the Fc receptor region is where complement attaches.
Disulfide bonds hold the immunoglobulin Y shape together at the center.
Repeat.
What is the virulence factor in Staph Aureus’s peptidoglycan layer that it uses to evade the immune system?
Protein A which binds the Fc portion of IgG at the site where complement would have bound thereby decreasing production of C3b, opsonization, and phagocytosis.
What virulence factor do Streptococcus pneumonia and Neisseria gonorrhea share in common?
IgA protease.
PERMANENT central diabetes inspidus is associated with injury to the ________
Whereas central diabetes inspidus that improves is probably due to injury to ______
Permanent - hypothalamic nuclei
Transient - posterior hypophysis. Activity likely returns due to hypertrophy of producing cells.
Enterococcus resistance mechanism:
Enterococcus are resistant to aminoglycosides transferring different chemical groups like acetyl groups to the antibiotic to prevent it interacting with their ribosome.
Vancomycin resistance in enterococcus occurs when they acquire a plasmid that codes for a ligase (VanA ligase) that changes their D-Ala, D-Ala wall to D-Ala, D-lactate.
Enterococcus resistance to penicillins like ampicillin come from producing a beta-lactamase and having low affinity penicillin binding proteins.
Which histones make up the nucleosome?
Which one is outside?
Histones 2,3,and 4 are at the core of the nucleosome.
Histone 1 is outside it.
A watery penile discharge, negative for Gonococcal infection that is followed two weeks later by conjunctivitis, right knee pain, and vesicular rash on palms and soles is concerning for…
Reactive arthritis following a genitourinary (Chlamydia) or enteric infection (Salmonella, Yersinia, Cloristidium difficile, Campylobacter, Shigella). Clinical presentation: Oligoarthritis, dactylitis, enthesitis. Association with HLA-B27.
Skin manifestations: keratoderma blennorhagicum, circinate balantis
Oral ulcers
If you suspect elder abuse, speak one on one with the patient first.
Repeat
Where does INTRAventricular hemorrhage in a preterm baby originate?
The germinal matrix - region in sub ventricular zone where neurons and glial cells migrate out of during brain development. IVH is associated with long-term neurodevelopmental impairment.
Increased frequency in premature babies and low birth weight babies.
How do you calculate renal BLOOD FLOW?
RBF = RPF / (1- HCT).
Recall RPF = PAH clearance.
Where in the kidney does Lithium exert its action in the setting of diabetes insipidus?
The collecting tubule. Lithium antagonizes the effect of vasopressin (ADH) on the collecting tubules and collecting ducts. Symptoms usually resolve on discontinuation but after years of chronic use, can be permanent.
A gram positive rod with a NARROW zone of Beta-hemolysis that grows well at 22C and can multiply at temperatures as low as 4C is concerning for…
How is it killed?
Listeria. Because it is intracellular, T-cell mediated immunity is required to kill it.
Mutations in Trypsin’s ability to cleave itself are associated with what clinical condition?
Hereditary pancreatitis.
How does the INACTIVATED flu vaccine work?
It works by facilitating the generation of neutralizing antibodies against hemagglutinin PREVENTING ENTRY of influenza into cells.
How is epinephrine synthesized and what hormone is this enzyme stimulated by?
Epinephrine is synthesized from norepinephrine by the enzyme phenylethanolamine-N-methyl transferase and it is under the influence of cortisol.
Air in the gallbladder and in the biliary duct suggest?
gallstone ileus – where a large gallstone has created a cholecysenetric fistula. The large gallstone usually comes to rest at the ileocecal valve in the ileum. Cholecystectomy is usually NOT required. What is required is SURGICAL REMOVAL OF THE STONE. Patients present with small bowel obstruction symptoms. Stone can be visualized on abdominal X-Ray.
A patient who first has a serum-sickness like picture and then experiences a rise in ALT and AST is concerning for…
Acute Hepatitis B infection
What causes fine skin wrinkles as we age?
Decreased PRODUCTION leads to net loss of collagen and elastin from the dermis.
A 15 year old boy with gait ataxia who also has kyphoscoliosis, pes cavus, and absent joint and position sense is suggestive of what inherited disease? What is he at risk for dying of?
Friedrich’s ataxia – it is an autosomal recessive condition where spinocerebellar tracts and dorsal columns degenerate. common cause of death is hypertrophic cardiomyopathy.
What is the nature of the vaccine for meningitis?
What is the best prophylaxis for family members of someone who is infected?
Capsular polysaccharide vaccine
Best prophylaxis for exposed family members: Rifampin (you cry and pee orange). Also, rifampin RAMPS up cytochrome P450 meaning little warfarin.
What is the long-term sequelae of hydrocephalus in a child which presents as irritability, poor feeding, increased head circumference, enlarged ventricles on CT?
Muscle hypertonicity (spasticity), visual disturbances, and learning difficulties. This is due to stretching of the periventricular pyramidal tracts.
Which immune cell has CD40?
Which has CD40 ligand?
Describe the process of B cell activation.
B cell has CD40
T cell has CD40 ligand.
A mature B cell encounters an antigen and becomes activated! It makes clones of itself. Some of these activated B cells become short-lived plasma cells and secrete IgM (T-cell INDEPENDENT).
The vast majority of the activated B-cells go to the lymph node to form a GERMINAL follicle which is the site of proliferation of activated B cells in the lymph node. A portion of these B cells become long-lived memory cells but the vast majority will be antibody secreting plasma cells.
Late in this active primary response of the B-cell, they interact with an ACTIVATED T-cell expressing CD40 ligand and undergo somatic hypermutation that leads to affinity maturation and immunoglobulin isotype switching to make IgG etc. In isotype switching, only the heavy chain changes.
This is NOT VDJ recombination.
What end of tRNA is the amino acid group attached?
3’ - 3 prime end.
The side loop closest to the 3’ end is the ribothymidine, pseudouridine, cytosine loop.
Where does VDJ recombination occur?
In the bone marrow! To maturing B-cells.
What is the difference between promoter regions and enhances/repressors in terms their function and location?
Enhancers and repressors can be located ANYWHERE along the gene. Even within it. Enhancers increase transcription of a gene by binding to transcription factors which are bound to promoter regions.
Promoters are ALWAYS upstream. Promoters are the binding site for RNA polymerase II (makes mRNA) and transcription factors. There are 2 types of promoters in EUKARYOTES 25 bases upstream is the TATA box, 70- 80 bases upstream is the CAAT.
If stratified analysis of an initial result shows an EVEN MORE PROFOUND, STATISTICALLY SIGNIFICANT relationship when the potential subgroups are stratified in analysis the phenomenon is ________
If stratified analysis of an initial result shows a WEAKER or STATISTICALLY INSIGNIFICANT result (look at p-value) when subgroups along the lines of variables that are potential other influencers of the results, the phenomenon is ________
Effect modification
Confounding
What is the role of IL-5?
IL-5 is secreted by T-helper 2 cells and it recruits and activates eosinophils!!! It has a role to play in extrinsic allergic asthma.
What bacterial agent that causes pneumonia must be cultures on charcoal yeast supplemented with L-cysteine and iron to survive??? Here’s a hint: it also best visualized with silver stain.
How do you diagnose it?
Legionella
Diagnose legionella with the urine antigen test.
If a child demonstrates symptoms of both absence seizures and generalized tonic-clonic seizures what drug ALONE is best to treat both?
How does this drug work?
Valproic acid.
It increases sodium channel inactivation and increases GABA by inhibiting the enzyme, GABA transaminase.
(Must know) what is the mechanism of action of morphine?
Morphine binds to opioid mu receptors and modulates synaptic transmission – opens K+ channels and closes Ca2+ reducing synaptic transmission. It thereby inhibits the release of ACh, NE, 5-HT, glutamate, and substance P.
How do benzodiazepines work?
Appropriate treatment of overdose:
Benzodiazepines work by increasing GABA-A action. The do this by increase the FREQUENCY of chloride channel opening.
Overdose: Flumazenil
How does phenytoin work?
It increases sodium channel inactivation. It exhibits zero order kinetics and ramps up the cytochrome P-450 system too.
How does Gabapentin work?
It inhibits high voltage inactivated Ca2+ channels.
Carbamazepine, phenytoin, phenobarbital, rifampin, and griseofulvin all share the following activity?
Ramp up cytochrome P-450 system.
How do barbiturates work?
What is the appropriate management of overdose on barbiturates?
They work by increasing the action of GABA-A. It does this by increasing the DURATION of Chloride channel opening.
Overdose: Supportive therapy.
How does Zolpidem (Ambien) work?
It acts at the BZ1 subtype of the GABA receptor. It can be reversed by Flumazenil even though Zolpidem is technically NOT a benzodiazepine.
What is blood solubility of an inhaled anesthetic reflective of?
How about lipid solubility?
It is reflective of speed of induction. A highly BLOOD soluble substance will have a slower induction while a less BLOOD soluble substance will have a more rapid induction.
LIPID solubility relates to POTENCY. The more LIPID soluble an inhaled anesthetic is, the more POTENT it is. Lipid solubility is related to MAC. Recall 1/MAC is proportional to potency.
What is the effect of INHALED anesthetics on cerebral blood flow?
They INCREASE cerebral blow flow and RECUCE cerebral metabolic demand.
How do arylcyclohexylamines like Ketamine work?
Block NMDA receptor. Increases cerebral blood flow.
How does Propofol work?
It potentiated GABA-A. Rapid anesthesia induction.
How can you tell which LOCAL anesthetics which end in -Caine are esters vs amides?
The Amides have 2 I’s in their name!!!
What is the mechanism of succinylcholine? What is it used for?
Succinylcholine is a DEPOLARIZING neuromuscular blockade agent. It is an acetylcholine receptor AGONIST.
In COPD or asthma, the RV/TLC ratio is much increased!!!! The Residual volume is the main increase.
Repeat.
An inhaled anesthetics destination is the brain. To get there it has to travel from the lungs to the blood to the brain. What is the implication of the arteriovenous gradient?
The AV concentration gradient relates ONSET of action of inhaled (gas) anesthetics. It represents tissue solubility because if the difference (AV gradient) is large, it means tissue solubility is HIGH. If tissue solubility is HIGH, then more of the inhaled anesthetic is needed to build up in the blood to then build up in the brain. This translates to a slower ONSET of ACTION.
How should incidence be calculated?
of new cases a year / (Total population - those already with disease).
What is the BIGGEST difference in response to the killed, inactivated polio vaccine vs the oral polio vaccine?
The duodenal IgA response! To generate mucosal immunity, it is important to administer the vaccine at the desired site and to administer a live vaccine!
What mnemonic reminds me of relationship of inferior Epigastric vessels and inguinal hernias?
MDs LIE. Medial direct inguinal hernia, lateral indirect inguinal hernia.
In lead poisoning what substance along the porphyrin synthesis pathway:
What vitamin is important for this pathway?
Delta-aminolevulinic acid.
Pyridoxine Vitamin B6.
An elderly patient who develops difficulty swallowing, choking, coughing and recurrent aspiration is concerning for…
Developing a Zenker diverticulum which results from IMPAIRED MUSCLE RELAXATION of circopharyngeus and other muscles of pharynx during swallowing. This diverticulum is a false diverticulum.
Hemoglobin C migrates the least on gel electrophoresis and it results from a _____ mutation
MISSENSE.
What drugs INHIBIT warfarin synthesis?
Isoniazid, trimethoprim, Fluconazole and cimetidine.
Which nucleus of the thalamus receives gustatory and trigeminal SENSORY input?
VPM – recall medial is face.
Lateral is body – spinothalamic and medial lemniscal input go to VPL.
What is the impact on prevalence of a therapy that prolongs survival but does not actually CURE?
It INCREASES prevalence.
When in the cardiac cycle does the opening snap of mitral stenosis occur? When is this in relation to the aortic valve closing and what is the relationship between the left ventricular and left atrial pressures at this time?
The opening snap of mitral stenosis corresponds to the tensing of abnormal mitral valve leaflets AFTER the mitral valve cusps has opened. It happens AFTER the aortic valve closes. The mitral valve does not open until Left ventricular pressure falls below left atrial pressure.
What kind of damage to DNA do Ionizing radiation (X-rays and gamma rays) cause?
They cause double stranded DNA breaks that can be repaired by homologous or non-homologous joining.
How is UV radiation induced damage to DNA repaired?
UV radiation causing thymidine dimers. It is repaired by nucleotide excision repair which begins with an endonuclease.
This UV specific endonuclease is what is missing in Xeroderma pigmentosum. (Autosomal recessive).
What should migratory Polyarthritis make me think of?
Rheumatic fever - Strep A
What does aromatase do?
Where is it located?
It converts androgens (testosterone and DHEA) into estrogens (estrone, estradiol). Estradiol is active estrogen.
Location: peripheral tissues.
What percentage of the filtered amount of the following substances is excreted by the kidney?
Sodium Urea Inulin PAH Glucose
Sodium - only 1% is excreted regardless of concentration within relatively physiologic range.
Urea - 55% is excreted at all concentrations similar to caveat above.
Inulin - 100% excreted. Recall, Inulin is neither secreted nor absorbed.
PAH - > 100% excreted because it is secreted!!!
Glucose – excreted in a concentration dependent manner. completely absorbed below threshold point of the Na+ co-transporters in the proximal convoluted tubule.
What are the 3 drugs used for MRSA? How do they each work and what are their side effects.
Vancomycin - Binds to D-alanine D-alanine glycopeptide. Adverse Effects: Red Man syndrome, Nephrotoxicity
Daptomycin - creates transmembrane channels that lead to depolarized cell membrane. Adverse effects: myopathy and CPK elevation; inactivated by pulmonary surfactant so useless against pneumonias.
Linezolid - inhibits protein synthesis by binding the 50S subunit. Adverse effects: Thrombocytopenia, Optic neuritis, High risk of serotonin syndrome.
High levels of what two substances reduce the risk of forming a gallstone by increasing cholesterol solubility?
Bile salts and phosphatidylcholine
It takes about 10-14 days of being at high altitude for the effects of the EPO in terms of increased red blood cells to be seen. Renal compensation for the respiratory alkalosis begins about 48hrs in.
Repeat
What bacteria has antiphagocytic D-glutamate capsule?
Anthrax. Widened mediastinum. Bacillus anthracis. Gram positive rod. Mediastinum widened due to hemorrhagic mediastinitis.
What class of fungal drugs INHIBIT cytochrome P-450 and thereby increase toxicity of drugs processed by it?
What is their anti fungal mechanism of action?
-Azoles
They work by inhibiting the demethylation of lanosterol into ergosterol. (Cell membrane)
Also note that cimetidine and omeprazole INHIBIT cytochrome P-450 as well
What part of the fungus structure is the target for caspofungin?
Is it cell wall or cell membrane?
Cell wall!
Note nitroglycerin and isosorbide undergo considerable first pass metabolism by liver if taken orally! What nitrate drug has high oral bioavailability instead?
Isosorbide mono nitrate.
To what common drug are the vast majority of catalase positive, coagulase negative Staph resistant? E.g. Staph epidermis.
What drug is best to treat these infections especially if bacteremia occurs?
Methicillin!
Vancomycin
