Uworld 23

Front 1

Kinesin and dynein

Back 1

-kinesin and dyne in are microtubule-associated motor proteins that function in the rapid transport of materials and organelles within cells

-dynein also functions in ciliary and flagellar movement

-kinesin participates in anterograde transport – moves intracellular vesicles and organelles toward the rapidly growing "plus ends" of microtubules

-dynein – retrograde transport – moves organelles TOWARD THE NUCLEUS

-these two motor proteins derive energy for movement from ATP hydrolysis

Front 2

Trisomy 21

Back 2

-detectable by cytogenetic karyotype analysis

-most common genetic cause of congenital mental retardation

-patients with Down syndrome are at risk of developing ACUTE LYMPHOBASTIC LEUKEMIA (ALL) and ACUTE MYELOGENOUS LEUKEMIA (AML)

Front 3

Common features of Down syndrome

-presentation: 35-yo with difficulty conceiving gives birth to boy with flat nasal bridge, small mouth, low-set ears

-karyotype show: trisomy at chromosome 21

Back 3

-mental retardation

-prominent epicanthal folds

-flat facial profile

-cleft palate

-nuchal fold thickening

-palmar simian crease

-endocardial cushion defects

-duodenal and jejunal atresia

-hypotonia

-gap between first and second toes

Front 4

Hepatitis A in kids

Back 4

-Hepatitis A virus infection is most commonly silent or subclinical ("anicteric") in children

--may also present as an acute self-limited illness with jaundice, malaise, fatigue, anorexia, nausea, vomiting, right upper quadrant pain (liver), or an aversion to smoking

-estimated that up to 70% of adults in US have anti-HAV IgG antibodies, with most positive individuals having never experienced an icteric illness

Front 5

Rate of blood flow in pulmonary and systemic circulations

Back 5

-pulmonary circulation is part of continuous circuit with systemic circulation

-rate of blood flow through pulmonary circulation must equal rate of blood flow in systemic circulation at all times

-vs. arterial pressures and oxygen contents of pulmonary systemic arterial systems are considerably different from each other, both at rest and during exercise

Front 6

Colchicine

Back 6

-can be used to treat acute gouty arthritis (although NSAIDs are first-line treatment)

-colchicine resolves symptoms in most patients with acute gouty arthritis

-colchicine primarily works by inhibition of microtubular polymerization

--binds to protein subunit of microtubules, and prevents their aggregation

--this disrupts membrane-dependent functions such as chemotaxis and phagocytosis – i.e., prevents leukocyte attraction and inflammation

-colchicine also reduces formation of leukotriene B4

-important adverse effects of colchicine are nausea, abdominal pain, and diarrhea

-colchicine should not be used in patients who are elderly or have renal dysfunction

-chronic low-dose colchicine can be used as prophylaxis against acute gouty arthritis

Front 7

Use of celecoxib

Back 7

-selective COX 2 inhibitors have no effect on platelet aggregation and cause little GI irritation

-reduced risks of bleeding and GI ulceration are their only advantages over traditional NSAIDs

-e.g., use celecoxib in treatment of back pain in patient with history of peptic ulcer disease

Front 8

Maternal blood type and antibodies

Back 8

-naturally occurring antibodies to other blood types (anti-A and anti-B) and IgM, and therefore do not cross the placenta

-so with maternal blood types A and B, erythroblastosis fettles and hemolytic disease of the newborn do NOT occur

-by contrast, in type O mothers, the antibodies are predominant IgG and CAN cross the placenta to cause fetal hemolysis

-IgG is able to cross placenta and remains circulating in bloodstream of infants, providing them with passive immunity for six months

-vs. IgA in colostrum and breast milk – coats baby's intestinal mucosa and provides protection from pathogens that the baby ingests

Front 9

Sternocleidomastoid

Back 9

-SCM muscle originates on medial clavicle and manubrium

-inserts on mastoid process of the skull

-could cause medial end of a fractured clavicle to be displaced upwardly

-SCM muscle innervated by CN 11 (accessory nerve – also innervates trapezius)

-SCM muscle functions to turn head in OPPOSITE direction

Front 10

Vagus nerve in the ear

Back 10

-vagus nerve provides some cutaneous sensation to the posterior external auditory canal via its small auricular branch

-sensation to the rest of the canal is from CN V3

-a vasovagal syncopal episode results from stimulation of the vagus nerve, causing a decrease in blood pressure and heart rate

Front 11

Cardiac tamponade

-34 year-old male – recent-onset dyspnea and fatigue – no significant PMH – low BP – weak pulse that becomes undetectable with inspiration
-also, jugular venous distention is seen

Back 11

-JVD is a key finding in this case
-jugular venous distension indicates central venous pressure in the superior vena cava
-acute onset central venous pressure elevation with hypotension and tachycardia can be seen with cardiac tamponade or tension pneumothorax

--however, tension pneumothroax usually presents with history of chest trauma, and no abnormalities on lung auscultation

-observation of Beck's triad on physical exam – hypotension, distended neck veins, and distant/muffled heart sounds on auscultation – with tachycardia are indicative of tamponade

Front 12

Presentation of cardiac tamponade in young man

Back 12

-history of antecedent respiratory illness points toward cardiac tamponade due to serous viral pericarditis and significant acute pericardial effusion

-loss of palpable pulse during inspiration is likely due to inspiratory fall in systolic BP

-pulsus paradoxus = drop in systolic BP of more than 10 mmHg on inspiration

--non-specific sign, but is suggestive of tamponade when coupled with acute onset hypotension, tachycardia, and jugular venous dissension (JVD)

Front 13

Relative risk

Back 13

2 x 2 table, with exposure in rows and outcomes in columns

-relative risk = [a/(a+b)]/ [c/(c+d)]

Front 14

Phenytoin

Back 14

-epilepsy medication: treatment of tonic-clonic and psychomotor seizures, and for seizure prophylaxis (post-head trauma and pre-neurosurgery)

-inhibits neuronal high-frequency firing by reducing ability of sodium channels to recover from inactivation –> increases refractory period

-phenytoin has undesirable cosmetic effects that limit its use – hirsutism, coarsening of facial features, acneiform skin rash, gingival hypertrophy

-phenytoin can cause generalized LYMPHADENOPATHY ("pseudolymphoma") without a serum sickness-like syndrome

Front 15

Peroxisomal diseases

Back 15

-peroxisomal diseases (as in peroxisomes) are rare inborn errors of metabolism in which peroxisomes are either absent or non-functional

-very long chain fatty acids or fatty acids with branch points at odd-numbered carbons can not undergo mitochondrial beta-oxidation

--so these fatty acids are metabolized by a special form of beta oxidation (very long chain facty acids) or by alpha oxidation (branched chain fatty acids such as phytanic acid) within peroxisomes

-these diseases commonly lead to neurologic defects from improper CNS myelination

Front 16

Histone H1

Back 16

-histone H1 is located outside the nucleosome core

-helps to package nucleosomes into more compact structures by binding and linking DNA between adjacent nucleosomes

-the nucleosome core is composed of two molecules each of H2A, H2B, H3, and H4, making eight total histone molecules in the core

-association of DNA with histones gives appearance of a "beaded chain" as this structure undergoes further rounds of coiling and association with other structural proteins, such as nuclear scaffold proteins, before ultimately forming chromosomes

Front 17

Mycoplasma pneumoniae infection

Back 17

-infection with mycoplasma pneumonia can result in formation of cold agglutins

-other illnesses resulting in cold agglutinin formation include EBV infection and hematologic malignancy

-cold agglutinins are antibodies specific for red blood cells that only cause agglutination (clumping) of RBCs at low temperatures

-cold agglutinins are responsible for transient anemia that can be seen in patients with a M. pneumoniae infection

Front 18

Fetal circulation – location of most highly oxygenated blood

Back 18

-the most highly oxygenated blood in the fetus is carried by the umbilical vein, which empties directly into the inferior vena cava via the ductus venosus

Front 19

Fetal circulation – adult remnants

Back 19

-umbilican vein –> ligamentum teres in adult

-ductus venosus –> ligamentum venosum in adult

-foramen ovale --> fossa ovale in adult

-ductus arteriosus --> ligamentum arteriosum in adult

-umbilical arteries –> medial umbilical ligaments in adult

Front 20

Non-dihydropyridine calcium channel blockers + beta-blockers

Back 20

-combined use of non-dihydropyridine calcium channel blockers (verapamil, diltiazem) with beta-adrenergic blockers (atenolol) can have additive negative chronotropic effects

--> severe bradycardia and hypotension

Front 21

Medications with negative chronotropic effects

Back 21

-medications with negative chronotropic effects include:

-beta-blockers (metoprolol, atenolol)

-non-dihydropyridine calcium channel blockers (verapamil, diltiazem)

-cardiac glycosides (digoxin)

-amiodarone and sotalol (anti-arrhythmia drugs)

-cholinergic agonists (pilocarpine, rivastigmine)

Front 22

Carotid sinus

Back 22

-carotid sinus is a dilatation of the internal carotid artery – lies at bifurcation of carotid artery

-increased blood pressure, or external pressure on the carotid sinuses (e.g., a tight collar), stimulate baroreceptors in the carotid sinus walls

-this baroreceptor stimulation leads to vasodilation, decreased heart rate and contractility, and decreased blood pressure

-afferent fibers from carotid sinus stretch receptors form a small carotid sinus nerve (Hering's nerve), which is a branch of the GLOSSOPHARYNGEAL NERVE (CN 9)

-vs. fibers from the aortic arch baroreceptors fun with the VAGUS NERVE

-afferent fibers from both sets of baroreceptors terminate in the solitary nucleus of the medulla

Front 23

Primary hyper-parathyroidism

Back 23

-primary hyper-parathyroidism si ususally caused by a parathyroid adenoma (85%) or by parathyroid hyperplasia (15%)

-parathyroid cancer is very uncommon cause

-excess serum calcium occurs by three mechanisms

--increased renal absorption of calcium

--increased GI absorption of calcium (indirectly, by 1,25-dihydroxy vitamin D formation – b/c pTH increases formation of vit. D in kidneys)

--increased bone resorption by osteoclast activation

-serum phosphorus in patients with hyper-parathyroidism is usually low because parathyroid hormone decreases phosphate resorption in proximal renal tubule.

Front 24

Skeletal changes in hyper-parathyroidism

Back 24

-for unclear reasons, cortical (compact) bone in appendicular skeleton (pectoral girdle, pelvic girdle, and limbs) is commonly involved inhyper-parthyroidism

-sub-periosteal thinning is a characteristic feature of hyper-parathyroidism

-radiologically, this thinning appears as sub-periosteal erosions in the medial side of the second and third phalanges of hand, and there is a granular "salt-and-pepper" appearance o fate skull

Front 25

Manifestations in hyper-parathyroidism

Back 25

-cardinal clinical manifestations are "bones, stones, groans, and psychiatric moans"

--bone loss

--renal stones

--GI upset/ulcers

--psychiatric disorders

-these symptoms are not as common today, since most cases are detected before bone or kidney symptoms appear.

--practice of routinely measuring calcium in chemistry profile allows for early recognition of disease

Front 26

Skeletal changes in vitamin D deficiency

Back 26

-vit D deficiency --> excessive unmineralized osteoid, and widened osteoid seams

-patients have low bone mineral densities, with increased risk for fractures

Front 27

Skeletal changes in osteoporosis

Back 27

-trabecular thinning with decreased interconnections is characteristic of osteoporosis

-total bone mass decreased, with normal architecture disrupted

Front 28

Skeletal changes in Paget's disease of the bone

Back 28

-mosaic pattern of lamellar bone with irregular sections of lamellar bone linked by "cement lines"

-the cement lines represent previous areas of bone resorption

Front 29

Skeletal changes in ostopeTrosis

Back 29

-osteopeTrosis = "marble bone disease"

-caused by decreased osteoclastic bone resorption

-histologically, osteopetrosis characterized by persistence of primary unmineralized spongiosa in the medullary canals

-vs. in normal individuals, bone marrow replaces the primary spongiosa

Front 30

Flecainide

Back 30

-flecainide is a class 1C anti-arrhythmic, typically used to treat supra-ventricular tachycardias

-class 1C anti-arrhythmics are potent sodium channel blockers – exhibit strong use-dependence by prolonging the QRS duration to greater extent at higher heart rates
--so patient would have greater QTc interval duration after stress test

-class 3 antiarrhythmics block depolarizing potassium current – demonstrate reverse use-dependence: the slower the heart rate, the more the QTc interval is prolonged

Front 31

CMV

Back 31

-cytomegalovirus is typically associated with subclinical infection in immunocompetent, with the occasional individual developing a mononucleosis-like syndrome that is mono spot negative

-in the immunocompromised, primary or reactivated CMV infection can result in severe retinitis, pneumonia, esophagitis, colitis, hepatitis

Front 32

Intestinal metaplasia in esophagus

Back 32

-intestinal metaplasia in the esophagus is a complication of long-standing GERD

-this metaplasia is known as Barrett esophagus

-originally a protective response to injury by acidic stomach contents, Barrett esophagus significantly increases the risk of esophageal adenocarcinoma