Uworld 23

Front 1

Pharyngeal pouch derivatives

Back 1

-pharyngeal pouch 1: epithelium of middle ear and auditory tube
-pharyngeal membrane 1: tympanic membrane
-pharyngeal groove 1: epithelium of external ear canal

-pharyngeal pouch 2: epithelium of palatine tonsil crypts
-membrane/groove obliterated

-pharyngeal pouch 3: thymus, inferior parathyroid glands
-membrane/pouch obliterated

-pharyngeal pouch 4: superior parathyroid glands, ultimobranchial body (later becomes C cells of thyroid gland – make calacitonin)

Front 2

Myasthenia gravis embryology

-patient presents with heaviness in her eyelids and weakness in hands, with anterior chest mass on imaging

Back 2

-myasthenia gravis is associated with abnormalities of the thymus (e.g., thymoma, thymic hyperplasia) –can present as anterior chest mass

-the thymus and inferior parathyroid glands arise from the third pharyngeal pouch

Front 3

Power (biostats)

Back 3

-power of a study indicates the probability of seeing a difference when there is one.

-power = 1 - beta

-beta is equal to type II error, which states that there is no difference between groups when one truly exists

-ex: if there is 20% probability of concluding that there is no difference when there is one is reality, than the power of a study is equal to 1 -0.2 = 0.8, or 80%

Front 4

Down syndrome and Alzheimer's

Back 4

-patients with down syndrome (trisomy 21) have increased risk of early-onset Alzheimer disease

-in such patients, there is development of senile plaques and NEUROFIBRILLAY TANGLES

-association btw. Down and Alzheimer may be due to fact that the APP gene is located on chromosome 21

-cleavage of APP (amyoid precursor protein) forma A beta-amyloid, which is the substance that accumulates in brain tissue and vessel walls

-since there are three copies of APP gene in Down syndrome patients, there is accelerated accumulation of amyloid, with Alzheimer-like changes

Front 5

Conditions associated with Down syndrome

Back 5

-early Alzheimer disease

-acute leukemias (AML and ALL)

-congenital heart disease: endocardial cushion defects, VSD, ASD

-GI defects: duodenal atresia, Hirschsprung disease

Front 6

Lewy bodies

Back 6

-Lew bodies are round, eosinophilic intracytoplasmic inclusions that contain neurofilaments

-Lewy bodies are seen in the substantial nigra in PARKINSON DISEASE

Front 7

Hypocretin-1 and 2

Back 7

-hypocretin-1 (orexin-A) and hypocretin-2 (orexin-B) are neuropeptides produced in lateral hypothalamus that function to promote wakefulness and inhibit REM sleep-related phenomena

-most patients who have NARCOLEPSY with cataplexy (sudden muscle paralysis triggered by intense emotions) demonstrate undetectable levels of hypocretin-1 in their CSF

Front 8

IL-12

Back 8

-IL-12 stimulates the differentiation of "naive" T-helper cells into the Th1 subpopulation

-patients with IL-12 receptor deficiency suffer from severe mycobacterial infections, due to inability to mount a strong cell-mediated granulomatous immune response

-these patients are treated with interferon-gamma (which is normally secreted by Th1 cells)

Front 9

Th1 cells

Back 9

-Th1 cells are involved in cell-mediated immunity

-function to activate macrophages and cytotoxic T-cells

-Th1 cells secrete IL-1, IFN-gamma, and lymphotoxin beta

-action of Th1 cells results in cytotoxicity, and delayed hypersensitivity

Front 10

Th2 cells

Back 10

-Th2 cells are involved in humoral (antibody-mediated) immunity

-Th2 cells activate B-cells and promote class switching

-Th2 cells secrete IL-4, 5, 10, 13

-action of Th2 cells results in secretion of antibodies

Front 11

Colchicine

Back 11

-treatment options for gouty arthritis are NSAIDs, colchicine, and glucocorticoids

-NSAIDs is first-line

-colchicine acts by binding to the intracellular protein tubulin and inhibiting its polymerization into microtubules

-this effect, in turn, disrupts membrane-dependent functions, such as chemotaxis and phagocytosis

-i.e., colchicine affects the cytoskeleton.

-important side effects of cochicines are nausea, abdominal pain, and diarrhea

-colchicine should be avoided in patients who are elderly or have renal dysfunction

Front 12

Genetics of CF

Back 12

-since CF is autosomal recessive, child will inherit disease if he/she independently inherits mutant allele from each parent (a 1/2 chance if the parent is a carrier)

-if carrier population is 1/30, then probability that child will have disease is (1/30 x 1/2) x (1/30 x 1/2) = 1/9,000

Front 13

Virdians streptococci

Back 13

-viridans streptococci produce dextrans from glucose – aid these organisms in colonizing host surfaces such as dental enamel and heart valves

-strep viridans causes subacute bacterial endocarditis, classically after dental surgery in patients with pre-existing cardiac valvular defects

-for this reason, antibiotic prophylaxis is used prior to dental work in patients with valvular abnormalities

Front 14

Mitochondrial DNA

Back 14

-mitochondrial DNA (mtDNA) is the most common non-nuclear DNA found in eukaryotic cells

-derived from mother

-this mtDNA resemble prokaryotic DNA

Front 15

CD8+ antigen recognition

Back 15

-CD8+ cells recognize foreign antigens presented with MHC class 1 proteins

-each MHC class 1 molecule consists of a HEAVY CHAIN and a BETA2-microglobulin

Front 16

MHC class 1

Back 16

-MCH class 1 consists of heavy chain and beta2-microgluobulin

-located on all nucleated cells

-function of MHC 1 is to present antigen to CD8+ cytotoxic T-cells

-MHC 1 presents antigens from virus and tumor proteins
--these antigens are processed in the cytoplasm

-presentation of antigen by MHC class 1 results in apoptosis of the presenting cell

Front 17

MHC class II

Back 17

-MHC class II is composed of alpha and beta polypeptide chains

-MHC II is found on antigen-presenting cells: B-cell, macrophages, dendritic cells, and Langerhans cells

-MHC II functions to present antigen to CD4+ T-helper lymphocytes

-MHC II present bacterial antigens
--these antigens are phagocytosed and digested by lysosomes, within which antigen binds to MHC II

-antigen presentation by MHC II results in activation of Th cells, which stimulate the cell-mediated (Th1) and humoral (Th2) immune responses

Front 18

Wolff-Parkinson-White syndrome

Back 18

-Wolff-Parkinson-White syndrome is an accessory AV conduction pathway

-this can manifest clinically as recurrent paroxysmal supra-ventricular tachycardia in an otherwise healthy individual

-in a WPW patient, the baseline ECG generally shows a triad of abnormalities, corresponding to ventricular pre-excitation: a shorted PR-interval, a delta wave at the start of the QRS complex, and a widened QRS interval

Front 19

Akathisia

Back 19

-akathisia is a movement disorder characterized by inner restlessness and inability to sit or stand in one position

-onset of akathisia can be a complication of ANTI-PSYCHOTIC THERAPY

-a diagnosis of akathisia is often missed, because movements and restlessness are misinterpreted as worsening psychotic behavior and agitation

--so instead of decreasing patient's dose, patient's neuroleptic dosing is often mistakenly increased, exacerbating the patient's akathisa

Front 20

Pupillary light reflex

Back 20

-pupillary light reflex is assessed by stinging light in an eye and observing response in that eye (direct) and in the opposite eye (consensual)

-optic nerve (CN 2) is responsible for the afferent limb of this reflex

-oculomotor nerve (CN 3) is responsible for efferent limb of pupillary light reflex

-in a patient with reflex pupillary constriction occurring on one side only (i.e., left-sided constriction only when light shined in left and right eyes), the contralateral (right) CN 3 is likely the culprit.

Front 21

CN 3 palsy

Back 21

-symptoms of oculomotor nerve (CN 3) palsy relate to the function of CN 3:

-a somatic component of the nerve innervates the inferior, superior, and medial rectus; inferior oblique; and levitator palpebrae muscles
--ptosis occurs due to paralysis of levitator palpebrae, and the unopposed action of the lateral rectus (CN 6) and superior oblique (CN 4) leads to a "down-and-out" gaze

-parasympathetic fibers of CN 3 innervate iris sphincter and ciliary muscle

--paralysis of these fibers causes a fixed dilated pupil and loss of accommodation

Front 22

Treating genital herpes due to HSV-2

Back 22

-combination of new onset gentile vesicular rash and positive Tzanch smear in a previously asymptomatic patient is suggestive of primary gentile herpes due to HSV-2

-recurrences of genital herpes can be reduced through DAILY TREATMENT WITH ORAL ACYCLOVIR, FAMCICLOVIR, or VALACYCLOVIR

--these drugs suppress reactivation of latent HSV infection

-condom use can help prevent a primary genital HSV infection, but does not prevent reactivation of latent infection

Front 23

B12 supplementation

Back 23

-patients undergoing total gastrectomy require lifelong vitamin B12 supplementation

-this is due to poor B12 absorption that occurs with intrinsic factor deficiency

--parietal cells in body and funds of stomach secrete intrinsic factor

Front 24

Pantothenic acid

Back 24

-biologically active form of pantothenic acid is coenzyme A

-coenzyme A binds with oxaloacetate in first step of TCA (Krebs) cycle to form citrate and then succinyl-CoA

-so pantothenic acid is necessary for conversions of oxaloacetate to citrate

Front 25

Pulsatile administration of GnRH agonists

Back 25

-pulsatile administration of GnRH agonists stimulates FSH and LH release, and is useful for treatment of infertility

-vs. non-pulsatile (constant) infusion of GnRH, or a longer-lasting analogue, actually SUPPRESSES FSH and LH release, and is therefore useful in treatment of conditions such as precocious puberty, prostate cancer, endometriosis, and dysfunctional uterine bleeding

-GnRH release from anterior hypothalamus in pulsatile manner is responsible for starting the menstrual cycle

Front 26

Diplacement

Back 26

-displacement is one of the immature defense mechanisms

-in displacement, a patient will redirect emotions from the person or object that is causing the negative emotions to a more acceptable, but still inappropriate, person or object

-vs. reaction formation – immature defense mechanism in which unacceptable feelings are ignored and the opposite sentiment is adopted

--ex: man is angry at his wife, and reacts by complimenting her

Front 27

Liver function tests in hyperlipidemia treatment

Back 27

-treatment with many of the hypo-lipidemic drugs (esp. statins) warrants monitoring of liver function tests

-statins are known to cause myopathy and liver toxicity in some patients

Front 28

Statins

-rosuvastatin
-atorvastatin
-simvastatin

Back 28

-statins work by inhibition grate-limiting step in cholesterol biosynthesis (HMG-CoA reductase)

-adverse effects include hepatotoxicity and muscle toxicity

Front 29

Fibrates

-gemfibrozil
-fenofibrate

Back 29

-fibrates work by increases lipoprotein lipase activity; increasing HDL synthesis; and decreasing hepatic VLDL secretion

-adverse effects: muscle tox, especially when combined with statins; gallstones

Front 30

Bile acid sequestrants

-cholestryamine
-colestipol
-colesevelam

Back 30

-bile acid sequestrants bind bile acids in intestine – decrease reabsorption of bile acids and increase de novo synthesis of bile acids from cholesterol (thereby lowering cholesterol levels)

-adverse effects of bile acids include nausea, bloating, cramping; plus decreased absorption of digoxin, warfarin, and fat-soluble vitamins

Front 31

Niacin

Back 31

-niacin treats hyper-lipidemia by decreasing lypolysis in adipose tissue, which causes decreased VLDL synthesis in liver; also increases HDL by reducing clearance of HDL

-side effects of niacin include flushing, warmth, pruritus; and hepatotoxicity

Front 32

Ezetimibe

Back 32

-ezetimibe decreases cholesterol absorption at the brush border of the intestine

-side effects include increased hepatotoxicity when coadministered with statins

Front 33

Control subjects in case-control study

Back 33

-selection of control subjects in case-control studies is intended to provide an accurate estimation of exposure frequency among the non-dieseased general population

-cases and controls are often matched in order to decrease confounding

-however, matching must be carefully performed so as to not introduce selection bias

-ex: in study of relationship of chemical waste exposure to AML, control group will be children both with and without exposure to chemical waste who DO NOT SUFFER FROM AML.

Front 34

Direct inguinal hernias

Back 34

-direct inguinal hernias are seen in older men

-hernia bulges through Hesselbach's triangle, medial to inferior epigastric vessels, to reach the EXTERNAL inguinal ring

-direct inguinal hernia is caused by weakness of the transversalis fascia

Front 35

Indirect inguinal hernia

Back 35

-indirect inguinal hernias are seen in male infants

-indirect inguinal hernias entern INTERNAL inguinal ring, LATERAL to the inferior epigastric vessels

-indirect inguinal hernia is caused by persistent processes vaginalis, and failure of INTERNAL inguinal ring to close

Front 36

Femoral hernias

Back 36

-femoral hernias most common in women

-femoral hernia protrudes through the FEMORAL RING, medial to the femoral vessels, and INFERIOR to the inguinal ligament

Front 37

Proteinuria

Back 37

-forthy or foamy urine may be caused by proteinuria

-heavy proteinuria, as seen in nephrotic syndrome, can cause regional or generalized interstitial edema, because the decreased concentrations of serum albumin and total protein lower the plasma oncotic pressure

--this increases net plasma filtration in capillary beds

Front 38

Common cardinal veins

Back 38

-the common cardinal veins of the developing embryo drain directly into the sinus venous

-these cardinal veins ultimately give rise to the superior vena cava (SVC) and other constituents of the systemic venous circulation

Front 39

Truncus arteriosus

Back 39

-ascending aorta and pulmonary trunk are derived from the truncus arterioles

-a portion of the aortic arch develops from the fourth aortic arch

-neural crest cell migration helps to partition the truncus arterioles into the two great arteries (aorta and pulmonary artery/trunk) by causing fusion and twistingg of the truncal and bulbar ridges

--this process normally results in spiral relationship between aorta and pulmonary artery

--failure of this septation process results in transposition of the great vessels and tetralogy of Fallot