5.10.2015 UWorld Notes

Question 1

65 yo woman LE paresthesias and fatigue. Upper GI endoscopy shows atrophy of gastric body and fundus and normal appearing antrum. Destruction of which gastric layer?

Answer 1

Combo of progressive fatigue, LE paresthesias, and megaloblastic RBCs is pernicious anemia. PA is autoimmune disorder caused by Ab mediated destruction of parietal cells in gastric body and fundus. Over time, this results in chronic atrophic gastritis (autoimmune gastritis). Loss of parietal cells with lymphocytic and plasma cell infiltration.

Parietal cells are oxyntic (pale pink) and found in upper glandular layer. They secrete intrinsic factor and gastric acid. IF is required for absorption of vitamin B12 in ileum and its absence leads to vitamin B12 deficiency. PA develops after critical # of parietal cells destoryed and hepatic stores of coalbumin become depleted.

Deeper aspect of gastric glands=preponderance of small basophilic granular chief cells that synthesize and secrete pepsinogen.
Muscularis mucosae=separates lamina propria from submucosa.
Well vascularized connective tissue=submucosa

Question 2

Ventral pancreatic primordium: Which pancreatic structures derived?

Answer 2

Uncinate process, part of pancreatic head, and proximal portion of main pancreatic duct comes from ventral pancreatic bud

Pancreatic tail, body, superior aspect of head, and small accessory pancreatic duct comes from dorsal pancreatic bud.

Dorsal and ventral pancreatic buds fuse in eight week of fetal life. Proximal part of dorsal pancreatic duct often degenerates but may persist as functional lesser pancreatic duct. Remainder of duct fuses with ventral duct form main pancreatic duct

Pancreas divsium=when ventral and dorsal pancreatic buds fail to fuse. Secretions are drained via two separate duct systems. Dominant dorsal duct opens into duodenum via minor papilla and drains majority of pancreas. Ventral duct opens into major papilla and drains inferior/posterior head and uncinate process.

Question 3

Serum Ab to phospholipase A2 receptor is indicative of…

Answer 3

Glomerulonephritis. PLA2R is transmembrane receptor in high concentrations in glomerular podocytes and is major antigen in pathogenesis of idiopathic membranous nephropathy.
Ab are mainly IgG and lead to immune deposits in glomerulus.

Minimal change disease is due to abnormal T cell production of glomerular permeability factor that affects glomerular capillary wall leading to fusion of foot processes and marked proteinuria.

Mixed cryoglobulinemia is found in pts with Hep C. Renal disease due to IgM deposition in glomerulus that leads to basement membrane thickening and cellular proliferation.

Renal disease in multiple myeloma is due to deposition of light chains and not been associated with PLA2R Ab.

Membranous nephropathy is seen in 20% of lupus patients. PLA2R Ab are not found.

Question 4

Seizure medications

Answer 4

Simple (no LOC; motor/sensory/autonomic/pyschic sx)/complex (LOC and automatisms eg lip smacking): Narrow spectrum: Carbamezepine, gabapentin, phenobarbital, phenytoin.

Generalized:
Tonic clonic (loss of consciousness and diffuse muscle contraction followed by rhythmic jerking) and myoclonic (no loss of consciousness/brief jerking movements): Topiramate, valproic acid, levetiracetam, lamotrigine. 

Status epilepticus=Diazepam

Tourette syn=Fluphenazine

Absence (Brief LOC, automatisms): Ethosuximide

Essential tremor=Propanolol (non selective B blocker)

Question 5

Obturator nerve exits though obturator foramen. Innervates?

Answer 5

Adductor compartment of thigh. Anterior branch innervates gracilis, pectineus, adductors longus and brevis. Posterior branch innervates obturator externus and adductor magnus.

Abduction of thigh: Tensor fascia lata and sartorius muscles. Supplied by superior gluteal and femoral nerves respectively. Anterior compartment of thigh.

Flexion of thigh: Psoas, iliacus, tensor fascia lata, sartorius. Psoas innervated by lumbar plexus. Iliacus innervated by femoral nerve.

Extension of thigh by gluteus maximus supplied by inferior gluteal nerve. Exits pelvis through greater sciatic foramen below piriformis.

Extension of leg through quradriceps femoris: Femoral nerve. Accesses thigh deep to center of inguinal ligament.

Question 6

H band contains only myosin thick filaments. A band contains whole thick myosin filament (actin filaments too).

Answer 6

During contraction, actin filaments slide over myosin filaments toward M line decreasing H band size. A band does not change size during contraction.

Question 7

In order to be radiolabeled by DNA probe, protein must be able to bind DNA. What are porteins that can bind DNA?

Answer 7

TFs, steroids, thyroid proteins, vit D receptors, retinoic acid receptors, DNA transcription and replication proteins, etc.

N-myc (mammalian transcription factors): Protein overexpressed in Burkitt lymphoma.

IGF1: binds cell membrane associated receptors with tyrosine kinase activity to produce anti-apoptotic and anabolic effects.

Question 8

Most gastric ulcers arise in lesser curvature of stomach. In transitional zone between acid-secreting epithelium of gastric corpus and gastrin producing epithelium of antrum. Glands in corpus contain parietal cells that produce HCL and intrinsic factor. Mucosal glands in antrum contain G cells that secrete gastrin.

What are arteries that supply stomach?

Answer 8

Proximal less curvature: Left gastric
Distal lesser curvature: Right gastric
Proximal greater curvature: Left gastroepiploic
Distal greater curvature: Right gastroepiploic
Proximal greater curvature: Short gastric arteries

Common hepatic artery perfuses liver, gallbladder, pylorus, duodenum, and pancreas. Arises from celiac trunk and ends when it bifurcates into proper hepatic and gastroduodenal arteries.

Question 9

Malignant otitis externa: Severe infection in elderly diabetic patients.

Answer 9

Pseudomonas aeruginosa.
Nonlactose fermenting, oxidase positive, motile gram negative rod. Patients present with ear pain and drainage. Granulation tissue seen in ear canal=important characteristic finding of MOE. Tympanic membrane intact.

Progression of infection leads to osteomyelitis of skull base and cranial nerve damage. Treatment: Systemic antibiotics such as ciprofloxacin.

Question 10

Tension pneumothorax

Answer 10

Increasing volume of air accumulates in pleural space. Lungs and mediastinum deviate to opposite side of chest. Increased pressure in chest cavity causes decreased systemic venous return to heart, leading to decreased cardiac output.

Signs and symptoms of tension pneumothorax include tachycardia, hypotension, tachypnea, hypoxemia, absence of breath sounds, and hyperresonance to percussion on affected side. Treatment is with emergency needle thoracostomy or chest tube.

Accessory nerve innervates SCM and trapezius muscles. May be injured if surgery to posterior triangle of neck (bounded by SCM, trapezius muscle, and clavicle).

Carotid body contains O2, CO2 and H+ chemoreceptors. Lies at bifurcation of common carotid artery (just inferior to hyoid bone).

Inferior thyroid artery injury=Hoarseness because runs adjacent to recurrent laryngeal nerve. Supplies inferior pole of thyroid gland.

Question 11

ADPKD

Answer 11

Multiple cysts in both kidneys that enlarge over decades. Asymptomatic until 4th or 5th decade when enlargement of cysts impairs renal function. Worsens with age. 50% progress to end stage renal disease by age 70.

Other complications: HTN, abdominal and flank pain, gross hematuria, UTI, kidney stones. Liver cysts and intracranial aneurysms. Liver cysts do not cause loss of liver function but may cause pain if large.

Renal cysts: Seen on imaging by 3rd to 4th decade. Do not enhance==differentiating them from solid metastases or malignancies.

ARPKD=Large cysts at birth; many kids die during first decade of life. Due to renal failure, hepatic fibrosis, pulmonary hypoplasia.

Prader Willi and Angelman syndromes: Caused by paternal and maternal chromosome 15 deletions respectively.

Question 12

Erythema of antral mucosa. Biopsy of affected mucosa shows inflammatory cell infiltrates.

Answer 12

B chronic gastritis: Inflammatory cell infiltrate (acute=neutrophil vs. chronic=lymphocyte and plasma cell predominant) gastritis.

Chronic H pylori is associated with increased risk of gastric adenocarcinoma and MALT lymphoma (low grade B cell lymphoma).

Zollinger Ellison syndrome: Hypersecretion of gastric acid leading to peptic ulcers in duodenum, abdominal pain, GERD, diararhea. Overproduction of gastric by gastrin secreting pancreatic islet cell tumor.

Crohn’s disease: Inflammatory bowel disease any portion of GI tract. Fevers, RLQ pain (terminal ileitis), diarrhea.

Gluten intolerance (celiac sprue): Lymphocytic infiltrates in small intestinal mucosa and blunting of small intestinal villi.

Megaloblastic anemia occurs in chronic gastritis: Affects body of stomach rather than antrum. Autoimmune destruction of parietal cells causes decreased intrinsic factor production and failure of Vit B12 absorption.

Question 13

Three main causes of HIV associated esophagitis:

Answer 13

Candida, cytomegalovirus, herpes virus.
All cause dysphagia and odynophagia (pain on swallowing).

Endoscopic findings: Candida=Patches of gray/white pseudomembranes on erythematous mucosa (yeast cells and pseudohyphae that invade mucosal cells)
HSV1=Small vesicles that evolve into punched out ulcers (eosinophilic intranuclear inclusions in multinuclear squamous cells at margins of ulcers)
CMV=Linear ulceration, hyperemia and ulcerations of mucosa (intranuclear and cytoplasmic inclusions).

Babesia divergens: Tick bite and causes babesiosis: NE U.S. influenze like sx, hepatosplenomegaly, anemia.

HIV positive patients: Toxoplasma causes ring enhancing brain lesions and chorioretinitis.

Isopora belli: Profuse watery diarrhea in HIV patients.

Herpes simplex NOT herpes zoster causes esophagitis in HIV patients.

Trypanosoma cruzi causes Chagas disease: Cardiomyopathy, achalasia, megacolon, megaureter in chronic disease.

Cryptococcosis causes meningitis not esophagitis in HIV patients.

Question 14

SA Node–>AV node–>LBB and RBB–>Purkinje Fibers

Answer 14

SA node rate 60-100 bpm. Impulses transmitted through conduction system to ventricles which depolarize from apex to base and from endocardium to epicardium.

P wave=Atrial depolarization
Ventricular depolarization=QRS complex
Ventricular repolarization=T wave

Complete (third degree) AV block: SA node impulses cause atrial contraction while impulses generated by AV node cause ventricular contraction. AV nodal cells become pacemakers. On ECG, atria and ventricles depolarize independently of each other. QRS complexes are narrow. AV node produces heart rate of 45-55 bpm.

When electrical impulses generated below AV node and His bundle, heart rate can slow down to 20 bpm. ECG shows prolonged abnormally shaped QRS complexes due to aberrant impulse conduction through ventricles.

Question 15

Maple syrup urine disease

Answer 15

Defective breakdown of branches chain aa: leucine, isoleucine, and valine.

Specific defect occurs in enzyme branched chain alpha keto acid dehydrogenase. Sx: Dystonia and poor feeding in first few days of life. Degradation is inhibited at alpha keto acid stage=leads to neurotoxicity.
Treatment: Dietary restriction of branched chain amino acids.

Question 16

Vagus nerve stimulates=Ach released. It produces bronchoconstriction by acting on muscarinic receptors. Ipratropium blocks actions of acetylcholine at muscarinic receptors preventing this effect. No bronchodilatoin effects. Simply reverses bronchoconstriction.

Answer 16

Ipratropium and similar asthma drugs are less effective than beta-2-adrenergic agonists: Starts working 60-90 minutes after treatment.
No systemic anticholinergic side effects because inhaled ipratropium is poorly absorbed from respiratory mucosa.

Albuterol=short acting selective beta-2-adrenergic agonist: Sympathomimetic. First line treatment of acute asthma: bronchodilatory effects are independent of parasympathetic innervation.

Methlxanthines: Theophylline and aminophylline cause bronchial dilation by decreasing phosphodiesterase activity increasing intracellular concentration of cAMP. Block adenosine receptors=increasing bronchodilatory effects.

Leukotrienes are synthesized from arachidonic acid via lipoxygenase pathwya. Zileuton inhibits this pathway reducing leukotriene production. Sileuton used as prophylactic therapy for asthma.

Flunisolide=Inhaled glucocorticoid; used for prophylactic treatment of bronchial asthma. Potent anti-inflammatory effects. First line prophylactic treatment.

Nifedipine: Blocks calcium influx into bronchial smooth muscle causing bronchodilation.

Question 17

Phospholipase C system

Answer 17

Alpha1 adrenergic, M1, M3, V1, H, oxytocin, angiotensin II, TRH, GnRH.
1. Binds ligand to receptor which causes exchange of GDP for GTP on Gq protein. Exposes phospholipase C activating site. Phospholipase C hydrolyzes PIP2 into DAG and IP3.

2. DAG stimulates protein kinase C which increases intracellular calcium.

Intracellular cAMP and cGMP concentrations increase during activation of adenylate or guanylate cyclase second messenger systems respectively. Sildenafil=Inhibts cGMP phosphodiesterase and results in smooth muscle relaxation in blood vessels.

GABA=Increases intracellular Cl- concentration. Hyperpolarization of neuron.

NO: Causes vasodilation; synthesized from arginine and O2 by NO-synthase.

Question 18

Erroneous aa/tRNA coupling by AA-tRNA synthetase causes wrong aa to be incorporated into growing polypeptide chain.

Answer 18

DNA glycosylases are enzymes involved in DNA base excision repair.

tRNA that is mischarged with incorrect aa and not corrected by AA-tRNA synthetase proofreading will incorporate wrong amino acid into growing polypeptide chain. No amino acid proofreading during protein translation.

Question 19

WBC casts are only formed in tubules where WBCs are precipitated by Tamm-Horsfall protein secreted by tubular epithelial cells. They are pathognomonic for…

Answer 19

Pyelonephrtitis when UTI present.

Bacteriuria and microscopic hematuria are found in both upper (acute pyelonephritis) and lower UTIs (cystitis, urethritis).

Question 20

Active form of vitamin D=calcitriol.

Answer 20

Calcitriol increases Ca and P absorption from intestine and kidneys. Chronic renal disease leads to diminished urinary excretion of phosphate and elevated serum phosphate levels. Serum phosphate forms complexes with serum calcium decreasing the level of calcium available to tissues.

Loss of renal parenchyma in kidney causes decreased renal calcitriol production. Calcitriol deficiency leads to decreased calcium absorption and increased calcium loss in urine.

Net effect: LOW SERUM CA and HIGH SERUM PHOSPHATE. THIS STIMULATES PTH.

Secondary hyperparathyroidism: High PTH, low calcium, high phosphate, low calcitriol. PTH mobilizes Ca from bones to increase serum calcium levels. Bone resorption=renal osteodystrophy causes bone pain and signs of osteopenia and soft tissue calcification on x-ray.

Calcitonin secreted by parafollicular cells of thyroid in response to elevated Ca levels. Lowers serum Ca by promoting bone mineralization and reducing intestinal calcium absorption.

Question 21

Treatment with ACE inhibitor can precipitate acute renal failure.

Answer 21

Angiotensin II is vasoconstrictor in kidneys. In pts with renovascular-hypertension, angiotensin II mediated vasoconstriction in necessary to maintain adequate GFR.

Kidney maintains GFR by dilating afferent arteriole and constricting efferent arteriole normally.

Inhibition of ACE leads to decrease in angiotensin II causing dilation in efferent arteriole thus increasing renal blood flow. This leads to drop in filtration fraction and GFR.

Increase in creatinine up to 30% in 2-5 days can be expected in patients who start on ACE inhibitors. This stabilizes in 2-3 weeks and is reversible upon drug discontinuation. However, for patients dependent on efferent arteriole constriction to maintain renal perfusion : ACE inhibitors can be detrimental causing acute renal failure.

Question 22

Atropin can be administered prior to bronchoscopy to decrease respiratory mucus secretions and promote bronchodilation. Can cause anti-muscarinic toxicity esp. in eledlery patients.

Answer 22

Atrophine can cause dry flushed skin, hyperthermia, mydriasis, cycloplegia, bronchodilation, tachycardia, constipation, urinary retention.

Physostigmine inhibits acetylcholinesterase peripherally and centrally. This counteracts atropine.

Diazepam can be used to treat atropine induced agitation but would not reverse antimuscarinic effects.
Neostigmine and edrophonium=has ammonium structure that prevents penetration at BBB at moderate doses; wouldn’t help CNS symptoms of antimuscarinic drug.

Question 23

T gondii is obligate intracellular protozoan. Cat id host.

Answer 23

Leads to encephalitis with multiple necrotizing brain lesions, fever, headache, AMS, focal neurologic findings.
HIV with seizures, ring enhancing lesions, and mass effect=Cerebral toxoplasmosis is likely diagnosis. Second most likely dx: CNS lymphoma

First line treatment; Pyrimethamine and sulfadiazine.

Amphotericin is used to treat cryptococcal meningitis in AIDs patietns: n/v, AMS, nucal rigidity. No ring enhancing lesions on imaging.

Ampicillin used to treat listeria. Can cause meninigitis in immunosuppressed but does not form ring-enhancing lesions.

Ganciclovir: Treating cytomegalovirus. Causes reinitis, esophagitis, pneumonia. Sx: Encephalitits, transverse myelitis, polyneuropathy.

TB: Granulomatous lesions in brain. 5 drug regimen.

Question 24

CNS lymphoma is…

Answer 24

b cell origin that occurs in HIV. Epstein Barr virus is in almost all cases. Diagnosis of lymphoma can be made by positive EBV polymerase chain reaction in CSF.

T cells associated in AIDS T cell lymphoma-not primary CNS lymphoma.

Question 25

Focal dystonia

Answer 25

Uncontrollable muscle contraction causing pain or discomfort and physical deformity in some cases.
Classic example: SCM cervical dystonia=TORTICOLLIS.

Local injection of botulinum toxin type B results in muscular relaxation because toxin prevents presynaptic release of Ach. No contraction can occur.

Clostridium botulinum is gram positive spore forming anaerobic bacillus that synthesizes potent neurotoxins intracelluarly then releases them by autolysis.

Antiphagocytic capsule is virulence factor for strep pneumo and h. influenzae and neisseria bacteria.

Hypervariable pili=N. meningitidis and N. gonorrhoeae.

Staph aureus has igG binding outer membrane protein (virulence factor Protein A). Binds Fc portion of IgG and prevents opsonization, phagocytosis, complement fixation.

Intracellular polyphophate granules are characteristic of corynebacetium diphtheriae. Granules in cytoplasm seen in methylene blue staining.

Question 26

OCPs inhibit ovulation by…

Answer 26

LH spike required to stimulate ovulation. OCPs prevent this and cause thickening of cervical mucus that prevents sperm from accessing uterus. OCPs have progestin which prevents growth of endometrium making it unsuitable for implantation of embryo. OCPs decrease synthersis of FSH and LH in anterior pituitary.

OCPs do not directly affect synthesis of prolactin and estrogen.

Question 27

Constipation in pts on chronic opiate therapy treated with

Answer 27

Osmotic laxatives (magnesium citrate, polyethylene glycol), stoll softeners, and enemas.

Osmostic laxatives are nonabsorbable orp poorly absorbable substances that attract water into intestinal lumen thus distending intestinal wall and increasing peristalsis.

Laxative effect is rapid.

Lactase deficiency is disease state characterized by osmotic diarrhea. Deficiency of brush border enzyme lactase causes inability to break down lactose into glucose and galactose. Undigested lactose is nonabsorbable osmotic substance and accumulation in small intestine lead sto increase in secretion of water and electrolytes into intestinal lumen. Lacatse deficiency present with abdominal pain, distension, watery diarrhea.

IBS: Constipation, abdominal pain, and distention, and diarrhea alternating without organic cause. Fecal water and electrolyte content are normal.
Crohn’s disease: Diarrhea: High electrolyte content due to poor absorption and increased losses from inflamed mucsoa.

CF (esp in kids) can cause rectal prolapse: Associated with pregnancy, constipation, and severe diarrhea.

Question 28

Glucocorticoids are potent stimulators of liver GneoG.

Answer 28

Stimulate formation of key gluconeogenic enzymes. Leads to hyperglycemia.

Glucocorticoids act to antagonize actions of insulin in muscle and adipose tissue favoring catabolism and lipolysis. Muscle weakness, skin thinning, impaired wound healing, osteoporosis, immunosuppression (decreased T cells and eosinophils; increased neutrophils because of demargination from blood vessel walls).

Question 29

Paracortex=region of lymph node populatd primarily by T lymphocytes and dendritic cells. Lies internal to cortex between follicles and medulla. Dendritic cells present Ag that they collect from blood and lymph to T lymphocytes in this region. Paracortex becomes enlarged by proliferation of T lymphocytes during adaptive cellular immune response. Which condition is this poorly developed?

Answer 29

DiGeorge Syndrome: Deficiency of mature T lymphocytes.

Outer cortex: Follicles are site of B lymphoctye localization and proliferation. Primary follicles are dense and dormant. Secondary follicles have pale germinal center containing proliferating B cells and follicular dendritic cells. In agammaglobulinemia: germinal centers and primary lymphoid follicles do not form due to absence of B cells.

Medullary cords contain B cells, plasma cells, macrophages. Medullary sinuses contain reticular cells and macrophages.

Subcapsular sinuses between capsule and cortex of lymph node. In direct communication with afferent lymphatic vessels and cortical sinuses that line trabecula. Cortical sinuses are continuous with medullary sinuses and single efferent lymphatic channel exiting the hilum.

Question 30

Xeroderma pigmentosum: Pigmented dry skin

Answer 30

AR condition due to decreased ability to repair DNA damage after UV light exposure (DNA excisional repair).

Erythema, scaling, hyperpigmentation, lentigo formation on light exposed areas. Skin shows atrophy, telangiectasias, areas of hypo and hyperpigmetnation. SC and malignant melanoma can develop at age 5-6.

Defect in excision of abnormal nt or defect in replacement of nt after excision.

Fanconi anemia: AR hypersensitivity to cross-linking agents.
Bloom syndrome: AR, hypersensitivity to UV damage and chemotherapeutic agents.
Lynch syndrome: hereditary nonpolyposis colorectal cancer. Abnormalities of genes responsible for DNA mismatch repair.

Question 31

DVT therapy

Answer 31

Anticoagulation therapy for three months to prevent recurrent thrombosis. Initial treatment often with heparin agents followed by bridging to oral anticoagulant.

Additional treatment options: Direct factor Xa inhibitors (apixaban, rivaroxaban) and direct thrombin inhibitor (dabigatran)

Meds that affect extrinsic pathway prolong PT. Inhibition of intrinsic pathway prolongs activated partial thromboplastin time. Thrombin time is prolonged with meds that directly or indirectly inhibit thrombin. Because factor Xa is located at junction of intrinsic and extrinsic pathways. Direct factor Xa inhibitors prolong both aPTT and PT with no effect on TT.

Factor VIIa inhibitors work on extrinsic pathway. They prolong PT with no effect on aPTT or TT.

Direct thrombin inhibitiros prevent formation of thrombin (factor IIa) resulting in prolongation of TT, PT, and aPTT.

Unfractionated heparin prolongs aPTT and TT (inactivates thrombin and Factor Xa). PT is prolonged theoretically but PT reagent contains heparin neutralizers that minimize this effect.

Question 32

Primary osteoporosis

Answer 32

Serum calcium and PTH in normal range.

Vitamin D deficiency/renal failure: High PTH with low serum calcium.

Primary hyperparathyroidism: High calcium levels and low PTH.

Question 33

Minute ventilation

Answer 33

Work done against elastic resistance of lung is increased when tidal volume is increased.
Work done against airflow resistance is increased when breathing frequency is increased.

Increase in elastic resistance: Pulmonary fibrosis, pulmonary edema. ARDS
Diseases that cause high airflow resistance: Asthma, COPD

Anxiety disorders: Rapid shallow breaths. Lungs are normal. Work done against airflow resistance will be increased.
Fixed upper airway obstruction: Goiter; increased airflow resistance which favors slow deep breaths.

Question 34

MI histology changes in healing process

Answer 34

0-4hrs: minimal change
4-12hrs: early coagulation necrosis, edema, hemorrhage, wavy fibers
12-24 hours: coagulation necrosis, marginal contraction band necrosis
1 to 5 days: Coagulation necrosis and neutrophilic infiltrate
5 to 10 days: macrophage phagocytosis of dead cells
10 to 14 days: Granulation tissue and neovascularization
2 weeks to 2 months: Collagen deposition/scar formation.

Question 35

Normal distribution: 68/95/99 rule. 1SD/2SD/3SD

Answer 35

Look at SD and normal bell curve.