Rahul Damania, MD, FAAP

A 69-year-old smoker presents with “double vision,” lower extremity muscle weakness with exertion, and diminished deep tendon reflexes. Results of neurologic, cardiovascular, and ophthalmologic examinations are negative. X-ray of the chest reveals a small circular lesion in the right lung hilum. A full cancer work-up reveals metastases throughout the body. A biopsy report from the pathologist gives the diagnosis of oat cell carcinoma. Which of the following is the most likely cause for this man’s diplopia and weakness?

(A) Antibodies against presynaptic calcium channels at the neuromuscular junction (B) Autoantibodies to acetylcholine receptors at the neuromuscular junction (C) Autoimmune disease with anti-double- stranded DNA, anti-DNA, and anti-Smith antibodies (D) Inflammatory disorder of synovial joints with pannus formation (E) Reactivation of a peripheral subpleural parenchymal lesion and hilar lymph nodes

Neuromuscular Junction

One Step Beyond

Neuromuscular Junction

Myasthenia Gravis

• What is the mechanism behind the likely pathology?• Antibodies to AchR → Myasthenia Gravis

• What imaging modality would be the next best step?• CT or X-Ray of the Chest → associated with thymoma

• What is the mechanism for the best initial therapy?• AchE inhibition

• What are the names of the drugs in this class?• Galantamine, Rivastigmine, Donepezil

• What other neurological condition would this class of medications be helpful for?• Alzheimer's disease

An 11-year-old girl is brought to the pediatrician with complaints of back pain. On physical examination, a right thoracic scoliotic curve is noted. An x-ray film indicates that the curve is 25 degrees. Girls with scoliosis need to be especially carefully watched during peak height velocity, during which the curvature can dramatically worsen. Given that peak height velocity occurs during a particular Tanner stage, what other physical attributes would one expect to occur in the girl at the same time?

(A) Elevation of the breast papilla only and no pubic hair (B) Enlargement of the breast and areola with a single contour and darker, coarse curled pubic hair (C) Mature breast adult quantity and pattern of pubic hair that extends to the thighs (D) Projection of the areola and papilla with separate contours and adult-type pubic hair limited to the genital area (E) Small breast buds with elevation of breast

Tanner Stage

One Step Beyond

Tanner Stage

Tanner Stage

A 27-year-old man walks into the emergency department in an agitated state. He complains of severe abdominal pain and eventually becomes combative, requiring five-point restraint. His vital signs show elevated blood pressure and tachycardia. When a straight catheter is inserted, reddish urine enters the Foley bag. The urine is negative for RBCs, and a toxicity screen is negative. His doctor suspects a porphyria; laboratory tests for urine porphobilinogen are positive. Which of the following enzyme deficiencies is responsible for this patient’s disorder? (A)Aminolevulinate dehydratase (B)Aminolevulinate synthase (C) Ferrochelatase(D) Heme oxygenase (E) Porphobilinogen deaminase(F) Uroporphyrinogen decarboxylase (G) Uroporphyrinogen III cosynthase

Heme Synthesis

One Step Beyond

Heme Synthesis

Glycine + succinylcoA

Delta ALA

Porphobilinogen

Hydroxymethylbilane

Uroporphyrinogen

Corporophyrinogen

Protoporphyrin

Heme

Delta ALA synthase: Sideroblastic Anemia, basophilic stippling with remnants of rRNA, X-linked

ALAD: Lead poisoning, child with dev delay, abd pain, and microcytic anemia

PROD: AIP, abd pain, port-wine urine, precipitated by drugs

UROD: PCT, blisters, red urine, hypertrichosis, photosensitivity

Ferrochetalase: lead poisoning –cannot incorporate iron into heme in the mitochondria

A group of oncologists is interested in determining whether a relationship exists between alcohol use and pancreatic cancer. The re-searchers enroll 1,000 patients, and subjects are placed into different groups depending on their level of alcohol consumption. The subjects are followed for 10 years; the data show no statistical difference in the number of pancreatic cancers between the groups. The above research is an example of which of the following kind of study? (A) Case-control study(B) Clinical treatment trial (C) Cross-sectional study(D) Prospective cohort study (E) Retrospective cohort study

Study Design

One Step Beyond

Study Design

Study Design

Study Designs

A retrospective cohort study is examining birth complications in women with diabetes. The study determines that babies are more likely to be born large for gestational age (LGA) if the mother has diabetes. The relative risk for the study is calculated to be 4. Which of the following accurately describes this relative risk? (A) The incidence rate of diabetes among mothers with LGA babies is 4 times that of non-LGA mothers (B) The incidence rate of LGA among women with diabetes is 4 times that of women without diabetes (C) The incidence rate of LGA among women without diabetes is 4 times that of women with diabetes (D) The odds of diabetes among mothers with LGA babies is 4 times that of non-LGA mothers (E) The odds of LGA among women with dia- betes is 4 times that of women without dia- betes

Study Design

One Step Beyond

Odds Ratio & Relative Risk

Biostatistics

35-year-old woman and her husband come to the physician because she has been acting strangely. The husband explains that approximately 3 weeks ago his wife stopped showing up for work, spent most of their life savings during this time, and seemed very irritable when he questioned her about this behavior. He also reports that she is no longer sleeping through the night and that she is now claiming to be the most intelligent woman in the world. Which of the following is the most likely diagnosis? (A) Amphetamine intoxication (B) Bipolar disorder(C) Hyperthyroidism(D) Schizoaffective disorder(E) Schizophrenia

Mood Disorders

One Step Beyond

Mood Disorders

Bipolar

• 25 yo found naked in Las Vegas store, last 1 week he is not sleeping, and thinks he is the king of the world. What may the next best step in management in the ED?• Toxicology Screen

• Distractable Insomnia Grandiose Flight of ideas Agitation Sexual exploits Talkative.• How many do you need to qualify mania?

• >3 symptoms for >1 week• May have some psychotic features • Bipolar II:

• Hypomanic predominant: • Symptoms less severe, >4 days, does not cause marked impairment and

does not have psychosis

A 4-month-old girl who was born full-term presents to her pediatrician with an upper respiratory infection. Her mother notes that this is the fifth time her daughter has had an upper respiratory infection since birth. Her past medical history is significant for seizures shortly after birth. In addition to pulmonary findings, the physical examination is notable for oropharyngeal candidiasis that the patient’s mother says has been occurring regularly. This child is presenting with a syndrome that is due to aberrant development of which of the following embryonic structures? (A) First and second aortic arches(B) First and second branchial arches (C) Fourth and sixth pharyngeal arches (D) Second and third branchial clefts (E) Third and fourth branchial pouches

Pharyngeal Derivatives

One Step Beyond

Pharyngeal Derivatives

Embryology

Pharyngeal Arch: Columns of tissue

between pharynx and external embryo

Mesoderm + Neural Crest

Pharyngeal Clefts: separate arches

externally and are grooves of ectoderm

epithelium

Pharyngeal Pouch: depressions

between arches and lined by endoderm epithelium

Pouch Derivation USMLE points

1st pouch Middle ear cavityEustachian tube “Ear”

2nd pouch Palatine tonsils ”2 tonsils”

3rd pouch Inferior ParathyroidsThymus

”3 is an inferior number”

4th pouchSuperior parathyroidsPara-follicular C-cells

of the thyroid

“4 is a superior number”

Calcitonin

A 65-year-old man presents to the office with complaints regarding his urine. He states that he has recently had bloody urine, but does not have any urinary pain, hesitation, dribbling, or increased frequency. He also says he has lost 4.5 kg (10 lb) over the past 2 months. A biopsy of the patient’s bladder wall is shown in the image. Which of the following risk factors has the strongest association with this patient’s disease? (A) History of aniline dye exposure(B) History of cyclophosphamide treatment (C) History of heavy cigarette smoking(D) History of pelvic irradiation(E) History of schistosomiasis infection

Risk Factors

One Step Beyond

Smoking

USMLE Smoking Associations

Bupropion & Varenicline for Cessation

Pancreatic CA

Bladder and Cervical CA

Squamous & Small Cell CA

Renal Cell CA

Esophageal CA Squamous & Adenocarcinoma

Laryngeal CA

Oropharyngeal CAAtherosclerosisAbdominal Aortic Aneurysms

Saccular Aneurysms

Colon Cancer

A 68-year-old white man with a history of diabetes mellitus, hypertension, increased cholesterol, sedentary lifestyle, and 40-year smoking history comes into the office complaining of severe substernal chest pressure that resolved when he sat down and relaxed. The patient states that he has “always” had episodes like this but they have not caused this much distress. Angina caused by silent myocardial ischemia is suspected. An ECG is performed and the patient is recommended to have an exercise stress test. Which of the following is a physiologic response to exercise? (A) Decreased arterial pH with strenuous exercise (B) Decreased oxygen consumption (C) Increased hypoxic vasoconstriction (D) No change in venous partial carbon dioxide pressure (E) Pulmonary blood flow remains unchanged

Smoking As Risk Factor

One Step Beyond

V/Q Mismatch

Summary• Hypoxemia:

• 1. Hypoventilation.• 2. Altitude. • 3. Diffusion impairment. • 4. **V/Q mismatch. • 5. Right to Left Shunt.

• Remember 1-2 have normal A-a gradient

Visual Pathways

A 65-year-old obese man with a 60-pack-year smoking history presents with partial loss of vision after suffering a stroke. Physical examination reveals a bilateral defect in the upper left visual quadrants. Where is this patient’s lesion most likely located?

(A) Dorsal optic radiation in the left parietal lobe

(B) Dorsal optic radiation in the right parietal lobe

(C) Left optic tract

(D) Loop of Meyer in the left temporal lobe

(E) Loop of Meyer in the right temporal lobe

(F) Right optic tract

One Step Beyond

Visual Pathways

Lesions Beyond the Chiasm = Homo

DysphagiaA 30-year-old woman presents to her physician complaining of chest pain and difficulty swallowing. Results of ECG and x-ray of the chest were normal, but the following image was seen during a barium swallow study. Which of the following actions is most likely absent in this patient?

(A) Contraction of the lower esophageal sphincter

(B) Contraction of the upper esophageal sphincter

(C) Initiation of swallowing in the oropharynx

D) Relaxation of the lower esophageal sphincter

(E) Relaxation of the upper esophageal sphincter

One Step Beyond

Dysphagia

Dysphagia

• Achalasia. What is the histopathology?• Loss of myenteric plexus.

• Between the inner circular and outler-longitudinal

• Achalasia:• Bird’s beak on swallow• High LES on manometry • Relate to Chagas Disease (T. cruzi) and CREST

Brain Hemorrhages

A 23-year-old man comes to the clinic complaining of a severe headache that started 2 hours ago. He describes the headache as being “the worst in his life.” His blood pressure is 138/95 mm Hg, and his heart rate is 56/min. On examination, the physician notes hyperextensible joints and increased skin elasticity, with hyperpigmentation over bony prominences. The examination is otherwise unremarkable. The patient states that he has not had any medical problems in the past. A CT scan of the head reveals blood in the sulci indicative of a subarachnoid hemorrhage. What is the most likely defect associated with this patient’s disease?

(A) Antibodies to U1RNP

(B) Deficient hydroxylation of propyl and lysyl

residues

(C) Keratin gene mutation

(D) Type III collagen gene mutation

(E) Type IV collagen gene mutation

One Step Beyond

Brain Haemorrhages

Subarachnoid Hemorrhage• Patient with U/S confirmed cystic kidneys, has

a sudden onset of headache, vomiting, and photophobia. Where is the most likely location of this pathology?• Diagnosis: Rupture of berry aneurysm → SAH• ACA and Anterior communicating artery junction

• Mechanism: At this junction there is no strong media, so aneurysms prone to occur and rupture

• Classic pattern on CT imaging:• Pattern of blood follows sulci and gyri

• CCB nimodipine is given to reduce risk of vasospasm

Epidural Hematoma

• What would be possible scenarios in the test question?• “Patient who got hit on the side of the head”• “Skull fracture”• “Patient after trauma who was AOx3, and then passes away 5 hours

later.• “Talk and Die”

• What is the affected artery?• Middle meningeal

• Branch off maxillary artery (one of terminal branches of external carotid)

Subdural Hemorrhage • What would be possible scenarios in the test question?

• “Baby who has bilateral retinal hemorrhages”• Child abuse • “Nursing home resident who fell” also “alcoholic”• Both have atrophy of brain, and this increases the risk of bleed in

subdural hematoma• Slow onset of symptoms

• What is the affected artery?• Tearing of the bridging veins

Lipid Lowering Agents

The targets of multiple lipid-lowering agents are labeled in the image. Which of the targets corresponds to the therapy associated with the most significant decrease in triglyceride levels?

(A) A

(B) B

(C) C

(D) D

One Step Beyond

Lipid Lowering Agents

Diuretic

A 72-year-old man comes to the emergency department because of shortness of breath and dyspnea on exertion for the past few days. Physical examination reveals pitting edema bilaterally in the lower extremities. The patient is given a combination drug therapy for his condition. Which of the following therapies, while effective, may lead to dangerous physiological sequelae when used in combination?

(A)Acetylsalicylic acid and a thiazide diuretic

(B) Acetylsalicylic acid and nitroprusside

(C) β-Blocker and a thiazide diuretic

(D) β-Blocker and spironolactone

(E) Digoxin and furosemide

(F) Digoxin and spironolactone

One Step Beyond

Barter & Gitlemen

Integrated Questions

• What is the difference between Barter’s syndrome and

Gitelman’s syndrome?

• Barter’s syndrome is to loop diuretic

• Gitleman’s syndrome is to thiazide

• What is Liddle syndrome?

• Pseudohypoaldosteronism

• Hyperaldosterone electrolyte abnormalities

• Aldosterone levels are nearly undetectable

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