Week 2

Question 1

A 7-year old male has a right leg cast made after a bicycle accident. After wearing the cast for some time, he complains of pain and numbness of the dorsum of his right foot and cannot dorsiflex his right ankle.

Where is the sight of nerve compression and which nerve is damaged?

Answer 1

► Site = fibular head
► Common peroneal (fibular) nerve is most commonly injured in the leg due to superficial location where it courses laterally around the neck of the fibula
► After coursing around neck of fibula, common peroneal divides into superficial and deep

• Superficial - muscles of lateral compartment of leg -> primary function is to evert the foot (damage results in foot inversion)
• Deep - innervate anterior compartment act as dorsiflexors of foot and toes (damage results in foot drop)

Question 2

Briefly describe the MAP-kinase signal transduction pathway

Answer 2

• ­Includes Ras protein, a G-protein that exists in inactive (GDP-containing) and active (GTP-containing) forms
• ­ Mutated (permanently activated) Ras is associated with the development of malignant tumors

Question 3

Common side effects of loop diuretics?

Answer 3

• Hypokalemia
• Hypomagnesemia
• Hypocalcemia

Less common:

• Volume depletion
• Hyponatremia
• ↓ GFR
• Hypotension
• Ototoxicity - higher dosages, rapid IV infusion, usually when combined with other ototoxic agents, resulting in tinnitus, vertigo, hearing impairment, or deafness, usually reversible

Question 4

Describe the embryological formation of the pancreas including the origin of each structure.

Answer 4

• ­Duodenal portion of foregut gives rise to dorsal and ventral pancreatic buds
• ­ Dorsal pancreatic bud: pancreatic tail, body, most of head, small accessory pancreatic duct
• ­ Ventral pancreatic bud (smaller): Uncinate process, portion of pancreatic head, proximal portion of main pancreatic duct.
• ­ Dorsal + ventral buds fuse during week 8, proximal part of dorsal (accessory) pancreatic duct degenerates, and remainder of accessory duct fuses with ventral duct to form the main pancreatic duct (of Wirsung)

Question 5

Describe the Ras-MAP kinase pathway

Answer 5

► Growth factor ligand binding to receptor tyrosine kinase ->
► Auto-phosphorylation of the receptor ->
► Phosphotyrosine produced interacts with number of proteis (SH2 domain proteins and SOS protein) ->
► Ras activation (GDP -> GTP from) and then initiates phosphorylation cascade->
► Raf kinase ->
► Activation of MAP (mitogen-activated protein) kinase ->
► Enters nucleus too influence gene transcription

Question 6

First arrhythmia to appear as a result of acute myocardial ischemia?

Answer 6

• Ventricular fibrillation
• Most common cause of lethal cardiac arrest in CAD related SCD
• Most common cause of death from MI in pre-hospital phase (prior to arrival in ER)

Question 7

How do integrins mediate adhesion?

Answer 7

► Integrin-mediated adhesion of cells to the basement membrane and ECM involves binding of integrins to
► Fibronectin, collagen, and laminin

Question 8

How does leptin work?

Answer 8

► Leptin is a protein hormone produced by adipocytes in proportion to the quantity of fat stored
► Acts on arcuate nucleus of hypothalamus to inhibit production of neuropeptide Y (decreasing appetite) and stimulate production of alpha-MSH (increasing satiety)
► Mutations in leptin gene or receptor result in hyperphagia and profound obesity

Question 9

Inulin

Answer 9

► Freely filtered at the glomerulus and neither reabsorbed nor secreted by the renal tubules
► Inulin clearance is commonly used to calculate GFR
► Like mannitol, no tubular reabsorption or secretion
► Filtered amount = excreted amount
► No tubular reabsorption or secretion

Question 10

Lung specimens with histoplasmosis would show:

Answer 10

Intracellular oval bodies within the macrophages, which ingest the fungus.
Dimorphic fungus affecting lungs and reticuloendothelial system
Histo Hides (within macrophages)

Question 11

Most common cause of death durin in-hospital phase of MI?

Answer 11

Ventricular failure
V-fibrillation is most common in pre-hospital phase

Question 12

Name medications that can cause hyperkalemia and the mechanism by which they do so?

Answer 12

• • ► Nonselective beta-adrenergic blockers** - interfere w/ beta-2 mediated intracellular potassium uptake
• *► ACE inhibitors** - inhibit angiotensin II formation ↓ aldosterone = retain potassium and excrete sodium
• *► ARBs** - block AT1 receptor, ↓ aldosterone
• *► K+-sparing diuretics** - Block ENaC or aldosterone receptor
• *► Cardiac glycosides (digoxin)** - inhibit Na+/K+-ATPase pump
• *► NSAIDS** - impaired local prostaglandin synthesis reduces renin and aldosterone secretion

Question 13

Neurofibromatosis type 1

Answer 13

AD, neurofibromas (plexiform and solitary), optic gliomas, (pigmented nodules of the iris) aka von Recklinghausen’s disease: Café-au-lait spots (cutaneous hyperpigmented macules) , neural tumors, Lisch nodules, long arm of chromosome 17

Question 14

Neurofibromatosis type 2

Answer 14

AD, Bilateral acoustic schwannomas, juvenile cataracts. May develop multiple meningiomas, gliomas, and ependymomas of the spinal cord. NF2 gene on chromosome 22; type 2 = 2 22

Question 15

PAH

Answer 15

• ­Net tubular secretion (Excreted amount >> Filtered amount)
• ­ Paraaminohippuric acid is freely filtered at the glomerulus and also secreted into urine by an energy-dependent organic acid transporter in the proximal tubule
• ­ The amount of PAH excreted is greater than filtered load.
• ­ Clearance of PAH = renal plasma flow
• ­ Creatinine

Question 16

Recurrent, indolent skin infections and gingivitis, PMH significant for delayed separation of umbilical cord that occurred at 10 weeks after birth. What is diagnosis and which protein is underexpressed?

Answer 16

► Leukocyte Adhesion Deficiency Syndrome results from AR genetic absence of CD18
► Leads to inability to synthesize LFA-1 integrin (CD18) proteins on phagocytes
► Necessary for leukocytes to exit bloodstream, and sequelae include recurrent skin infections WITHOUT pus formation, delayed detachement of the umbilical cord and poor wound healing
► Integrins are essential for migration of leukocytes from the vascular space to the tissues where they exert their effect
► Integrins mediate second step - firm adhesion

Question 17

Remedies for acute EP symptoms?

Answer 17

Acute EP symptoms are related to imbalance between dopamine D2 and muscarinic M1 activity in the nigrostriatal tract
M1 receptor antagonists such as diphenhydramine and benztropine re-establish the dopaminergic-cholinergic balance and remedy acute EP symptoms

Question 18

SCD

Answer 18

Defined as cardiac arrest that begins within one hour of precipitating event and ultimately proves fatal
Approximately 80% of SCD are due to CAD
Pathogenesis: Acute plaque change producing acute myocardial ischemia -> electrical instability in heart generating porentially lethal arrhythmia

Question 19

The dorsal pancreatic bud gives rise to:

Answer 19

Pancreatic tail, body, most of head, small accessory pancreatic duct

Question 20

The ventral pancreatic bud gives rise to:

Answer 20

Uncinate process, portion of pancreatic head, proximal portion of main pancreatic duct

Question 21

Toxicities of HCTZ

Answer 21

HypoKNa with MAlk and

• Hypokalemia
• Hyponatremia
• Metabolic alkalosis

HyperGLUC - Hypokalemic metabolic alkalosis, hyponatremia,

• hyperGlycemia,
• hyperLipidemia,
• hyperUricemia, and
• hyperCalcemia (may help with osteoporosis). Sulfa allergy

Question 22

Type of cells that line the oropharynx, laryngopharynx, anterior epiglotis, upper half of posterior epiglottis, and vocal folds (true vocal cords)

Answer 22

Stratified squamous epithelium

Question 23

Type of cells that lines the nose, paranasal sinuses, nasopharynx, most of larynx, laryngeal vestibule (false vocal folds) and tracheobronchial tree

Answer 23

Pseudostratified, columnar, mucus-secreting epithelium

Question 24

Von Hippel-Lindau disease

Answer 24

AD, hemangioblastomas of retina/cerebellum/medulla; half develop multiple bilateral renal cell carcinomas, pheochromocytoma, liver cysts; Deletion of VHL gene (tumor suppressor) on chromosome 3 (3p); Constitutive expression of HIF (transcription factor) and activation of angiogenic growth factors

Question 25

What drug can be used to treat thyrotoxicosis? Why?

Answer 25

Propanolol - MOA is dual:
↓ effect of sympathetic adrenergic impulses reaching target organs
↓ rate of peripheral conversion of T4 to T3

Question 26

What happens to male neonates with 5α-reductase deficiency?

Answer 26

► Born with feminized external genitalia that typically masculinize at puberty -> voice deepening, penile and scrotal growth, and testicular descent.
► Small phallus and hypospadias are commonly found

Question 27

What happens to Urea? What is it relative to GFR?

Answer 27

­Urea is filtered at the glomerulus and then passively reabosrbed in the proximal tubule and inner medullary collecting ducts. It is also passively secreted by the thin regions of the loop of henle. The remainder of the nephron is impermeable to urea.

­ The net result is excretion of 10-70% of the filtered urea load, depending on urinary flow rate and concentration. Urea clearance is therefore normally less than GFR

Question 28

What is a Pancreas divisum?

Answer 28

Failure of dorsal and ventral pancreatic buds to fuse
­ Pancreatic secretions drained by 2 duct systems

• ­ Dominant dorsal duct (of santorini) opens into duodenum via the minor papilla, majority of drainage
• ­ Smaller ventral duct of Wirsung opens into the major papilla, draining inferior/posterior portion of head and Uncinate process.
• ­ 5% of population, usually asymptomatic
• ­ May predispose to recurrent pancreatitis

Question 29

What is a Renal angiomyolipoma and its association?

Answer 29

Benign tumor composed of blood vessels, smooth muscle, and fat
Bilateral angiomyolipomas are associated with tuberous sclerosis (80-90% of time), an AD condition
Diagnosed with abdominal CT

Question 30

What is the “triangle of treatment” for thyrotoxicosis? How can propranolol work?

Answer 30

Triangle:

1. Thyroid hormone synthesis and release
2. Peripheral conversion of T4 to the more active T3
3. Sympathetic outflow and/or its actions on target organs

Beta receptor blockers contribute to he latter 2 therapeutic objectives.
Reduce HR and subjective feelings of anxiety/agitation
Reduces peripheral conversion of T4 to T3

Question 31

What is the effect of ACE inhibitors on serum electrolytes?

Answer 31

► Block conversion of Ang I to Ang II, thus reducing vasoconstriction and aldosterone secretion
► ↓ aldosterone causes ↑ K+ retention, which can lead to hyperkalemia
► Hyperkalemia secondary to ACE inhibitor therapy is most common in patients with renal insufficiency and pin patients taking K+-sparing diuretics (amiloride, triamterene, spironolactone) or K+ supplements

Question 32

What is the location of the apex, what forms it, and what is the approximate vertical span of the lung in the rib cage?

Answer 32

► Left ventricle forms the apex and reaches as far as the fifth intercostal space at the left midclavicular line.
► Approximate lung span is from above the first rib to 7th intercostal space

Question 33

What is the most reliable test to confirm menopause?

Answer 33

Measuring serum FSH, generally aboe 30 U/L
FSH levels increase because of loss of estrogen feedback (estrogen not produced from ovaries)

Question 34

What is transformation and which bacteria have this capability?

Answer 34

Ability to take up DNA from the environment (competence), the uptake and expression of chromosomal fragments from the environment made abailavle when another bacterial cell dies and undergoes lysis.
SHiN
S. pneumoniae, H. influenzae type B, and Neisseria

Question 35

What would happen to the clearance of glucose if there was inhibition of the sodium-coupled, carrier-mediated transport of glucose by the proximal tubule?

Answer 35

• ­Glucose is normally filtered at the glomerulus and completely reabsorbed by the proximal tubule
• ­ Glucose clearance would approach the value of GFR
• ­ GFR is estimated by calculating the clearance of inulin

Question 36

Which cell type is DIRECTLY responsible for the intimal response that takes place in atherosclerosis?

Answer 36

► Medial Smooth muscle cells (SMCs) migrate across the internal elastic lamina into the intima.
► This is followed by SMC proliferation and collagen synthesis to produce a neointima ->
► Results in reactive intimal hyperplasia
► $ Vascular reaction to endothelial and intimal injury is intimal hyperplasia and fibrosis, predominantly mediated by reactive smooth muscle cells that migrate from the media to intima

Question 37

Which viruses are capable of genetic shifts?

Answer 37

Viruses with segmented genomes (orthomyxoviruses and rotaviruses) are capable of genetic shifts through reassortment.
Reassortment involves exchange of entire genome segments, a far more dramatic process than point mutations

Question 38

$ What causes systolic heart failure?

Answer 38

► Acute massive myocardial infarction
► Results from imparied myocardial contractility
► Reduced EF > reduces SV at normal LVEDV, thus reducing CO
► LVEDP and LVEDV must BOTH increase to abnormally high levels (which improves SV via the F-S mechanism

Question 39

A 70-year old Caucasian male presents to your office for evaluation of skin lesions to his forehead. On PE you find that these papules have a sandpaper texture by palpitation. The lesions are illustrated in the slide below. Most likely diagnosis?

Answer 39

** Actinic keratosis (AK)** - erythematous papules with a central skale due to hyperkaratosis.
Sandpaper-like texture on palpitation is typical
Lesions small and flat but may enlarge and become elevate, sie usually does not exceed 10 mm
Hyperkeratosis may become prominent turning into “cutaneous horns”
Develop on chronically sun-exposed areas of skin
Convert to squamous cell carcinoma in approximately 1% of cases

Question 40

Compare and contrast systolic heart failure to diastolic heart failure

Answer 40

** Diastolic** - ↓ ventricular diastolic compliance but normal ventricular contractile performance -> LVEDP must increase to achieve normal LVEDV and SV

** Systolic** - ↓ Ventricular contractile performance (↓EF) and requires:
↑LVEDP and
↑LVEDV

These allow ↑SV

Question 41

How would the P-V curve shift in diastolic heart failure? Why? What happens to LVEDP, LVEDV, and LVEF? When does decompensation occur?

Answer 41

► Up and to the left
► ↑↑ Left ventricular end-diastolic pressure
► Normal/Slightly decreased LV end-diastolic volume (compensation to maintain near normal LVEDV)
► Normal LV ejection fraction

Question 42

What is diastolic heart failure? What parameter is different from systolic heart failure?

Answer 42

► Pumping function involves ↓ ventricular compliance not impaired myocardial contractility
► Caused by either impaired myocardial relaxation (from ischemia) or ↑ ventricular wall stiffness (eg, amyloid deposition)
► Long standing HTN can impair both myocardial relaxation and ↑ wall stiffness
► Normal ejection fraction - reduced ventricular compliance, contractility unchanged

Question 43

What is the ARR? NNT?

Answer 43

► Absolute risk reduction (ARR) is the event rate in placebo group minus the event rate in the treatment group, tells us the reduction in risk associated with treatment as compared to placebo.
► Number needed to treat (NNT) is 1/ARR, the number of patients you would need to treat in order to save/effect one life.

Question 44

What is the difference between sensitivity and specificity of a test?

Answer 44

Sensitivity - Test’s ability to identify the true presence of disease, if 100% it will ALWAYS pick up the disease if there
Specificity - test’s ability to identify the true absence of disease, if 100%, a negative test result means 100% certainty that disease is absent

Question 45

The following is a tissue taken from the cerebellum of an 86 year old man at autopsy. How long after the CVA did this lesion occur?

Answer 45

“red neurons” (eosinphilic cytoplasm, pyknotic nuclei, loss of Nissl substance) occuring 12-48 hours after injury

Red neurons. Note the brightly eosinophilic staining cells with the pyknotic nuclei within spaces representing apoptotic neurons.

Question 46

Which agent is often used to treat diabetic neuropathy but has many adverse side effects including urinary retention in a patient with BPH? Name the side effects?

Answer 46

Amitriptyline can be used to treat neuropathy in a diabetic. Side effects are

inhibition of presynaptic neurotransmitter (NE and 5HT) reuptake = tremor, insomnia;

Bloackade of cardiac fast sodium channels = conduction defects, arrhythmias, hypotension;

Antagonism of central and peripheral muscarinic acetylcholine receptors = Hyperthermia, flushing, dilated pupils, intestinal ileus, urinary retention, sinus tachycardia;

Antagonism of peripheral alpha-1 adrenergic receptors - peripheral vasodilation (orthostatic hypotension);

Antagonism of histmaine (H1) receptros - Sedation

Question 47

Apoplexy

Answer 47

stroke or bleeding within internal organs

Question 48

Describe the histology of bronchi from proximal to terminal.

Answer 48

Bronchi are pseudostratified columnar ciliated epithelium with goblet cells and submucosal mucoserous glands. By the level of the terminal bronchioles, epithelium is ciliated simple cuboidal.

Question 49

To which lymph nodes does the glands penis drain to?

Answer 49

Deep inguinal nodes receive lymph drainage from glans penis and superficial nodes.

Question 50

How can Campylobacter be acquired?

Answer 50

Acquired fecal-oral from domestic animals, such as cattle, sheep, dogs, chickens. Common in farm and laboratory workers. Also contaminated food, undercooked poultry and unpasteurized milk.

Question 51

Most common acquired chorea of childhood?

Answer 51

** Sydenham chorea** - sole neurologic manifestation of acute rheumatic fever. No risk for renal disease in rheumatic fever.

Question 52

The most common anatomical abnormality producing mitral regurgitation?

Answer 52

myxomatous degeneration (mitral valve prolapse)

Question 53

What do Duodenal S-cells secrete?

Answer 53

Secretin in response to increasing H+ concentration. Secretin increases pancreatic bicarbonate secretion. Chloride content of pancreatic secretions decreases in proportion to bicarbonate concentration increases

Question 54

During a first pregnancy, can erythroblastosis fetalis occur in a newborn?

Answer 54

With maternal blood types A and B, Erythroblastosis fetalis and hemolytic disease of the newborn do not occur, as naturally occurring antibodies (anti-A and -B) are of the IgM type and cannot cross the placenta. In contrast, in type O mothers, the antibodies are predominantly IgG and can cross the placenta to cause fetal hemolysis. Can occur in the first pregnancy because exposure to A- or B-like antigens are present in foods, bacteria, and viruses.