Uworld: 5-29

Front 1

Classical Galactosemia:
Mode of Inheritance

Back 1

AR--in general, most enzyme deficiency conditions follow an autosomal recessive inheritance pattern, whereas diseases due tod efective non-catalytic proteins tend to follow an autosomal dominant pattern.

Front 2

CFTR Protein:
Channel type

Back 2

ATP-gated chloride channel

Front 3

71-year old male receives killed viral vaccine.

When he is subsequently exposed to this virus, what happens?

Back 3

Host circulating antibodies interfere with binding of hemagglutinin (HA--in case of flu) to sialic acid-containing oligosaccharides of host cell plasma membrane glycoprotein receptors.

Live virus is prevented from entering cells via receptor-mediated endocytosis.

Front 4

Which drugs prolong the QT interval?

Which of these does not predispose patients to torsade de points?

Back 4

Class IA antiarrhythmics (Procainamide, Disopyrimide, Quinidine)

Class III antiarrhythmics (Sotalol, Ibutilide, Dofetilide, Amiodarone)--note these are K+ blockers

Only one that does not predispose to Torsades is AMIODARONE

Front 5

VSD:
Associated murmur

Back 5

Holosystolic murmur over left sternal border

Front 6

ASD:
Associated murmur

Back 6

Fixed wide splitting of S2

Front 7

Equation for drug clearance.

Back 7

Clearance = (0.7*Vd)/(t1/2)

Front 8

How many half-lives until a drug is completely eliminated?

Back 8

5 half-lives

Front 9

Polyarteritis Nodosa:
Vasculature involved

Back 9

Kidneys
Heart
Liver
GI
Cutaneous

LUNGS ARE VERY RARELY INVOLVED

Front 10

Back 10

E: the polyadenylation signal sequence at the 3' end of the mRNA transcript is responsible for addition of the poly-A tail. The poly-A tail is NOT transcribed from DNA, but rather added as posttranscriptional modification downstream of a consensus sequence (AAUAAA).

Tail protects mRNA from degradation within cytoplasm after it exits nucleus.

Also note the following regions:
A - Contains AUG start codon (first exon in transcribed gene)

B - this is an intron being spliced out of the mRNA molecule. Introns aren't TRANSLATED during protein synthesis, but they are transcribed by RNA polymerase.

C/D: THese are other exonic regions of mRNA that were transcribed from DNA template. There's a stop codon (UAA) between C and D regions, thus, region C will be translated while region D will not.

Front 11

Cystic Fibrosis:
Mutation type

Back 11

Frameshift mutation caused by 2 base-pair deletion in CFTR protein.

Front 12

Most common cause of viral meningitis.

Back 12

Enteroviruses--this family includes coxsackie, echo, and polio.

Front 13

What is a paradoxical embolism?
What allows for it?

Back 13

Paradoxical emboli originate in venous system, but cross over into arterial circulation (bypassing the lungs) via an abnormal connection between left and right heard (ATRIAL SEPTAL DEFECT).

Front 14

Systolic ejection murmur that increases on standing

Back 14

Aortic stenosis or Hypertrophic cardiomyopathy

Front 15

Early diastolic decrescendo murmur decreased by amyl nitrite

Back 15

Amyl nitrite-->venous dilation (decreased venous return)

So:
Aortic Regurgitation

Front 16

Late diastolic murmur eliminated by atrial fibrillation

Back 16

Mitral and/or tricuspid stenosis

Presystolic murmur can result from mitral or TC valve stenosis and/or physiologically increased blood flow across these valves. Presystolic accentuation occurs due to atrial contraction. Atrial fibrillation could eliminate an AV valve stenotic murmur by removing the atrial contraction during late diastole.

Front 17

Which bacteria inactivate EF-2 via ribosylation, thus inhibiting host cell protein synthesis?

Back 17

C. diphtheriae
Pseudomonas aeruginosa

Front 18

Which bacteria activate adenylate cyclase via ADP ribosylation, increasing cAMP production in the host cell?

Back 18

Bordetella pertussis (inc'd histamine sensitivity and phagocyte dysfunction)

Vibrio cholera (secretory diarrhea, dehydration, electrolyte imbalances)

Front 19

What is the molecular pathophys of organophosphate poisoning?

Back 19

Profound and prolonged cholinesterase inhibition (organophosphates bind irreversibly)

Treat with muscarinic agonists like atropine in addition to pralidoxime (cholinesterase reactivator)

Front 20

What substance provides the fastest reversal of warfarin's effects?

Back 20

FRESH FROZEN PLASMA!!!!!!!!!

Should also give Vitamin K to re-synthesize clotting factors, but this takes time.

Front 21

Heparin antidote

Back 21

Protamine

Front 22

Plasminogen activator antidote

Back 22

Aminocaproic acid

Front 23

What is the most common outcome in HBV-infected individuals?

Back 23

>95% of adults will experience acute hepatitis with mild or subclinical symptoms that will COMPLETELY RESOLVE.

Only 4-5% progress to stable chronic hepatitis. Of those, 50-80% will remain stable w/o e/o cirrhosis.

HCC arises in 10% of pts w/chronic hepatitis and cirrhosis

Front 24

Patient unable to adduct left eye
Lacks corneal reflex

Nerves involved
Where is the likely location of the lesion?
What other nerves are likely to be affected?

Back 24

Eye adduction = medial rectus; controlled by CN III (oculomotor)

Corneal reflex (sensation limb) mediated by V1

V1, CN III, CN IV, CN VI all exit through the superior orbital fissure

Front 25

Equation for number needed to treat.

Back 25

1/ARR
= 1/[(event rate in placebo - event rate in treatment]

Front 26

Papulovesicular rashes on extensor surfaces

Back 26

Dermatitis herpetiformis (Celiac dz)

IgA deposits will be found in tips of dermal papillae

Front 27

Villous blunting

Back 27

Celiac dz

Front 28

When does Graft Vs Host disease arise (procedure wise)?

Back 28

Bone Marrow transplants
OR transplants of donor tissue rich in lymphocytes:
Liver
Skin
Intestine

Front 29

14 year-old child
Delayed puberty
Anosmia

Diagnosis
Pathophys

Back 29

Kallmann's syndrome

Failure of GnRH-secreting neurons to migrate from origin in olfactory placode to normal location in hypothalamus.

Front 30

37 year-old woman
Longstanding diastolic murmur
Diaes of stroke

Pathophys

Back 30

Mitral stenosis-->atrial enlargement-->atrial thromboses

Front 31

Left atrium:

Diagnosis

Back 31

Rheumatic Fever:

-Black arrows show distortion of mitral valve leaflets

-White arrows show fusion at leaflet edges

-Large surface area of walls of LA suggest atrial dilatation

ALL CHARACTERISTIC OF RHEUMATIC MITRAL VALVULAR DISEASE

Front 32

Most common cause of mitral stenosis.

Back 32

Rheumatic Heart Dz

Front 33

Coronary sinus dilatation:
Pathophys

Back 33

Coronary sinus = endpoint of venous drainage from coronary blood supply

Contains deoxygenated blood and drains directly into right atrium

Because it communicates freely with RA, it may become dilated secondary to any factor causing RA dilatation; the most common such factor is PULMONARY ARTERY HTN.

Front 34

Patient is incapacitated.

Who makes medical decisions?

Back 34

NEXT OF KIN

Front 35

Identify murmur.
When would it be heard?

Back 35

Aortic stenosis; heard loudest at point B and less intensely at point A (crescendo-decrescendo!)

Front 36

38 year-old male
Periodic, non-peristaltic esophageal contractions of large amplitude and long duration

Diagnosis
Work-up

Back 36

Diffuse esophageal spasm

May mimic angina pectoris (chest pain)
Requires full cardiac evaluation

Front 37

Which pancreatic enzymes are secreted in ACTIVE form?

Back 37

Amylase
Lipase

Everything else is in zymogen form.

Front 38

Describe changes to E. coli's lac operon genes in:
-Presence of lactose, absence of glucose
-Presence of glucose

Back 38

Culture of E. coli in lactose-containing media:
-Conformational change in repressor gene, releasing it from OPERATOR
-Allows for increased transcription of lac operon

Culturing E coli in media containing glucose:
-Glucose decreases activity of adenylyl cyclase-->reduces intracellular cAMP
-Dec'd cAMP-->dec'd expression of lac operon structural genes
-High cAMP-->activates Catabolite Activator Protein (CAP)-->positively regulates lac-operon

Note: Mutations of repressor protein or its binding site at operator will prevent repression of genes of lac operon; results in constitutive transcription of genes of lac operon, even in presence of glucose

Front 39

Given this information, describe which channels are used to achieve:
Resting permeability
Ligand-gated ion channel permeability (black arrow)
Voltage-gated ion channel permeability (red arrow)

Back 39

Resting membrane potential is negative, so membrane is most permeable to an ion with a negative equilibrium potential such as potassium (or chloride, theoretically).

At black arrow, an increase in membrane potential to above zero occurs. This indicates taht the membrane has become permeable to an ion with positive equilibrium potential such as sodium or calcium.

At red arrow, a drop occurs, so membrane must become more permeable to an ion with negative equilibrium potential such as potassium or chloride.

So:
Resting membrane perm: K+
Ligand-gated perm: Na+
Voltage-gated perm: Cl-

Front 40

Factors that utilize JAK/STAT signaling pathway.

Back 40

Colony-stimulating factors
Prolactin
Growth hormones (no PDGF)
Cytokines

Also, they all use tyrosine kinase-associated receptors (in addition to JAK/STAT signaling pathway)

Front 41

72 year-old man
Wild flinging movements of right arm as of 2 hours ago
Long-standing HTN

Diagnosis
Pathophys

Back 41

Wild, flinging movements of extremities on one side of body = HEMIBALLISM

Due to damage of contralateral SUBTHALAMIC NUCLEUS--most commonly from lacunar stroke

Patients often have long h/o HTN

Front 42

What metabolic reactions depend on the HMP shunt?

Back 42

HMP shunt is important for regenerating NADPH (only method of reducing glutathione and thus repairing oxidative damage)

Reactions that utilize NADPH:
-Cholesterol synthesis
-Fatty acid synthesis
-Steroid synthesis
-Drug metabolism

Front 43

Carbamazepine:
MOA
AEs

Back 43

Blocks voltage-gated Na+ channels in cortical neurons

AEs:
Bone marrow suppression***
Hepatotoxicity
SIADH

Front 44

Argatroban:
MOA

Back 44

Binds directly to thrombin active site (direct thrombin inhibitors)

Front 45

Abciximab:
MOA

Back 45

GP IIb/IIIa surface receptor antagonist

Front 46

Lepirudin:
MOA

Back 46

-irudin = DIRECT THROMBIN INHIBITOR

Front 47

An external stimulus applied to a cell increases the activity of dihydrofolate reducatse.

How does this affect the cell cycle?

Back 47

Increase in DHF means increase in DNA synthesis, so cell is going to givide.

Front 48

Rb:
Molecular functions
Describe active/inactive states

Back 48

Retinoblastoma protein regulates G1-->S phase transition.

Two forms:
Hypophosphorylated--ACTIVE
HypERphosphorylated--INactive

Resting cells have hypophosphorylated

When cell is stimulated by growth factor, Rb is hyperphosphorylated, releases E2F transcription factor, and cell progresses from G1 to S.

If Rb protein is hypophosphorylated, it binds E2F transcription factor, and G1-->S does NOT occur.

Front 49

How does genome replication of HBV differ from that of Herpesvirus?

Back 49

HBV has reverse transcriptase so:
dsDNA-->Template +RNA-->Progeny dsDNA

Herpesvirus, poxvirus, adenovirus, and papovavirus:
dsDNA-->Template dsDNA-->progeny dsDNA

Front 50

What protein is mutated in Marfan's?

Back 50

Fibrillin-1

Front 51

HIV gp41 vs gp120:
Roles

Back 51

gp41: penetration into target cells
gp120: attachment to target cells

Front 52

Identify Drug A.

Back 52

Drug is prolonging potassium efflux from the cell in addition to action potential length

Drugs that do this are class III antiarrhythmics (K+ channel blockers);
Sotalol
Ibutilide
Dofetilide
Amiodarone

Front 53

Nephritic vs Nephrotic Syndrome:
Diagnosis

Back 53

PSGN = Nephritic Syndrome;
Mild proteinuria <1 g/day
RBC casts in urine

Nephrotic: massive proteinuria >3.5 g/day, hypoalbuminemia, hyperlipidemia, lipiduria, generalized edema
NO RBC CASTS in urine

Front 54

40 year-old female
Right knee injury
Given opioid analgesic
Develops severe abdominal pain in RUQ

Pathophsy

Back 54

Opioid analgesics can cause contraction of SMOOTH MUSCLES in SPHINCTER OF ODDI leading to inc'd pressure of bile duct and gall bladder-->biliary colic

Front 55

How can sorbitol reduction on MacConkey agar distinguish strains of E. coli?

Provide molecular effects of their toxins.

Back 55

E. coli O157:H7 does NOT ferment sorbitol; toxin inactivates 60S ribosomal subunit in human cells, leading to inhibition of protein synthesis and eventual cell death (can also result in hemolytic-uremic syndrome-->low PLT, microangiopathic hemolytic anemia, renal insufficiency (uremia))

Other strains of E. coli RAPIDLY ferment E. coli

Front 56

Calories per gram of:
Carbohydrate
Fat
Protein

Back 56

1 g carb has 4 calories
1 g fat has 9 calories
1 g protein has 4 calories

Front 57

Draw a diagram of the three types of groin hernias. Include relevant anatomical structures.

Back 57

Front 58

Intracranial mass biopsy

Back 58

Area of necrosis surrounded by tumor cells = pseudopalisading necrosis

Dx: GLIOBLASTOMA MULTIFORME

Features necrosis and vascular proliferation

Front 59

Which intracranial mass would exhibit psammoma bodies?

Back 59

Meningiomas

Front 60

A 27 year-old medical student is coughed on by a patient who suffers from an active pulmonary tuberculosis infection.

The student has never been exposed to M. tuberculosis before.

What will likely happen (on cellular level) during first week after exposure?

Back 60

Bacterial proliferation within alveolar macrophages

Front 61

50 year-old male
Sudden severe headache, double vision, bitemporal hemianopsia
Reports decreased libido and mild headaches for a few months

Diagnosis
Pathophys
Treatment

Back 61

Pituitary apoplexy--acute bleeding into a preexisting pituitary adenoma

Presentation consists of both acute and chronic symptoms:
Chronic symptoms (of longstanding pituitary tumor): mild headaches and decreased libido

Acute symptoms: severe HA, visual disturbances

Although this may mimic a SAH, note that BITEMPORAL HEMIANOPSIA is present only in pituitary hemorrhage.

Patients suffering from pituitary apoplexy develop CV collapse because ACTH deficiency leads to adrenocortical insufficiency.

Treat with steroids and urgent neurosurgical consult.

Front 62

65 year-old male
Pulmonary mass
Shoulder pain, persistent hiccups, dyspnea, hoarseness

Specific pathophys of symptoms

Back 62

1) Hiccups/diaphragmatic paralysis with dyspnea due to compression of phrenic nerve from C3-C5 (innervates ipsilateral hemidiaphragm)

2) Shoulder pain: due to brachial plexus involvement; pain distribution in C8, T1, T2 nerve roots

3) Hoarseness: Involvement of recurrent laryngeal nerve

Front 63

47 year-old female
Yellowish-red-purple skin rash on chest
Breast exhibits pitting edema and brawny induration
Biopsy reveals carcinoma

Pathophys of presentation

Back 63

Peau d'orange (orange peel finding): neoplastic cells are plugging dermal lymphatic channels and resulting in skin tenderness and discoloration (pale pink to deep red brown to purple)

Front 64

34 year-old female
Recent onset of mood swings, difficulty concentrating, hand tremor
Neck discomfort, particularly on swallowing
Flu-like symptoms few weeks ago
Elevated Sed Rate
Thyroid scan shows diffuse decrease in iodine uptake

Diagnosis
Pathophys
Histologic findings

Back 64

Subacute granulomatous thyroiditis--AKA de Quervain's thyroiditis (a form of thyrotoxicosis)

Possibly caused by viral infection-->thyroid inflammation-->release of stored thyroid hormones, but does not cause excessive production of T4, which is why iodine uptake is decreased

Histology will show mixed, celullar infiltration with occasional multinucleate giant cells

Front 65

65 year-old male
Bilateral visual difficulty progressing over last year
Funduscopy reveals yellow retinal lesions clustered in macula

Diagnosis
Pathophys
What would you see on visual field examination?

Back 65

Macula = yellow spot near center of retina; it's densely packed with cones and holds the highest visual acuity of all regions of the retina.

Macular lesions impaire central vision and result in central scotomata (SCOTOMATA refers to any visual defect surrounded by unimpaired field of vision)

Patient is likely to have Macular Degenration--progressive loss of central vision due to deposition of fatty tissue behind retina (dry MD) or neovascularization of retina (wet MD)

Front 66

44 year-old female
DImpling of skin, inversion of right breast nipple
Underlying invasive carcinoma

Pathophysiology of presentation

Back 66

Nipple inversion observed when tumor invades suspensory Cooper ligaments

Note: should lymphatic drainage become impeded by tumor, lymphedema, pitting and thickening of the skin--such that it adopts the appearance of an orange peel--may occur.

Front 67

Why do men have higher hematocrit levels than women?

Back 67

Androgens stimulate RBC production--note: THIS IS EXAGGERATED IN STEROID ABUSE

Front 68

What are the effects of exogenous testosterone abuse (physiologic and general)?

Back 68

Decreased FSH/LH-->Dec'd testicular size/sperm production/endogenous testosterone secretion

May also cause acne, voice deepening, male pattern bladness

Front 69

2 year-old male
Spontaneous bursts of non-rhythmic conjugate eye movements
Hypotonia, myoclonus
Abdominal mass

Diagnosis
Pathophys
Specific mutation

Back 69

Non-rhtyhmic conjugate eye movements a/w NEUROBLASTOMA

Develops from neuroblasts in adrenal medulla and increases excretion of catecholamines in urine

Due to amplification of N-myc gene

Front 70

44 year-old male
h/o heavy alcohol consumption
Presents with nosebleed
Hepatomegaly, ascites, flapping hand tremor

Diagnosis
Prognostic factors

Back 70

Patient has findings consistent with alcoholic cirhosis

Serum albumin and Prothrombin TIme (PT) are indicators of liver's synthetic function.

Hypoalbuminemia would suggest dec'd hepatic albumin synthesis, while a prolonged PT signifies diminished synthesis of coagulation factors.

Hypoalbuminemia and prolonged PT are signs of liver failure and indicate poor prognosis.

Note: Transaminase elevations do not reflect liver function and do not predict outcomes.

Front 71

What anti-HTN medication increases calcium levels?

Back 71

HCTZZ!!!!!!!!!!!!!!!!!

Causes inc'd resorption of calcium in DISTAL tubule, causing relative hypercalcemia as well as hypocalciuria

Front 72

ssDNA virus

Back 72

Parvovirus

Front 73

Which amino acid does the following titration correspond to?

Back 73

Titration curve reveals three different pKa, each of which demonstrates a buffering effect on pH as more base is added.

Thus, amino acid must have three titratable protons.

Amino acids w/three titratable protons include:
Histidine
Arginine
Lysine
Aspartatic acid
Glutamic acid
Cysteine
Tyrosine


HATCLAG