6/19 UWorld

Question 1

What is the different probe used for Southern and Northern blot

Answer 1

Southern blot uses a DNA probe to detect DNA sample

Norther blot uses a DNA probe to detect RNA sample

Question 2

Describe the different locations of GLUT2 vs. GLUT4 and whether or not they are insulin-dependent

Answer 2

• GLUT2
  
  • Present on regulatory cells (liver, kidney, pancreas)
  • Insulin independent
• GLUT4
  
  • Present on skeletal muscle and adipose tissue
  • Insulin dependent

Question 3

Glucokinase:

• Location
• Vmax
• Km

Answer 3

Located on cells that regulate glucose (liver and b-pancreas)

High Km = low glucose affinity; need a lot of glucose present in order for it to work (this makes sense because if glucose is low you don’t want it in regulatory cells, you want it out and being used)

High Vmax = once it is used, it works very quickly

Question 4

Hexokinase

• Location
• Km
• Vmax

Answer 4

Located on all cells

Low Km (higher glucose affinity)

Low Vmax (works slower)

Question 5

What is the rate-limiting enzyme for glycolysis and gluconeogenesis

Answer 5

Glycolysis = phosphofructokinase I (PFKI)

Gluconeogenesis = fructose-1,6-bisphosphatase

Question 6

What substrates enhance and inhibit PFKI

Answer 6

Enhanced by energy depleted substrates = AMP, F26BP

Inhibited extra energy cycles = by ATP and citrate

Question 7

What substrates activate/inhbit pyruvate kinase

Answer 7

Activated by F16BP (an upstream product of glycolysis)

Inhibited by ATP and alanine

Question 8

Describe how/where insulin and glucagon affect glycolysis/gluconeogenesis

Answer 8

• Insulin activates PFK2, which converts F6P to F26BP
  
  • F26BP is an activator of glycolysis (activates PFKI) and an inhibitor of gluconeogeneis (inhibits F16BPase)
• Glucagon activates Fructose bisphosphatase 2, which converts F26BP to F6P, which can then undergo gluconeogesis

Question 9

What are the retroperitoneal structures

Answer 9

o SAD PUCKER

§ S à Suprarenal (adrenal gland)

§ A à Aorta and IVC

§ D à Duodenum (2nd through 4th parts)

§ P à Pancreas (except tail)

§ U à Ureters

§ C à Colon (descending and ascending)

§ K à Kidneys

§ E à Esophagus (thoracic portion)

§ R à Rectum (partially)

Question 10

The conversion of PEP to pyruvate is irreversible. What steps/enzymes are used in gluconeogenesis to bypass this irreversible step?

Answer 10

• Pyruvate is converted to oxaloacetate via pyruvate carboxylase (uses biotin B7)
• Oxaloacetate converted to PEP via phosphoenolpyruvate carboxykinase (PEPCK)

Question 11

Besides pyruvate carboxylase and PEPCK, what are the other 2 unique enzymes needed for gluconeogensis

Answer 11

• Fructose-1,6-bisphosphatase
  
  • Converts F16BP to F6P
  • Rate limiting step of gluconeogenesis
• Glucose-6-phosphatase
  
  • Converts G6P to glucose
  • Present only in liver and kidney (not muscle)

Question 12

What are the 3 openings in the diaphragm

Answer 12

• THINK: I ate ten eggs at twelve
  
  • I ate = “I” for IVC and “ate” for T8
  • Ten eggs = “Ten” for T10 and “eggs” for esophAGus and vAGus
  • At twelve = “At” for AAT (Aorta, Azygous, Thoracic) and twelve for T12

Question 13

What nerve innervate the diaphragm

Answer 13

• Diaphragm is innervated by C3, C4, and C5
  
  • THINK: C3, 4, 5, keeps the diaphragm alive

Question 14

Label the lung volume graph

Answer 14

Question 15

What lung volumes make up vital capacity

Answer 15

Everything except for residual volume (inspiratory reserve + tidal volume + expiratory reserve)

Question 16

What lung volumes make up functional residual capacity

Answer 16

Expiratory reserve + residual volume

Question 17

In healthy individuals, is the amount of O2 recieved perfusion-limited or diffusion-limited

Answer 17

Perfusion-limited

• Gas equilibrates along the length of the capillary, and increased O2 can only occur via increased blood flow

Vs. diffusion-limited in emphysema and fibrosis

• Gas does not equilibrate by the time blood reaches the end of the capillary

Question 18

What values define pulmonary HTN

Answer 18

• Pulmonary arterial pressure > 25 at rest (normal = 10 mm Hg)
• Pulmonary arterial pressure > 35 during exercise

Question 19

Differentiate between R and T forms of Hb

Answer 19

• Taut (T) form
  
  • Low O2 affinity – deoxygenated
  • THINK: Taut in Tissues
• Relaxed (R) form
  
  • High O2 affinity – oxygenated
  • THINK: Relaxed in respiratory area

Question 20

Is there a R-shift or L-shift of curve in carboxyhemoglobin

Answer 20

L-shift

• Hb bound to O2 is decreased because it is bound to CO instead = the height of curve is lower
  
  • Decreased O2 content in the blood
• The heme groups NOT bound to CO have increased affinity for O2 = L shift of curve
  
  • This makes it more difficult for O2 to be unloaded in tissues

Question 21

Clinical presentation of carboxyhemoglobin vs. methemoglobin

Answer 21

• Carboxy hemoglobin
  
  • Headaches, dizziness, and cherry red skin
• Methemoglobin
  
  • Cyanosis
  • Chocolate-colored blood

Question 22

What is the alveolar gas equation

Answer 22

• Amount of O2 in the alveoli = amount of O2 in inspired air – amount of O2 consumed
  
  • pAO2 = pIO2 – (paCO2 / R)
    
    • pAO2 = alveolar pO2
    • pIO2 = pO2 in inspired air
    • paCO2 = arterial pCO2
  • pAO2 = 150 – (paCO2 / 0.8)

Question 23

What is the value of a normal A-a gradient

Answer 23

• Normal = 10-15 mm Hg
• Increased A-a gradient means that there is a problem with O2 equilibrating between alveoli and arteries:
  
  • Shunting or V/Q mismatch
  • Fibrosis (thickened diffusion barrier)
  • Increased FiO2 (increases pAO2 by flooding alveoli with O2, but there is still a limit as to how much O2 can go into the arteries)
  • Age

Question 24

Causes of hypoxemia that result in normal A-a gradient

Answer 24

• Normal A-a gradient (low pAO2 and low paO2)
  
  • High altitude
  • Hypoventilation

Question 25

Causes of hypoxemia that result in high A-a gradient

Answer 25

* High A-a gradient (normal pAO2 and low paO2) * Pulmonary fibrosis * R-to-L cardiac shunt (blood bypasses pulmonary vasculature and does not get oxygenated) * V/Q mismatch

Question 26

EKG changes in PE

Answer 26

* EKG changes: * SIQ3T3 = wide S in lead I, large Q and inverted T in lead III

Question 27

What are the lab values seen in a PE (pO2, pCO2, and pH)

Answer 27

Low pO2 -- due to PE Low pCO2 -- due to compensatory hyperventilation (respiratory alkalosis) High pH -- due to low pCO2

Question 28

Adverse effects of amniotic fluid embolism

Answer 28

* Can lead to DIC, especially postpartum

Question 29

In CO poisoning, what will you see in paO2, saO2, and oxygen content?

Answer 29

SaO2 = decreased (CO competes with O2) PaO2 = normal Total oxygen content = decreased

Question 30

In polycythemia, what will you see in paO2, saO2, and oxygen content?

Answer 30

PaO2 = normal SaO2 = normal Total O2 content = increased

Question 31

In anemia, what will you see in paO2, saO2, and oxygen content?

Answer 31

Oxygen content will be decreased because hemoglobin is decreased SaO2 measures the saturation of the hemoglobin that you do have, so it won’t change since the remaining hemoglobin will be normally saturated PaO2 measures O2 dissolved in blood, which has nothing to do with Hb, so will also be normal

Question 32

What is detection bias

Answer 32

· Refers to the fact that a risk factor itself may lead to extensive diagnostic investigation and increase the probability that a disease is identified · E.g. smokers may undergo increased imaging surveillance due to smoking status, which would detect more cases of cancer in general

Question 33

Enzyme deficiency and presentation of von Gierke

Answer 33

* Deficient glucose-6-phosphatase * Causes a defect in both glycogenolysis and gluconeogenesis * Presentation: * Severe fasting hypoglycemia, lactic acidosis, hepatomegaly & steatosis, hyperuricemia & hyperlipidemia

Question 34

Enzyme deficiency and presentation of Pompe

Answer 34

* Deficient in lysosomal alpha-1,4-glucosidase * Enzyme usually degrades small amounts of glycogen trapped in lysosomes * Enzyme deficiency leads to glycogen accumulation within lysosomes (appears as periodic acid-schiff-positive material * Presentation: * Normal glucose levels * Cardiomegaly, hypertrophic cardiomyopathy, exercise intolerance, hypotonia * THINK: Pompe = fat = symptoms of obesity * Shortened life expectancy

Question 35

Enzyme deficiency and presentation of Cori disease

Answer 35

* Deficient in debranching enzymes * THINK: Cori wants me to climb his “straight branch” * Causes a defect in glycogenolysis but gluconeogenesis is fine * Presentation: * o Milder version of Von Gierke disease * o Hepatomegaly, ketotic hypoglycemia, hypotonia and weakness, abnormal glycogen with very short outer chains

Question 36

Enzyme deficiency and presentation of McArdle Disease

Answer 36

* Deficient in skeletal muscle glycogen phosphorylase * McArdle = Muscle * Can make glycogen but can’t break it down * Increased glycogen in muscle à increased osmotic pressure à swelling and lysis of myocytes à rhabdomyolysis à myoglobin in serum à myoglobin in urine (myoglobulinuria) * Presentation: * o Weakness and fatigue with exercise * o No rise in blood lactate levels after exercise

Question 37

Stimulation of what nerve can improve the symptoms of obstructive sleep apnea

Answer 37

Stimulation of the hypoglossal nerve using an implantable nerve stimulator causes the tongue to move forward slightly, increased the anteroposterior diameter of the airways

Question 38

Criteria of manic epidose

Answer 38

* Lasting at least one week * At least one of these criteria: DIG FAST * D – Distractibility * I – Irresponsibility * G – Grandiosity * F – Flight of ideas (e.g. racing thoughts) * A – Goal-directed Activity / Agitation * S – decreased need for Sleep * T – Talkativeness

Question 39

MOA behind tyramine toxicity

Answer 39

* Tyramine naturally occurring monoamine compound found in aged meats, alcoholic beverages, and fermented dairy products * Tyramine acts as a catecholamine releasing agent, but before it gets to the general circulation it is metabolized in the GI tract by MAO-A * But if you inhibit MAO-A, all the Tyramine flows in the circulation and acts as a sympathomimetic agent, displacing NE from neuronal storage vesicles * Tyramine toxicity can precipitate a hypertensive crisis (e.g. HTN, blurry vision, diaphoresis)

Question 40

Treatment of Phentolamine

Answer 40

Phentolamine (alpha-1 and alpha-2 antagonist)

Question 41

What is the feared complication associated with antiphospholipid antibodies

Answer 41

Hypercoagulable state Often presents with multiple spontaneous abortions Antibodies associated with SLE

Question 42

Symptoms associated with SLE

Answer 42

* RASH OR PAIN * R – Rash (malar or discoid) * A – Arthritis (non-erosive, 2 joints) * S – Serositis (e.g. pleuritic, pericarditis) * H – Hematologic disorders (hemolytic anemia, leukopenia, lymphopenia, thrombocytopenia) * O – Oral/nasopharyngeal ulcers (painless) * R – Renal disease (diffuse proliferative glomerulonephritis or membranous glomerulonephritis) * P – Photosensitivity * A – Antinuclear antibodies (+ANA) * I – Immunologic disorder (anti-dsDNA, anti-Smith, anti-histone, or anti-phospholipid/anti-cardiolipin) * N – Neurologic disorders (seizures, psychosis)

Question 43

In what part of the brain do you see atrophy in Huntingtons

Answer 43

Caudate and putamen

Question 44

In what disease will you see dementia + visual hallucinations

Answer 44

Lewy body dementia

Question 45

Is BPH due to hypertrophy or hyperplasia

Answer 45

Hyperplasia

Question 46

What is Mittelschmerz

Answer 46

Transient mid-cycle ovulatory pain Associated with peritoneal irritation

Question 47

What are the stimulators and products of theca and granulosa cells?

Answer 47

* Theca cells * Stimulated by LH * Produce androstenedione from cholesterol via desmolase * Granulosa cells * Stimulated by FSH * Produce estrogen (estradiol) from androstenedione via aromatase

Question 48

Describe pathogenesis of PCOS

Answer 48

* Increases LH = stimulation of theca cells = increased androgen production by theca cells = increased peripheral conversion of androgens into estrone in adipose tissue = decreased FSH (negative feedback) = decreased stimulation of granulosa cells = degeneration of follicles = cystic follicles

Question 49

What is the associated cause and complication of vaginal adenosis

Answer 49

* Associated with diethylstilbestrol (DES) in utero and clear cell adenocarcinoma * Adenosis: * Persistence of columnar epithelium within the upper vagina * Lower 1/3 of vagina derived from urogenital sinus = squamous epithelium * Upper 2/3 of vagina derived from Mullerian duct = columnar epithelium * Normally, squamous epithelium will grow upwards to replace the columnar epithelium

Question 50

Common metastatic location of prostate cancer

Answer 50

Bone

Question 51

Serious complication of invasive cervical carcinoma

Answer 51

* Lateral invasion can block ureters leading to hydronephrosis and postrenal failure