GI Part II (Post-Midterm; COMPLETE; doesn't include cards from the first half) Flashcards Preview

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Flashcards in GI Part II (Post-Midterm; COMPLETE; doesn't include cards from the first half) Deck (39):
1

What is the major product of waste nitrogen in humans?

Choices:

Urea

Ammonia

Uric acid

Creatinine

Nitric oxide

Urea

Explanation:

  • Ammonia, uric acid and creatinine are all waste products of nitrogen metabolism, but urea is the major one in humans. Ammonia is the easiest to make from amino acids (via transaminations and the GDH reaction), but is highly toxic. Nevertheless, it is the major excretory product in fish; they are not poisoned because they can rapidly eliminate this toxic waste product through their gills into the large water supply in their environment.
  • Birds and reptiles with a limited water supply cannot afford to make urea because it requires too much water for elimination. Therefore, their main excretory product is a semisolid suspension of uric acid.
  • Creatinine is formed from creatine phosphate in a spontaneous side reaction. There are no pathways to funnel large amounts of waste nitrogen into it.
  • Nitric oxide is a signaling molecule produced in low amounts. At the levels required to be an excretory product it would be highly toxic.

2

Which one of the following is a reactant or product of all transamination reactions?

Choices:

Alanine

Aspartate

Glutamate

Glutamine

Glutamate

Explanation: All transaminases use the glutamate/alpha-ketoglutarate pair. This way waste nitrogen can be funneled into one molecule, glutamate. Glutamate can also serve as a nitrogen donor in amino acid synthesis. The pool of N is therefore mobile, and can be shifted from one molecule to another.

3

A bolus of N-15 labeled alanine was injected into a rat and the fate of the label followed over several days. During the time course of the experiment, the label can be expected to be found in all of the following EXCEPT which one?

Choices:

Urinary ammonia

Nucleic acids

Proteins

Sphingolipids

Urea

The alpha amino groups of nonessential amino acids

The side chain nitrogen atoms of essential amino acids

The side chain nitrogen atoms of essential amino acids

Explanation:

  • The label can be transferred from alanine to alpha-ketoglutarate, forming a pool of labeled glutamate. The GDH reaction can then produce a pool of labeled ammonia, from which glutamine synthetase can form glutamine containing label in the amide side chain.
  • With labeled glutamate, glutamine, and ammonia in the cell, all the compounds listed can be synthesized except the nonessential amino acids. While the alpha-amino groups of essential amino acids are exchangeable via transamination reactions, the side chain nitrogen of tryptophan, for example, is fixed in an indole ring, and not a substrate for a transaminase.

4

Which one of the following is both a product of the urea cycle and an intermediate of the citric acid cycle?

Choices:

Carbamic acid

Fumarate

Malate

Ornithine

Succinate

Fumarate

Explanation:

Fumarate is the only intermediate that is a product of the urea cycle and an intermediate of citric acid cycle. This is not just a curiosity, but an important part of the nitrogen excretion system. Fumarate cannot be allowed to accumulate each time a urea molecule is made; it must be used or recycled somehow. The recycling pathway employs part of the TCA cycle: fumarate => malate => OAA. From there OAA can be transaminated to aspartate, a substrate for the urea cycle. The urea cycle plus the recycling of fumarate to aspartate is called the Krebs bi-cycle. See lecture slides. In the fasted state, fumarate can be converted to glucose by this route: fumarate => malate => OAA => PEP =>=> glucose.

5

In the starved state, which class of amino acids is preferentially degraded in skeletal muscle?

Choices:

Acidic

Basic

Aromatic

Branched chain

Branched Chain

Explanation:

In the fasted state, muscle breaks down contractile proteins to help satisfy its own energy needs. From the pool of amino acids produced by hydrolysis, branched chain amino acids are preferentially oxidized, probably because they are the most energy-rich amino acids, their carbon skeletons resembling short, branched fatty acids. Approximately 20% of the muscle’s energy demands are met by BCAA oxidation.

6

Which one of the following amino acids CANNOT be synthesized by humans from glucose and nitrogen taken from the blood “nitrogen pool?”

Choices:

Alanine

Arginine

Serine

Glycine

Valine

Glutamic acid

Aspartic acid

Valine

Explanation:

This question is equivalent to asking, “Which one of the following amino acids is essential?” A non-essential amino acid is one that can be synthesized in the body, de novo, from compounds that contain the elements C, H, O, and N. A more useful operational definition is an amino acid that can be made from glucose and a nitrogen source. As a rule, any biomolecule that is not “essential” can be synthesized from glucose and, if needed, an endogenous source of nitrogen, phosphate, sulfur, and metals. The list includes fatty acids, triglycerides, purines, pyrimidines, heme, neurotransmitters, membrane lipids, etc.

7

In the starved state, what is the major fate of the nitrogen atoms of glutamine in the kidney?

Choices:

They are used to synthesize urea.

They are used to synthesize purines and pyrimidines.

They are used to synthesize alanine.

They are excreted in the urine as ammonium ions.

They are used to synthesize branched chain amino acids.

They are excreted in the urine as ammonium ions

Explanation:

Both nitrogens of glutamine are excreted into the urine as ammonia. Since ammonia is a base, it picks up protons and is really excreted as ammonium ion. The effect is to remove protons from the body, so ammonia is often referred to as a blood buffer that helps the bicarbonate system during a fast. This help is essential because ketone bodies, which are made in abundance during a fast, put a severe acid load on the blood buffering system. Without the help of the ammonia buffer, the bicarbonate system would be overwhelmed after about a week of starvation.

8

Which one of the following can cause both hypoglycemia and hyperuricemia?

Choices:

  • Inability of kidney to re-uptake uric acid
  • Deficiency of glucose 6-phosphatase
  • Low activity of phosphoribosyl pyrophosphate (PRPP) synthetase
  • Partial or complete lack of xanthine oxidase
  • Point mutations that result in superactive forms of hypoxanthine-guanine phosphoribosyltransferase (HGPRT)

Deficiency of glucose 6-phosphatase

Explanation:

  • Glucose 6-phosphatase deficiency, which causes Type I glycogen storage disease (also known as von Gierke's disease) results in hypoglycemia because the liver cannot convert G-6-P to free glucose. The pool of G-6-P increases and flows into the HMP shunt causing increased levels of the product ribose 5-phosphate. High levels of R-5-P in turn enter into the pathway of de novo purine biosynthesis, resulting in overproduction of purine nucleotides. The over-abundant purines are degraded to uric acid, which accounts for the hyperuricemia (and predisposes these patients to attacks of gout). {Although this specific disorder was not covered in lecture this week, the question can be answered by applying your knowledge of both nucleotide and carbohydrate metabolism.}
  • Inability of kidney to re-uptake uric acid causes increased excretion and tends to lower the levels of uric acid in blood over time. Drugs that bind to the the urate transporter (URAT1) in the proximal tubule act to increase the excretion of uric acid in just this way, by inhibiting uric acid reuptake from the tubule lumen. Such "uricosuric" drugs can be used without causing problems with hypoglycemia.
  • Low activity of PRPP synthetase would cause decreased levels of purine biosynthesis. By contrast, abnormally high levels of the enzyme lead to hyperuricemia (as seen for mutations that interfere with normal allosteric regulation of the enzyme, and make it more active by preventing normal feedback inhibition).
  • Partial or complete lack of xanthine oxidase can be mimicked by a drug such as allopurinol. Since uric acid is produced by this enzyme, levels of uric acid decline when the enzyme activity is low, and does not lead to hyperuricemia.
  • Point mutations that result in superactive forms of hypoxanthine-guanine phosphoribosyltransferase (HGPRT) would cause more efficient salvage of purine bases and lower uric acid levels, not cause hyperuricemia.

9

A 6-month-old boy presents unable to crawl and with poor ability to sit up unsupported. The mother reports finding what looked like orange sand in his diaper. Chemical analysis showed the material consisted mainly of uric acid colored by small amounts of blood. Cultured fibroblasts showed normal rates of purine biosynthesis but a decreased ability to reutilize purine bases. What enzyme is most likely to be deficient in this patient?

Choices:

Xanthine oxidase

PRPP synthetase

Glutamine phosphoribosyl amidotransferase

UMP synthase

Hypoxanthine-guanine phosphoribosyltransferase

Hypoxanthine-guanine phosphoribosyltransferase

Explanation:

The presence of uric acid crystals in urine ("sand" in the diaper) indicates extremely high levels of uric acid are being excreted. The motor disability and hypotonia evident from the clinical picture taken together with the lab findings suggest Lesch-Nyhan disorder -- the condition in which the purine salvage enzyme HGPRT is lacking entirely. The bizarre self-injurious behavior associated with this disorder manifest later on in childhood. Without functional salvage activity, purine bases are destined to be degraded to uric acid. The resulting decreased nucleotide pools together with increased PRPP levels lead to loss of feedback inhibition and dysregulation of the de novo synthesis pathway. This causes even higher levels of purines to be produced, which can go nowhere else but to form uric acid.

Xanthine oxidase produces uric acid (converts the bases hypoxanthine to xanthine, and xanthine to uric acid), so deficiency of that enzyme would not lead to increased uric acid. PRPP synthetase and the phosphoribosyl amidotransferase enzyme (aka PRA synthase) are involved in de novo synthesis of purines, so deficiency is likewise unlikely to cause uric acid overproduction. UMP synthase is a bifunctional enzyme in the pyrimidine biosynthesis pathway, unrelated to purine nucleotide degradation.

10

A 52-year-old man is seen in the clinic with pain and swelling in his left foot. He has had joint pains and muscle aches occasionally over the last 15 years. He denies recent trauma, but reports a high level of pain and sensitivity in the affected foot. He is a self-employed butcher who works standing for long periods of time at the counter, so this is especially disabling to him. He is divorced and lives alone, smokes 1 pack per day for 28 years and drinks alcohol on weekends, sometimes heavily. He recently went hunting and brought back a wild pig and several rabbits. He processed the meat and made sausages for his friends. On examination, the first metatarsophalangeal joint appears red and swollen, and was warm to the touch. The joint was aspirated, and synovial fluid sent to the lab for analysis.

Results from synovial fluid analysis:

Appearance: Straw-colored

Leukocytes: 8750/µL

PMNs: 85%

RBCs: None

Blood glucose to synovial fluid glucose ratio: 4

Culture (Gram stain): Negative Thin, needle shaped, yellow crystals present. Polarized light microscopic examination of crystals showed strong negative birefringence -- characteristic of monosodium urate.

Which one of the following is most appropriate to include in the immediate treatment of this disorder?

Choices:

Methotrexate

Allopurinol

Colchicine

Folate

Vitamin B12

 

Colchicine 

Explanation:

  • Laboratory analysis demonstrating that the aspirated crystals are in fact monosodium urate is required for a definitive diagnosis of gout. Treatment of an acute inflammatory attack of gout is often initiated with NSAIDs and/or colchicine.
  • Colchicine binds to tubulin and blocks microtubule formation. This stops the separation of chromosome pairs during mitosis (spindle poison with arrest in metaphase) and also blocks amoeboid movements and phagocytosis by neutrophils, thus interrupting the inflammatory cycle (but, due to extreme toxicity, serious side effects can develop and the therapeutic window is narrow).
  • Allopurinol is used to control levels of uric acid over the longer term. However, the immediate need for this patient is relief from the painful attack, so allopurinol is not the most appropriate drug to include at the start of the treatment. We can speculate that a fair amount of organ meats might have been left over from the patient's recent hunting trip (he even tried giving them away to his friends). Possibly he also ended up consuming a lot of those leftovers -- with organ meats being especially high in purine nucleotides, degradation of purines in large excess can cause uric acid levels to spike. Alcohol consumption also predisposes individuals to attacks of gout. In part, the mechanism involves lactic acid, produced from metabolism of alcohol, and effects of lactic acid that impair kidney excretion of uric acid. Perhaps alcohol and overindulgence in the purine-rich sausages might have precipitated this attack. Patients with gout are advised to minimize alcohol intake and avoid purine rich foods.
  • Methotrexate inhibits dihydrofolate reductase. Its use in chemotherapy is actually associated with increased levels of uric acid due to increased degradation of purine nucleotides that takes place as tumor cells are destroyed -- so called "tumor lysis syndrome" that results in hyperuricemia and can complicate treatment by impairing kidney function. Folate and B12 are used in treating specific anemia states.

11

Methotrexate, a potent inhibitor of dihydrofolate reductase, blocks the rapid proliferation of cells. This effect is best explained by the fact that formation of dTMP is accompanied by oxidation of N5 ,N10 methylenetetrahydrofolate, and the fact that

Choices:

  • ribonucleotide reductase is inhibited by dATP.
  • ribonucleotide reductase does not require N5,N10 methylene-tetrahydrofolate for activity.
  • CTP synthetase is allosterically activated by GTP.
  • carbamoyl phosphate synthetase II is inhibited by UTP and CTP.
  • cells require the tetrahydro form of folic acid derivatives for synthesis of both dTMP and purine nucleotides

cells require the tetrahydro form of folic acid derivatives for synthesis of both dTMP and purine nucleotides.

Explanation:

  • The question is intended to re-emphasize the underlying mechanism of how folate acts in the body, to recall why regeneration of the tetrahydro form is critical to maintain function of folate, and to reiterate how blocking dihydrofolate reductase in the cycle involving thymidylate synthase is the basis for action of the important chemotherapy drug methotrexate.
  • All other answers are true statements (and several of them have significance on their own, for other reasons) but they do not explain the basis of action of the folate analog methotrexate

12

A 23-year-old Asian woman had the peripheral blood smear shown below which was prepared as part of a routine physical exam. The best term to describe her cells is

Choices:

Acanthocytes

Dacrocytes

Macrocytic

Microcytic

Normocytic

Poikilocytes

Spherocytes

Q image thumb

Normocytic

Explanation:

  • The image shows cells with central pallor that have a size equivalent to the size of a lymphocyte nucleus. These cells would be normocytic.
  • Microcytic cells would be smaller and have more central pallor.
  • Macrocytes are larger and usually have an oval shape.
  • Dacrocyte is another term for tear drop cells.
  • Spherocytes do not have central pallor.
  • Acanthocytes are spiculated cells, meaning they have spike like projections.
  • Poikilocyte is a broad term that simply implies varied abnormal shapes are observed. Acanthocytes and dacrocytes are sub-classifications of poikilocytes.

TIP: 2LT Edmondson made an amazing study sheet. It has images for all of these cell types and can be found on our Facebook.

13

A 66-year-old female presents with a two month history of the feeling of food sticking in her throat. She has a long history of hypochromatic microcytic anemia (MCV of 72), and she is noticed to have atrophic glossitis on your physical exam. A Barium swallow indicates the reason for the difficulty swallowing is an esophageal web.

With which of the following disorders is the above constellation of findings associated?

Choices:

Alpha-thalassemia

Hemochromatosis

Megaloblastic anemia

Iron deficiency anemia

Sickle cell anemia

Iron deficiency anemia

Explanation:

The syndrome described is Plummer Vinson syndrome which consists of esophageal web, microcytic hypochromic anemia and atrophic glossitis. Alpha-thalassemia is associated with a microcytic anemia, however does not have esophageal disease. The other choices are not consistent with a microcytic anemia.

14

A 62-year-old male complains of fatigue and weakness that gradually worsened over the last 8 months. This is associated with cramping abdominal pain and decreased stool caliber. A complete blood count and serum iron value are consistent with iron-deficiency hypochromic microcytic anemia. Which one of the following options regarding the pathogenesis of the disease in this particular patient is true?

Choices:

APC mutations associated with invasiveness.

P53 mutations occur at late stages.

HFE mutations cause the iron loss.

Associated with increased stool bulk.

Associated with familial adenomatous polyposis.

P53 mutations occur at late stages

Explanation:

Colonic adenocarcinoma should be the main clinical consideration for this patient with iron-deficiency anemia, weight loss and decreased stool caliber. Colon adenocarcinomas, through unknown mechanisms, are associated with decreased dietary fiber causing decreased stool bulk. In the absence of early total colectomy, familial adenomatous polyposis is associated with a 100% risk of developing adenocarcinoma, presentation at this late age (62 years) would be distinctly unexpected. The classic adenoma-carcinoma sequence accounts for about 80% of sporadic adenocarcinomas. In this sequence APC gene mutations are early events and P53 mutations are late events of tumor progression. HFE mutations are associated with hereditary hemochromatosis, a disease characterized by excessive iron accumulation in parenchymal organs such as liver, heart and pancreas.

15

A 25-year-old woman with systemic lupus erythematosus (SLE) is being evaluated for a chronic anemia. She takes a non-steroidal anti-inflammatory (NSAID) drug for arthritis but no other medications. Her hemoglobin is 9.8 g/dl (12-16), and hematocrit is 29% (36-46%). The MCV is 102 fl (80-100). The MCHC is 38% (31-36%). The reticulocyte count is 10% (0.5-1.5%). Which one of the following possibilities is the most likely cause of her anemia?

Choices:

  • Anemia of chronic inflammatory disease
  • Autoimmune hemolysis
  • Iron deficiency from chronic gastrointestinal blood loss due to gastritis
  • Mixed iron deficiency and vitamin B12 deficiency (from autoimmune destruction of parietal cells)
  • Renal failure from SLE

Autoimmune hemolysis

Explanation:

The elevated reticulocyte count and MCV of 102 supports a diagnosis of a hemolytic anemia. Antibody mediated destruction of red cells is a feature of SLE and may present as a hemolytic anemia.

16

Which one of the following histories best fits the peripheral blood smear shown below?

Choices:

An 18-year-old African American man with autoinfarcted spleen

A 20-year-old woman with acute blood loss secondary to a gunshot wound

A 23-year-old woman with an artificial mitral valve

A 50-year-old woman with gastric atrophy and glossitis

A 60-year-old man with chronic blood loss

Q image thumb

A 60-year-old man with chronic blood loss

Explanation:

  • The image shows a hypochromic microcytic population of cells consistent with iron deficiency anemia. Chronic blood loss would lead to iron deficiency.
  • An 18-year-old African American man with autoinfarcted spleen fits with sickle cell anemia.
  • A 20-year-old woman with acute blood loss secondary to a gunshot wound would be a normocytic anemia.
  • A 23-year-old woman with an artificial mitral valve would correspond to hemolytic anemia.
  • A 50-year-old woman with gastric atrophy and glossitis would be consistent with megaloblastic anemia.

17

A patient developed gradual onset of fatigue associated with a decreased hematocrit following an ill-defined infection. Which one of the following would best support a hemolytic cause for his anemia?

Choices:

Decreased reticulocyte count

Elevated lactate dehydrogenase isozyme 1 (LDH1) in serum

Hypersegmented neutrophils

Negative Coombs test

Presence of basophilic stippling

Elevated lactate dehydrogenase isozyme 1 (LDH1) in serum

Explanation:

  • LDH1 is the major isozyme of lactate dehydrogenase present in red blood cells. Hemolysis of red cells increases the level of LDH1 in serum, such that it surpasses other isoforms (so-called LDH 1/2 flip, where the relative levels of LDH isozymes provide an easily distinguishable electrophoretic pattern). Blood has to be handled carefully to prevent inadvertent hemolysis that would throw off the serum distribution (false positive).
  • Reticulocytes are increased in hemolytic anemias.
  • The Coombs test may be positive for immune mediated hemolysis.
  • Hypersegmented neutrophils go with B12 deficiency.
  • Basophilic stippling goes with lead poisoning

18

An American diplomat of South Asian ancestry was assigned to Uganda and was placed on anti-malarial prophylaxis. Three days after arriving in Kampala, he was noted to be suddenly ill with jaundice, hemoglobinemia, hemoglobinuria, and falling hematocrit. A peripheral blood smear following supravital staining is shown below. Which one of the following complications would most likely occur in this patient? 

Choices:

Aplastic crisis

Chronic myelogenous leukemia

Disseminated intravascular coagulation (DIC)

Splenic sequestration

Venous thromboembolism

Q image thumb

Splenic sequestration

Explanation:

The case best fits with glucose 6-phosphate dehydrogenase (G6PD) deficiency due to ingestion of antimalarials. The erythrocytes show Heinz bodies. As the abnormal red blood cells circulate through the spleen, RBC damage leads to splenic sequestration.

19

An increase in urinary leukotrienes (e.g., LTE4) in response to aspirin is thought to arise from

Choices:

inhibition of phospholipase A2.

inhibition of leukotriene breakdown.

inhibition of prostaglandin synthesis.

antagonism of the leukotriene receptor.

inhibition of γ-glutamyl transpeptidase. 

inhibition of prostaglandin synthesis.

Explanation:

The leukotrienes LTC4, LTD4, and LTE4 are potent mediators of bronchial constriction. Aspirin irreversibly inhibits COX-1 and COX-2 in the tissues and blocks prostaglandin synthesis. This leads to a buildup of arachidonic acid, which is converted into the HPETE class of eicosanoids. Further enzymatic steps including one catalyzed by glutathione-dependent γ-glutamyl transpeptidase lead to the formation of the “cysteinylleukotrienes” including LTE4.

20

Production of isoprostanes from membrane lipids requires the activity of which one of the following?

Choices:

Lipoxygenase

Fatty acyl-CoA desaturase

Prostaglandin  H synthase

Phospholipase A2

Fatty acid amide hydrolase

Phospholipase A2

Explanation:

Isoprostanes exert eicosanoid-like effects and are generated by free-radical mediated oxidation of membrane lipids containing arachidonic acid (AA). Oxidation of AA associated with membrane glycerophospholipids activates phospholipase A2, which catalyzes the removal of the isoprostane from the membrane. Isoprostanes may activate numerous GPCRs within the same cell or neighboring cells

21

Individuals taking COX-2 specific NSAIDs may have an increased risk for myocardial infarction and stroke, due to a reduction in the synthesis of which one of the following?

Choices:

Thromboxane A2 (TxA_2)

Prostacyclin (PGI_2)

Angiotensin II

Lipoxin A4 (LXA_4)

Isoprostanes

Prostacyclin (PGI_2) 

Explanation:

Platelets express COX-1 exclusively and produce thromboxane A2 (TxA2) as a key regulator of aggregation. The endothelial cells that line blood vessels express COX-2 and produce prostacyclin (PGI2). PGI2 exerts vasodilatory and anti-thrombotic effects that counter the pro-thrombotic effects of TxA2. Specific inhibition of COX-2 blocks PGI2 synthesis in vascular endothelial cells, which in turn leaves the effects of TxA2 unopposed and generates conditions that favor the formation of thrombi.

22

Which of the following are involved in promoting anticoagulant/anti-thrombotic functions of healthy vascular endothelial cells? (Choose all that apply)

Choices:

  • Expression of tissue plasminogen activator (t-PA)
  • Secretion of α2-antiplasmin
  • Membrane bound ecto-ADPase
  • Activation of protein C by thrombin bound to thrombomodulin leading to formation of activated protein C-protein S complex (APC)
  • Expression of plasminogen activator inhibitor 1 (PAI-1)
  • Antithrombin III (ATIII) and tissue factor pathway inhibitor (TFPI) bound to cell-surface heparan sulfate

  • Expression of tissue plasminogen activator (t-PA)
  • Membrane bound ecto-ADPase 
  • Activation of protein C by thrombin bound to thrombomodulin leading to formation of activated protein C-protein S complex (APC) 
  • Antithrombin III (ATIII) and tissue factor pathway inhibitor (TFPI) bound to cell-surface heparan sulfate

Explanation:

  • α2-Antiplasmin is synthesized in liver and inhibits circulating plasmin to protect against systemic fibrinolysis, and therefore has a pro-coagulant effect. Deficiency of α2-antiplasmin causes bleeding.
  • Plasminogen activator inhibitor 1 (PAI-1) is expressed by endothelial cells, and has a major regulatory function to keep tPA in check. Thus, it has pro-coagulant effect.

23

Increased bleeding tendency due to dietary deficiency of an essential fat-soluble vitamin results from the inability to synthesize which set of plasma protein clotting factors in their functional forms?

Choices:

  • V, VII, VIII, IX
  • V, VII, IX, X V, VIII, IX, X
  • VII, VIII, IX, X
  • VII, VIII, IX, thrombin
  • VII, VIII, X, thrombin
  • VII, IX, X, thrombin
  • V, VII, IX, thrombin
  • V, VII, X, thrombin

VII, IX, X, thrombin

Explanation:

The fat-soluble vitamins are A, D,E, and K. Recall that vitamin K is required to support proper "K"oagulation becasue it is used for posttranslational synthesis of gamma carboxy groups on specific coagulation factors made in the liver. We remember those factors as "2-7-9-10". Factor II is thrombin, so the correct answer is VII, IX, X, thrombin.

24

An infant boy is brought to the emergency room because of significant bleeding into a knee joint. His parents (who themselves have no abnormal bleeding histories) are unaware of any significant trauma he might have suffered. The PT was normal, but the aPTT was significantly prolonged. A factor VIII assay was within normal limits. If you had only enough plasma left for one more assay, which one of the following would you choose to measure?

Choices:

Factor II

Factor VII

Factor IX

Factor X

von Willebrand factor

Factor IX

Explanation:

Prolongation of the aPTT with hemarthrosis suggests hemophilia. Factor VIII and IX deficiency are the etiologies for hemophilia. If the Factor VIII level is normal, then the patient should be worked up for Factor IX deficiency. 

25

A point mutation (marked with * in the figure below) in the human elastin gene results in the autosomal dominant disorder Supravalvular Aortic Stenosis (SVAS), an obstructive vascular disease that affects the aorta, carotid, coronary and pulmonary arteries. The relative positions of the recognition sites for the restriction enzyme ClaI (ATCGAT) in the elastin gene are indicated in the figure. Southern analysis of total genomic DNA from an individual who is heterozygous for the disease-causing allele was carried out after ClaI digestion using a probe located in the region indicated. What size DNA band(s) will be detected?

Choices:

1.5 kb

4 kb

5.5 kb

1.5 and 4 kb

1.5 and 5.5 kb

4 and 5.5 kb

Q image thumb

4 and 5.5 kb

Explanation:

Heterozygosity and the position of the probe account for the two bands of 4 and 5.5 kb. The normal allele is cut into 1.5 and 4 kb, but the probe detects only the 4 kb fragment. In the abnormal allele the ClaI site is mutated and therefore is cut to give a single 5.5 kb fragment, which includes the region detected by the probe

26

Comparing the chemistries of traditional Sanger’s method and the Next Generation (Next-Gen) methods such as the Illumina platform, all of the following statements are correct EXCEPT for which one?

Choices:

  • Both methods involve the use of fluorescently labeled dNTPs.
  • Both methods use dideoxy NTP analogs.
  • The Illumina approach is unique because it uses dNTPs with reversible terminators.
  • Gel electrophoretic separation of the sequencing reaction products is required only in the traditional method.
  • DNA molecules that serve as templates for the sequencing reaction are immobilized on a solid support in the Next-Gen approaches but not in the Sanger method.

Both methods use dideoxy NTP analogs.

Explanation:

In comparison with traditional Sanger sequencing, in which electrophoresis is used for bulk separation to analyze randomly terminated fragments produced by polymerase in the presence of dideoxy NTPs, the NextGen systems use micro imaging of tiny amounts of individual islands or clusters of identical DNA molecules (fragments on a chip in the Illumina format, or on other solid substrates such as single micro beads in other methods) as they are copied, with single nucleotides incorporated one step at a time. For each cluster, each time a new nucleotide is incorporated, a signal is analyzed to determine whether it was A,T, G, or C. The fragments are relatively short, and reads are short, but there are millions of clusters being analyzed. The fact that no separation of dideoxy NTP chain terminated bulk reactions is used is a fundamental conceptual distinction from the traditional Sanger method.

27

In the mass spectrometer, the peptide mass fingerprint of a polypeptide is determined by which one of the following?

Choices:

Overall charge of the polypeptide at neutral pH

Shape of the polypeptide in its native folded state

Amino acid sequence of the polypeptide

Isoelectric point of the polypeptide

Number and position of inter-chain hydrogen bonds in the polypeptide 

Amino acid sequence of the polypeptide 

Explanation:

The mass spectrometer measures the masses of peptides present in a complex mixture of fragments of the original polypeptide produced by trypsin digestion. Because trypsin specifically cleaves after basic amino acids, arginine and lysine, the unique sequence of the original polypeptide dictates the positions of cleavage, and therefore generates a unique fingerprint set of peptides of characteristic masses.

28

A 60-year-old retired newspaper editor has had a mild, unexplained anemia for 4 years and has complained of increasing fatigue. CBC reveals pancytopenia. Bone marrow examination reveals ringed sideroblasts and abnormal megakaryocytes.

He is most likely at risk for which one of the following lesions?

Choices:

Acute myelogenous leukemia

Chronic myelogenous leukemia

Hairy cell leukemia

Large cell lymphoma

Small cell lymphoma

Acute myelogenous leukemia 

Explanation:

The presence of ringed sideroblasts and abnormal megakaryocytes suggests a myelodysplastic syndrome. 10- 40% of patients develop AML due to acquisition of additional mutations in stem cells.

29

What is the prognosis of a patient who develops AML in the setting of myelodysplasia?

Choices:

Favorable

Unfavorable

Unfavorable

Explanation:

Patient data indicate AML arising for patients with prior myelodysplastic syndromes have a poor prognosis. In contrast, AML with recurrent chromosomal translocations, e.g. t(8;21) have a favorable prognosis.

30

A 3-year-old girl is brought to the Pediatric Clinic with fever, weight loss, and easy bruising. Physical exam reveals generalized lymphadenopathy, petechiae, ecchymoses, and hepatosplenomegaly. Examination of peripheral blood revealed numerous lymphoblasts. Which one of the following is characteristic of these cells?

Choices:

  • Differentiation of the cells can be induced by administration of retinoic acid
  • Expression of terminal deoxynucleotidyltransferase (TdT)
  • Numerous Auer rods are seen in cytoplasm
  • Positive staining by lysosomal nonspecific esterases
  • Reaction for acid phosphatase in the presence of tartrate

Expression of terminal deoxynucleotidyltransferase (TdT) 

Explanation:

  • The patient’s scenario is consistent with ALL. ALL is associated with expression of TdT.
  • Differentiation of the cells induced by administration of retinoic acid refers to acute promyelocytic leukemia.
  • Numerous Auer rods seen in cytoplasm is consistent with AML.
  • Positive staining by lysosomal nonspecific esterases refers to either the M4 or M5 subtype of AML.
  • Reaction for acid phosphatase in the presence of tartrate refers to Hairy cell leukemia.

31

All of the following are true with respect to case definitions in outbreak investigations EXCEPT which one?

Choices:

Case definitions should be made such that they are both highly sensitive and highly specific.

Case definitions allow comparisons across different geographic regions.

Case definitions standardize who is reported as having the disease.

Case definitions are often provided in different levels of accuracy.

Case definitions should be made such that they are both highly sensitive and highly specific.

Explanation:

A wide case definition will be highly sensitive, while a restricted case definition will be highly specific. It is impossible for a case definition to be both wide and restricted at the same time. A solution is to develop case definitions with different levels of accuracy, e.g. suspected cases, probable cases, and confirmed cases.

32

Quarantine is defined as the separation and restriction of movement of persons who are ill.

Choices:

True

False

False

Explanation:

Quarantine is the separation and restriction of movement of persons who are exposed but not ill. The separation and restriction of movement of persons who ARE ill is isolation.

33

A 35-year-old woman with a history of systemic lupus erythematosus (SLE) has a history of repeated first trimester miscarriages. She undergoes preliminary blood tests to determine potential causes. Which one of the following is the most likely explanation for prolonged PT and aPTT that are not corrected to normal by addition of fresh plasma from a normal person (in the test system, i.e. performing a mixing study)?

Choices:

Antithrombin III deficiency

Circulating anticoagulant

Factor VIII deficiency

Liver disease

von Willebrand disease

Circulating anticoagulant 

Explanation:

  • Prolongation of the aPTT and PT that are not corrected in a mixing study indicate the presence of an inhibitor not a factor deficiency.
  • Some patients develop antiphospholipid antibodies. Manifestations include thrombosis and recurrent pregnancy loss. In vitro, there is prolongation of the PT and aPTT due to interference with coagulation factors. These antibodies may be seen in association with connective tissue disorders (secondary antiphospholipid syndrome or in the absence of connective tissue disorders (primary antiphospholipid syndrome).

34

Which of the following organisms is associated with a 25-year-old with headache and neck stiffness, bleeding into body cavities, oozing from blood lines and petechiae that show on lab testing prolonged PT and aPTT with thrombocytopenia and elevated fibrin split products?

Choices:

Escherichia coli

Neisseria meningitidis

Group B Streptococcus

Streptococcus pneumoniae

Streptococcus mutans

Neisseria meningitidis

Explanation:

  • The scenario describes a patient with DIC (prolonged PT and aPTT with thrombocytopenia and elevated fibrin split products). DIC in association with headache and neck stiffness should suggest the possibility of meningococcemia.
  • Neisseria meningitidis is the responsible organism and the most common agent involved in bacterial meningitis in adolescents and adults.
  • E. coli and Group B Streptococcus cause meningitis in newborns but not commonly in adults.
  • Streptococcus pneumoniae is more common in the elderly. Streptococcus mutans is responsible for dental caries.

35

A 52-year-old male is brought to the emergency room after his wife found him collapsed on the floor with abundant blood on his face and floor. The patient has a 19-year history of alcoholism, but denied abuse of other drugs or unprotected sex on a prior visit. On physical examination the lung fields are clear, there is splenomegaly and a small liver difficult to palpate in part due to the presence of ascites. Laboratory studies show low serum albumin, elevated blood ammonia, thrombocytopenia of 60,000/mm3 (normal 150,000- 400,000) and prolonged PT and PTT. Endoscopy reveals enlarged bleeding esophageal veins. The patient develops another severe bleeding per mouth episode and dies. Autopsy images are shown below.

Which of the following mechanisms best explains the cause of death?

Choices:

  • Marked increase of portal venous pressure.
  • Thrombocytopenia due to liver failure.
  • Coagulopathy from liver failure.
  • Disseminated intravascular coagulation.
  • Thrombocytopenia due to hypersplenism.

Q image thumb

Marked increase of portal venous pressure.

Explanation:

The patient died from massive esophageal varices bleeding secondary to alcoholic cirrhosis. The liver images show cirrhosis, in this case the etiology (alcoholic) is inferred from the clinical history. Patients with cirrhosis or liver failure may bleed from multiple causes. Liver failure may be associated with decreased synthesis of coagulation factors such as fibrinogen, prothrombin, and factors V, VII, IX and X. Coagulation factor deficiency explains prolonged PT and PTT, not the localized venous esophageal bleeding. Thrombocytopenia may be explained on the basis of splenomegaly causing hypersplenism. Hypersplenism may cause thrombocytopenia and anemia but would not be a likely cause of this localized severe bleeding; also note that the platelet levels are not markedly low as to favor spontaneous severe bleeding. Disseminated intravascular coagulation presents as uncontrollable bleeding and thrombosis affecting multiple sites. Cirrhotic patients may have this complication if they develop sepsis. This localized severe bleeding is caused by ruptured esophageal varices. The diffuse fibrosis of the cirrhotic liver compresses hepatic intraparenchymal vessels creating portal hypertension that may be transmitted to esophageal veins and hemorrhoidal vessels. It may also be the cause of ascites (decreased albumin an additional factor), splenomegaly, spontaneous bacterial peritonitis and hepatorenal syndrome.

36

A 58-year-old female develops jaundice, hypoglycemia and altered behavior on 8 hours post coronary bypass surgery. Imaging studies show decreased liver size. After reviewing the chart you suspect acute liver failure secondary to anesthesia with halothane. Which one of the following laboratory changes would support your diagnosis of acute liver failure the most?

Choices:

Prolonged PTT.

Prolonged PT.

Hypoalbuminemia.

Hyperbilirubinemia.

Elevated alkaline phosphatase.

 

Prolonged PT.

Explanation: 

Prolonged PT in this context would be caused by factor VII deficiency, a factor with a 3-6 hour half-life on plasma. Coagulation factors II, V, IX and X are also produced in the liver, but have longer half-lives (ranging from 12-40 hours) that would be detected by prolonged PTT, or prolonged PT and PTT, but would not be compatible with the time evolution of this case. Of course, massive elevations of AST and ALT would be expected due to hepatocyte necrosis. The correct answer is “b”. Albumin has a 2-3 week half-life; hypoalbuminemia is more typical of chronic liver failure, such as cirrhosis. Hyperbilirubinemia would be expected, since the patient is jaundiced, but by itself does not indicate liver failure. Elevated alkaline phosphatase reflects bile duct injury and obstruction to flow, not liver failure.

37

Which of the following were important factors in bringing malaria under control in the South Pacific in mid- 1944. (Choose all that apply)

Choices:

  • Atabrine
  • Salvarsan
  • Sulfanilamide
  • DDT
  • Area Mosquito Control Teams
  • Command interest

 

  • Atabrine 
  • DDT 
  • Area Mosquito Control Teams 
  • Command interest

Explanation:

  • Atabrine, DDT, Area mosquito control and Command Interest all helped to control malaria, however, Command interest was the single MOST IMPORTANT FACTOR, because, the military physician is powerless without command support.
  • Salvarsan (1910) is considered to be the first modern drug. Although it was effective against only a relatively narrow range of diseases (syphilis and trypanosomiasis), it was developed by the same general method still widely used today, by pursuing a "lead compound", i.e., a compound that had some amount of weak activity, perhaps still with undesirable side effects, but that will lead to an effective drug by systematic chemical modifications and testing for improved biological activity.
  • Sulfanilamide (1935) is credited as the first antibiotic.

38

In individuals with hereditary spherocytosis, anemia results from:

  • defects in proteins needed to form the erythrocyte membrane cytoskeleton
  • defects in the maturation of reticulocytes to form erythrocytes
  • decreased production of 2,3-bisphosphoglycerate
  • decreased production of erythropoietin in the kidney
  • decreased production of globin chains needed for the synthesis of hemoglobin

defects in proteins needed to form the erythrocyte membrane cytoskeleton

Hereditary spherocytosis (HS) is caused by defects in erythrocyte cytoskeletal proteins, which include alpha and beta chains of spectrin, ankyrin, band 3 & band 4.2.  Cytoskeletal structural defects render the erythrocyte less deformable and prone to splenic sequestration.  Defects in structural proteins are difficult to compensate, therefore a dominant inheritance pattern is seen in a majority of cases.  Anemia, splenomegaly and jaundice are characteristics of the disorder.  Anema is due to increased destruction of RBCs, with average lifetimes shortened from 120 days to as low as 10-20 days.  Increased heme breakdown manifests as jaundice due to unconjugated bilirubin.  Cholecystitis develops with darkly pigmented bilirubin stones, and patients may undergo cholecystectomy.  Splenomegaly is the result of congestion of the chords of Billroth and increased numbers of phagocytes.  Splenectomy treats the anemia, but increases risk of infections due to loss of its important filtering function for blood-borne bacteria.  See Robbins 9th Ed, pp. 632-634.

39

A 40-year-old single, white woman presents in the emergency room in an agitated state, weeping, and complaining of severe abdominal pain.  The patient's history reveals similar past episodes.  A well-healed surgical scar is noted on her abdomen.  Her physical examination and laboratory tests appear largely normal, with the exception that high levels of porphobilinogen are found in the urine.  This patient's disorder most likely results from an inability to deaminate a pyrrole intermediate to form hydroxymethylbilane in the pathway of heme biosynthesis.  Which one of the following is the most likely diagnosis?

Choices:

  • Congenital erythropoietic porphyria
  • Variegate porphyria
  • Porphyria cutanea tarda
  • Acute intermittent porphyria
  • Erythropoietic protoporphyria

ACUTE INTERMITTENT PORPHYRIA

Acute intermittent porphyria (AIP) is an autosomal dominant disorder that results from the deficiency of porphobilinogen deaminase (PBG deaminase, which is also known as Uroporphyrinogen synthase, UROS, or hydroxymethylbilane synthase).  Intermittent attacks are provoked by a number of drugs such as, gonadal steroids (e.g. birth control pills), barbiturates, and alcohol, to name a few.  These drugs are metabolized by cytochrome P-450 systems, which become induced.  Cyt P-450 induction causes an increased need for heme biosynthesis, an event that leads to accumulation of toxic intermediates because a bottleneck in the pathway is created due to a reduced level of a specific heme biosynthetic enzyme.  Elevated urinary PBG is a useful diagnostic for AIP.

The other choices include deficiencies that produce photo-sensitive porphyrias due to the accumulation of porphyrins (from incomplete conversions of intermediates in the pathway) and are marked by cutaneous involvement not seen in AIP.  Neurovisceral and abdominal pain, which is characteristic of AIP, is less often seen in the other porphyrias.  The surgical scar may be due to a prior exploratory laparotomy.  Since there is no anatomical basis for AIP, exploratory surgery would have shown nothing abnormal.