GI Part II (Post-Midterm; COMPLETE; doesn't include cards from the first half) Flashcards
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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
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
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.
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.
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.
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.
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
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.
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
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.
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 kb
- 5 and 4 kb
- 5 and 5.5 kb
4 and 5.5 kb
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
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.
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.
