Final test 2023 complete with answers

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Feb 20, 2024

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A. Epithelial Cells 1. Hard Question: You are using an antibody to a Protein X and you find that Protein X is found on the basolateral membrane. However, you thought the protein has a function at the apical membrane. Are you wrong? Could a basolateral protein go up to the apical membrane? If so why do you not see this protein with your antibody on the apical surface? Is this an artifact or is it revealing something about the history of the protein molecule. Please write down some thoughts: A basolateral protein can go up to the apical membrane and vice versa via transcytosis. It is possible that protein x is currently only required on the basolateral membrane, which is why it is no longer present on the apical side. 2. Why do you think the basal membrane of most epithelia do not have microvilli (many small projections)? Hint: think about the function of the basal membrane vs the apical membrane Microvilli are involved in fluid transport and absorption. Microvilli would not prove useful in basal surface of epithelial cells, which serves to connect epithelial tissue to connective tissue . 3. Epithelial Cells are special because (choose one answer): a. Most epithelia have the identical proteins on each surface so that substances can move in random directions. b. In most epithelia, substances never move through the paracellular space between cells. c. Most epithelia have spaces between cells so that substances can traverse the paracellular space driven by electrochemical gradients. d. In most epithelia, electrochemical gradients drive Na out of cells. e. In most epithelia, electrochemical gradients drive K into cells. 4. Pick 3 Electrogenic Transporters (choose one answer): a. Na K ATPase, Na Cl Co-transporter, Na Channels b. K Channels, H+ATPase, and Na::H Counter (Anti) Transporter c. Na::glucose Co-transporter, 3NA + 2K + ATPase, Cl Channels. d. Na::Cl Co-transporter, Na::H antiporter, HK ATPase 5. In order to move Glucose into a cell, it must be coupled to Na. But for Na/glucose to enter the cell, the following is required (choose 2 correct answers based on image below): a. A gradient of Na (high outside=> low inside) b. A gradient of Na (high inside=> low outside) c. A Na/K ATPase on the opposite membrane to pump Na out of the cell d. A Na/H antiporter to bring Na into the cell. e. A Na/bicarbonate cotransporter to remove Na from the cell.
6. In the figure above, please indicate why a coupled Na-Glucose cotransporter could never work to expel glucose from cell into blood at basal membrane? Refer to concentrations in Table. a. If the Na-Glucose transporter were at the basolateral membrane, it would not work because the glucose gradient is inward, into the cell b. If the Na-Glucose transporter were at the basolateral membrane, it would not work because there are no Na gradients c. If the Na-Glucose transporter were at the basolateral membrane, it would not work because there are no glucose gradients. d. If the Na-Glucose transporter were at the basolateral membrane, it would not work because the Na gradient is inward, into the cell. 7. In the figure above, please indicate why a coupled Na-Glucose cotransporter is not needed at the basal surface to release glucose to the blood? Please state in one sentence. Hint please look at the table. A glucose transporter is already accomplishing this by moving glucose out of the cell. Na Glu Na K Glu APICAL Lumen BASAL Blood -90mv -85mv 0mv -90mv
8. Very Hard Question (Extra Credit): In the figure below, we see that there is more Cl outside the cell than inside the cell. Hence, it is intuitive that Cl would move from outside the cell into the cell. However, the inside of the plasma membrane is negatively charged at -75mv compared to outside and this should repel Cl from entering. Consequently, which wins? Choose the two correct solutions to this problem. a. If the reversal potential for Cl (Nernst equilibrium for Cl) is more positive than -75 mv (the cell resting potential), then Cl leaves the cell b. If the reversal potential for Cl (Nernst equilibrium for Cl) is more negative than -75 mv (the cell resting potential), then Cl enters the cell. c. If the reversal potential for Cl (Nernst equilibrium for Cl) is more positive than -75 mv (the cell resting potential), then Cl enters the cell d. If the reversal potential for Cl (Nernst equilibrium for Cl) is more negative than -75 mv (the cell resting potential), then Cl leaves the cell. -75mv 10mM 100mM
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9. All mammalian cells have a negative resting transmembrane potential. Why is the inside of a cell so negative? (choose the most important reason): a. Cl Channels (allowing Cl in)? b. Na Channels (allowing Na in)? c. Na:H exchanger (allowing Na in)? d. K Channels (allowing K out)? 10. The movement of any molecule is given by the flux equation J (flux) = Permeability x Area x Driving Force Lets say the flux of water is being studied and more Aquaporin channels are inserted. Which term increases? a. Permeability? b. Area? c. Driving Force? 11. Note that the two cells below are identical (although some transporters are shown in one cell alone simply to simplify the drawing). Note that the blue protein with the arrows moving in alternative direction is the Na K ATPase, that expels 3 Na from the cell and moves 2 K from outside into the cell. Is the paracellular secretion of Na+ (movement of Na+ from blood to lumen): A. Primary? B. Secondary? C. Tertiary? D. Quaternary? 12. In the cell above why does Cl leave the cell? Please make suggestions as to mechanism. Cl moves through the Cl channel due to the increase in electronegativity caused by K moving into the cell B. Cystic Fibrosis, a disease of the movement of salt and water across epithelial cells
13. Why did Paul di Sant’Agnese think that cystic fibrosis was a defect in NaCl transport? Remember he suddenly realized it on a hot summer’s week in the Emergency Room. noticed children with condition had high frequency of heat prostration 14. Do you think the overheated sweating children’s blood pressure was high, normal, or low? low 15. If you were seeing these overheated patients, would you give then intravenous saline (NaCl-stays extracellularly) or D5W (dextrose 5gr/100ml water-is absorbed by cells) to raise their blood pressure? Please explain your choice of fluids. D5W to compensate for dehydration & raise bp back to normal rate 16. List the target organs of the cystic fibrosis disease (what cells are affected, and in which organs). lungs, bronchi, pancreas, sweat glands, intestines, nasal passageways- inflammation & increased mucus production can lead to blockage 17. How do you prove that the mutated CFTR gene causes the CF disease (i.e. CFTR is the CF gene)? Please list 5 reasons. Think about human genetics, cells, and mice and drug therapy to make the proof. Please be rigorous. 1. mutant present in sick children 2. correctable in wild type cftr 3. acts like cAMP regulated channel 4. expressed at affected sites 5. KO mice- meconium ileus 18. Why does delta F508 cause CF (i.e. what is wrong with CFTR protein when it’s mutated and missing phenylalanine at position 508)? causes to become degraded before it reaches golgi 19. Two children are sent to your office because their physician believes they both have CF. a. One has been taking pancreatin, inhaled antibiotic therapy and has been
hospitalized many times. b. The second patient has never really been ill, but he has relatives who have been very sick with CF and on evaluation is found to have mutations in CFTR. Please explain the difference between the children. a is homozygotic for mutation, b is heterozygotic for mutation 20. A recent breakthrough in medications for CF: There is a drug that can help CFTR get to the cell surface called lumacaftor. There is a second drug that can open CFTR and allow it to function called ivacaftor. One patient has CFTR delta F508 mutation; a second patient has CFTR R334W mutation. Which patient should get which drug? Pick two correct answers. Do not worry about combination medications. a. R334W must get lumacaftor b. R334W must get ivacaftor c. delF508 must get lumacaftor d. del508 must get ivacaftor 21. Match the defect in CF children with age of patients. Just draw lines between medical event and the age of the patient when the defect becomes apparent. More than one connection is allowed but indicate the most obvious. Medical events Age of patient when defect becomes apparent Pneumonia new born Abnormalities of sweating childhood Meconium ileus adulthood Problems digesting meat old age Epithelial Pharmacology 22. In what type of patients is using a prostaglandin to treat an ulcer a reasonable approach? patients currently on chronic non-steroidal anti-inflammatories
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23. What exactly does your prostaglandin therapy stimulate in the stomach? stimulates mucus & bicarbonate secretion 24. What exactly does your prostaglandin therapy inhibit in the stomach? inhibits acid secretion 25. Why do patients become B12 deficient on proton pump inhibitors? What’s the connection? Disruption of stomach acidity levels caused by ppis 26. What is the difference between a slow metabolizer and a fast metabolizer of omeprazole in terms of relief of symptoms or clearance of Helicobacter Pylori? Poor metabolizers tend to exhibit more relief & decrease of symptoms in regard to H. pylori clearance 27. Which diuretic is more powerful—proximal, loop, distal, collecting duct? loop diuretics 28. Why do proximal tubule diuretics not work much at all? Less agents to block Na reabsorption 29. Think: Supposed there is a molecule in the urine of this collecting duct with a big negative charge like
an antibiotic called carbenicillin. Would there be more secretion of K from the principal cell, Yes or No? How about H+ from the intercalated cell (at the bottom of the figure), Yes or No? Increase in H+ secretion from intercalated cell 30. How do K sparing diuretics spare K? Hint: A type of K sparing diuretic is a Na channel blocker. Please explain in detail why a Na Channel blocker stops loss of K into the urine. (A way to think about this is the converse, active Na channel causes K loss into the urine). By directly inhibiting Na channels, thus curtailing the Na-K exchange that would otherwise take place. This enables K to effectively raise its levels. Principal Cell Intercalated Cell
31. Another type of K sparing diuretic is an aldosterone antagonist. Why is this a K sparing diuretic i.e. why does an aldosterone agonist cause hyperkalemia in the blood? Aldosterone causes the nephron to reabsorb Na & H2O, but leave K behind. This is due to its inhibition in regard to influencing Na-K pumps (no exchange occurs) 32. Hard question (extra credit): Why do thiazide diuretics prevent kidney stones? Please refer to the image below and describe to me issues concerning Ca uptake. Thiazide diuretics lower urine calcium levels by redirecting calcium from urine o bloodstream 33. A patient presents to the Emergency Department with low blood pressure. Do you want to infuse saline or D5W? Please defend your choice. D5W to compensate for dehydration & raise bp back to normal rate 34. A patient presents to the Emergency Department after losing a lot of watery urine due to a kidney disease called Nephrogenic Diabetes Insipidus. Do you want to infuse saline or D 5 Water? Please defend your choice.
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saline to promote water retention 35. Please match diet with diuretic. Please draw lines between the diuretic and diet. More than one connection is possible. Bonus question. Diuretic The patient should eat this type of diet Amiloride (Na Channel-collecting duct) High K diet Lasix (Loop of Henle) Low Calcium diet Hydrochlothiazide (distal convoluted) Low K diet High calcium diet 36. A patient comes with really abnormal blood tests. You ask the patient whether they are using diuretics. You suspect they are using thiazide diuretics to lose “water” weight because of the following lab tests; a. Hi K, Low Calcium b. Lo K, High calcium Preeclampsia 37. The RBC’s cells at the black arrows are indicative of pre-eclampsia. The cells are called schistocytes. Schistocytes can be found in the following diseases; there are two correct answers. A. Pre-eclampsia with new anemia B. Asthma without anemia C. Congestive heart failure without anemia D. A sick partially closed heart valve (“stenotic”) with new anemia
38. Magnesium drips are used in preeclampsia, because used to prevent seizures & prolong pregnancy to improve fetal outcome 39. Early delivery of the fetus cures preeclampsia, because it is believed to stem from an issue with the placenta . 40. If a baby is 30 weeks old and needed a bit more time for maturation, what medications would you give the mother that would help the baby mature: ____ steroids___________________________________________ 41. What medicine directly help baby’s lungs ____________ betamethasone_________________________________________? 42. Why don’t most blood vessels require VEGF signaling and are not affected by pre- eclampsia ________because they have capillaries sealed by pericytes___________________________? 43. What is the evidence that inhibition of VEGF by soluble Flt causes preeclampsia? I can think of 3-4 different demonstrations that sFLT was the culprit. a. soluble Fit higher in placenta with pre-eclampsia, levels resolve after delivery b. fulfills Koch’s postulates c. Causes proteinuria d. causes enddotheliosis 44. Please speculate why the placenta synthesizes sFlt at all-- and how can you test your idea?
Cardiovascular Pharmacology 45. A patient presents to you with a stroke. Do you think the patient might also have coronary artery disease? How can you test your hypothesis? It’s possible, there’s a strong correlation- would test postulate with CT scan 46. There are two EKG’s below; which patient has an NSTEMI and which patient has a STEM? 1. NSTEMI 2. STEMI
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47. C- myocardial infarction near AV node 48. 4 Left Right
49. B- acute MI in lateral wall 50. Why are there always deep S-Waves (indeed it looks like a Q) in lead AvR? because of the location of the electrical exis 51. A Q wave in VI, V2, V3 but no ST elevation means a. an old MI in the anterior wall of the heart b. a new MI in the anterior wall of the heart c. an old MI in the lateral wall of the heart d. a new MI in the lateral wall of the heart 52. A man comes to see you. His EKG has P-waves but there is a very long delay before the QRS and the pulse is only 60 beats per minute. Please explain—and tell me where the injury is in the heart? AV node has taken over as pacemaker
53. Plavix reduces the incidents of MI by blocking a. The QRS complex b. platelet aggregation via the purinergic receptor c. The production of thromboxane through inhibiting cyclooxygenase d. The production of thromboxane through stimulating cyclooxygenase 54. Aspirin reduces the incidents of MI by blocking a. The QRS complex b. platelet aggregation via the purinergic receptor c. The production of thromboxane through inhibiting cyclooxygenase d. The production of thromboxane through stimulating cyclooxygenase 55. Extra Credit: The QRS complex is usually tight and narrow, but in your patient is very broad. Which ones of the following possibilities might explain this finding (there are two correct answers): a. There was an MI in the Sinus Node b. There was an MI in the top of the AV node but the HIS bundle is OK. c. There is something delaying the function of the left Purkinje fibers d. There is something delaying the function of the right Purkinje fibers 56. Where is the myocardial infarction? What part of the heart? Is it a small heart attack or a large heart attack?
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Lateral wall, small heart attack 57. Extra Credit. The EKG below show an abnormality. There appear to be two P-waves at arrows. Can you speculate on their origin? Why does this happen? AV block, near purkinge fibers
58. A 90 year old has atrophic gastritis – a disease of chronic loss of parietal cells from the stomach lining. You are concerned the patient will have a deficit of vitamin a. Vitamin C b. Vitamin A c . Vitamin B12 d. Vitamin D 59. A 30 year old pre-menopausal healthy woman and a 65 year old diabetic male both have cramps and soreness of one of their calves. Which is most likely? Which is your second choice? a. The woman has a blood clot and the man has cardiovascular disease b. The man has a blood clot and the woman has cardiovascular disease c. The woman has a stroke and the man has prostate cancer d. The woman has a blood clot and the man has blood clot. 1- a, 2-d 60. A cell has two types of channels: K and Na. Pick two correct descriptions (see image below). a. in an action potential K channels play a critical role in depolarizing a cell b. in an action potential Na channels play a critical role in depolarizing a cell c. in an action potential K channels play a critical role in repolarizing a cell d. in an action potential Na channels play a critical role in repolarizing a cell
61. A cell can rely on both electrogenic and electroneutral transport. Na crosses this cell. Please indicate which pathway is 100% electrogenic, and which pathway is 100% electroneutral. a. circled pathways are electrogenic b. circled pathways are electroneutral 3 2
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