Review for Systems

Here they are. This gives us all the info we're going to get. As I said before, pray hard and study hard, and it will turn out O.K. Merry Christmas, etc. if I do not see y'all Friday.

Sweatman-
This is graduate school. If you make a statement, prepare to back it up with an example. Even if you contradict something he said, if you can defend it, fine. He grades for structure and logic in your answer- beginning, middle,end, and don’t repeat yourself. Essay form, with flow. Illustrate does not mean draw pictures, it means give examples. Pictures do not substitute for text for him. He gave examples and papers to read- look over the papers for examples again before you try to answer his question.


Nutting- if he says describe, he means write out a description. A chart or diagram or flow chart with just a sentence will NOT do. The chart, graph or diagram is for illustrative purposes, NOT for answering the entire question. He wants text answers.
What are 3 main things he emphasized? hint about what he wants us to know about?
1. Sex determination and reproduction male and female
2. hypothalamus and pituitary and regulation (- and + feedback)
Be sure you are careful in words when talking about whether hormone secretion has changed or whether the tissue response has changed.
3. Calcium/phosphate/bones.
Handout- Look over those questions at the end. They exemplify his questions.
Which part of pituitary gland conmmunicates information directly via nerves? posterior pituitary.
Where is decision made- hypothalamus. Posterior pituitary hormones are synthesized in hypothalamus and get to posterior pituitary through center of axon, not surface as you might think from the diagram in the note packet. Stored at nerve terminal. Released as result of string of action potentials starting in hypothalamus. Hormone dumped into capillaries, to veins, to heart, to rest of body.
Anterior pituitary- how do signals get from hypothalamus to anterior pituitary? portal system via hypothalamic releasing hormones. Some stimulatory and some inhibitory. KNOW currently accepted RH names and hormones they control from table.
What are they?GnRH (stimulates FSH and LH-gonadotropins), CRH (stimulates ACTH or corticotropin, stimulates adrenal cortex), TRH(stimulates TSH, indirectly stimulates T3 and T4 from thyroid), PIH (inhibits prolactin secretion- is dopamine. A dopamine agonist decreases PRL secretion)
Hypothalamus is always suppressing PRL with dopamine. PRL stimulates milk synthesis. Takes a couple of hours. Suckling stimulates oxytocin to stimulate milk letdown. PRL is also stimulated by suckling.
Other RH: GHRH(stimulates GHsecretion- GH is also regulated in an inhibitory way by somatostatin. For a Burst of GH, the body releases GHRH and stops somatostatin. Most GH comes out in deep sleep. Most ACTH is secreted just before and when you get up. ACTH stimulates cortisol, which protects against stresses, like hypoglycemia from fasting- make more glucose in liver.
Couple others- ghrelin (like GHRH- not on test). Gonadotropins- there is not a known gonadotropin inhibiting hormone. There may be a gonadotropin surge attenuating factor in ovulating women.
Know FSH and LH forward and backward.
Be able for all the hormones to take the hormone and fill out the chart from fig 7. and draw in arrows for long loop and short loop inhibitory feedback, and any positive feedback that might occur.
Especially for male and female sex cells and hormones. Know what hormones feed back and what they affect. Understand negative and positive feedback.
Know general pattern of control of reproduction. Backward and forward. Estrogen briefly positively causes surge in LH resulting in ovulation in females.
Be able to draw and explain menstrual cycle graph. Be able to describe in the essay format Sweatman described: introduction,bulk, conclusion.
Likely to give you questions of a problem-solving nature like you had in the conference. Scenario- figure out what is going on- what would you measure and how would you get around problem. Might put in statement to refer to normal situation as appropriate. Do not draw a whole figure from the notes and say it is answer- write paragraph. Go for most likely causes of problems. Say to measure LH or FSH or hCG, for example. You do not have to give too many details about how to measure. hCG rescues corpus luteum from disintegrating. hCG is made by placenta (uterine lining) caused by implantation of blastocyst. Can also trigger hCG with grain of sand or other object in uterus. hCG peaks 1st trimester- goes away after placenta delivered. E and P increase until just before end. Beginning produced by corpus luteum (ovary). After a while- produced by placenta itself in ever increasing amounts. Another placental hormone- hPL- human placental lactogen which promotes expansion of milk glands- E and P block synthesis of milk during pregnancy. Placenta delivered- Estrogen,Progesterone, hPL plummet. Milk prod starts.
3rd area Ca/P
Suggestion: know what we take in and where it goes, normal Ca levels. In practice problems, a lot of normal values given.
What does PTH do? How is vitamin D activated? Where do you lose Ca? urine.
Ca not well absorbed. Net of oral absorption is about 10%. Know protective mechanism for hypocalcemia- enhance reabsorption in kidney. Ca regulated in distal tubule- most reabsorption proximal, little in loop, enhanced absorption in distal tubule.
Absorption from gut stimulated by 1,25 dihydroxy vitamin D. KNOW how it is activated. D2 (ergosterol) is from diet. cholecalciferol (D3) is from UV light on skin. Liver puts hydroxyl at 25. Kidney proximal tubule puts OH at 1. Stimulated by PTH. Liver damage- no 1st intermediate. Kidney problem- you get no 1,25. Give massive doses of 25 or calcitriol, which is really expensive. Vitamin D is like a steroid. Acts through nucleus and affecting gene transcription. PTH acts fast on kidney, moderately fast on bone. Vitamin D is like grease for a revolving door. Allows Ca into or out of bone to prevent hypocalcemia (fatal affect on heart and intercostal muscles, mostly heart)
End syllabus are study questions. Go through them.
Prob 2:
how do you answer it? follow the outline given.
Use figures like figure 1 in that section as well as description.
Problem 3:
phosphate- from meat and sodas. Excess is a problem- binds Ca. Excess is dumped in urine. PTH causes more bone breakdown- Ca and PO4 to blood- want to keep ionized Ca high, must eliminate phosphate in kidney. Decrease reabsorption PO4.
Prob 4: PTH secreting adenoma- plasma Ca up. Urine Ca- enhances reabsorption. Phosphate-inhibits reabsorption. Dump phosphate. Increase synththesis vitamin D. Get hypercalcemia. Plasma Ca chronically elevated, Ca excretion increased due to increased load. Figure out phosphate in plasma and urine.
Prob 5:
see paper.
Look over his questions.
Do not “vomit” on paper- organize your thoughts.

Tavalin
Ponder his self-study questions.

2. Think about stomach- sublingually the base would be right, but in the stomach the acid will be non-ionized. The base would be absorption in the small intestine, with better microenvironment.
3. Know volume of different compartments. 40 TBW, 4 blood. Unless stated, assume nothing. This drug retained in plasma compartment, bound to proteins in blood.
4. Descending phase is the parameter most affected by elimination. See beginning of his lectures.
5. cyt p450-functionalization or activation of compound to make it more polar, ionized, soluble.
More reactive for subsequent metabolism.
6. conjugation reactions- adding AAs, glucoronidation, sulfation, acetylation- add moiety to parent compound- make more polar generally.
Know metabolism of his favorite molecule, ethanol.
7. What are major routes of elimination- urine, feces, exhalation lungs, skin.
8. Make urine more basic to speed elimination. ion trapping- drug resides in a compartment due to its pH. Basic drugs tend to reside in stomach. Acidic will reside in intestines.

9. Be able to work it one way or other. Answer 24 hours.
With half lives, a constant fraction is removes per unit time.
10. You remove a constant amount every hour-zero order. HAlf lives are first order.
11. Assume act at same receptor with same response. Could give 100 mg every 2 hrs or 300 every 6.
12. Plateau principle- takes 5 half-lives to reach steady state. If administered every 6 hours-change dose interval, changes steady state level (final concentration) Interval dominated by elimination kinetics. Interval determines variability and plateau fluctuations (in perfect world). Longer interval, bigger fluctuations. Shorter interval, higher escalation drug concentration and less variability in drug concentration. When should you measure drug concentration to titrate? Measure at peak and trough (toxicity, and minimum effective dose).
13. Loading dose- relationship of dose and target concentration is similar to volume of distribution. Only difference is you have a bioavailability factor, which he said is 100% in this question. So it does not matter.
Volume of distribution is the theoretical volume in which administered dose appears to be contained.
Volume >TBW- it concentrates somewhere (lipids, etc). Dose is outside plasma compartment. concentration decreases in plasma.
14. 60%
His question has multiple parts- 6 or 7. With each part , be able to calculate or interpret like the thinking questions he gave us. For why- no diatribes, answer with a sentence or a small paragraph.