Epi/NE increase heart rate and inc contractility to increase cardiac output.
E/NE also increases vasoconstriction which increases peripheral resistance (blood vessels down stream of the arteries constrict, so their diameter gets smaller, so bloodflow exiting goes down, which increases bloodpressure).
If we put both of these together Blood Pressure (or mean arterior pressure MAP) (MAP is the product of cardiac output times peripheral resistance), so if we increase sympathetic NS activity, that increases cardiac output, increases perf resistance, which increases MAP.
Somebody suffering bloodloss, BP falls (MAP falls), to compensate for BP drop, increase in sympathetic NS stimulation, increases Epi/NE release, inc cardiac output, inc perf resist, inc in MAP.
You should have a good uncderstanding of the aqnate=amony of the symp neurons and the AM, draw the biosynth pathway including structure and enzyme names, what all the acronyms mean, and understand in preinciple what will happen to metabolic, and nervous systems when increase decrease of epi/norepi.
E/NE actions on the respritory system:
1) bind to beta-adrenergic receptors in the smooth muscle of bronchials (part of the tubing that carry air to the lungs). when it binds to the beta-adren. rec. it leads to smooth muscle relaxation, which increases the diameter of the bronchials, which decreases the resistance of air flow, and greatly increase air flow. albuterol is a beta-adrenergic binding agent that causes relaxation to open air flow into the lungs of asthma people.
2) E/NE raise arousal (you become more alert), regulate the secretion of a bunch of hormones such as renin secretion and inhibit insulin secretion.
3) E/NE increase metabolic rate and they increase thermogenesis. they increase the activity of outer-ring deiodinase in brown fat. that increases thyroid activity, by converting T4 into T3. Brown fat looks brown because it contains lots of mitochondria, and is the site of non-shivering thermogenesis. T3 stims synth or expression of the molecule thermogenin that is a therm0protein that uncouples from atp generation. they increase lypolysis, and triglyceride breakdown in fat, which increases the fatty acid concentration in fat, that increase opens the proton channels (the thermogenins). if you have an increase in the more active thyroid hormon, that sets it up to make more thermogenins, and they in themselves are closed. they can be regulated. if nor/epi are high, they are open and you have a rapid ability to gen more heat.
steroidogenesis.... You need to learn the boisynth path for these.... (on handout)you need to be able to draw all of the structures, and enzyme names, and patheways. you have to know everything on the sheet.... The parent of all of them is cholesterol. Part of it is chopped off and yo uare left with a ring structure with certain functional groups attached. If you count up thenumber of carbons in all of them, the first three are all 21 C steroids, the last 2 have 19, and then 18. Those are the natural versions, and they synthetic/man-made have different numbers. But you can count the number of carbons in the naturals to tell what the bioacti will be.
What is made hs to do with what enzymes are expressed in any particular cell, and no cells make every single steroid. If something goes wrong in the pathway, that influences other things being made in the pathway.
The way the handout works is it starts with cholesterol (you can look at another handout of cholsterol with a nomenclature of steroicogenic enzymes), and it shows the first structure of the pathway (prenenolone vs cholesterol, the side chanin is cleaved from pregnenolone to make cholesterol). You will want to mem prenenolone, and then memorize the numbering system fof the carbons. if you mem that scheme and then you learn the anems of the enzymes, you can figure out what the next structure cdown the line will look like. if you don't do that and you just go for mem them, you will probably drive yousrlf nuts. they loook too similar to each other.
the second part of the second sheet, gives all the enzymes with multiple names shown. We are going to use the 'trivial names' because they tell what it is actually doing. 17-alpha-hydroxylase; 17, 20 lyase: that tells exactly what it does... adds an OH at 17, and cleaves between 17 and 20.
There are 5 classes of steroid molecules:
Progestins
glucocorticoids
mineralocorticoids
androgens
estrogens
You want to look at the chart and id stuff you already know. At the lower left are mineralocorts ( lower left three)(aldosterone, corticosterone, and beta deoxycortosterone). next to that is glucocorticoid (2), the theird column (all ) is androgens. and the three to the far right are estrogens.
the way the enzymes work is tricky. the enzyme arrows point to what it catalyzes. If it doesn't go all the way across, then it doesn't make that item.
dezmolase is called 'side chain cleavage enzyme', 3 beta...(directly bleow it) goes by the name 3 beta hydroxy steroid dehydrogenase (3besta-hsd). it acts on carbon 3 to an OH, and something else.
and the lowest left enzyme is called aldosterone synthase (makes aldosterone).
The four major steroidogenic tissues testes, ovaries, adrenal cortex, and placenta.
You will run into 'peripheral conversion of steroids', means that step doesn't take place in a traditional steroidogenic tissue (like maybe body fat instead).
Let's talk about where they get cholesterol from, and what is the rate limiting step:
Cholesterol sources: some steroidogenic cells synth it from scratch from acetate. Most of the time, most of the cholesterol comes from the blood in the form of LDL (low density lypoproteins) they take them up, and use the cholesterol that is part of the LDL. uptaek is a place that steroidogenesis can be regulated. sites of steroid synth iwithin a cell... in either the mitochonodria, or in smooth ER. the cholesterol, and all of the subsequent molecules are shuttled between them. Smooth ER is called that because it doesn't lots of ribosomes attached. Ribosomes aren't needed for steroid synth. Steroids are not stored inside the cell. Cholesterol is processed through the pathway, it is highly lipid soluble, and goes right out of the cells. There are no vessicle storage of steroids. there is no way to regulate its release once it is made. If we look at the rate limiting step in the pathway, it is right at the beginning... it is the cleavage of the side-chain from cholesterol. It turns out that side-chain cleavage enzyme is in the inner mitochondrial membrane, and getting cholesterol to the inner mit mem is what makes it the rate limiting step. There is a protein repsonsible (StAR): steroidogenic acute regulatory protein, and it somehow fascilitates shuddling of cholesterol between the inner and outer mit mems. People with a mutation in StAR form little or no steroids. All of the regulatory pathways taht we are going to talk about, all of them act on StAR, as well as all the other enzymes in the pathway.
Last part of the general stuff: mech of steroid action... (handout in class)
Nuclear hormone receptor family... steroid receptors are part of that family. they jhave a hormoen binding domain and a DNA binding domain. thyroid hormones work differently than the steroids do. the thyroid response cell works in a dimer, binds, corepresors replaced by coacts. this is different. the basic concept is at the tope of the sheet.... read sheet. (fig 3-8 from je friffin and SR ojeda) availabel on eres) and fig 3-11 JE Griffin and SR Ojeda.
This is true for all of the molecules on the big pathway for steroids. there are distinct receptors for everything, but with some overlap between mineralocorts, and glucocorticoid receptors.
Adrenal cortex:
looks like a piramid with the inner part being the medulla. there are layers around the medulla (3 layers). the outer layer is called the zona-glomerulosa produces aldosterone; middle layer is called zona-fasiculata; innermost layer is zona-reticularis, both of which produce glucocortocoids and androgens. An easy way to remmber this as GFR from the outside in. (same acronym as from kidneys)
the ZGA layer is the only one that expresses aldosterone synthase. the products of the inner 2 are: androgens: androstenedioe, and DHEA (both are considered 'weak' androgens' which means they ahve relativly low affinity for receptors, not much testosterone or dihydortestosterone, and extermely little estrogens); and specific glucocorticoids: cortisol and corticosterone, these 2 are the most important in humans.
Glucocorticoids: (hypothalamic-pit-adreanl axis handout)...CRH: cortico releaseing hormone if there is no CRH then the pathway shuts down.
A stressor activiates this pathway.
