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    Exam 3 NotesLecture 17 June 30, 2011

    The endocrine system and the nervous system are sister systems because theendocrine system is controlling hormones and in a way some hormones are

    neurotransmitters (as used in the nervous system). If it is released in a synaptic

    space, it will be a neurotransmitter. If it is produced in, for example, the medulla of

    the adrenal gland, it is acting as a hormone.

    Hormones are substances released from a cell that will enter a nearby capillary bedand will be carried in the blood to various places in the body. Examples of hormones

    include estrogen, testosterone, epinephrine, thyroxin, oxytoxin, progesterone, LH

    (lutenizing hormone), FSH (follicle stimulating hormone), ADH (anti dieuretic

    hormone), dopamine, glucagon, insulin, parathormone, and thyrocalcitonin.

    Nervous System vs. Endocrine System

    The main difference between these two systems is that the nervous system causessomething to happen quickly and end quickly. The endocrine system might start

    slowly and have a longer range for it to be effective, and then die out.

    Endocrine vs. Exocrine

    The most effective way to separate exocrine glands is holocrine (whole cell isproduct), apocrine, and merocrine. Exocrine glands have ducts which carry

    substances to the outside world while endocrine glands are groups of cells that make

    something to be transported primarily by blood, usually a hormone.

    Local vs. Traditional

    Local hormones are putting things outside of themselves and are not picked up bycapillaries, such as:

    o Histamines causes, for example in your nose, if you are allergic tosomething it sets up a response in your nose only and is local because it

    doesnt leave.

    o Prostaglandins reside in smooth muscle cells in uterus crampso Nitric oxide not a protein produced and acts like a hormone.

    Traditional hormones are made by something and picked up by capillaries. Thecapillaries, in glandular tissue, have bigger holes than other capillaries are

    fenestrated (have bigger holes). They are then carried throughout the body via blood.

    Some are just proteins (insulin) and some are derived by steroids and other things.

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    Hydrophobic vs. Hydrophilic

    Hydrophobic means that the substance is not soluble in water. Steroidal-basedhormones, such as testosterone, are hydrophobic. This makes a difference on how

    they are carried throughout their body.

    Hydrophilic means that the substance is soluble in water. Insulin is hydrophilic. Hydrophilic will usually be unbound and hydrophobic will usually be bound, but there

    are exceptions such as thyroxin (thyroxin hormone) and is not a steroid but comes

    from an amino acid, tyrosine, and does not like water and is fat soluble.

    Bound vs. Unbound

    If you have a cell that just made insulin, the insulin will enter the capillary and iswater-soluble. It can go right on into the plasma of the blood and can just float along

    with the flow. It has no need to be carried, it is said to be unbound. Unbound are

    much more vulnerable because they are just swimming along and their half-life is

    shorter.

    However, if the product of the cell is steroidal-based (such as testosterone, estrogen,progesterone, cortisol, aldosterone, etc.), when it gets into the capillary it is not

    soluble and must be assisted and is picked up by a protein, usually it is albumin,

    which is a solute in blood that keeps your blood pressure and volume stable and

    comes from the liver (primary secretory gland of body). If a persons liver is badly

    diseased cannot make albumin anymore and has fluid in their joints because they

    dont have the albumin to hold the water in the blood. Another job is to pick up

    cholesterols and steroidal-based hormones and carry them. Otherwise, theyll be

    carried by something and are said to be bound. If it is bound, it is more secure and

    not as vulnerable. Its half-life is greater.

    Osmotic pressure: If you have blood in your blood vessels and it gets to a capillary,which is thin, what will keep the water of your blood in that capillary? What keeps the

    water in there is albumin.

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    Cyclic AMP vs. Gene Activating

    There are two ways in which hormones can be found working.o cAMP sometimes called the second messenger system; hormones that work

    like cAMP are those that are water soluble. Water-soluble hormones use cAMP,

    even though some use a variation of cAMP.

    o Gene activating hormones that work like gene activation are those that arenot water-soluble and are sometimes steroidal such as estrogen, progesterone,

    testosterone, cortisol, aldosterone, and thyroxin (thyroid hormone), however

    thyroxin is not steroid based.

    The standard glucose level is 90 mg / 100 ml. The sensor, if it rises, is the beta cellswhich says to release insulin (first messenger), in the islets of Langerhans in the

    pancreas. The first messenger goes into the blood is water-soluble and is unbound

    and looks for a target cell (such as this fat cell in the hip). The first messenger will

    have to find a receptor on the target cell. Here, it will join its receptor.

    This piece of cell membrane is depicted in the target cell near it. The molecule ofinsulin will be attracted to a peripheral protein receptor. It makes the protein, which

    on the inside has attached to it an inactive GTP (guanine triphosphate) and is anintraperipheral protein and the union of insulin with this allows it to become activated

    (G protein). The activated molecule then turns on the enzyme adenylcyclase.

    Insulin (first messenger) cannot go into the cell because it is water soluble, whichmeans it is not soluble in fat. However, cAMP (second messenger) knows that the

    insulin is trying to tell the cell to take in a glucose molecule so it can either burn it up

    for energy or store it away as fat or glycogen.

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    Near the membrane of the cell, there are whirls of ATP made in the mitochondrionwith six seconds available. That ATP is sitting there waiting to be used. In the

    presence of the turned on adenylcyclase and will take two phosphates from ATP and

    make sure theyre chopped off and turns it into cAMP, which is called your second

    messenger.

    cAMP runs all around your cell and living in your cell are various kinds ofproteinkinases, which are enzymes that are responsible for setting up a cascade effect ofchemical reactions in the cell if they are turned on and theyre only turned on if the

    other steps occur. Protein kinases allow for opening and closing and also to make the

    product or turn off/on an enzyme. Once cAMP has done its job, we must shut it down

    by molecules of phosphodiesterase, which are molecules floating around the cell and

    tells cAMP to stop.

    What can be turned on based upon the nature of the cell you are talking about. Forexample, a beta cell will release insulin and if it has something attached to it telling it

    what to release, it cannot release anything else. What makes it do that is protein

    kinases. If you havent snacked, the alpha cells say to release insulin, in the islets of

    Langerhans in the pancreas. Glucagon is released (and can go to the same cell

    different receptors) and picks glucose out after all these steps.

    Bottom line: Adenylcyclase it turned on converts ATP is to cAMP, and then cAMP runsaround tapping protein kinases which needs to betapped by that cell.

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    Lecture 18 July 5, 2011

    Cyclic AMP vs. Gene Activating (continued)

    All the fat-soluble hormones when it is time for them to be transported, they dontlike water, and therefore they dont mix well in water. So they have to be transported

    by a special carrier molecule.

    Lets say a male has low testosterone (low T). It will encourage testosterone (whichis made in interstitial cells of leydig). After it is released, it is going to enter the blood

    and carried all over. It is on the short list, so it is fat-soluble, and is bound and has a

    longer half-life. When testosterone enters the skeletal muscle cell, it looks for a

    unique protein receptor. When it finds it, it binds to it whether the receptor is in the

    cytoplasm or nucleus. If it finds it in the nucleus, it will crack the genetic whip. It

    will direct your DNA to do something. In this case, it will tell it to make actin and

    myosin because testosterone is supposed to help guys build muscle, and you can

    build up more muscle by making more actin and myosin.

    Lets say a female has low estrogen (low E). The cells that make a lot of estrogenare follicle cells of the ovary. (What makes the follicle cell release estrogen is usually

    the presence of FSH, to be discussed later). Estrogen is on the short list, bound, less

    vulnerable, longer half-life, etc. Estrogen will get off of its protein carrier, leaving the

    blood, and attach to a receptor in the cytoplasm or nucleus of the fat cell. It cracks

    the genetic whip once it is in the nucleus and tells the DNA that it is time to conserve

    and store energy in the form of fat, so that any glucose that may come in (or other

    forms of energy), will be converted into fat. Or, enzymes that are here will be turned

    on. Certain levels of fat are necessary for women for menstrual cycles and to produceoffspring. Estrogen loves to affect fat and connective tissue.

    Remember: long list is cAMP, short list is gene activating!Neuronal vs. Humoral vs. Ant. Pit./Hypothal. Axis

    All of the hormones we have mentioned are not being released 24/7. Growthhormone is produced while you are sleeping, we do not make testosterone 24/7 in a

    five year old, and sometimes they are only produced in cycles. Controlling hormones

    and making sure theyre being produced when they should is a big job. When we stop

    doing this when we are supposed to, we have a disease. If we dont have enough

    insulin, we have diabetes. If we have too much thyroxin, we have hyperthyroidism. If

    we have too much cortisol, we get stress disorders.

    There are three primary ways we can control the release or lack of release ofhormones neuronal, humoral (hormonal), and anterior pituitary/hypothalamic axis

    mechanism.

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    Neuronal All of our body and all of our glands will be influenced by cells of theautonomic nervous system sympathetic and parasympathetic nervous systems.

    Neuronal simply means that the nervous system has something to do with it. The

    nervous system always has something to say but is not going to be the primary

    way in which our body controls hormones, unless you have an abnormality, such as a

    tumor of the adrenal medulla. It is rather secondary in controlling of hormones.

    Humoral (Hormonal) The relationship that exists between either two hormones,or a hormone and a particular standard or factor, and plays off one another. A good

    example of a humoral relationship is the level of glucose (90 mg/100ml of blood)

    because if you digress in either direction, that encourages you to either release

    insulin or glucagon. It is considered a humoral relationship because when you digress

    it puts into motion something (in this case either the production of insulin or

    glucagon). If your body is producing a lot of stress hormone (cortisol), that tends to

    make your body produce more thyroxin and insulin. This is also considered a humoral

    relationship. Calcium and phosphate levels, when they go up or down, causes you to

    produce parathormone or thyrocalcitonin, which is also a humoral relationship. We

    know that if cortisol rises from stress, it will go to make more insulin, which will make

    you produce hormones that make you feel hungry, which is a hormonal humoral

    relationship. Humoral refers to body temperature, levels of glucose and calcium, etc.

    that will return to the standard. When it is two hormones working off of one another,

    it is called hormonal humoral.

    Anterior pituitary/hypothalamic mechanism The posterior pituitary is also calledthe neurohypophysis, while the anterior pituitary is also called the

    adenohypophysis. Axons tend to twist in the infundibulum therefore making thedirection of this mechanism a little off. The adenohypophysis is called this because

    it is glandular tissue. The neurohypophysis is called this because it is really derived

    from the nervous system tissue.

    The supraoptic nucleus makes ADH, while the paraventricular nucleus makesoxytocin. It will travel down and get stored in the ends of the knobs and will be

    eventually carried into the blood.

    The neurosecretory nucleus consists of a pair (at least 7-8 different kinds of cellsmaking something special). They are axon-type structures and are in close proximity

    to a large tuft of capillaries the primary capillary bed. This capillary bed then

    forms into a single vessel (portal vessel or hypophyseal portalportal means

    that it is a vessel connecting two capillary beds), and travels down into the anterior

    pituitary. Once you are in the anterior pituitary, there are target cells. The

    secondary capillary bed will now form and be a part of a vein, which will take it

    back to systemic circulation. It came from an arteriole and goes back to a vein.

    An arteriole gives rise to a capillary bed. Usually a capillary bed goes into avenule/vein.

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    Lets say that the estrogen level is low, it being low will be sensed by certain cells (inthe top of the drawing, by the primary capillary bed). The cells say that they have the

    ability to make FSHRH (follicle stimulating hormone releasing hormone). It

    will be carried down the portal vessel, will get into the second capillary bed, and will

    get out of the capillary bed. FSHRH is on the long list so it uses cAMP and is water-

    soluble. FSHRH gets out of the capillary bed and looks for its target cell. The target

    cell has a special receptor, which tells FSHRH that that particular cell is its target cell.The FSHRH attaches to the receptor, causing the G protein to be awakened, which in

    turn awakens adenocyclase, which in turn takes ATP and turns it into cAMP. cAMP

    runs around in the target cell doing all kinds of things. cAMP tells this target cell to

    make FSH. FSH, then, is going to come out of the target cell. FSH will now go into

    the capillary bed and will go over to the ovary, where there are follicle cells

    surrounding an egg. It gets out of the blood and finds its receptors on follicular cells.

    FSH is water soluble, so it acts like cAMP. cAMP happens again. It tells this target cell

    to make estrogen. Estrogen (short list) will slip into the blood and get bound and

    travel around and go up and say, Hey you were successful. Some of the estrogen

    will go to the females fat cells. This is called full circle because it is showing the full

    picture.

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    Lecture 19 July 6, 2011

    Factors are hormones coming from the hypothalamus (old term), now anythingproduced here will inhibit something or encourage something to be released. Once

    they get down to the second capillary bed, they connect to a receptor on the target

    cell, and cAMP happens. When cAMP happens, the G protein is activated (GTP

    converted to GDP), then adenocyclase is activated, then ATP converts to cAMP which

    turns on a set of protein kinases. As a result of turning on protein kinases, it can tellto secrete something. What happens in that cell is based on its potential (or job).

    The following hormones you should be familiar with (made in hypothalamus):o GHRH (Growth Hormone Releasing Hormone)

    Make GHo GHIH (Growth Hormone Inhibiting Hormone) (Somatostatin)

    Doesnt make GHo Prolactin Releasing Hormone

    Make prolactino Prolactin Inhibiting Hormone

    Doesnt make prolactino ACTHRH (Adrenal Corticotropic Hormone Releasing Hormone) or Cortico

    Releasing Hormone

    Make corticotropin (adrenocorticotropic)o FSHRH (Follicle Stimulating Hormone Releasing Hormone)

    Make FSHo LHRH (Luteinizing Hormone Releasing Hormone) or ICSH (Interstitial Cell

    Stimulating Hormone in guys) Make LH

    The first four have both releasing and inhibiting, while the bottom four is onlyreleasing. The first four have closer control over the target cell.

    Growth Hormone

    Growth Hormone Releasing Hormone (GHRH) or Growth Hormone InhibitingHormone (GHIH) either made growth hormone or did not make it depending upon

    what you made in the hypothalamus. If you made GH, it runs all about the body, it is

    not going to just one gland (as do other hormones). If both the turn on and turn

    off work together, there is better control of the product.

    While you are sleeping, your growth hormone tends to be released. Growth hormonewill be inclined to be reduced when its level is low. It is more prevalent in early

    childhood through puberty. It also has something to do with the thickness of your

    skin. When a baby is born, it has not had the effects of its own GH (soft skin). GH

    hormone can be given if the epiphyseal plate is still there in bone.

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    If GH is low, GHRH is made, enters the primary capillary bed, runs on down thehypophyseal portal vessel, gets out of the capillary and looks for its target cell. GHRH

    hooks on to its receptor and cAMP happens, telling the cell to make GH. Growth

    hormone is going to virtually go to every cell in your body, it is water-soluble, so

    cAMP happens. GH tells the cell to either increase in size or to reproduce to make

    more of them (mitosis).

    It is not a steroid because it does not crack the genetic whip and slip into thenucleus.

    GHRH and GHIH can be produced at the same time. They will go to a target and theirtarget will be the same. So that if you have 1 GHRH and 1 GHIH, nothing will be

    done. If, however, you have 100 GHIH and 50 GHRH, GHRH will happen.

    Prolactin

    Prolactin has the same type of fine tuning as found in the growth hormoneexample. Prolactin Releasing Hormone and/or Inhibiting Hormone is made inthe hypothalamus and travels

    All of the target cells for prolactin are in a category called acidophils (first four)which pick up a red pigment, while a basophil (last four) picks up a blue pigment.

    (This is 318 material)

    Thyroid

    Thyroid problems are very major problems for your endocrine system. Too much ortoo little plays a role in your emotional well-being, the cycles of reproduction,

    sterility, psychosis, heart problems, underweight/overweight, etc.

    The thyroid gland is around your trachea and there are many cells with a nucleus inthe middle follicles. Arranged between are cells C cells that make thyrocalcitonin,

    which lower the calcium and phosphates in the blood.

    The Thyroid Stimulating Hormone (TSH), made in the anterior pituitary, enters acapillary and latches on (cAMP happens) which TSHRH from the hypothalamus told to

    produce, and then tells the follicle cell to release thyroxin.

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    Thyroid hormone makes T3 and T4. Thyroxin is often referred to as T4 (TSH alsoencourages the release of triiodothyronine referred to as T3).

    Thyroxin is produced (short list) so it gets into the list and is bound and its half-life islonger. When it gets to its destination, it will come off its carrier and when it finds its

    target (receptor), it will do something. When it gets into the nucleus and cracks the

    genetic whip, thyroxin will control and regulate metabolism of carbohydrates. It

    encourages the cells to increase enzymes necessary for that to happen. **Thyroxin is

    the most important molecule in your metabolic life because it influences your

    carbohydrate metabolism**

    Often times we find that we have high levels of thyroxin. A person who hashyperthyroidism can eat whatever they want and not gain weight. AS a result of

    this, their intestines have to work a little faster. If you are breaking down huge

    amounts of carbohydrates, you are also producing a lot of heat, making you warm all

    the time. It activates and turns on your neurons so that you cant sleep very well at

    night. It makes you have more of a need for blood the blood volume goes up, the

    heart has to work more and it starts to work faster so that it can go into a state oftachycardia, which means a heart rate above 100 beats per minute. When that

    happens, it could also lead to arrhythmia and you can faint or die.

    Radiating the thyroid with iodine usually helps with this problem to remove thethyroid. They usually do not want to surgically remove it because it is loaded with

    blood vessels and you have a severe bleeding potential. The only cells that have a

    pumper molecule that can pump iodine into it are these cells. The more active a

    gland is, the more vulnerable it is to carcinogens and radiation so, whenever you go

    to the dentist or get a mammogram, you need to ask for a collar to protect the

    thyroid gland.

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    Lecture 20 July 7, 2011

    Thyroid (continued)

    Scattered between follicles in between tissue are C cells (or parafollicular cells)that make and release thyrocalcitonin. The purpose is to lower calcium and lower

    phosphates in blood plasma.

    o Suppress osteoclast activityo Increase activity of osteoblasts (put mineral into bone; not in blood)o Lower number of osteoclasts

    It has a humoral relationship with parathormone TSH has nothing to do with this. Embedded in the dorsal or posterior part of the gland are four parathyroid

    glands. The cell of this gland is the chiefcell, which releases parathormone

    (parathyroid hormone). This will increase calcium and decrease phosphates. This

    uses the cAMP method. When parathormone is produced, it goes to three targets

    and finds receptors:

    o Intestine If the milk is in your small intestine and cannot go into yourblood unless vitamin D is present. This allows both calcium and phosphate to

    go into blood. Vitamin D is activated and increases calcium and increases

    phosphates.

    o Bone Osteoclasts are the cells that destroy bone. Parathormone also likesto go to the osteoclasts and tell them to break down the minerals and put

    them in the blood. In this case, it increases calcium and increases

    phosphates.o Kidney Parathromone will go to a nephron unit and it will tell calcium to

    stay in the body and tell phosphates to get out. When the phosphate goes

    into your urine, it is capable of holding hydrogen ions and acts like a buffer.

    It pumps the phosphates into the potential urine and it retrieves the calcium

    so that it is not lost. This is the only target of parathormone that increases

    calcium and decreases phosphates.

    Pancreas

    Majority of the pancreas is an exocrine gland, composed of cells that releasedigestive juices. When it is releasing insulin and glucagon it is classified as an

    endocrine type gland.

    Type II Diabetes is usually a problem because a person does not eat properly,their weight is out of control, and they do not have a good exercise program. The

    bottom line problem for this type of person is the fact that one of their typical

    target cells (anywhere in the body) cannot get glucose to enter it. Maybe this is

    because they do not make insulin, that the Beta cells might have been destroyed.

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    If these Beta cells are destroyed, they cannot make insulin. It could be that it

    makes plenty of insulin, but when the insulin gets to the cell, it doesnt recognize it

    as its target. It doesnt recognize its target because of being overweight and lack

    of exercise. Since the glucose cannot get into the cell it accumulates in the blood

    plasma and when the blood passes through the kidneys, its job it to pump out all

    this extra glucose. As a result, the kidneys have a whole bunch of glucose to pull

    out of the urine. But, it has so much glucose in the potential urine that it cannotget it out.

    Every time a sugar goes into your urine, water has to follow- this is the law!When you have a solute, water goes with it. So individuals with Type I Diabetes

    will have sugar in their urine and they will have a lot more urine than the average

    person. Volume of urine tends to be up (which means you are getting rid of a lot

    of urine), which means they are losing a lot of water and so these people tend to

    be thirsty all the time.

    Even though the kidney will get rid of the extra sugar, it will never get rid of all ofthe extra sugar. A Type II diabetic will always have a slightly elevated glucose all

    the time.

    Over long periods of time, the elevated glucose interferes with the personsinability to heal.

    It also sets the stage for them to be more susceptible to yeast infections(especially women with vaginal yeast infections). So, if you constantly have a lot

    of yeast problems, you will more than likely be tested for glucose in the urine.

    The most important and the most harmful side effect of Diabetes is the fact thatglucose cannot get into the cell to be broken down into clean fuel (ATP, carbondioxide, and water) so instead fat will enter the cell. Each cell will break down the

    fat and a lot of the intermediate metabolic end products are going to be acids.

    These acids will accumulate, causing you to reduce your pH. (It increases the H+

    ions, lowering the pH.) A low pH is acidic, but it means you have a high number of

    H+ ions. This creates potential acidosis. We try to maintain our bodys pH

    between 7.35 and 7.45. If you go below this you are going towards acidosis, if

    you go above this you are going towards alkalosis. We tend to have more

    problems with acidosis, than alkalosis.

    A constant pH lower than normal is bad for the body. Because the body prefers, ifanything, to be towards alkalosis. Every time you hurt your muscle, over exercise,

    fail to expire your carbon dioxide properly you are going towards acidosis. If you

    are having a heart attack or having spasms of the muscles, you are making acid.

    And so your body has to try to maintain your levels. Well, a diabetic is just adding

    fuel to that fire because they are always a little too acidotic at all times.

    Therefore, acidosis is not desired! If it is maintained too long, or you go too acidic

    you will die (7.2). If acidosis is left untreated, it can lead to death and comas.

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    If you are burning fat, aside from acidosis, you are overburdening your systemand potentially making LDLs (Low Density Lipoproteins) and VLDLs (Very Low

    Density Lipoproteins). LDLs have a huge piece of fat being carried around in the

    blood vascular system by a little piece of carrier protein. VLDLs have an even

    BIGGER piece of fat being carried around the blood vascular system by a little

    piece of carrier protein. If the fat is too heavy for the carrier protein, it gets held

    up in the lining of your blood vessels. If you have too much lining the bloodvessels, it can get embedded and minerals can deposit on it and form plaque

    (atherosclerosis).

    Atherosclerosis narrows the blood vessels and makes them roughened; in timethey can become so narrow that the blood cannot get through blood vessels easily.

    This will create friction and resistance, which leads to high blood pressure. The

    majority of diabetics are dying from cardiovascular complications. Atherosclerosis

    leads to high blood pressure. High blood pressure leads to cardiovascular disease.

    Cardiovascular disease leads to death.

    Atherosclerosis, especially as it proceeds down to the extremities, block thevessels somewhat, so that the flow to these parts is reduced and so the neurons

    there do not get the oxygen and glucose that they need to survive. Therefore, the

    neurons become less sensitive.

    Adrenal Cortex

    There are two adrenal glands, and they sit on top of the kidney and protected bya fat pad. There are different layers from outermost to innermost:

    o Zona glomerulosa make a group of hormones called mineralcorticoids(they are controlling minerals or electrolytes); the only one we should know

    is on the short list aldosterone (gene activating) and will make sure your

    sodium level goes up and potassium level goes down. Aldosterone gets in

    the blood and is carried to the kidney and goes to the part of the nephron

    unit and regulates if it needs to pull sodium out of urine. In order to do this,

    we have to pump out a potassium. Every time you keep a sodium, water

    comes with it, and you are increasing blood volume, thus increasing blood

    pressure.

    o Zona fasiculata make a group of hormones called glucocorticoids. Thiswill play a role in the release of cortisol, a stress hormone. If your

    hypothalamus senses that you have too much stress, one of its options is to

    produce ACTHRH (adrenocorticotropic hormone releasing hormone).

    ACTHRH goes down the hypophyseal portal vessel, goes down to the

    anterior pituitary, making ACTH (adrenocorticotropic hormone). This

    enters the blood through the little vessel and runs to the cells of the zona

    fasiculata. ACTH hangs on to the outside and cAMP happens, telling the cell

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    to make cortisol. Cortisol will run to all the target cells in the body and will

    slip in, encouraging gluconeogenesis, protein and fat mobilization, and

    strengthen lysosomes.

    o Zona reticularis make a group of hormones called gonadocorticoids, inparticular, androgens, which are precursors to male hormones (females

    make them too). Example old ladies in nursing homes kind of looking like

    old men (Dr. Alciatore lol)o Adrenal medulla the core of the adrenal gland; this is a sympathetic

    nervous structure, not an endocrine gland. It releases epinephrine or

    norepinephrine.

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    Cortisol steroidal hormone acting like gene activating. It is produced in the zonafasiculata layer of the adrenal cortex. ACTH coming from the anterior pituitary will

    eventually cause cortisol to be released.

    Gluconeogenesis means the conversion of nutrients into carbohydrates (likefats and proteins); this happens especially in liver cells as a prompting of cortisol;

    it also encourages us to mobilize and make available in the blood carbohydrates

    and proteins that could be used either for further energy release or tissue repair;

    another thing is if the cortisol level is appropriate, the thin membranes of

    lysosomes become strengthened. You do not want your own lysosomes to just

    breakdown because it will destroy the proteins of the cell in your body, and you

    will destroy your cell. In other words, cortisol does the following:

    o Increase in carbohydrates and proteinso Mobilization of fats and proteinso Strengthen lysosomes (not double phospholipid layer and can break open

    and release enzymes to destroy the cell)

    In todays world, stress is not as physical as it used to be, it is more emotional.Doing physical activity is utilizing your bodys resources better. When you make

    cortisol, it goes up to the hypothalamus and tells it to stop making cortisol. If it

    doesnt go up to the hypothalamus, it never tells it to stop making cortisol and you

    have high cortisol levels.

    Stress

    Hypothalamus

    ACTHRH

    AnteriorPituitary

    Adrenal Cotex -Zona fasiculata

    Cortisol

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    Physical vs. Chemical Digestion

    Physical digestion make body absorb something, not changing it chemically atall, just making it physically smaller by chewing. You end up with the exact same

    thing.

    Chemical digestion You want to start with something and end up with somethingelse getting it down to its building blocks. When you are finished, you will not beable to put it back together under normal circumstances.

    In the mouth, there is chewing, pulverizing, and preparing food to be swallowed.When it is capable of being swallowed, it has enough moisture and is small

    enough, so that when you swallow it you wont have a reflux. When it is ready to

    be swallowed, it is called the bolus.

    Histology

    The first portion of the small intestine is the duodenum. Shown in the diagram isthe lumen (where food is at innermost). The type of tissue here is simple

    columnar epithelium. Remember, in this type of epithelial tissue, you find goblet

    cells, microvilli, and basement membranes (which separates the epithelium from

    what lies below connective tissue). Microvilli will enhance the amount of

    surface area.

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    Duodenum

    Lets say we have amino acids, glucose, fatty acids and glycerols, vitamins,medications, etc. That hamburger could have come from the old Jack in the Box

    maybe even some E. coli! What we want to do with all of this (instead of it going

    straight down) is pass through these lining cells. The boundary will be a layer of

    muscle, called the muscularis mucosa. The lumen is the space within the duodenum. The lumen is considered outside

    your body. Until the cereal you ate for breakfast can leave the lumen and pass

    through the simple columnar epithelial cells, it is not part of your body.

    Layers:o Mucosa

    Simple columnar epithelium; this lines the intestine. In this layer,there are fibroblasts making fibers if were healthy, well have a lot

    of these fibers (collagen extracellular proteins). If we have a whole

    bunch of fibers, this connective tissue is dense. If there is little, it is

    loose or areolar. Macrophages are defense cells that gobble up

    debris. Plasma cells are the ones that shoot the bullets sometimes

    by themselves, sometimes in clumps. Plasma cells are lympohocytes

    that have the ability to make antibodies, which are the bullets. You

    might find them in larger clumps at which they are called lymphoidal

    tissue. Some lymphoidal tissue is very dispersed and some form

    aggregations. Sometimes they get so formed that they have capsules

    around them or they become what we call a Peyers patch. Someregions of your intestine are going to need bigger guns than other

    regions. You will also find mast cells in this connective tissue that

    releases things such as hitamines and has something to do with

    determining the level of fluidity of the consistency of the ground

    substance because mast cells can release a substance called heparin

    (which is an anticoagulant). We need the defense cells to protect from

    things such as E. coli. In some cases, you may find glands (can be

    making watery stuff, mucous stuff, or enzymes). The stuff in the

    intestine has become very liquidy and has come from glands

    embedded in the mucosa. There may be some poorly developed nerve

    nets. This layers job is to connect the epithelium to whats below it.

    The whole thing is the mucosa connective tissue and epithelium.

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    o Submucosa This layer is below the mucosa and above the muscle layer. You will

    find more of all that other stuff that is in the mucosa, but limited

    glands. Anything you would find in the mucosas connective tissue you

    could find in the submucosas connective tissue. All of the cells and

    blood vessels will be in here and will be dense irregular, with swatches

    of not so dense. Whenever connective tissue is around importantglands it is not as dense. The submucosa has a better defined,

    regulating neuronal plexus in order for that tube to get glands to

    release stuff into the space, it must be told to do so. If a gland is just

    sitting there, it wont be constantly releasing stuff. The

    parasympathetic system is there to turn on the system. Imagine a

    long fish net tube. At the top of the tube there is a very developed

    nerve net, called the submucosal plexus whenever the nerve net is

    turned on, it can affect what is in the glands and how much will be

    released/or not released. It must be told by the nervous system or a

    hormone to let its product out.

    o Muscularis Externis The bulk of the intestine is muscularis externis. When you grab the

    cats intestine, this is what you are touching. Down here you are going

    to have lots of blood vessels and some lymph vessels. These will be

    important in maintaining fluid levels and for absorbing fats. Lying

    below the musclaris externis is smooth muscle. Most of the time in

    your tube, the muscle layer will have tow layers one that goes

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    around circularly (closest to lumen) and the other is longitudinal cells.

    Lying in between these two layers of muscle will be another fishnet

    stocking, but this one is the myenteric plexus and it takes care of

    the speed and contraction of the tube. The tube will have the following

    types of movement:

    Mass movement in colon Segmentation unique motion action found in small intestine Mixing found uniquely in the stomach and turns into chyme (a

    kind of malt)

    Peristalsis rhythmicity, which is gradual and constant The law of the gut allows a polarized anal-ward pathway. The law

    says that these nerve nets, especially the myenteric plexus, are

    polarized so that the movement is going to go down. Common sense

    tells you that you want what is in the tube to go down and not up.

    Some babies are born with their polarity in the other direction and

    they do not survive. That wave of depolarization is a type of

    peristalsis. The myenteric plexus is found between circular and

    longitudinal muscle, which controls movement, not the release of

    substance, into the lumen. It is also hooked to the sympathetic

    system.

    o Serosa Consists of simple squamous epithelium and a basement membrane

    and lined between it is some serousy connective tissue and some

    glands. The two things together release a watery fluid to allow it to slipand slide.

    Esophagus

    The esophagus is a long tube that lies dorsal to the trachea. The lining of theesophagus is mucosy stratified squamous epithelium (like skin).

    The upper 1/3 of the esophagus is skeletal muscle, while the lower 2/3 of theesophagus is smooth muscle. The myenteric plexus begins at the bottom 2/3 of

    the esophagus. From the esophagus down, there is peristalsis which is

    constant, slow, sending of a message every few seconds. If the tube doesnt

    maintain that movement, the food can go nowhere.

    There are a number of longitudinal folds (like accordion pleats). Because you wantto be able to go left and right if need be. The longitudinal folds allow the

    esophagus to give and take.

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    Lecture 22 July 11, 2011

    Diagram:o Liver only digestive thing is to make bileo Salivary Glands make salivao Gallbladder store bileo Pancreas make pancreatic juice

    Mouth

    The mouth physically breaks down food to swallow, but enzymes in saliva beginsome chemical digestion. Majority of the mouth is a mucousy stratified squamous

    and is mostly skeletal muscle.

    The back of the mouth is the oropharynx, while the back of the nose is thenasopharynx. The part that is shared is the laryngopharynx.

    The most common substance in the saliva is water. There are three primary glands that contribute to your saliva:

    o Parotid near your ear; cells secrete a liquidy serous fluid, which makes upmost of the saliva. It secretes salivary amylase and lingual lipase. Mumps

    affects this gland (parotid). It is making majority of the enzymes.

    o Submandibular near your mandible; half produces liquidy serous fluidand the other half produces mucus.

    o Sublingual near the floor of your mouth; cells of this gland releasemucus. Helps create the bolus. It is releasing while you are sleeping.

    Saliva liquefies and enhances taste and smell of food. It is mostly water but thereis also mucus. You can find electrolytes and bicarbonate ions which helps as a

    buffer. There are two important enzymes located here (next page). Also here are

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    lysozymes, which help prevent tooth decay, IgA antibodies that inhibit growth of

    bacteria in mouth, and kallikrein, which encourages salivation.

    The two enzymes of interest are salivary amylase (begins breakdown of starches it likes the mouth, but not the stomach) and lingual lipase(which doesnt work

    until it is in the stomach because the mouth is not acidic enough, but is made in

    the mouth)

    o Salivary AmylaseS.A. + CHO ESC dextrin + E

    Lingual Lipase made in the parotid and submandibularTrachea

    The trachea contains cartilaginous rings that are C-shaped. The esophagus lies onthe inside (opening) of the C.

    Esophagus

    The job of the esophagus is to take the bolus and put it into the stomach. Theupper 1/3 of the esophagus is skeletal muscle and the remaining 2/3 is smooth

    muscle (until external anal sphincter, which is skeletal). This allows you to be able

    to control your swallowing and throwing up. You could not throw up on your own if

    you did not have skeletal muscle. The inside lining is mucousy stratified

    squamous. The longitudinal folds in the mucosa allows for expansion (left and

    right, if need be). The longitudinal folds allow the esophagus to give and take.

    The tissue into which the esophagus blends into is called adventitia. Adventitiameans the connective tissue that holds the esophagus in place. For example: all ofyour blood vessels are always embedded in a type of connective tissue, they are

    never running around the cell because they would be susceptible to ripping or

    breaking up.

    The four unique things of the esophagus:o Mucousy stratified squamouso Longitudinal foldso The differences between skeletal and smooth muscleo Existence of adventitia.

    The bolus is making its way down the esophagus and as it does so it physicallytouches the sides of the esophagus, which encourages a wave of peristalsis. The

    wave of peristalsis precedes the bolus. As it approaches the cardiac sphincter, it

    makes it open. The bolus passes through the cardiac sphincter and goes into the

    stomach.

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    Stomach

    The job of the stomach is to be the best blender in the world. The uniquehistology of the stomach contains not only circular muscle and longitudinal muscle,

    but also a third oblique muscle layer, so that the stomach churns the food in three

    ways. It also has folds or ridges called rugae. The rugae are like accordion pleats

    so with the three different muscles and the rugae, the stuff in the stomach hasno choice but to become physically smaller and beaten up. While it is churning, it

    is adding fluids (extracellular fluids).

    Another unique feature of the stomach is the existence of a bunch of glands, whichare called gastric glands. The holes that lead to these gastric glands are called

    gastric pits. The gastric gland is like a test tube and it is an exocrine gland.

    There are three kinds of cells in the gastric gland:o Neck cells the ones towards the opening; they make lots of mucouso Parietal cells make hydrochloric acid (HCl) and intrinsic factors (IF)o Chief cells make pepsinogen (which is an inactive enzyme)

    The stomach is mixing all of these ingredients with the bolus. Intrensic factors help you absorb vitamin B12 from food B12 helps you make the

    right amount of red blood cells. If you do not have enough RBC, you will be

    anemic and wont have the ability to transport oxygen.

    Pepsinogen sitting in the stomach must be turned on (which is the job of HCl andIF). The on condition is called pepsin. Pepsin acts on the big proteins (like the

    hamburger and cheese) and chops it into big pieces fragmentation.

    Fragmentation puts it into smaller pieces. The lingual lipase (because it likesacid) will now be acting upon neutral fats and breaking it down into glycerols and

    fatty acids.

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    Tissue in esophagus at the bottom (mucousy stratified squamous) is not adaptedfor low pH like the stomach is. pH in the cardiac region is a little less acidic and

    starts simple columnar tissue. The pH of the stomach is very acidic, about 2. The

    goal of the sphincter is to protect esophageal mucosa from damaging stomach acid

    exposure to acid can eventually cause esophageal cancer because the trachea

    is not adapted for acid.

    Your stomach turns the food into a liquid called chyme and adds to it a level ofacidity.

    The stomach is not working 24/7. We have some built in mechanisms that help uscontrol the production of stuff in our stomach the sympathetic turns it off,

    parasympathetic turns it on. The autonomic system (very influenced by the brain),

    allows people to have sensitive GI tracts when they are stressed or nervous.

    Controlling the stomach is more hormonal, not neuronal.

    There are three phases that control stomach activity:o Cephalic thought and smell, possibly even pictures of the food; sends

    messages to your stomach to start getting these glands to release gastric

    juice. You can turn it off just as fast by bad experiences.

    o Gastric if you decide to eat the food and it physically goes down as abolus and physically touches the lining of the stomach, it presses on some

    mucosal lining cells (the stomach and entire tract except esophagus is

    lined by simple columnar epithelium so can be called mucosal lining cells).

    Some have a brushed border (microvilli), which have a lot of enzymes that

    will be used. Some of those cells will not be releasing enzymes. Instead,

    they will be releasing a hormone (hormones go into blood). In the mucosa,the enteroendocrine cells (G cells) will make a hormone called gastrin.

    Because it is a hormone, it is going in the blood and goes to the gastric

    glands and says it is time to make some gastric juices. The more gastrin

    your produce, the more gastric juices produced.

    o Intestinal When the stomach builds up enough pressure (the mixing andperistalsis reaches 55 mmHg), the stuff is ready to leave the stomach and is

    squirted out of the pyloric sphincter, a few milliliters at a time. Fortunately,

    there are some other enteroendocrine cells at the beginning of the small

    intestine. As the chyme presses on these cells, it makes some more gastrin,

    because it is telling the body that its just releasing food, surely theyll be

    some more to follow. Soon thereafter, as the food progresses down the

    small intestine, other enteroendocine cells release hormones called

    enterogastrones and cholecystsokinin (CCK). These groups of hormones

    will be released into the blood and will go back to the stomach and tell them

    to shut down (cAMP).

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    Lecture 23 July 12, 2011

    Stomach (continued)

    The pyloric valve will open at a level of intensity at 50mmHg/pressure. If it doesntget there, the valve will not open. The stomach forces the sphincter to open,

    allowing just a few milliliters of chyme to come out at a time, and when it does, it

    touches cells called mucosal lining cells. Some of the mucosal lining cells arebrushed border cells, goblets, or enteroendocrine cells. As the food touches, it

    depends on the chemistry as to what hormones are produced. Coming from the

    stomach is chyme which contains the following:

    o CHO whole complex carbohydrates that have not been touchedo Disaccharides the product of some digestiono Fats whole fats that have never been touchedo Glycerol/fatty acids fats that have been touchedo Proteins have not been touched and have been fragmented by pepsino Nucleic acids untouched nucleic acids (no break down of them)

    Pancreas

    The two parts of the pancreascome together as one head. The pancreatic ductcomes behind the small intestine and will join with a duct originally coming from

    the liver and together they join at an area called an ampulla. There is a sphincter

    here called the sphincter of oddi. The liver (accessory organ) has a duct coming

    from it called the hepatic duct. The only digestive thing the liver does is make

    bile. The bile comes down the duct and if the sphincter of oddi is open, it will joinwith pancreatic juice and be squirted into the duodenum. If it is not open, it can

    be backed up and stored in the gallbladder. This is called a common duct

    because it means it can travel in both ways.

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    The pancreatic juice and bile is squirted into the duodenum and mingles withwhat is coming from the stomach. It is important that it be able to mix up. The

    unique kind of movement to get things in the middle to touch the surfaces is called

    segmentation, or spading. That makes sure that the center core touches the

    outside.

    Whats coming from the stomach is a malt-like consistency. When it is runningthrough the small intestine, it has to become runny (like water), which is what thecrypts of Liberkuhn do.

    There are a number ofpancreatic juices, coming from the pancreas:o Pancreatic amylaseits substrate is carbohydrates

    P. amylase + CHO dextrin (disaccharide) + Eo Pancreatic lipaseits substrate is neutral fats (such as triglycerides)

    P. lipase + fats glycerol + F.A. + Eo Pancreatic nucleaseits substrate is nucleic acids

    P. nuclease + nucleic acids nucleotides + Eo Zymogen granules enzymes that are inactive, that will act on proteins

    and stay inactive. If they start to turn on, you have a lot of protein lining the

    ducts, so you start to digest your ductwork. We want to keep these inactive,

    until they get into the small intestine.

    o Bicarbonate ions negatively charged ion that has the ability to act as abuffer. It neutralizes acids (your built in source of tums)

    Intestine

    The most important part of the small intestine is the duodenum and is theskinniest part of the tube, compared to the colon, but has a far larger amount of

    surface area because it contains:

    o Microvilli, which increase surface area. Each layer of mucosa has little hillscalled vili, and once you have all these hills you make a larger mountain,

    plicae circularis. You have now made a huge surface area to make things

    go in and out of the body. All three enhace surface area.

    The lining of the intestine itself must be able to slip and slide and be buffered and:o Mucus mucus can be put in by goblet cells, mucous glands in the mucosa,

    or Brunners glands which are in the duodenum only (in the submucosa).

    o Crypts of Liberkuhn shallow grave like glands that make copious (lots)of extracellular fluid (has electrolytes)

    o Mucosal lining cells some of them are goblet cells, some are makinghormones, and some are going to be making enzymes. Mucosal lining cells

    are going to be making the following enzymes: sucrose, maltase, lactase,

    amylase, lipase, dipeptidase, and enterokinase. They will also make the

    following hormones: secretin, cholecystokinin (CCK), GIP, and enterogastrin.

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    The inactive enzymes made in the pancreas will come down into the smallintestine and become active and turn on:

    o Trypsinogen Trypsino Chymotrypsinogen Chymotrypsino Procarboxypeptidase Carboxypeptidase

    The job of these enzymes is to chop the fragmented proteins further down andturn them into dipeptides eventually. A dipeptide is two amino acids hooked

    together by a peptide bond.

    Enzymes made by mucosal lining cells:o Sucrase + Sucrose G + F + Eo Maltase + Maltose G + G + Eo Lactose + Lactose G + Galactose + Eo Amylase + CHO Disaccharides + E

    3 sources of amylase!o Lipase + Fats Glycerol + F.A. + Eo Dipeptidase + Dipeptides AA + E

    When all is said and done, you have all the big carbohydrates, fats, nucleic acids,and proteins broken down into amino acids, monosaccharides, glycerols and fatty

    acids, and nucleotides. If you have troubles with enzymes or acid, it can lead to

    problems with this tract. When the food starts coming out of the stomach, we have chyme coming out. Secretin is a hormone that goes to the pancreas and tells it to release

    bicarbonate ions (because something is acidic) to help neutralize the acidity of

    small intestine. Long list and acts like cAMP and goes to the outside of pancreas

    and says to make bicarbonate. This will help neutralize the small intestine.

    Cholecystokinin (CCK) is a hormone that does two things:1. Goes to all the muscles of the ducts (including the gallbladder) and

    encourage peristalsis, so that bile can be squirted into the small intestine.

    The bile takes a big blob of fat and hangs onto it and ends up making tiny

    droplets of fat (which is physical). This is to make it have more surface area

    so that you can eventually break down fat.

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    2. It will also go to the pancreas and say that not only is the stuff coming outfatty, but we assume it has a lot of protein in it as well, so it tells the

    pancreas to up the enzymes of the pancreas (including zymogen granules).

    GIPis now thought to be something different, just remember its anotherhormone produced.

    Absorption Digestion ends when everything is broken down. It is useless for you to have

    digestion if you cannot successfully pull those things from the lumen to the inside

    of the body. (Thats right its considered the outside of the body). You must pull

    the stuff through those simple columnar cells into underlying capillaries so that

    nutrients can be carried all over a process called absorption.

    Lets say that you have a big blob of a neutral flat (not a fat cell). The first thingthat has to happen is that it has to be emulsified by bile. The bile is the product of

    the breakdown of a number of cells, especially red blood cells. Its pigment comes

    from pigments of blood cells made by the liver. The combination of the fat and bile

    make fat droplets. The fat droplets, in turn, must be acted upon by lipase (we

    have three sources mouth, pancreas, and lining of small intestine). If this is

    successful, we will produce fatty acids and glycerol. Digestion is finished. The fatty

    acids and glycerol cannot get into the lining cell without special help. These

    molecules (fatty acids and glycerol) will be picked up by a bile salt. The bile salt, in

    conjunction with the fatty acids and glycerol, will form an entity called a micelle.

    The micelle is now capable of going into the lining cell and the bile salt will drop off

    the fatty acid and glycerol. This cell has a special ability it can take the fatty acidand glycerol and reconstitute it into the fat it was before. It encapsulates the fat

    with a very thin film of protein called a chylomicron. It needs a protein around

    it to be carried. The chylomicron can now go out the bottom portion of the cell and

    make it into the lacteal. The lacteal will drop it and put it into the cardiovascular

    system and make its way to the liver.

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    There are some special structures in the small intestine that belong to theylympathic system, called lacteals. Lacteals are a special kind of capillary in the

    digestive system that picks up fats and eventually joins the circulation system and

    dumps the fat into the blood vessel system.

    The lymphatic system is a system of vessels that accompany the cardiovascularvessels and they carry lymph, which have molecules absorbed in the lacteal.

    The liver is the metabolism capital of your body. Its job is to take the chylomicronand if you have too many chylomicrons, it may put them on the LDLs. If you have

    too many LDLs, you can have high blood pressure and atherosclerosis. Some of us

    are fortunate enough to have it make HDLs (which are good) and help pick up bad

    stuff.

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    Lecture 24 July 13, 2011

    End of Digestive System Large Intestine

    The large intestine is responsible for (or contains):o Water & electrolyte absorptiono Vitamin synthesis (K & B)o Packaging of feceso No villio Haustra & Teniae colio Mass movemento Defacation

    In the small intestine, majority of the digestion and absorption is occurring. Whenyou are retrieving the nutrients you have eaten and pull it into your blood, largequantities of water are coming with it. The most important place for significant

    water absorption is usually the small intestine. If the mass takes too long to form,

    too much water and electrolytes may be taken out, causing constipation.

    The ileocecal valve is between the small and large intestine and is there so thatwhat is in the large intestine cannot back up. When the potential feces exits at the

    ileocecal valve, it will be congregating around the ascending colon. While the

    potential waste material is sitting here, water is being removed (water moves,

    following electrolytes, so electrolytes too). In the colon, there is normal flora (E.

    coli and other bacteria friendly bacteria if they stay here).

    The job of the normal flora is to take the nutrients that remain and get somethingout of them, something that it gets is vitamin K (necessary for blood clotting) and

    vitamin B. If you take antibiotics, you are essentially killing these microorganisms,

    which result in decreases of these vitamins.

    Packaging is also occurring

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    Structure of the colon:o There are no villi in the colono It has a much wider diameter than the small intestine. From the outside, the

    large intestine looks puffered. In the colon, the outer sheath that is

    supposed to go up and down isnt complete, it is in strips. The long strips of

    smooth muscle are called tenicae coli. The puffering of the connective

    tissue is called the hasutra. There is no typical peristalsis in the colon.

    The mass in the ascending colon will move about three times a day (variable) aprocess called mass movement. Also, the average person movement moves

    down towards the rectum once or twice a day or every other day (variable also).

    As the mass moves down the rectum, it sets up a defecation reflex. The mass

    will progress down, and as it does, the type of movement happening makes the

    inner sphincter (smooth muscle) open. After about age 3 or 4, the person has

    control over the skeletal sphincter so that they can defecate at the proper time.

    Back to Endocrine System (Quickly)

    The supraoptic makes ADH and the paraventricular makes oxytocin. They aretransported down those axons and are stored at the end and are released because

    the hypothalamus tells them to be released. They go into the cardiovascularsystem and are carried to their targets. Know where ADH goes and what it does.

    (ADH goes to kidneys and tells them to put water back into circulation).

    It is a nervous system structure not an endocrine gland.Respiratory System

    The purpose of the respiratory system is to take air (mixture of gases) and bringit into alveolar sacs, so that they oxygen passes through the respiratory

    membrane, enters the blood-vascular system, and goes to all cells of the body. In

    the cells, oxygen will be used for cellular respiration. The product of cellular

    respiration is CO2. The CO2 will exit those cells, be picked up by the blood, brought

    to the heart, then lung, and be released.

    Flowchart of air: Trachea Bronchi Primary Bronchi Secondary Bronchi Tertiary Bronchi Bronchioles Terminal Bronchioles Respiratory Bronchioles

    The alveolar sac looks like a bunch of grapes. All around the surface of thesesacs are masses of capillaries.

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    We eventually replace the psuedostratified squamous in the trachea with simplesquamous all the way at the end of the tree. As you decrease the tissues, you

    decrease the diameter, but you give off a lot of branches like a tree. Basically, you

    start out with one big pipe that becomes smaller and smaller (like a tree). There

    are two reasons we must have this tree effect system:

    1. To increase surface area for adequate gas exchange.2. To slow air down if you bring a lot of air forcefully and it enters a

    lung without all that tree slowing it down, the lung would blow up. The

    only way you can slow it down is with friction. Along its way, the air is

    being warmed, the goblet cells are picking up dust and junk, and the

    cilia are feeding in a direction towards the outside to sweep them out.

    All of these pathways are responsible for bringing air in during inhaling andreleasing air during exhalation. However, once the air makes it to the alveolar sac,

    there is a chance the gas (oxygen) can be exchanged with a capillary and enter

    your blood, that is why it is called a respiratory bronchiole. The relationship

    between the alveolar sac and a piece of the capillary is called the respiratory

    membrane (very important).

    The lungs are enclosed by the rib cage (thoracic cavity). Two watery, serousymembranes are the visceral pleura and parietal pleura note that there is a space

    here in the diagram, but there is no space in the body (known as a potential

    space). If they would stop hanging out together, youd get a space in there. The

    potential space is known as the pleural cavity.

    The pressure around the alveolar sac is known as intrapulmonary pressure.This is the end of your tree where the air comes in and where the capillary will

    be.

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    What allows these two serous membranes to hang around together and adhere toone another and maintain no free space is the fact that you must keep this space

    at a negative pressure. If you are just sitting (resting), the pressure in the

    potential space will always have less pressure compared to what is in the

    intrapulmonary and the world outside.

    The diaphragm moves up and moves down. The ribcage moves out, then movesback. If you push down the diaphragm, pull out the ribs, you are increasing the

    size of the alveolar sac. If you are increasing the size of the sac, you are

    decreasing the pressure. The air outside is weighing on your nose (760 mmHg). If

    we want this air to go through our passageways to get to our alveoli sacs, we

    must decrease the pressure. The intrapleural pressure will always be a negativepressure (-4 mmHg).

    The phrenic nerve allows the diaphragm to contract, and comes from a cervicalplexus. It will permeate intercostal muscles between your ribs. When the brain

    fires, it goes down the phrenic and into the intercostals, and makes the diaphragm

    push down and the cavity go out.

    Inspiration is considered as an active process, while exhalation is considered anpassive process. In order for you to breathe in, you must actually send a

    message from your brain. When you exhale, you dont have a message what

    makes you exhale is that the tissues will naturally recoil.

    90% of patients who have breathing problems in the ER will go because ofexpiration problems. People with emphysema, instead of having nice arealar sacs,

    they have more rounded ones and they have decreased their surface area and

    have destroyed elastic fibers and cannot snap back with ease. So since they cant

    snap back, you cant get your air out with ease and if you cant get your air out

    easily, you will have no place to bring air in (even though your brain tells you to).

    All the air becomes trapped.

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    Lecture 25 July 14, 2011

    The visceral and parietal pleura are serous membranes so that the visceraladheres to the parietal. The pleural cavity is potential space. You must have a

    negative pressure in the space to keep it as a potential space, and not a real

    space. Wherever the ribs go, the lung will go with it. We must maintain 4 mm Hg

    less than outside. It must be 4 mm Hg all the time or else the alveolar sacs of

    the lungs would collapse. Air outside weighs 760 mm Hg. If you were stabbed inthe pleural cavity with an ice pick and some one pulled out the ice pick, the

    outside air will go barreling into the pleural cavity. That heavier air will make the

    lung collapse.

    Breathing in is inhalation or inspiration. This is active which means that you haveno choice in the matter, a message is being sent each time you inhale. A message

    is being sent every time you need to inhale. When you inhale, your diaphragm is

    going down and you lungs are expanding. The sacs are getting bigger. The air in

    the tubes is under less pressure. Breathing out is exhalation or expiration. This is

    passive, which means that no message is being sent to do it.

    There are two factors that help us maintain this space:o Pull lung to thoracic wall

    Visceral/parietal layers Positive pressure in alveolar sac

    o Pull lung away from thoracic wall Natural recoiling of tissues Surface tension in alveolar sacs

    In premature babies, in their type II cells, do not make surfactant. Surfactant isthe detergent, which helps keep the water tension under control. If the baby is not

    making this, it has to spend a lot of energy to keep the sacs inflated.

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    The last group of bronchioles are respiratory bronchioles and prior to that areterminal bronchioles.

    At sea level, air is a mixture of gases:o Nitrogen 78%o Oxygen 21%o Other stuff 1%

    When the air gets in the alveolar sac, it must press against the membrane andtries to get across the membrane.

    Piece of capillary and alveolar sac:

    Respiratory Membrane

    There is an optimal thickness of the respiratory membrane if its too thick, thediffusion of oxygen is decreased and if its too thin, you may expect things to moveinto the alveolar sac (water and fluids). You want it to increase surface area and

    want to keep the respiratory membrane healthy you want macrophages and dust

    cells to gobble up stuff if someone sneezes on you! You want elastic fibers there so

    they could expand and snap back. The number one problem for a person who

    smokes is that their elastic fibers will lose their snapbackness or will be gone

    altogether (nicotine and tar would also change the shape of the alveolar sacs and

    destroy surfaces, no snapping back, and no pushing air out emphysema). Since

    the respiratory membrane is between you and the world, it is vulnerable. The cells

    have to be replaced more often since they are exposed to the elements (cell

    division). In children and teenagers, there is a lot of cell division. They can be

    more vulnerable to carcinogens (create cancer). This is why it is worse for young

    kids to smoke than for adults. When someone is pregnant, you dont want to

    expose the fetus to x-rays because of their membranes.

    In the alveolar sac, the squamous cells are known as Type I cells and thecuboidal cells are known as Type II cells. There will be cells running around here

    known as dust cells. In between the two basement membranes (shown above) will

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    be loose areolar connective tissue embedded with fibroblasts (making elastic

    fibers), mast cells (adjusts thick and thinness of cell releases heparin),

    macrophages, and plasma cells (which shoot bullets). This area is part of the

    respiratory membrane.

    When air comes in, it tries to get across the respiratory membrane. However,there is a law of partial pressure, which determines how much pressure is exerted

    by certain gases. If your total amount of pressure is 760 mmHg and 21% is 159mmHg, which is known as partial pressure (PO2) oxygen. Most of the pressure

    then is coming from nitrogen the nitrogen will eventually be exhaled because it

    is not soluble through cell membranes at sea level. If you are diving (below sea

    level), nitrogen will be able to go through the membrane and into your blood

    because it is soluble, thats why people must come up slowly from diving so the

    nitrogen can move back out.

    Solubility of Gases

    o Nitrogen 0.5o Oxygen 1o Carbon Dioxide 20

    Fortunately, we are putting carbon dioxide out in the other directionbecause it is 20X more soluble than oxygen.

    Air Exchange

    In the alveolar sac, you would think that the PO2 would be 159 mmHg, but whenair passes through these mucousy membrane passageways, some of the oxygen isused to help the lining cells. By the time it gets to the alveolar sac, it will be about

    104 mmHg (not lost, just used along the way by lining cells). The PCO2 is about

    39-40 mmHg. Now, we want the oxygen to go across.

    Deoxygenated blood has just come from the right ventricle of the heart. When itgets to the capillary near the alveolar sac it is considered dirty because it has a

    lot less oxygen. The PO2 in deoxygenated blood will be about 40 mmHg. It will also

    have the highest level of PCO2 of 45-46 mmHg. When the blood passes through, it

    stays in the capillaries for about 1-3 seconds.

    Oxygenated blood will leave the capillary near the alveolar sac and is consideredclean because it has a lot of oxygen PO2 level is 101 mmHg and the PCO2 level

    is 40mmHg. This blood will go to the left atrium of the heart, left ventricle, out

    through the aorta, all the way to your big toe!

    The PO2 in your big toe is 101 mmHg and the PCO2 is 40 mmHg clean,oxygenated. Here, you will found a capillary bed. We do not have enough blood in

    our body to have blood in all capillaries at one time. If blood goes into the

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    capillary, it goes through the precapillary sphincter. Our bodies must decide if

    we should put blood into the capillary beds or not the deciding factor to use a

    capillary bed (opening sphincter) depends if the tissues show (cellular respiration):

    o High PCO2 (potential acidosis) Most important substance to control what goes on in respiratory

    system too much leads to acidosis, which tells your body that it

    needs oxygen.o Low PO2o Low pH (potential acidosis)o High temperature

    If the precapillary sphincter decides to open, the PO2 will be 40 mmHg and thePCO2 will be 45 mmHg. The blood will go into the capillary, then right atrium, right

    ventricle, pulmonary trunk (pulmonary artery), then lung, goes through

    respiratory membrane (gets cleaned up), goes to left atrium, down left ventricle,

    through the aorta (through all parts of the body), eventually becoming an

    arteriole, then back to a capillary. Then, all over again BAM BAM BAM BAM BAM

    BAM.

    Since we cannot have blood in all the capillary beds at one time, some of themhave to stay closed. If they are closed, the blood goes through into a thoroughfare

    (bypass), the PO2 will be 101 mmHg and PCO2 will be 40 mmHg.

    Breathing Rate

    Shown are the pons and the medulla oblongata (control the number of times webreathe). In the medulla, we have the medullary rythmicity center or dorsal

    regulatory group. The dorsal is considered inspiratory, while ventral is

    considered expiratory.

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    In the pons we have the pneumotoxic and apneustic nuclei known as thepontine group, which work with the inspiratory nucleus. These two nuclei makes

    sure that every breath you take is rhythmic and flowing, not halting.

    The inspiratory circuit sends a series of messages through its neurons (lasts about2 seconds). While it is doing that, it sends a message to the phrenic nerve to

    move the diaphragm. While you are inspiring, it also sends a message to the

    expiratory and says to not interfere. The message being sent to the diaphragmand the intercostals tells the diaphragm to go down and the ribs to go out, causing

    the spaces to get bigger. The inspiratory circuit becomes tired and stops sending

    messages to itself, the expiratory circuit, and the diaphragm for about 3 seconds,

    then starts again. So you breathe in 2 seconds, and breath out 3 seconds.

    This is the place that if youre at a party and funneling, it can make yourinspiratory circuit take a longer nap and you stop breathing, and die.

    After the fatigue is over, the inspiratory circuit stars up again, starts anotherinspirations, and then fatigues again.

    The expiratory message does not send messages. The sacs, in the absence of amessage, will snap back on their own. (Think of the elastic on a pair of

    underwear.) Exhalation is called passive because the expiratory circuit is not

    sending a message. The only time the expiratory significantly helps you is when

    you tell yourself to exhale. After the fatigue is over, the inspiratory circuit starts

    up again, starts another inspiration, and then fatigues again. Then through the

    recoiling of tissues, muscles, and elastic fibers, you passively exhale.

    You breathe 15-17 times a minute

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    Lecture 26 July 15, 2011

    Medullary rhythmicity center is the most important factor for how many times youbreathe (12-15 times). The pontine (apneustic and pnemotaxic) in the pons works

    with the inspiratory to keep breathing smooth and regular. Remember, the

    expiratory does not send messages.

    Factors Affecting Breathing Rate Emotion (limbic system)

    o Hyperventilate (grief) When someone is breathing more often than they should You are moving CO2 out of your body You create a state of alkalosis (you cannot make an acid)

    o Hypoventilate When someone is not breathing as often as they should You are keeping CO2 in your body You create a state of acidosis (you can make an acid)

    Peripheral chemoreceptorso In the walls of your aortic arches are receptors that pick up on the level of

    oxygen (PO2). When the PO2 level goes too low (below 60mmHg), it will go

    to the brain and say breathe some more.

    Hering-Breur stretch receptorso Lining your alveolar sacs (embedded) are pressure receptors, which prevent

    you from breathing too deeply. If you inhale too much, you are spending too

    much time. This regards to inhalation. Deflation reflex

    o This helps you control so that you dont breathe too much out. If you exhaletoo much, you are also spending too much time.

    Irritantso Temperature, dust, stuff in air can affect your breathing rate.

    Cortexo You can use your cortex any time you want to, to regulate how many times

    you breathe. Singers have good control over the cortex.

    CSF methodo This is a method that affects your breathing rate as you are exercising.

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    Transportation of Oxygen

    The red blood cell (about the size of the capillary) does not have nucleus, butinstead a large molecule ofhemoglobin (iron and protein). The hemoglobin has

    sites on it to which oxygen wants to attach. The attraction of oxygen to the sites is

    called an affinity. So, oxygen wants to go into the red blood cell due to:

    o Affinityo Gradient (PO2 from 101 mmHg to 40 mmHg)o Temperature is less in alveolio Environment is more alkaline in alveoli

    Bohr effect If the pH is acidic, oxygen will want to come out the blood and gointo the needy tissue to raise the pH.

    o Lets say the blood with all the loaded oxygen will be transported throughthe body and now, it is in the capillary next to the cell that needs it.

    High PCO2 Low pH (acidosis) High temperature (heat)

    The PO2 in the cell is 20 mmHg and the PCO2 in the cell is 0 because once CO2 ismade it must get out of there and is 20X soluble. It does not accumulate in there.

    It gets out and accumulates to 45-46 and CO2 goes into blood.

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    Transportation of Carbon Dioxide

    There are three was to transport CO2 around the body, to the lungs:o Dissolved in plasma of blood (7%)o Carbaminohemoglobin (23%)

    Globin is made of protein. There is amine group at one end (NH2) andsays it will hold the CO2. (Carbaminohemoglobin carbon dioxide onthe amino group of the hemoglobin molecule!)

    o Bicarbonate (70%) We will have an enzyme called carbonic anhydrase, which takes a

    gas and water and makes carbonic acid (H2CO3). In this cell, H2CO3

    doesnt stay together and dissociates, becoming a H+ ion and HCO3

    (bicarbonate ion). Carbonic anhydrase is still here.

    The bicarbonate ion will slip out and go into the plasma of the blood. Ifit shifts out, in its place (so no charge problem), chloride ions will go in

    called the chloride shift. So if this chloride is going in, and that H+

    ion is by itself, we have a potential problem because the two make

    HCl, a strong acid. A strong acid dissociates and H+ ions can run

    around destroying and lowering pH. Fortunately, we have more NH2

    groups on the ends of these proteins. The H+ decides to go to the

    NH2, and acts as a buffer because the NH2 holds the H+ ions.

    Lets say you are exercising up a storm, you are producing acid.We have to have something there to hold potential H+ ions.

    Bicarbonate ions in plasma (HCO3) is now a buffer because it

    picks up an H+ ion and becomes H2CO3, to keep from lowering

    your pH.

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    Lets say instead of becoming too acidic, you become tooalkaline. This means that you have too much OH ions. H2CO3 can

    give up an H+ ion and go to HCO3.

    As the blood approaches the lung, the bicarbonate has to shift back inand the chloride must shift back out. The H+ ion (from NH3) will come

    down to bicarbonate (HCO3) to make carbonic acid H2CO3. Carbonic

    acid (with carbonic anhydrase) will become water and carbon dioxide,

    and out goes the CO2. This is a great example of a reversible reaction.