don't be the darkness

Thursday, April 30, 2009

Lecture 38

Human Sexual Response
- (Four stages)
  - Excitation – excitation increasing
  - Plateau stage – excitation leveling off
  - Orgasm
  - Resolution – female vs. male resolution
Excitation
- Happens in both male and female
  - Heart rate begins to rise
  - Blood pressure begins to rise
  - Voluntary muscle tensing occurs
  - Erection of the nipples
    - In females early erection of nipples due to smooth muscle contraction
    - In females late nipple erection is due to Vasocongestion
    - n male nipple erection is inconsistent, only occurs in approx 60% males, and in most not until plateau stage, 40% are vasoconstrictive
- In male alone
  - Contraction of the dartos muscle (smooth muscle)
  - Vasocongestion of the scrotal skin in male, thickens and elevates the scrotal sack
  - Contraction of the cremaster in the male (skeletal muscle in the spermatochore), this is the start of the contraction and continues through the plateau stage, lifts testis towards body and rotates them
  - Vasocongestion of the penis – called the erection
  - Vasocongestion of the
    - Cavernosa - some diminished blood return - due to tissues pressing against walls
    - Spongiosum stay soft, because no diminished blood return
    - Both due to vasodilatation of arterioles plus diminished blood return due to swelling tissues
  - Now, erection of the penis is mainly elongation
- In the female
  - the vagina lubricates, not due to any secretion by any glands but due to neurons releasing VIP (vasoactive intestinal peptide) which causes local cells to kick electrolytes out into vagina and then fluid follows due to transudation
    - Vaginal lubrication is one of early signs of excitation in female
    - Quantity not a good indicator of level of sexual arousal
  - Vasocongestion of the genital region in female
    - Outer lips of the vagina will flatten and move apart
    - Labia majora increase in size
    - Labia minora thicken and expand
    - Clitoris becomes erect, increases slightly in size, not always discernible in lab settings
    - Inner two thirds of the vagina will lengthen and expand
    - Uterus is going to increase in size and begin to elevate into the pelvic cavity
    - Vasocongestion of the areola starts (area around the nipple)
    - Vasocongestion of the breasts begins
    - Sexual flush follows (appears in 75% of females)
      - first appears in epigastric region and then spreads to the breasts
      - Never appears anywhere else
      - Cannot be seen under normal levels of illumination
Plateau stage (also referred to as "dumb phase", because brain lacks blood)
- In both male and female
  - respirations increase, but only towards end of plateau stage
  - Heart rate continues to rise
  - Blood pressure continues to rise
  - Involuntary muscle tensing starts
- In the male
  - sexual flush appears in 25% of males (much smaller percentage than in females), appears in the epigastric and then spreads (but not to same extent as seen in female)
  - Testis will vasocongest, increasing in size
  - Elevation of the testis continues via cremaster muscle contraction
  - Erect penis increases in size, but mainly circumferentially and not in length
  - Calpers gland in the male will release secretion - Set to adjust the pH of the urethra - Will contain some semen
- In females
  - sexual flush becomes very extensive (in some females but not all)
  - breasts continue to increase in size through the plateau stage
    - Areolas going to become engorged and you see what you think is a small nipple
  - Outer one third of vagina expands but not as much as inner two thirds and forms the orgasmic platform
  - Posterior two thirds have expanded into what is called the seminal basin
  - During the plateau stage the uterus will fully elevate into the false pelvis and tip back
  - The labia minora will turn bright red to burgundy in color
Orgasm
- Male and female
  - Respirations peak during orgasm as high as 40 (per min)
  - Heart rate peaks at approx 110-180 bpm
  - Blood pressure peaks (all values relative to "normal")
    - male
      - systolic goes up 40-100mmHg
      - diastolic up 20-50mmHg
    - female
      - systolic up 30-80mmHg
      - diastolic up 20-40mmHg
  - Sexual flush intensity will parallel orgasmic intensity
  - Only voluntary tensing occurs
- Male orgasm (2 halves)
  - First half = emission
    - Bladder neck contracts making posterior urethra a closed chamber
    - Vas deferens contracts
    - Seminal vesicles and prostate gland begin series of contractions
    - Posterior urethra becomes filled with semen
  - Second half = ejaculation
    - Contractions of the prostate and seminal vesicles continues
    - Sphincter urethra will pop open and the bulbospongiosus and the ichiocavernosus plus other perineal muscles (muscles in area of perineum) undergo involuntary contractions - Entire smooth muscle of urethra will contact in pulsitial fashion
    - Pulsing sends semen out of the penis in spurts
- Female orgasm
  - Orgasmic platform has a series of contractions at the same time the uterus has a series of contractions
  - Contractions in the uterus end in intrauterine pressure drops
  - The cervix shoots down into the seminal pool during pressure drops
Resolution - return to the normal values
- Rapid
  - in males and females
    - respiration, heart rate, blood pressure, back to normal, sexual flush disappears, genital vasocongestion can be prolonged in some males - prolonged erection after male has ejaculated
  - in the female
    - Areola and nipple size resolution will be rapid
- Prolonged
  - in males and females
    - muscle tensing
  - In the male alone
    - nipple erection can be prolonged
    - in the male there are sweaty palms and soles of the feet (inconsistent finding)
  - in the female
    - breast size will be prolonged
    - uterus will slowly drop down into the cervix
    - cervix will drop down into seminal basin -
    - in the female you find widespread thin film of perspiration (not due to physical activity though)

Lecture 37

within one minute post-ejaculation the seminal plasma coagulates in the vagina
-the semen contains fibrinogen which it got from seminal vesicle and it has a clotting enzyme it got from the prostate which can change fibrinogen to fibrin and the two mix during ejaculation
-the prostate also puts out profibroglycin in and this is quickly activated
-coagulin breaks down 20-30 minutes
-gelling of the plasma for this short time helps the semen stay in place until cervix drops down into it
-three types of sperm
-seekers: trying to fertilize oocyte, vast minority of the sperm, move about 3mm/min, which is about 0.001 mph
-killers: swim, kill very quickly, kill sperm from other males
-blockers: don't swim very well at all, crooked tails, link tails to fill crevices in vagina, only pass same male sperm
-as the sperm move through the female tract they become capacitated (capacitation is sometimes considered a maturation of the sperm, the removal of glycoproteins and other proteins from the head of the sperm, enahcnes their ability to adhere ot the oocyte and release hydrolytic enzymes, takes 7 hours)
-when sperm reach isthmus of the fallopian tube, they stop being hypermobile and their mobility is greatly reduced, they are drawn there by a chemotaxic factor release by the ovum
-some sperm go on and head to oocyte but most sperm are stored in the isthumus of the fallopian tube until ovulation and when it occurs the sperm become hypermobile again, the sperm will be released and fertilize the oocyte, fertilization usually takes place in the ampulla
-avg ejaculation is ~3.5mL and average sperm count is 120 million/mL
-semen can be as high as 6mL in volume
-sperm count can be as high as 250million/mL, but using the averages during sexual intercourse 420million sperm are deposited in the vagina
-100million die immediateily
-a few thousand reach the fallopian tube, only 50-100 will reach the oocyte

Female Sexual Cycle
- Female sexual cycle is divided into ovarian cycle and uterine cycle –
Ovarian cycle
- Follicular phase – when early teriary follicles are stimulated to mature until 1 ovulates - already reached tertiary stage before they are stimulated
- Ovulation
- Leuteal phase – corpus leudium is secreting hormones including progesterone (big one )
Uterine cycle
- The uterine cycle starts with menses – this is the menstruation – this is passing blood from the vagina – this starts with blood vessels of functional layer becoming neurcrotic and they open up and blood seems into the functional layer itself – this layer then shluffs off down to the site of the hemorrhages - Fibro bysin is stopping blood clots form happening – the blood and tissue are passed out of the body via the vagina – called menstruation – the first day of menstruation is considered first day of womans cycle –
- Proliferative Phase - The uterine cycle then goes into this – this is when the functional layer of endometrial is built and thickens – but cervical lining doesn't thicken – however cervical mucus thins and becomes more alkaline so it is more favorable for sperm
- Secratory phase – during this phase the thickening of the endometrium is stopped – it now secretes a glygogen rich nutrient solution and prolactin – this feeds fertilized oveum until implantation occurs – role of prolactin unkown
  - LHRH /FSHRS – are pulsatile – different at different ages – after puberty become pulsitile again - LH or FSH become secreted - pulse on apprx. 1 hour cycle – however cycles aren't synchronized - the pulsatile burst are more frequent in follicular phase than leuteal phase – during the follicular phase – LH – FSH production are greatly stimulated in the anterior pituitary – however release is held to low levels by estrogen – thus a store of FSH and LH build up in the anterior pituitary
  - During follicular phase the number of theca interna and granulosa cells greatly increase – 6-12 follicles are growing 1 will ovulate – the increasing number of these cells produces higher and higher levels of estrogen until it gets to 200-300 pg/ml – and stays there for 36 hours – quick release of estrogen – quick reversal of inhibitory effect and it stimulates release of LH – this stimulation occurs on apprx. Day 11-13 of the woman's cycle - the stimulation of the burst of LH begins approximately 36 hours prior to ovulation - It will peak approx. 16 hours prior to ovulation.
  - The surge in LH increases the secretion of steroidal hormones by the graafian follicle- The graafian follicle is the un-ovulated follicle starts to produce steroid hormone (progesterone) - Progesterone levels start to rise - This is called luteinzation of the follicle - The progesterone level will rise then have a spike - The spike does two things causes temperature spike and causes burst of release of FSH - The only effect of the spike of FSH is to inhibit or turning off FSH - The spike in LH will induce the oocyte to complete meiosis I and to enter into meiosis II - Oocyte was frozen in prophase of meiosis I but not frozen in metaphase meiosis II - It remain in metaphase II until fertilization.
Ovulation
- The LH and the FSH combine to cause swelling of the tertiary follicle a few days prior to ovulation - The original production of the tertiary follicle was strictly due to FSH, no LH receptors - When It began in follicular phase LH started to appear on the granulose cells and increase in number all through that phase - Now the FSH is shut down and LH takes over - FSH and LH act together to get to ovulation but the pressure in the follicle stays about the same about 15-20 mmHG
- The spike in LH causes the theca externa of the graafian follicle to release collagenase which weakens the capsular walls which allows more swelling which allows new blood vessel to grow into the follicular wall - The follicle secretes vasodilators which increase the transudation and increase the swelling of the follicle - Just prior to ovulation a protrusion appears in the outer wall of the follicle. This is called stigma - The stigma will exist about 30 minutes. After about 30 minutes the stigma starts to leak fluid - Thus the follicle is shrinking and dropping in pressure - what causes the explosion of ovulation are the specialized cells of the theca externa (smooth muscle cells) - they are stretched around as the follicle as got bigger, when it shrinks the start to contract - Once they contract for about 2 minutes there is a giant contraction –this is what causes ovulation
- The oocyte is released in to the abdominal cavity - The oocyte is still surrounded by the zona pellcuiea. It is also surrounded by the corona radiadae (first layer of granulosa cells outside the zona pellcuiea) and the cumulus oophorus -The remainder of the follicle is left in the ovary - The remainder left there becomes the corpus luteum - The CL produces progesterone, estrogens, and relaxin - As LH levels drop the CL becomes non functional - It becomes non functional approx 4 days prior to the start of the menstrual cycle - The degradation of the CL is possibly due to a oxidosen reaction of prostaglandins
- If fertilization occurs HCG (human chorionic gonadotroin) is secreted by the chorion and binds to the same receptors as the LH - So when the LH drops the receptors still stay stimulated and the CL stays functional - The chorian eventually become the placenta. HCG is the first placenta hormone. HC somatomamotropin works on estrogen and progesterone to promote breast development/growth - HCT HC thyrotroin increase the maternal metabolism - Relaxin has several roles - Inhibit myometrial contractions - Also relaxes pubis synthesis and other pelvic joints. In preparation for child birth. It relaxes the cervix -The last two hormones from the placenta are estrogen and progesterone.
Fertilization
- When the sperm comes in contact with the cumulus oophorus it releases hyaluronidase which dissolves the cumulus oophorus - Sperm goes to the zona of the oocte and loosely attaches to ZP-2 glycoprotein (weak bond) Then it will bond to the ZP-3 glycoprotein (species specific) - The sperm then undergoes the acrasomal rxn - The sperm head binds to the carbohydrate of the glycoprotein and the protein cause the acrasomal rxn
  - Acrasomal rxn - is when the sperm releases digestive enzymes, which eat through the zona. Then it enters the perivitelline space (the space between the oocyte and the zona) - It goes through that space and comes in contact with the plasma membrane of the oocyte. Binds with fertilin and cryitestin, binds then to: Izumo from the sperm head fuses at this point. This point is called fertilization (when fusion occurs)
- The head of the sperm will release NO, which opens calcium channels which causes calcium waves across the oocyte - the calcium stimulates the oocyte to finish meiosis II -The polar body disintegrates - Following the calcium wave will occur for the next few hours lasting only a few minutes - the calcium spurts cause cortical granules - the granules release their contents into the perivitelline space - This causes two effects
  - Water is dragged out into the perivitelline space- This increases the size of the perivitelline space preventing more sperm to enter - Shrinks the sona pulling the plasma membrane away from the zona
  - The second effect changes the shape of the ZP-3 and the digestive enzymes stop being effective. Even though the sperm can still bond to the ZP-2 it cannot bond the ZP-3. This is called a block to poly sperm.
- The tail is always destroyed weather it breaks off outside or dissolves inside (also includes the mitochondria.) Every mitochondria in your body came from your mother - The nuclear envelope is dissolved and a pronucleus is made - The only thing that survives are the chromatin material and the centrioles - The DNA then replicates - The centrioles from the parents form a spindle - The envelopes come up from each side and mitosis is completed. - 2 daughter cells with same nucleus are made. 30 hours have passed since fertilization has occurred.
Pregnancy
- Chance of pregnancy – based on normal men and women
  - 7 days prior = 0%
  - 6 days prior to ovulation 0% people got pregnant
  - 5 days prior to ovulation 8% got pregnant
  - 2 days prior 36% got pregnant and stays there till the day of ovulation
  - Thru 1, thru day of ovulation = same
  - The day after ovulation it drops to 0% immediately.
- Spike shows how the sperm can live up to 5 days in the isthmus of the fallopian tube
- The oocyte has short viability - that's what the flat part/drop off represent
- Types of Labor
  - Rule #1 = there are no rules
  - Rule #2 = number 1 never change
  - Braxton Hicks contractions - First described by John Braxton Hicks - Coming from the mother - Caused by estrogen produced which increase the number of oxytocin receptors in the mitometrium and the dissidua(part of placenta) - To the point where the receptors are 100-fold more than during early point in gestation - When there were very few receptors there are no contractions (in the early months)
    - Used to be called false labor, but that's a misnomer
  - True labor - Coming from the baby (baby saying I'm ready to be born) - When the baby is ready to leave, it gives a rise in fetal oxytocin which stimulates the dissidua oxytocin receptors - Receptors release prostaglandins which stimulate myometrial contractions - Cervix is separate organ from the uterus - Uterus contracts – cervix expanding - As cervix dilates stretch receptors send back neural signals to the hypothalamus which increases the oxytocin which increases the contractions of the uterus and dilation of the cervix (positive feedback system, continues until baby is released)
  - As baby moves into vagins, stretch reflexes in walls of vagina reflexively activate abdominal muscle contractions at the same time as uterine contractions
  - At same time, mother gets urge to contract abdominal muscles too. Called pushing - this aids in delivery of baby, although most places say to fight the urge to push until cervix is dilated 10cm - once mother starts, its virtually impossible to stop
  - After baby is born series of contractions continue until placenta is delivered

Lecture 36

Pancreatic Hormones, cont.

Glucagon
1. produced by the alpha cells of the pancreas
2. secretion due to low glucose levels of blood entering pancreas
3. cortisol stimulating glucagon
4. exercise will stimulate glucagon
5. direct sympathetic innervation
6. Actions of glucagon:
  1. increase glycogen breakdown by the liver
  2. decrease glucose uptake by the cells
  3. increase gluconeogenesis
  4. increase protein catabolism
  5. increase amino acid uptake and destruction by the liver
  6. increase lipolysis (breakdown of adipose tissue)
7. ***blood metabolite levels are increased***
Somatostatin
1. produced by the delta cells of the pancreas
2. is growth hormone inhibiting hormone but not actually working on growth hormone
3. secretion stimulated by CCK and by same factors that cause insulin release
4. action to inhibit the secretion of the other three hormones
5. sympathetic nervous system is helping to close the _____ duct
Pancreatic
Polypeptide
1. prodcued by the pancreatic polypeptide (pp) cells of the pancreas
2. released in response to the
  1. protein meal
  2. Fasting
  3. Exercising
  4. low blood sugar
3. Hypoglycemia will cause release
4. Actions:
  1. slow food absorption, make it more constant
Pineal Gland
Melatonin
1. See chart in notes
2. Produced by parenchymal cells
3. Secreted in response to sympathetic stimulation will originate in the paraventricular nucleus of the hypothalamus
4. The suprachiasmatic nucleus (SCN) where have circadian clock suppresses the paraventricular nucleus during the daytime and does nto suppress it at night, this pineal gland is not receiving light input it is receiving sympathetic stimulation, so less melatonin
5. Constant during light, increases in dark (circadian night) and then spikes at 4am, then levels off to baseline in the light
6. Actions:
  1. Thought to play a role in the sleep/wake cycle, but not well understood
  2. Affects LHRH release in some animals, not due to direct stimulation but due to in way of passing day length information to other parts of the brain
  3. In human children melatonin stimulates growth hormone release and that's the reason that we seem to have growth spurts, night growth spurts
  4. Blind kids don't grow as fast unless they get melatonin injections
Erythropoeitin
1. Produced by
  1. kidneys (85%) and the liver (15%)
2. Secretion is due to
  1. hypoxia (low partial pressure of oxygen)
  2. There is a heme type protein in liver and kidney and when the protein is not oxygenated it stimulates the secretion of EPO, when it is oxygenated it inhibits EPO
  3. Testosterone
3. Actions of EPO are
  1. to stimulate RBC production, shorten maturation time
Leptin
1. Produced by adipose cytes
2. More fat you have more leptin you have
3. Leptin levels are monitored by the weight regulatory system of the hypothalamus and they respond, low levels increase food intake and reduce metabolism, high levels or leptin decrease food intake and increase metabolism
(end of endocrineology)

Reproduction
Male
1. Spermatogenesis is the entire production of sperms
  1. Takes place in the seminiferous tublules of the testes
  2. Scrotum makes environment ideal for sperm production
    1. Has temp. of about 32 Deg. C - ideal
  3. Panpiniform plexus wraps around cord
    1. Venus blood is cooling constantly
      1. Testosterone is going from veins to arteries to maintain high level of testosterone (casusing spermatogenesis)
  4. Spermatogonia -
    1. 3 types:
      1. Type A Dark - True Stem cells
        Undergo mitosis to form 2 more spermatogonia
        Become
      2. type A Pale cells
        The cells of these don't break apart they stay together and form strings of cells with thin bridges of cytoplasm between them
        
        the bridges are going to mean that the whole strand of cells will be synchronized in cell divisions
        the number of mitotic cell divisions done in human is not known
        Eventually all the Type A pale produce a
      3. Type B spermatogonia
        Type B spermatognia are still linked together
        each of the type B are two primary spermatocytes
        the string of primary spermatocytes enter meiosis I
        crossover of the parents chromatids occur in Meiosis I prophase
        this creates new gene combinations
    2. Type A dark on the basilar lamina between the sarcoma cells, each successive generations from the initial multiplication has been rising up between the sertoli cells
    3. the sertoli cells have a tight junction, which will open up and allow the string of cells to rise up and then will close behind it
    4. during meiosis I the homologous c'somes will separate (govern the same trait)
    5. at the end of meiosis I this string has become a string of secondary spermatocytes
    6. the secondary spermatocytes enter into meosis II, spreading into a string of spermogens which are still strung together but can be easily broken apart
    7. spermogens have a haploid number
    8. Spermatogenesis – conversion of spermatids to spermatozoa
      1. no further cell division, it is a metamorphosis
    9. the spermatids are near the lumen of the seminiferous tubule and will form a special bond with the sertoli cell and the spermatid becomes completed surrounded by the plasma membrane of the sertoli cell
    10. tail starts to form outside PM and will grow into the lumen of the tubule of the sertoli cells
    11. head stays embedded, but has cytoplasm around it, as metamorphosis proceeds orientation is maintained and tail starts to grow and the head grows and the whole thing moves towards the edge of the sertoli cells
    12. towards the end of metamorphosis the head is stripped of cytoplasm and moves away from the sertoli cells
    13. sertoli cell releases head and holds onto the extra cytoplasm = spermeation
      1. 64 days have passed since first pale cell
    14. excess cytoplasm is called residual body and is destroyed by the sertoli cell
    15. newly formed spermatozoa can't swim yet, but to move it the sertoli cell secretes huge amount of fluid, the fluid flows out of the seminiferous tubules to the efferent ductules and the head of the epidydymis is absorbing the fluid, ciliated cells push the sperm
    16. efferent ductules and epidydimis have smooth muscle elements that help move the sperm along by peristaltic contractions
    17. in the epidydmis itself the sperm become mobile, this is maturation of the sperm, a matter of aging, epidydimis not doing anything to cause this to occur
    18. although they're mobile they will still be pushed along by peristaltic contractions through the vas deferens
    19. during ejaculation the sperm become hypermobile
    20. the sperm are fixed in various fluids during ejaculation, 60% of the fluid comes from seminal vesicle, 30% comes from the prostrate gland, 10% epidydimis and vas deferens = SEMEN
    21. Cowper's gland secretes a clear thick mucus that neutralizes acid from urine and lubricates the urethra and is done pre-ejaculatory, can contain sperm, this is why do not use withdrawal method for protection
    22. pH of semen = 7.5
    23. semen contains fructose and citric acid as well as prostoglandins (make cervical mucus more receptive to sperm, theory that it possibly generates reverse peristalsis in uterus and fallopian tubes to move sperm along)
    24. semen contains TGF-beta, same in bone remodeling
      1. sperm will use this to suppress the female immune system, so she doesn't have an immune response to the sperm

Lecture 35

Bone formation = ossification

-has two steps

1. lay down a matrix called osteoid (90-95% collagen and the rest is a gelatinous called the ground substance)

2. mineralization = laying down of hydroxy apatite (non-soluble)

-just seems to occur, not set up by one particular thing

-all tissue in our body contain compounds that block mineralization

-osteoid does not contain these compounds that block mineralization

-sometimes in old age these compounds break down and you can see muscles turn to bone

-osteoid is made by osteoblasts

-osteoblasts cannot reproduce and they are made by osteoprogenator cells

-once an osteoblast makes an osteoid it can't reproduce

-as an osteoprogenitor cell, they can reproduce and make osteoblasts, but they can't make osteoid

-osteoprogenitor cells live in the osteum (inner lining of bone), periosteum (outer lining of bone), and haversian canals

-in utero bone is made by two methods:

1. intramembranous ossification

-take a sheet of essentially progenitor cells called mesenchyme and the sheet will eventually become the bone

-mesenchyme cells differentiate to become osteoblasts which then deposit osteoid, the osteoid then mineralizes over time

-flat and irregular bones form this way

2. endochondral ossification

-when hear chondro should be thinking has something to do with hyaline cartilage

-hyaline cartilage forms the shape of a bone and then the osteoblasts will deteriorate and destroy the hyaline cartilage and replace it with osteoid

-short and long bones are created by this process

-osteoid production continues until the articular and epiphyseal cartilage is left

-chondroblasts building the outside, osteoblasts are eating the inside and replacing it with bone

-osteoblasts build the bones

-osteocytes = function as bone cells, when an osteoblast gets trapped in the bone and builds so much osteoid around it that it gets trapped, then it is called an osteocyte and will remain there forever, function as bone cells

-flat bones grow at periphery by intramembranous ossification

-long bones grow at ends

-chondrocytes = hyelin cartilage was built by chondroblasts which become chrondrocytes when we them in hyelin cartilage, get traipped in the hyaline cartilage

-thickening of the bone is done by intramembranous ossification

-as gets thicker on outside via intramembranous ossification, osteoclasts will eat out the inside so they are light

-bone growth regulated by insulin-like growth factor 1

-growth continues until the epiphyseal cartilage closes, can see this on an x-ray

-osteoblasts build osteoid which mineralizes to bone

-osteoclastss tear bone down

Remodeling:

osteoblasts/osteoclasts important for bone remodeling
bones are very dynamic and the remodeling process is important for repairing minor cracks that occurred in mineralization, but as part of the stress on the bone the collagen that is laid down, during stressful activities some of the collagen bonds have been broken, so you're replacing old collagen with new collagen (that has solid bonds) and doing minor crack repair
remodeling will reshape
- strength of the bone = collagen
- hardness of the bone = mineralization
remodeling can do shape changes in response to stress (bone can thicken and become thin)
bone grain (which way haversian canal is facing) direction can change
- joggers have different patterns to their bones than loggers b/c there are different stresses on the bone
remodeling replaces the distal femur every 5-6 months
- the entire skeleton is replaced 10 times in a lifetime
Involves osteoblasts and osteoclasts
- osteoclasts seal over the tight junctions of the bone
- apical membrane pumps H+ ions in and creates a pH of about 4 and this is the limit and this eats a hole in the bone
- the osteoclasts slowly eats down the hole in the bone and as it dissolves the bone it takes in any Ca and phosphate and will pass them out into the intersitium behind
- it will also pass out an activated TGF-beta (transforming growth factor-beta)
  - TGF-beta was in the osteoid and was placed their in an inactive form by the osteoblast
  - as the osteoclast ate through the bone it picked up inactive TGF-beta, activated it and kicked it back out to the interstitum
  - TGF-beta causes osteoblasts to go down and start to replace the bone with osteoid and will form lacuna (layers, lamella)
  - prevents mineralization of the osteoid
    
    -Ca and phosphate goes into the bloodstream b/c it will inhibit mineralization
    -at the center of haversian canal have a blood vessel which is stimulated to grow down following the osteoclast
    -after it gets down to the bottom the osteoid will start to mineralize automatically and we have changed the shape of the bone and also strengthened the bone
    -osteoblasts can activate/prevent the maturation of osteoclasts and therefore the osteoblasts are the major regulators of remodeling
    -if an osteoclast is activated it secretes interferon-beta which prevents the activation of other osteoclasts

-blood Ca levels are monitored by parathyroid hormone = PTH

-PTH is secreted in response to a drop in blood Ca levels

-PTH is turned off by increased blood Ca levels

-Actions of PTH

1. osteocytes are stimulated to take up exchangeable Ca

-in bone hydroxyl apatite is the major Ca salt in there and it is not soluble, but there are some soluble salts which can be exchangeable

-there is a certain amount of exchangeable Ca that the osteocytes can pass through their cytoplasmic extensions in the canuliculi into the blood, this will stimulate the osteocytes to take up exchangeable Ca and release it into the ECF

2. PTH increases remodeling by direct stimulation of the osteoclasts which releases non-exchangeable Ca

3. increase Ca reabsorption by the thick ascending loops of henle and the distal tubules of the nephron

4. interferes with phosphate reabsorption, increase phosphate secretion

5. increase production of 1, 25 dihydroxycolicalciferol (calicitrol = Vitamin D) by proximal tubules of kidney

-PTH is the sole regulator of blood Ca levels, has a half-life of 20 minutes and then is destroyed by the liver

-in skin have coli calciferol, produced in skin from 70-hydro cholesterol

-skin is in the sunlight and it is the sunlight that changes that to cholicalciferol, once it is produced it circulates to the liver and they add 25 and it becomes cholicalciferol

-this system is pretty much unregulated, but will feedback on itself

-25 dihydroxycaliciferic circulates to the proximal tubule of the kidney where it is taken up and 1-hydroxy is added to make it a di-hydroxy and then its release depends on PTH (stimulated creation/release of 1, 25)

-actions of 1,25 dihydroxcalciferic:

1. facilitates osteocyte pumping of exchangeable Ca

2. causes increase production of Ca binding protein, Calbindin D

-Calbindin D facilitates uptake of Ca by the intestine and the kidney

3. decrease phosphate, but 1,25-dihydroxcalciferic increases the amount of phosphate reabsorption by the kidney

4. stimulates bone remodeling by increasing the number of osteoclasts

-Calcitonin à released by thyroid gland

-What is the stimulus to release calcitonin?

-in mammals is due to the infusion of Ca solutions intravenously

-calcitonin first discovered in fish who change from fresh to salt water

-calcitonin inhibits osteoclasts, stops the release of Ca to the blood, and increases Ca excretion in the urine

-inhibits gastrin, slowing gut to decrease the amount of Ca pushed into the system

-half-life = 10 minutes

-quick but brief reduction of blood Ca levels

-productor rather than a regulator of blood Ca

Pancreatic Hormones:

Pancreas secretes seceral hormones:

Insulin
1. produced by theca cells of the pancreas
2. secreted in response to metabolites entering into pancreatic circulation
3. some CNS regulation
4. metabolites are:
  1. glucose, a.a., thetaketo acids
5. parasympathetic --> increase insulin secretion
6. sympathetic --> decrease insulin secretion
7. brain can't regulate the insulin level
8. insulin action occurs at three speeds
  1. rapid
    1. occur in seconds after being released into bloodstream
    2. increase glucose, a.a., and potassium uptake by the cells
  2. intermediate
    1. occurs in minutes
    2. increase protein synthesis (anabolism), decrease protein degradation, increase glycogen synthesis, decrease glycogen breakdown, activates glyolytic enzymes within cells
    3. inhibit gluconeogenic enzymes
  3. delayed
    1. hours later
    2. increases lipogenic enzymes

Lecture 34

Estrogens

-actions

1. facilitate the growth of the ovarian follicle

2. thickens the endometrium in the first half of the menstrual cycle, growth of decidua due to estrogen

3. causes duct growth in breasts

4. increase libido (need for sexual activity, males seek sexual activity on a fairly stable basis)

5. secondary sex characteristics including enlargement of the breasts

-places a small role in the enhancement of other minor sex characteristics that you find in a castrate male (have same characteristics)

1. high voice

2. broad hips

3. more head hair

4. narrower shoulders

5. flat top pattern of pubic hair

6. decrease LHRH

-estrogen is a group, secreted as estradiol (secreted form of estrogen, most powerful form of estrogen), in bloodstream this goes back to estrone in a reversible reaction

-estrone is a weaker form of estradiol, can get taken up by the liver and change it to estriol (the weakest estrogen)

-Progesterone

-stimulates the growth of the lobules and asoni in the breasts

-increases the rate of estradiol release to the lesser active forms, increase conversion to lesser active forms

-maintains the endometrium during secretory phase of the mensutral cycle and also during pregnancy

-thermogenic, just prior to ovulation there is a spike in progesterone and that can give a little spike ot the women's temperature, this is how certain monitor when ovulation will occur (monitor their basal temperature)

-Follicle stimulating hormone releasing factor

-released in a pulsatile fashion and will cause the release of FSH (will be turned off by inhibin – sole function is to turn off FSH)

-in male FSH causes sertoli cells of the seminiferous tubule to produce androgen binding protein (binds to testosterone to hold it in the seminiferous tubules to increase spermatogenesis, testosterone causes spermatogenesis and ABP enhances it), causes sertoli cells to secrete inhibin to turn off flow, only cells in male with FSH receptors are sertoli cells

-in female causes:

-early maturation of ovarian follicles and shares the responsibility of the final maturation of the follicles to the graffian stage

-stimulate granulosa cells to change androstendione to estradiol

-causes granulosa cells to secrete inhibin

-only cells in female that have FSH receptors are the granulosa cells

-Corticotropic Releasing Hormone (CRH)

-released constantly however it is increased by

1. fever

2. hypoglycemia

3. stress

-secretion of CRH is decreased by

1. glucocorticoids

-action of CRH causes the release of ACTH

-CRH has a variable pattern of secretion

-we can monitor the variable pattern of CRH by minotring the levels of ACTH (ACTH is irregular bursts)

-75% of ACTH release in the morning is between 4 and 10am

-CRH exhibits a similar pattern of release

-Actions of ACTH

1. stimulate release of glucocorticoids from the adrenal cortex

2. stimulates the release of some gonadocorticoids from the zona reticularis (much lesser effect)

3. stimulates the release of mineralcorticoids from the zona glomerulosa

-Glucocorticoids:

1. cortisol

-circulates in the blood attached to an alpha globulin called transcortin (carrying protein) and cortisol is inactive when it is bound

-day/night rhythm of cortisol release will be interrupted by stress which increases CRH and thus increases cortisol

-actions of cortisol:

1. stimulate gluconeogenesis

2. mobilize fat stores, cause cells to use more free fatty acids and less glucose

3. increase blood a.a. level by causing protein breakdown by the cells, this is both a catabolic and an anabolic system, causes protein breakdown in cells which increase blood a.a which are then taken up by the liver and the liver is stimulated to increase the production of blood plasma proteins

4. acts as a permissive action for other hormones, a co-factor

-glucagon and catecholamines have a calorigenic affect can't this effect in the absence of cortisol

-catecholamines exert a lipolitic affect which doesn't work in the absence of cortisol

-smooth muscle unresponsive to circulating catecholamines in the absence of cortisol

5. changes the WBC count in favor of neutrophils

6. increases the number of platelets and RBCs

7. cortisol acts as an anti-inflammatory and anti-allergen

2. corticosterone

-ratio of cortisol to corticosterone is 7:1

-Gonadocorticoids

-released as androgens including DHEA and androstenodione

-both DHEA and androstenodione will quickly change to testosterone and estradiol in the blood, this is the source of opposite sex hormones for both males and females (source of estrogen in the male, testosterone in the female, unsure of why this happens)

-proposed gonadocorticoid stimulating hormone but have not yet found it

-ACTH causes a small release but cannot account for all of it

-Mineralcorticoids – release caused by ACTH

1. Renin = produced by the kidney

-change the blood protein angiotensinogen to angiotensin I

-angiotension I's only role is to change to angiotensin II via the enzyme ACE which is found at the surface of endothelial cells

-after converted to angiotensin II (most happens it the lungs, first chance have to touch an endothelial cell is in the lung)

-role of angiotensin II

1. vasoconstricts arterioles

2. increases aldosterone release

3. major regulator of aldosterone release

4. contract mesengeal cells in the kidney (mesengeal cells on the glomerular capillaries)

5. increase ADH secretions and thirst sensations

6. increase ACTH secretion

-mineralcorticoids made by the zona glomerulosa of the adrenal cortex

2. aldosterone (angiotensin II is the main regulator of aldosterone)

-95% of mineralcorticoid activity is due to aldosterone release

-aldosterone released in response to angiotensin II, increase in plasma K

-if drop level of Na this will stimulate aldosterone release (FALSE)

-actions of aldoesterone

1. increase Na uptake by kidney and colon

2. decrease the amount of Na we put into tears and sweat

3. increase excretion of hydrogen (follows K out, kick potassium ion out and hydrogen ion follows) and potassium ions (running pump faster)

3. Atrial natriuretic factor

-produced by the atria of the heart

-secretion is due to an increase of NaCl in the plasma or an increase in extracellular fluid (blood volume)

-actions:

1. relax the mesengeal cells of the glomerulus increase the surface area for filtrate, cause to lose more filtrate

2. decrease aldosterone release

3. inhibits ADH secretion, inhibits ADH water induced reabsorption in the iMCDt cells, no effect on ADH induced urea reabsorption

4. inhibits rennin secretion which results in a decrease in BP

5. causes vasodilation – NOT TRUE

Vessels have dialated but this is b/c the atrial natriuretic factor is an inhibitor of vasconstrictors

Tuesday, April 28, 2009

Lecture 33

Hormones of the Hypothalamus:
- secretes two hormones via the posterior pituitary
  - Oxytocin
    - Always being produced by the body at least at low levels
      - released in a positive feedback mechanism (more oxytocin released more that is released)
    - Actions:
      - Causes milk let down of the breasts
        When the baby starts nursing the mother's breast, oxytocin will increase contracting the breast and milk will come out quicker, nursing continues to increase the oxytocin until the milk is gone
      - Birthing: Oxytocin causes uterine contractions which stretch the cervix, stretch receptors in the cervix send positive stimuli to release more oxytocin until the baby comes out
      - Increases in both men and women during sexual intercourses, surges during orgasm
  - ADH = Anti-Diuretic Hormone = Vasopressin
    - Vasopressin is a brand name!
    - Increased by the same things that cause thirst
      - Increased osmotic pressure of the blood (main regulator)
        osmotic receptors in hypothalamus
      - Decreased firing of blood pressure baroreceptors
      - Increased angiotensin II
      - Stress
    - Actions:
      - Causes an increase in water uptake by the kidney
      - Increase glucogenolysis of liver (minor action)
        More glycogen in blood stream
      - Increase ACTH (minor action)
- Hormones that are regulators of the anterior pituitary
  - Releasing inhibiting hormone system
    - two hormones produced to regulate the secretion of a hormone in the anterior pituitary (two hormone system)
      - have a releasing hormone and an inhibiting hormone
    - In this system of the hypothalamus the inhibiting hormone is being fired and created tonally and it is the one regulating
    - Inhibiting produced by tonally firing neurons - more firing, more hormone
      - May need episodic spikes when more hormone is needed
        Generated by releasing hormone, which is released periodically
  -Hormones regulated by this system include:
  - Growth Hormone (GH)
    - Regulated by GIH (Somatostatin) and GRH
    - GIH created on a tonal base
    - GRH not created all the time and is left until you need a spike
      - Released by:
        Low blood levels of growth hormone
        Hypoglycemia (low blood sugar)
        Increase in blood a.a.
        Decrease in blood free fatty acids
        Exercise and stress
    - Actions of GH:
      - GH causes the liver to secrete insulin like growth factor #1
      - actions of insulin like growth factor #1
        increase growth in young
        increase protein anabolism (building)
        inhibits insulin
        increase free fatty acids in the plasma
        turns off the release of GRH and GH and increase the release of GIH
  - Prolactin
    - Prolactin inhibiting hormone = PIH (dopamine)
      - Released tonally
    - PRH (releasing)
      - Is released episodically in response to:
        Estrogen and breast feeding
    - Actions of prolactin
      - Stimulate the secretion of milk
      - Increases maternal behavior in the female
      - No known role for prolactin in the male????
      - Increase PIH release
  B. (single hormone system) Stimulating Hormone Releasing
  - Thyroid stimulating hormone (TSH)
    - Thyrotropin releasing hormone (TRH) is being made by the hypothalamus which will stimulate the release of thyroid stimulating hormone by the anterior pituitary
      - Stimulates TSH
    - TSH stimulates the release of T3 and T4 by the thyroid gland
      - TRH increased when the environment is cold and also during pregnancy
      - TRH decreases when envt warm, stress, and anxiety
      - Have balls of epithelial cells in thyroid (colloid)
      - Colloid produces hormones from glycoprotein thyroglobulin
        In here, Tyrodine??? Changed and iodine atoms are added - 3 or 4
      - T3 and T4 (number referring to the number of iodine atoms)
      - T4 is secreted by the thyroid, T3 is the most active form it changes to in the target tissue
      - 93% of what is released is T4
      - T3 is 4x as active as T4
      - almost all of T4 is changed to TS at the target tissue
      - T3 - Triodylsomthin
      - T4 - Thyroxin
        Physiologists piss off chemists with inability to call right thing, just call it T3/T4
    - Actions of T3 and T4
      - Increase ALL aspects of glucose metabolism
      - Increase ALL aspects of fat metabolism
      - Decrease plasma levels of cholesterol, phospholipids, and triglycerides
      - Increase the basal metabolic rate
      - Increase HR
      - Increase protein catabolism
      - Affect Sleep
        high levels of T3/T4 will have insomnia
        low levels of T3/T4 you sleep too much
      - Promotes normal growth/activity in children
        Lack and become stunted
      - Feedback on TRH (minor effect)
      - Feedback on TSH (major effect)
- Sex Hormones
  - LHRH = Luteinizing Hormone Releasing Hormone
    - It was originally called LHRH but then they found that it also released FSH so they changed the name to GnRH
      - Pulsatile release of LH didn't match release of FSH (might be other way around??)
    - They found GnRH had three different isoforms, but only one of these isoforms released FSH and no LH so they called it FSHRF
    - LHRH is released in a pulsatile fashion by the hypothalamus
    - En Utero it was released in a pulsatile fashion as part of fetal development, but when you were born it stopped being released in pulsatile fashion but was still being released, when LHRH released pulsatile it causes
      - LHRH stops being produced in a pulsatile fashion, no LH released
      - Puberty: LHRH pulsating again and you get LH production
    - LH release by the anterior pituitary
      - LH is produced by the pulsatile release of LHRH
      - LH release also pulsatile
    - LHRH is inhibited by estrogen and testosterone
    - Action of LH in the male is to cause interstitial cells of the seminiferous tubules to secrete testosterone
      - Actions of testosterone
        Cause spermatogenesis in seminiferous tubules
        Secondary sex characteristics in the male
        low voice, increased aggression, increased muscle mass, increased body hair, decreased sensitivity to pain
        3. decreases LH and LHRH secretion
    - ONLY 2 ANDROGENS
      - Testosterone
      - Dihydroteststerone
      - These are the only ones that can interact with androgen receptors
    - Action of LH in the female:
      - cause the theca interna cells on follicle to secrete estrogen and or androstenedione (is a precursor to estrogen)
      - androstenedione shares the responsibility for final follicular maturation of FSH (FSH solely responsible for taking you up to the tertiary stage of follicle maturation)
      - Stimulates ovulation, ovulation comes from the LH spike
      - Causes the formation of the corpus luteum (produces mainly progesterone, relaxin, and estrogens)

Lecture 32

Energy (NRG)
- If we take a bomb calorimeter – can put food in and with O2 – put wire – ignite food stuff – food stuff burns into ashes – monitoring how much H20 increase in heat – counting calories of heat – amount of gross energy
- 1calorie = the amount of heat it takes to raise 1g of H20 1 degree Celsius – kcal/calorie – on food really mean kcal
  - 1g of carbohydrates and burn them in bomb calorimeter get 4.1kcal - - 1gr of protein and burn it 4.35kcal - - Lipids = 9.3kcal
- Not all the calories we eat are digested – subtract amount in feces as fecal energy
  - Gross energy – facal matter = digestive energy, digestive energy – urine energy = metabolic energy, metabolic energy – specific heat of digestion = net energy
    
    * Specific heat of digestion varies between foods
  - Net energy not used in NY state because heat is retained during cold months – in NY we feed by digestible energy levels
- Smaller animal has larger surface area per kg of body weight
  - Kg^.66 – net body size of animal – adjests for body size and not metabolis, K^.75 (learn this one), adjusts for both body size and metabolism
- Calories in vs. calories out
  - Diet – balance calories in compared to calories out
  - Couch potatoes – 2,000 cal per day – laborer/ athlete 6,000-7,000 kcal/day
  - No such thing as empty calories – in corn there is carotene which makes vitamin A - Fat not only higher in calories but also more concentrated – fat is not water soluble when carbs and protein are water soluble – potatoes are made more of water - fat very concentrated – carbs and proteins usually formed in watery matrix
Fat
- is higher in calories and is more concentrated form of food
- much of what we eat is lipid
- Lipids NOT water soluble, whereas proteins/CHOs are water soluble and tend to be in a matrix
Phospholipids
- are necessary for plasma membrane, cholesterol needed to maintain these membranes along with hormone production
  - three essential fatty acids:
    - Linoleic
    - Linolenic
    - Aracnidonic
- all 29 carbon acids, your body cannot create 29 carbon acids so they have to be consumed, but these acids will end up being changed to prostaglandins (used as a signaling boat for other cells)
Polyunsaturates
- OK cold
  - Cook them, creates more free radicals
  - Use monosaturates instead
Vitamins
- hypovitaminosis can occur if fat soluble vitamins are overfed
Elements:
-Ca and Phosphate ratios must be balanced
- are taken in at a ratio of 2:1 (Ca : Phosphate)
- Can get dibasic phosphate which is a balanced calcium/phosphate level
- 3:1 ratio: Greater Ca than phosphorous you will have an arthritic animal
- 1:1 ratio: get an osteoporosis animal
- NOT mutually exclusive - one doesn't reverse the other
Liver Function
- Sugar metabolism
  - Galactose and fructose converted to glucose in the liver
    - Drainage from GI tract is going right to liver first
  - the liver will create glucose from non-CHO sources or the breakdown products of proteins = gluconeogenesis
  - liver will synthesize glycogen
- Protein metabolism
  - the liver produces many blood proteins
  - Interconversion of amino acids takes place in the liver
    - Take one in, and change it to essential a.a.
  - Deamination
    - Destroying a.a.
    - Amine group breaking off
    - Take bicarb and make urea and glutamine from it
      - only site of urea production in the human body
- Fat metabolism
  - Liver burns fatty acid and supply energy for other body functions
  - Creates:
    - cholesterol
    - phospholipids
    - most lipoproteins
  - Stores:
    - Glycogen,
    - Vitamin B12, A, D, and E
    - Iron in the form of Ferrotin
    - 0.5 – 1L of blood when it is not needed elsewhere
  - Produces:
    - Bile (emulsifies fats)
      - Secretes into GI tract
  - Removes:
    - Hormones, drugs, toxins from circulation
      - By chemically changing them or excreting them in bile
Endocrinology
- Study of hormones
- Hormones of the GI Tract:
  - Gastrin:
    - Produced by
      - The stomach and duodenum
    - Turned on by
      - Vagal activity (sympathetic activity)
      - Increase in the stomach contents (especially protein)
    - Turned off by (regulated by)
      - HCl in the stomach
      - Secretin
    - Actions of gastrin:
      - Increase the secretion of HCl and pepsinogen (changes to pepsin by HCl and is used to digests proteins)
      - Increase motility of the whole GI tract (peristalsis)
  - Secretion:
    - Produced by
      - Duodenum mucosa
    - Turned on by:
      - Acid in the duodenum (when the acid leaves the stomach and heads into the GI tract it causes secretin to be secreted)
    - Turned off by:
      - Neutralization of this acid
    - Actions:
      - Stimulates duck cells to make HCO3 rich solution from the pancreatic duct cells (neutralizes pH)
      - Closes the pyloric sphincter (holds the acid in the stomach)
    - 1902 Baylus and Starling discovered secretin, they proposed that there were other chemical signalers in the body and that they should be called hormones (secretin = first hormone discovered)
  - Cholecystokinin-Pancreozymin = CCK-Pz = CCK
    - Produced by
      - The duodenum mucosa
    - Turned on by
      - Fats and proteins in the duodenum mucosa
    - Turned off by:
      - Absence of fats and proteins in the duodenum mucosa
    - Actions:
      - CCK levels are monitored by the satiety center (hypothalamus) to keep track of the amount of fats/proteins in the GI tract
        Contracts gallbladder
        Causes pancreozymin (digestion enzyme) secretion by the pancreas
        helps to close the pyloric sphincter (just like secretin)
  - Gastrin Inhibitory Peptide (GIP)
    - Produced by
      - Duodenum and jejunum
    - Turned on by:
      - fat or glucose in the duodenum
    - Turned off by:
      - absence of fats/glucose in the duodenum
    - Actions:
      - promotes insulin secretion
      - inhibits gastrin secretion
  - Vasoactive intestinal polypeptide (VIP)
    - Produced by
      - neurons of the GI tract
    - Turned on by
      - CNS
    - Turned off by
      - CNS
    - Actions:
      - Increases secretion of H2O and electrolytes into the GI tract
        throws electrolytes into GI tract and water follows in via obligatory H2O flow
      - dilates peripheral blood vessels
      - inhibits gastrin
  - Enterogastrone:
    - Doesn't exist:
      - GIP and VIP account for anything that is attributed to enterogastrone
  - Motilin
    - Produced by
      - The duodenum mucosa
    - don't know what turns it ON/OFF
    - Causes gut motility between meals
      - When nothing is stimulating the gastrin to be secreted (have empty stomach) you still need to keep the motility going and this is done by motilin
  - Neurotensin
    - produced by
      - Ilial mucosa
    - Turned on by:
      - Free fatty acids in the small intestine
    - Turned off by:
      - lack of free fatty acids in the small intestine
    - Actions:
      - Reduces got motility
      - increases ilial blood flow
        We have some free fatty acids and the ilium doesn't want them to escape b/c the free fatty acids are good for energy, so we slow the motility of the gut and increase the ilial blood flow to pick up more of these free fatty acids
  - Substance P
    - Produced by
      - Intestinal mucosa
    - Actions
      - Increase motility of small intestine
    - Hormones are things that you put into the bloodstream, but Substance P is NEVER put into the bloodstream it is put into the lumen of the small intestine – is it really a hormone? – never appears in the blood
  - Somatostatin = Growth Hormone Inhibiting Hormone
    - Produced by
      - Stomach
      - Duodenum
      - Pancreas
    - Turned on by:
      - HCl in the intestine
      - Sympathetic stimulation
    - Turned off by
      - Lack of those things
    - Actions:
      - Inhibits:
        Gastrin
        VIP
        GIP
        Motilin
        Secretin
        CCK
      - decreases absorption of
        Glucose
        a.a.
        Triglycerides
      - shuts the gut down (this is what the sympathetic system is using to turn the gut off)