Exam 4 Part VII Flashcards
Regulation of GH secretion.
Increased by GHRH from hypothalamus
Some conditions that cause GnRH secretion:
decreased fatty acids in blood
hypoglycemia
increased amino acids in blood fasting or a protein meal
stress: starvation, exercise, trauma
the first 2 hours of slow-wave sleep →↑↑ GH
low GH levels
Decreased by GHIH =
Decreased by GHIH = somatostatin from hypothalamus, also δ cells in pancreas.
growth hormone deficiency
Deficiency: in childhood: dwarfism, e.g., panhypopituitary dwarf. Much is from GH lack, also lack of TSH.
excess GH
before the epiphyses of the long bones fuse: giantism or gigantism
in adulthood: acromegaly: many soft tissues grow, bones that can grow do, other bones thicken.
acromegaly symptoms
Everything keeps growing: cardiomegaly, huge valves, feet, hands
Colon polyps → colon cancer
Had 2 hips replaced
Diabetes
Only thing painful about surgery for tumor: skin was so thick, they couldn’t get an IV in - hematomas
Iodine is preferentially pumped into the follicle cells from the blood (iodine trapping). From there iodine moves into the lumen of the follicle and combines with
thyroglobulin
thyroglobulin
Thyroglobulin is a protein stored in the lumen, and thyroxine (tetra-iodothyronine=T4) and triiodothyronine (T3) are formed from within it.
Then when T3 and T4 are needed for use, thyroglobulin is taken up by pinocytosis into the cell, and T3 and T4 are released from the
thyroglobulin molecule and travel into the blood.
There is a long latency before the effects of
There is a long latency before the effects of thyroid hormones can be seen: 12 hours to 3 days and then the effects continue for a long time (days).
B. Effects of thyroid hormones:
increased metabolic rate protein synthesis\ gluconeogenesis breakdown of fats use of glucose stimulates growth rapid cerebration
Inc. TRH from hypothalamus causes
Inc. TRH from hypothalamus causes TSH from pituitary to stimulate the thyroid gland.
condition that stimulates TRH
Condition that stimulates: cold. Obese people cold room to lose weight
conditions that suppress TRH
Conditions that suppress: Excitement & anxiety, conditions that stim. the sym. system, perhaps because they cause inc. body heat.
In childhood: cretinism:
In childhood: cretinism: failure to grow, mental deficiency becomes irreversible, may be necessary to receive certain kinds of stimulation before a certain age
In adulthood: myxedema:
In adulthood: myxedema: Low BMR, weight gain, poor cold tolerance, slow mentation: “myxedema is the one disease that can be diagnosed over the telephone.”
Hashimoto’s:
Hashimoto’s: thyroglobulin &/or thyroid peroxidase, etc., antibodies. Most common type of hypothyroidism in U.S.
iodine deficiency goiter:
iodine deficiency goiter: endemic goiter in the “goiter belts” because of lack of iodine in the soil. Central Europe & Great Lakes. Is TSH high or low?
excess TH
C. Excess: hyperthyroidism: high BMR, nervousness, irritability, weight oss, fatigue, hyperphagia, heat intolerance, fine tremor of the fingers, warm skin. One form is Grave’s disease.
Autoantibodies to TSH receptor
Autoantibodies to TSH receptor (TSI = thyroid-stimulating immunoglobulin) cause gland to hyperfunction (in 3/4 of Grave’s yield hyper-, ¼ yields hypothyroidism). Exophthalmic goiter can occur. Also causes enhanced responses to sym. stim. (increases synthesis of adrenergic receptors). Can have high C.O. failure.
adrenocortical hormone
They are steroids, formed from cholesterol, degraded in the liver
A. Mineralocorticoids:
A. Mineralocorticoids: Aldosterone – very potent; Corticosterone – intermediate between mineralocorticoid and glucocorticoid
effects of aldosterone
tubular reabsorption of sodium
tubular secretion of K+
`Regulation of aldosterone secretion
Controlled almost independently of other adrenocortical hormones
regulation of aldosterone secretion: Controlled almost independently of other adrenocortical hormones Decreasing importance:
K+ concentration of extracellular fluid
quantity of body sodium. If Na+ drops, bl. vol. drops renin
ACTH – has a permissive effect on aldosterone secretion. Without it, the gland atrophies, including to a mild extent the cells that produce aldosterone.
aldosterone deficiency
Deficiency: Part of Addison’s disease: autoimmune destruction of adrenals often. Orthostatic hypotension (volume contraction = volume depletion), hyperkalemia (→ cardiac arrest, fibrillation). Without salt therapy, or mineralocorticoid therapy, the person will tend to die from blood volume loss & low cardiac output within 3 days to 2 weeks. Small boy consumed huge quantities of salt
aldosterone excess
Excess: Conn’s syndrome: primary aldosteronism: hypokalemia (secreting too much) also cardiac arrhythmias, and muscle weakness (comes from low K+, has an effect to dec. excitability), often hypertension (from inc. Na+ reabsorption).
glucocorticoids
cortisol (=hydrocortisone) – very potent
corticosterone: intermediate between mineralo- & glucocorticoids
prednisone, dexamethasone – synthetic, more potent than cortisol
Effects of glucocorticoids
increase gluconeogenesis
decreases glucose utilization by cells
decreases protein synthesis (except in liver and GI tract)
increases removal of fat from adipose tissue
increase glycogenesis in liver
Amino acids and fats are used by most tissues, glucose is conserved for the CNS.
anti inflammatory
glucocorticoids Regulation of secretion: “stress”
Regulation of secretion: “stress”
CRH from hypothalamus causes ACTH release from the anterior pituitary
glucocorticoids and stress: conditions that cause secretion
hypoglycemia
any injury or disease
extremes in temperature or any other physiological stress, e.g., sleep deprivation
peaks about 8 AM
Deficiency of both mineralocorticoids and glucocorticoids:
Deficiency of both mineralocorticoids and glucocorticoids: Addison’s disease (hypoadrenalism). The mineralocorticoid treatment will prevent immediate death, but the inability to mobilize energy resources to combat stress can make the person susceptible to any stress or disease.
excess glucocorticoids
Excess: Cushing’s syndrome could be both often cortisol
(hyperadrenalism). Lack of protein deposition: muscle weakness, fractures, poor wound-healing; “buffalo hump and moon face;” adrenal diabetes” due to hyperglycemic effect of glucocorticoids, (17 –hydroxysteroids increased in urine); psychosis – megalomaniacal type. Increased appetite (hyperphagia).
Cortisol, by preventing glucose utilization by cells, can
Cortisol, by preventing glucose utilization by cells, can cause starvation & death of some brain cells, particularly in the hippocampus, involving memory.
In the Metabolic Syndrome,
cortisol is probably a part. Metabolic Syndrome: Htn, truncal obesity, diabetes, poor lipid profile. Consider metabolic syndrome as contributing to type II diabetes??
C. Sex steroids – small amounts of mostly androgens (DHEA = dehydroepiandrosterone, and androstenedione) are produced by the
dehydroepiandrosterone, and androstenedione) are produced by the adrenal cortices. These may be involved in the growth spurt, and female libido has been attributed to adrenal and ovarian androgens.
Adrenogenital syndrome caused by a
Adrenogenital syndrome caused by a tumor or can be caused by 21B-hydroxylase deficiency → no cortisol produced → ↑ ACTH → ↑ androgens = congenital adrenal hyperplasia, has masculinizing effects. [17-ketosteroids] Metabolites from androgens increased in urine.
A. Insulin,
A. Insulin, a small protein produced by the beta cells of the endocrine pancreas (islets of Langerhans)
insulin effects
increases glucose transport into cells (brain not dependent)
increases glycogenesis in liver and muscles decreases gluconeogenesis in liver
inc. amino acid & fatty acid transport into cells (used for synthesis
insulin stimulated by
Stim. by hyperglycemia, as after a meal “pushes” FAs, AAs. & glucose into cells (facilitated diffusion).
Overall, insulin is a
Overall, insulin is a “hormone of plenty.” It promotes synthesis of protein & fats & glucose utilization. (Insulin, along with thyroid hormones and GH is necessary for normal growth.)
regulation/secretion of insulin stiumlated by
blood glucose
certain amino acids potentiate the ability of high blood glucose to stimulate secretion
food → ↑ parasym. activity, CCK, GIP = glucose-dependent insulinotropic peptide
excess insulin Excess: 1° maybe rare, 2° to hyperglycemia from
Excess: 1° maybe rare, 2° to hyperglycemia from insulin resistance
excess insulin
hyperinsulinism
insulin shock: Hypoglycemia from administering too much insulin.
insulin shock
Causes increased excitability of the nervous system that can lead to convulsions. Also the hypoglycemia can cause brain damage → coma
Type 1 – Insulin-dependent (IDDM), also called juvenile diabetes –
Autoimmune destruction of pancreatic Beta cells. Some people get this later. If uncorrected early, small in stature – illustrates the fact that is necessary for growth
Type 2 – Non insulin-dependent (NIDDM)
Maturity – onset diabetes” (now occurring in children as young as 10.): more genetic of the 2 types. Obesity is a risk factor (Obesity may be a sign of the genetic difficulty of getting glucose into cells: starved cells cause overeating?)
Insulin resistance:
Insulin resistance: impairment of biologic responses to insulin, can be due to defects from insulin abnormalities to insulin action cascade in target cells. Often considered a problem with the receptor, not necessarily.
diabetes type 2 symptoms
Symptoms: Polyuria, polydipsia, polyphagia, weight loss in IDDM, acidosis. Diabetic coma can come from the acidosis & exacerbated by the dehydration.
. Some complications of chronic diabetes:
. Some complications of chronic diabetes: retinopathy, neuropathy, peripheral vascular problems (some associated with atherosclerosis) including foot ulcers, nephropathy, susceptibility to infection, poor wound-healing.
B. Glucagon,
B. Glucagon, a polypeptide produced by alpha cells of endocrine pancreas
glucagon effects
increases glycogenolysis in liver
increases gluconeogenesis in liver
increases use of fats for energy
Glucagon is a hyperglycemic agent.
Regulation of glucagon secretion:
Regulation of secretion: stimulated by hypoglycemia, exercise
C. Somatostatin,
polypeptide from delta cells of the islets of Langerhans. It has been suggested that its role is to slow the assimilation of food from the gut. It is the same as hypothalamic GHIH. Also inhibits insulin and glucagon release. (The “Oh, shut up.” hormone.)
Hormonal control of blood glucose
liver – blood glucose buffer system
hypoglycemic hormone: insulin
hyperglycemic hormones (4): Glucagon and epinephrine ( glycogenolysis), GH and cortisol, (glucose util. by cells)
hyperglycemic hormones (4):
hyperglycemic hormones (4): Glucagon and epinephrine ( glycogenolysis), GH and cortisol, (glucose util. by cells)
The 5 hormones that increase the removal of fat from adipose tissue & increase its use for energy:
glucagon, epinephrine, GH, cortisol, T3/T4
The 2 hormones that increase glycogenolysis:
Glucagon and epinephrine
The 2 hormones that promote the use of all 3 types of food for energy:
Glucagon and T3/T4
The 3 hormones that increase glycogenesis:
Cortisol and GH (by glucose util. hyperglycemicglycogenesis) & insulin (stim. by eating)
3 hormones necessary for growth:
Insulin, T3/T4 (protein anabolic at normal levels), GH (panhypopituitary dwarfism is partly low GH). Sex hormones? NO: Castrati – very tall, unimpeded effect of growth hormone. Testosterone (or estrogen) caps your final height. Precocious puberty in either sex → short in stature.
spermatogenesis
It begins occurring at puberty and continues throughout life. In meiosis, the precursors to germ cells go from the diploid number of chromosomes to the haploid number, taking about 75 days to go from germinal cell to sperm.
Hormones that stimulate spermatogenesis
Testosterone, produced by the interstitial cells(=Leydig cells), is necessary for sperm development.
LH: stimulates the interstitial cells
FSH: stimulates the Sertoli cells (=nurse cells) to providenutrition for the developing sperm and to convert spermatids into sperm (spermiation)
Seminal vesicles
Their secretions form part of the semen. The secretions contain mucoid material including:
seminal vesicles Their secretions form part of the semen. The secretions contain mucoid material including:
fructose and other nutrients for sperm
prostaglandins – aid fertilization:
prostaglandins – aid fertilization:
react with cervical mucus to make it more receptive to sperm
maybe cause reverse peristalsis in uterus and fallopian tubes – tohelp sperm move toward ovaries (Guyton mentions that a few reach the upper end of the fallopian tube in 5 minutes.)
Prostate gland
It secretes a thin, alkaline fluid. Alkalinity is important for successful fertilization. The fluid in the vas deferens is acidic (sperm end-products), the vagina is acidic (3.5 – 4.0), and a too acidic environment immobilizes the sperm.
Semen, which is what is ejaculated, is mostly
Semen, which is what is ejaculated, is mostly seminal vesicle fluid, with fluid from the vas deferens, prostate and mucous glands contributing.
B. Male Sexual Response
The most important stimuli are local ones to the genitals and psychic stimuli. One indication that psychic ones alone can be effective is nocturnal emissions that can occur during dreaming.
In terms of nervous control of sexual response,
In terms of nervous control of sexual response, parasympathetic impulses are responsible for erection including releasing NO which dilates the arteries of the penis which causes blood flow to the cavernous sinuses.
(Stimulants like amphetamines can
(Stimulants like amphetamines can impede erection.) Emission (movement of semen into the urethra) and ejaculation are under sympathetic control.
C. Testosterone – produced by
C. Testosterone – produced by interstitial cells (Leydig) of testes. Only a small amount of androgens are produced by the adrenals, where the main androgen is DHEA. (Sertoli cells– provide nutrition)
effects of testosterone
development of sperm
primary sex characteristics
testosterone and development of primary sex characteristics
7 weeks: development of male genitals rather than female
3 months: (equivalent in rat): - testosterone -> male hypothalamus
- no testosterone -> female hypothal.: later will cycle, exhibit
DES = diethylstilbesterol, a synthetic estrogen, given to prevent
miscarriage but functionally increases testosterone. Later incidence of homosexuality/bisexuality, left-handedness, autoimmunity. This is a statistical increase in the likelihood, not determining.
secondary sex characteristics
distribution of body hair (including baldness when there is a genetic background for it) voice, fat distribution (apple more than pear)
increased protein synthesis
protein anabolic-> inc. muscle mass. Also inc. bone mass because inc. bone matrix (protein-collagen)
increaed BMR
♂s are more metabolically costly. At fertilization, more ♂s because of faster sperm, but at birth fewer ♂s than ♀s. The year following 9- 11, throughout the U.S., there were 12% fewer ♂s born than usual.
increased RBCs: higher Hct
closure of epiphyses
Control of testosterone secretion
LHRH = GnRH -> LH ->testosterone from Leydig cells [before puberty GnRH not released, some maturation between rest of N.S. and hypothalamus at puberty required for GnRH secretion – might be amygdala]
testosterone feedback suppression
Feedback suppression: high testosterone (as in taking anabolic steroids)decreases GnRH-> involution of testes, can cause liver damage also
Female Sexual Response
Psychic and local stimuli are again the determining factors.
The clitoris is an erectile tissue like the erectile tissue of the male in that it is controlled by
The clitoris is an erectile tissue like the erectile tissue of the male in that it is controlled by parasympathetic impulses and also becomes filled with blood.
Parasympathetic stimulation also controls
Bartholin’s glands
(beneath the labia minora), which secrete mucus and provide most of the lubrication for intercourse.
). Guyton refers to the fact that fertilization by intercourse is more effective than
artificial insemination. He speculates that part of this may be due to orgasm, which increases uterine and fallopian tube mobility, which would aid the sperm. Also, the cervical canal is dilated for up to ½ hour afterward.
Estrogen – produced by
Estrogen – produced by follicle cells of ovary & by placenta
development of ovum
(FSH initiates)
growth of uterus:
growth of uterus: the myometrium; and, in the endometrium, the cyclic growth of blood vessels
secondary sexual characteristics (estrogen)
secondary sexual characteristics
ducts of mammary glands, broadening of pelvic bone, fat deposition: pear
other metabolic effects: (estrogen)
closure of the epiphyses
decreased blood cholesterol ( atherosclerosis, gallstones)
increased protein synthesis, including bones
estrogen is controlled by
“controlled by FSH”
Progesterone:
Progesterone: corpus luteum of ovary, placenta during pregnancy
Progesterone: corpus luteum of ovary, placenta during pregnancy
further development of the endometrium
inhibits uterine contractions during pregnancy
growth of secretory cells of mammary glands
with estrogen, inhibits ovum production during pregnancy
progesterone controlled by
“controlled by LH”
Neg. Feedback from estrogen and Inhibin from .
Neg. Feedback from estrogen and Inhibin from ovaries on FSH, LH at beginning of cycle and again near the end of cycle. Positive Feedback of estrogen just before ovulation.
FSH ->
FSH -> increases estrogen -> endometrium develops
increased estrogen causes
Ovum develops increases LH (slowly) - accelerates growth of 1° follicle
increased estrogen ->
ovum matures
increased LH (positive feedback)
“LH surge”
necessary for ovulation
Ovulation
Growth of corpus luteum
progesterone and estrogen
decreased LH neg feedback
increases progesterone
final development of endometrium
no fertilization
decreased LH -> decreased progesterone -> menstruation
classic birth control pills –
based on feedback suppression e.g. high estrogen at beginning of cycle suppresses FSH (also high progesterone suppresses LH, but not necessary if FSH suppressed)
(A reason for including the progesterone is that progesterone protects against some effects of estrogen, e.g., uterine cancer)
starvation or too little body fat
starvation or too little body fat
or sometimes very strenuous exercise can cause a person to become anovulatory.
underarm sweat from male swabbed onto the upper lip of a female has been reported to influence her
cycling. The claim is that for women who cycle shorter or longer than 29 days (the optimal for fertility), this male armpit sweat brought them toward 29.
armpit sweat of one female swabbed onto another female’s upper lip causes
causes 2nd woman to cycle with the 1st (the sweat donor). Presumably by pheromones.
Chorion of embryo -> human chorionic gonadatropin (HCG) maintains
Chorion of embryo human chorionic gonadatropin (HCG) maintains corpus luteum which is producing progesterone and estrogen.
(HCG is elevated at the
(HCG is elevated at the beginning of pregnancy, then gone. Pregnancy test)
Pregnancy
Estrogen & Progesterone:
Pregnancy
Estrogen & Progesterone: inhibit ovulation (inhibit hypothalamus, anterior pituitary
Estrogen: growth of vagina
Relaxin produced by
Estrogen: growth of vagina
Relaxin produced by ovaries, uterus, placenta & mammary glands:
Progesterone:
Progesterone: inhibits uterine contractions
Late pregnancy – progesterone somewhat, still high Estrogen remains
high
uterine contractions increased
Size of fetus stretches uterus HypothalamusPosterior pituitary Oxytocin
Strong uterine contractions which contributes to delivery, vasoconstriction after delivery helps prevent too much blood loss
High cortisol →
High cortisol → thinning and thus opening of cervix, surfactant production
At birth and after:
At birth and after:
PL: milk production
Oxytocin: milk letdown or ejection, upon infant signals, such as suckling, baby sounds (indicates it’s a fast reflex)
bone composition
hydroxyapatites: Ca++ phosphate compounds
CaCO3 comp’ds also
organic matrix: collagen fibers, ground substance
Osteoblasts secrete
Osteoblasts secrete collagen and ground substance. Some of them become trapped in this extracellular material and become osteocytes. The calcium salts begin to precipitate along the collagen fibers at regular intervals, growing into hydroxyapatite crystals over a period of weeks or months.
Osteoblasts secrete collagen and ground substance. Some of them become trapped in this extracellular material and become
osteocytes. The calcium salts begin to precipitate along the collagen fibers at regular intervals, growing into hydroxyapatite crystals over a period of weeks or months.
About 20 to 30% of the salts remain in an
amorphous, non-crystallized form that can be resorbed when there in need for more Ca++ in the extracellular fluid.
Value of continual remodeling
Bone adjust its strength to the degree of stress (pressure) put on it.
The shape of the bone can be rearranged for proper support by deposition and resorption of bone in keeping with stress patterns. Greatest osteoblast activity at the site of pressure. Pressure on crystals is believed to generate electricity → ↑ osteoblast activity
New organic matrix needs to replace old, which degenerates.
The shape of the bone can be rearranged for proper support by
deposition and resorption of bone in keeping with stress patterns. Greatest osteoblast activity at the site of pressure. Pressure on crystals is believed to generate electricity → ↑ osteoblast activity
Normally the rates of deposition and resorption are equal so bone mass remains .
constant
Osteoclasts
Osteoclasts send out villus-like projections that secrete: proteolytic enzymes, several acids. The “villi” also phagocytize fragments of bone salts and collagen. This whole process results in tunnels which are then invaded by osteoblasts
Bisphosphonates inhibit
Bisphosphonates inhibit osteoclast activity, therefore little osteoblast activity → no new bone!
Fracture repair
Fracture repair
All existing osteoblasts are maximally activated, and new osteoblasts are formed from bone stem cells. Shortly there is a large bulge of tissue, matrix, and Ca salt deposits between the two broken ends of bone, which is called a callus.
To accelerate rate of fracture healing Many bone surgeons use:
mechanical fixation apparatus (screws or pins, etc.) – holds ends together, pt. can use immediately, causes stress on bone rate of healing
pulsating EMF – weak currents, osteoblasts more active calcif., vasc., ossification. Caveat (warning): One expert claims there’s no evidence that it works.
Blood alkaline phosphatase is an indication of
bone deposition. Osteoblasts secrete it when depositing.
Hypocalcemia
Hypocalcemia
35% reduced increases hypocalcemia tetany. In hypoPTHism.
inc. perm. to Na+ -> spontaneous A.P.s (action potentials), occasionally convulsions, laryngeal spasm -> obstruct respiration
Hypercalcemia, nervous system
Hypercalcemia, nervous system depressed
hypercalcemia
Changes heart rhythm, constipation & lack of appetite – dec. contractility of GI. 2x normal level Ca PO4 ppt. in body
hypercalcemia: Blood Ca++ levels are partially
Blood Ca++ levels are partially maintained because exchangeable Ca in the form of readily mobilizable salts exists in bone. This rxn. so rapid that, if high Ca++, a single passage of blood through bone will remove most of excess.
Most of the dietary Ca is excreted in the feces, some in urine. Vitamin D increases
absorption of Ca from the intestines, resorption from bone and retention from the urine in the kidneys. (
vitamin D pathway
-> Vit. D2 from milk from cholesterol7-dehydrocholesterol -> Vit. D3 -> Kidney (under influence of PTH)increase intestinal Ca absorption 1,25 dihydroxycholecalciferol
(by increasing Ca++ - binding protein mainly, also increasing phosphate abs., but less important because PO4 is absorbed readily.)
Vitamin D production inc. by:
Vitamin D production inc. by: PTH, decrease serum phosphate and decrease in its own levels
Parathyroid hormone:
Parathyroid hormone: Stim. by bl. Ca++
Infusion of parathyroid hormone causes a rise in
Infusion of parathyroid hormone causes a rise in blood Ca and a depression of phosphate.
The effects of PTH on Ca and phosphate mobilization at the bone are the
same: PTH causes the resorption of both from bone. However, PTH causes differing effects at the kidney: it causes decreased Ca and increased phosphate excretion from the kidneys.
The decrease in blood phosphate with PTH means that the increased phosphate excretion at the kidney is the
overriding effect.(Incidentally, much of the action of parathyroid hormone on bone resorption, & maybe on other things, seems to be through Vitamin D.)
Calcitonin:
Calcitonin: Stim. by increased blood Ca++
calicitonin Produced in the
Produced in the thyroid, it reduces blood Ca by increasing deposition of Ca in bone and osteoblast activity. The most prolonged effect is in decreasing formation of new osteoclasts.
. In adults, calcitonin only has a very weak effect on plasma Ca concentration, because
PTH has such a strong effect in maintaining Ca++ and because bone depos. & resorption not going on at a high rate in adults.
Overall control of blood Ca++
buffer function of exchangeable Ca++
2nd line of defense:
- in a few min decreases bl. Ca++->increases PTHexchangeable Ca++
- in prolonged Ca++ excess or deficiency – PTH is main defense
very long-term: although large reserve in bones, finally PTH & Vit. D -> abs. in gut and reabs. in kidney
Calcium & phosphate make bones
Calcium & phosphate make bones hard: compressional strength
Vitamin D
Ca++ abs. in int., in kidney & from bone. Lack in childhood =
rickets, weak bones in children, also in winter. Defective bone growth, because not enough Ca++ or PO4 -2.
Osteomalacia =
Osteomalacia = rickets of adulthood, failure to absorb fat (e.g., bile duct obstruction) ->steatorrhea (thus lack of Vit. D. abs.) -> demineralization→ malleability of bone.
increased PO4 -2 abs. in gut →
PO4 -2 Levels in blood ↑
Hypervitaminosis D:
wt. loss, calcification of many soft tissues and eventual renal failure
Parathyroid hormone
Infusion increased blood Ca++, increaed abs. from bone, increased reabs. in kidney,
decreased PO4 -2 reabs. in kidney→decreased PO4 -2 levels in blood drop
Long-term, PTH activates
osteoclasts
HypoPTH:
HypoPTH: death by laryngospasm. HyperPTH: hypercalcemia, hypophosphatemia, demineralization of bones, Ca++ kidney stones.
Sex hormones: estrogen, testosterone, DHEA – in puberty cause
growth spurt increase osteoblast activity. Also cause epiphyseal plate to close, so if precocious puberty is not corrected, the person would be very short in stature.
Inversely, the tall stature of the castrati (GH effects on height unimpeded by testosterone) illustrates that
that sex hormones are not needed for normal bodily growth.
Post- menopausal estrogen lack osteoporosis =
decreased bone mass. Estrogen is protein anabolic. At risk for osteoporosis: White, blond, blue-eyed, skinny women, not men, not Black women.
“Exercise” or “stress” pressure on bone Immobility,
“Exercise” or “stress” pressure on bone Immobility, weightlessness loss of bone. Swimming should not be the only exercise of post-menopausal women.
Old age:
Old age: Protein anabolic function low, etc. Inactivity is a likely culprit. Absorption of nutrients not as good, also maybe diet, e.g., lack of folic acid or B12 (needed for DNA and RNA synthesis) → ↓ production of endothelial lining of gut → ↓ absorption
Cushing’s disease –
hyperadrenalism
increased glucocorticoids , decreased protein deposition -> fractures Exogenous for asthma, autoimmunity, organ transplants, etc.
Alcohol
Maybe decreased absorption, does inhibit folic acid absorption maybe other problems, in any event, weakened bones.
Fluoride
Promotes deposition of salts, among other effects. Used experimentally in osteoporosis
Magnesium
Magnesium
Needed for PTH synthesis
Vitamins A & C
“Both affect utilization of Ca++ and PO4 -2”
Deficiency of A: failure of bone growth
Deficiency of C: problem with collagen, lack of formation of new blood vessels
Serotonin from gut:
Serotonin from gut:
An estimated 80-95% of the body’s serotonin is in the gut’s enterochromaffin cells where it stimulates gut motility. Serotonin finds its way into other tissues and inhibits bone mass. SSRIs likewise decrease bone mass.
Bisphosphonates (such as Fosamax, Boniva etc.) inhibit
t osteoclast activity, thus reduce breakdown of bone. It inhibits new bone formation by osteoblasts also. A disturbing result, osteonecrosis, 1st observed in jaw, has led to the warning that such substances should not be used for more than 10 yrs. Also found recently, femur fractures.
Growth hormone:
Growth hormone: hypopituitary dwarf (GH inc. protein synthesis, cell division)
Insulin: (glucose and other substrate into cells)
juvenile diabetes – uncorrected – short in stature
babies of diabetic mothers are large, because of insulin secretion from fetus
T3/T4:
T3/T4: cretinism – lack in childhood
PTH
Blood Ca++ increased
effects Ca++ & Po4-3 resoprtion (or reabs.) from bone Ca++ reabs. from kidneys stimulated by blood Ca++
Blood PO4-3 decreases ->
decreased PO4-3 reabs. from kidney
Activated
Vit. D3
(1,25-dihydroxy- cholecalciferal)
effects Ca++ abs. in intestines serum PO4-3 Ca++ resorption from bone PTH, low Ca++ reabs. from kidneys stimulated by decreased serum phosphate increased PTH
(Much of the effects of PTH are thought to be through activated
Vit. D3, however they differ in their effects on PO4-3 being kept in the body.)
calcitonin
effects
increased Ca++ deposition in bone (not much effect on blood Ca++ levels in adults partly because PTH is much more powerful mechanism)
effect
increaed blood calcium
