Physiology Flashcards
(156 cards)
1
Q
<p>Difference Between Peptide and Steroid Hormones?</p>
A
<p>Peptide: Activate receptors on the cell surface. Stored in secretory vesicles. Signal transduction cascades affect a variety of cell processes. Response is rapid (seconds to minutes)
Steroid : enter the cell and activate nuclear receptors (in the nucleus sometimes cytoplasm). Diffuses through the cell membrane to regulate gene transcription. Takes hours to days to respond. Are produced on demand and not stored. </p>
2
Q
<p>Thyroid Hormones T3/T4 are what kind of hormone and how do they act on target cells?</p>
A
<p>T3 (Thyroxine) and T4 (Triiodothyronine) are amino acid hormones that act like steroids and enter the cell and activate nuclear receptors. They are hydrophobic and very long lived.</p>
3
Q
<p>What is Hypoparathyroidism: </p>
A
<p>Primary defect in the gland. Patient has low PTH hormone because cannot create PTH and has high levels of Ph and low levels of Ca. </p>
4
Q
<p>What is Pseudohypoparathyroidism:</p>
A
<p>Molecular alteration in alpha s subunit of heterotrimeric G protein results in impairment in the ability of PTH to regulate body Ca and Ph levels. Patients have low Ca levels and high Phosphate levels. Increased circulating concentrations of PTH. Increased risk of hypothyroidism. Gonadal dysfunction in women. </p>
5
Q
<p>What regulates the Adrenal Medulla?</p>
A
<p>SNS. Adrenal secretes NE and Epi in the Medulla of the Adrenal Gland.</p>
6
Q
<p>Where is Growth hormone is produced and how is it regulated? </p>
A
<p>Regulated by Hypothalamus by GHRH which increases production and Somatostatin which inhibits.
GH acts through IGF-1 which is produced in the liver. It enhances GH actions. </p>
7
Q
<p>What does the Parathyroid Secrete?</p>
A
<p>It Secretes PTH which causes Increase in Ca and decrease in Phosphorus</p>
8
Q
<p>When you have a meal high in protein, how does that affect
glucagon, insulin and growth hormone?</p>
A
<p>When there is a meal high in protein, glucagon is released so that the amino acids can be converted to glucose. Once high levels of glucose are formed, insulin is released to store it. The high levels of amino acid increase levels of GH because it is used to build muscle. </p>
9
Q
T/F: Is GH chronically present in the plasma?
A
F : GH is Released in a cyclical fashion. Strenuous exercise to build muscle releases GH. Peaks at Midnight
10
Q
What is the cellular origin of the Anterior/Posterior Pituitary?
A
Anterior (adenohypophysis): Endothelial Origin and is Vascularized by the Hypothalamus. It receives venous blood carrying neuropeptides from the hypothalamus and pituitary gland. Hormones are Proteins. Regulated through portal circulation.
Posterior ( neurohypophysis): Neural Origin and receives arterial blood. Axons from hypothalamic nuclei extend to posterior pituitary where the hormones are stored until release. Smaller molecular mass peptides. ADH and Oxytocin.
11
Q
Types of Hormones Released in the Hypothalamus to the Anterior Pituitary:
A
GHRH: Growth Hormone ( inhibited by Somatostatin)
TRH: TSH (Thyroid follicular cells and stimulated to make thyroid hormone).
CRH: ACTH ( Fasciculata and reticularis of adrenal cortex to make corticosteroids).
GnRH: FSH (Make Estrogen, initiate spermatogenesis)
GnRH: LH
Dopamine: Inhibits Prolactin ( Milk production)
12
Q
Types of Hormones Released in the Hypothalamus to the Posterior Pituitary:
A
AVP: AVP ( water permeability)
OT: Oxytocin ( Uterus and Breast)
13
Q
Example of long loop negative feedback in males and females? Name a positive feedback example?
A
Long Loop Feedback: From peripheral glands to HY/Pit Axis. Example would be testosterone production inhibits both the anterior pit and hypothalamus from producing testosterone.
Short Loop Feedback: from AP to hypothalamus
Positive Feedback : LH surge. Prolactin stimulated hypothalamus to increased Tyrotrophic Releasing Hormone to increase Prolactin production during breast feeding. Oxytocin stimulates milk ejection from the breasts in response to sucking. Or uterine contraction due to response to dilation of the cervix.
14
Q
Describe how prolactin is regulated?
A
Prolactin is under tonic inhibitory control by Dopamine which is always released from the hypothalamus. TRH stimulated prolactin release. Prolactin exherts negative feedback on its on release by enhancing hypothalamus dopamine release via short loop pathway.
15
Q
What happens to prolactin if the infundibular stalk is severed?
A
If the stalk is severed then dopamine cannot be released. Therefore a decrease in dopamine will be seen and an increase in Prolactin will be seen. Treatment would be a Dopamine Agonist which will inhibit the effects of prolactin.
16
Q
What does Oxytocin do?
A
Neuropeptide that stimulates milk ejection from the breast in response in suckling. It is secreted in response to sight, smell or sound of the infant. Comes from the Paraventricular nuclei in Hypothalamus.
17
Q
What does ADH do?
A
ADH increased secretion due to increased osmolarity of Extracellular fluid (dehydration) and decreased blood pressure. Increases water reabsorption by the kidney V2 receptor. Causes contraction of Vascular Smooth Muscle V1 receptor. Increased in total peripheral resistance.
High ADH: low volume of concentrated urine
18
Q
What is Central Diabetes insipidus?
A
Failure to secrete ADH from posterior pituitary. Patients have large volumes of dilute urine and bodily fluids become concentrated. Hypernatremia. Polydipsia (frequent drinking due to extreme thirst).
19
Q
What is Hypopituitarism?
A
Insufficiency of pituitary to release hormones or Insufficiency of hypothalamic releasing hormones. Caused by tumors, TBI, subarachnoid hemorrhage.
20
Q
How is GH regulated?
A
GH is Produced in anterior pituitary. Regulated by GHRH produced in the arcuate nucleus of the hypothalamus which stimulates/enhances GH.
Somatostatin is produced in the periventricular region of the hypothalamus and inhibits. Integration results in episodic, pulsatile secretion.
Ghrelin in stomach and pancreas. Positive mediator of growth hormone. It stimulates hunger
21
Q
Excess GH during puberty and after puberty results in which two clinical conditions?
A
During Puberty: Gigantism.
After Puberty: Acromegaly ( enlarged hands and feet and increased in tongue size).
22
Q
How is GH expressed in the plasma?
A
It is seen in a pulsatile nature when both Somatostatin and GHRH are integrated. Pulses are at night. Large pulse amplitude during puberty. Large pulses occur shortly after REM begins. Strenuous exercise cause increase in GH ( building muscle). This is why sleep increases growth. Because sleep is where GH is pulsing. Therefore drugs that disrupt sleep can decrease growth ( ADHD drugs).
23
Q
Name 8 factors that stimulate GH Secretion
A
Deep sleep, Exercise, Amino Acid, Hypoglycemia/Fasting, Sex steroids, Stress, alpha adrenergic agonists ( constrict blood vessels) and dopamine agonist ( suppress in acromegaly).
24
Q
Name 7 factors that inhibit GH secretion
A
Obesity ( decreases GH pulses) GH IGF 1 Beta Adrenergic ( Dilate) Hyperglycemia Free Fatty Acids Glucocorticoids ( steroid hormones)
25
How is GH activated by its receptor?
There is no inherent tyrosine kinase activity. Binding of GH causes conformational change causes a repositioning of the associated JAK tyrosine kinases which phosphorylates STAT which dimerizes and translocates to the nucleus to act as transcription activators. Increase expression of CISH ( mediator of GH).
26
What effect does GH specifically have on the liver and brain?
GH increases IGF 1 secretion from liver. Both IGF-1 and GH inhibit the production of GHRH and enhance the activity of somatostatin ( to inhibit GH in the anterior pituitary).
27
How does GHRH increase secretion of GH?
GHRH stimulates G protein receptors to raise Ca and cAMP levels. cAMP activates protein kinase A which phosphorylates transcription factor CREB, augmenting ( increasing) the transcription of Pit 1, transcription factor that up regulates GH and GHRH receptors.
28
What effect does GH have on Liver, Muscle, Skeletal Bone, Adipose Tissue and Brain.
Liver: Stimulate IGF-1 ( hepatic glucose production) Direct Effects
Adipose: Direct Effect. Fatty acid oxidation during fasting. Reducing Lipogenesis and lipoprotein lipase ( it removes TG and FA from bloodstream).Lipolysis.
Muscle: Glucose and AA uptake increases. Protein Synthesis goes up. Increase in lean body mass.
Bone: AA uptake, protein synthesis. Increases both osteoclasts and osteoblasts in bones. osteoclasts needed to remodel osteoblasts. Increase chrondrocyte maturation.
Brain: Induced by sleep, hypoglycemia and stress. Inhibited by aging, disease and glucose.
29
what is GH and insulin relationship?
GH counteracts the action of insulin by decreasing lipogenesis and stimulating hepatic glucose production. GH increases insulin secretion but inhibits the action of insulin.
30
What is the relationship between Food and IGF-1
A lack of food or poor nutrition can lead to a decrease in IGF-1. Celiac Disease/Nutritional deficiency leads to reduced levels of IGF – 1 and slower growth. No nutrition causes no production of IFG 1 ( seen in celiac and eating disorders anorexia).
31
Difference between insulin, IGF 1 and 2.
Insulin cleaves peptide C where as it is not cleaved in IGF 1 or 2
32
How is the signaling pathway of IGF 1 different from GH?
IGF 1 receptors are already tyrosine kinases and therefore do not have to associate with one as seen in GH. It phosphorylates itself and activates the Ras/Map or P13 kinase pathway that regulate cellular transcription.
33
What is IGF 1 and 2 seen in the plasma during development
rapid growth during the first few years is due to IGF 2 and then IGF 1 has an important impact during puberty.
34
What is Laron Syndrome?
GH receptor mutation causing low IGF 1 and normal/elevated GH hormone. Mild Growth Retardation. No acne/diabetes.
35
What does Low and High Levels of GH cause?
Both can cause insulin resistance. Due to the fact that low GH is inhibited by obesity and an increase in interstitial mass which increases risk for CVD and diabetes.
36
GH deficiency can cause?
Increase in visceral adipose tissue, CVD, insulin resistance, depression and lazy.
Decreases Myocardial Fcn "get up and go" very sluggish.
Loss of muscles mass and increase in interstitial body fat.
37
GH is approved for use in which GH deficiency diseases?
Prader Willi, Chronic renal insufficiency, small for gestational age.
38
How does hypothyroidism effect GH?
Decrease in thyroxine shunts GH production which leads to stunted growth. Thyroxine is needed to transcribe GH ( found in the promoter region of GH).
39
Short Stature with Normal Hormone Status is seen in which diseases?
Down Syndrome and Turners Syndrome.
| In turners is due to the haploinsufficincy of the SHOX gene since they only have one X chromosome.
40
What is Klinefelters syndrome?
People with an extra sex chromosome may get a third copy of the SHOX gene making them taller than average.
Deletion of the SHOX locus leads to short stature.
41
A patient who is pregnant may have high levels of TH present due to the upregulation of estrogen, why is this not a concern to the physician?
Because the bound TH is what is measured and can be higher and lower than normal but the free TH is what regulates the TRH/TSH axis therefore the total TH levels will be high but the free TH will be normal.
42
What does the thyroid gland do?
Thyroid regulates vertebrate growth, development and metabolism.
Growth and Development in Young Child. Interact with GH.
Enhance the Use of Vitamins.
In adults: Major Regulator of your Basal Metabolic Rate
43
How is Thyroid Hormone synthesized?
Thyroid glands contain follicles, which contain follicular epithelial cells (thyrocytes) that are the site of thyroid hormone synthesis and release. The basal side of the cell responds to TSH and the apical side of the cell is filled with TG that store thyroid hormone.
44
How is Thyroid Hormone stored and secreted?
Stored form of TH is associated with Thyroglobulin (TG) in the colloid. It will release TH in response to TSH from the anterior pituitary.
TRH from hypothalamus causes TSH to be released from the anterior pituitary which acts on the thyroid gland. Thyroid produces T3/4 which has a negative feedback on the anterior pituitary (TSH)
45
How is TH (T3/4) produced?
T3 and T4 are synthesized from the amino acid tyrosine on thyroglobulin (TG) and require iodine in the diet. Iodine is stored In the thyroid gland in association with colloidal TG.
In the ER, Tyroglobulin (TG) molecules are produced and exocytose into the lumen of the follicle. Iodine enters the thyrocyte via Na/I cotransporter due to the Na/K ATP gradient and exits via the I/Cl antiporter into the follicular lumen. Iodine is oxidized by thyroid peroxidase and substituted for the H+ on the benzene ring of tyrosine residues of thyroglobin.
Binding of one iodine forms Monoiodotyrosine (MIT) and two iodine will form diodotyrosine (DIT) ( organification).
T3: DIT coupled with MIT
T4: 2 DIT coupled together.
46
Once TG, MIT, DIT, T3 and T4 are formed. How is it released?
The colloid droplets is endocytosed back into the follicle cell. TSH stimulates lysosomes in follicular epithlial cells to release T3/T4 out of the cell and Deiodinase recycles the MIT and DIT into I and goes back into the thyroid follicle lumen.
47
What form of TH does the thyroid hormone secrete?
T4 formation is preferred and secreted more. Most TH is bound to thyroid-binding globulin (TBG). Other TH binding proteins are thansthyretin and albumin.
48
Differences Between T3/T4?
T4 : more stable, longer half life, more produced and can be changed to T3 via deiodinase.
T3: More potent, less produced, shorter half life
rT3: biologically inactive.
49
How does Thyroid hormones act on target cells?
FREE T4/T3 enter the cell and some of the T4 is converted to T3 and they enter the cell and bind to RXR and TR to induce transcription factors.
50
What transcriptional effects does TH have on organs?
Increase metabolic rate and O2 consumption,
Works with GH to promote bone formation
Increase Mitochondria, Respiratory Enzymes, Na/K ATPase
Increase Cardiac Output, Urea and renal function
CNS development
51
TH deficiency in infants results in?
Mental retardation( cretinism) and Growth Retardation
52
Difference in Hyperthyroidism and Hypothyroidism?
Hyperthyroidism: Increase BMR. Muscle Wasting occurs because proteolysis outweights synthesis. Increase gluconeogenesis and glycogenolysis. Increase heat production which Increased B adrenergic receptors (vasodilation) for enhanced sensitivity to Epi and NE. Low TSH seen in plasma due to excessive negative feedback by the high circulating T3/4.
Hypothyroidsm: Decrease BMR. Serum Cholesterol increases risk for astheroclerosis. Decrease in gluconeogenesis and glycogenolysis. High levels of TSH seen due to low levels of T3/4 not sending a negative feedback.
53
How is thyroid function regulated?
TRH stimulates TSH release by activating GPCR linked to PLC. It generates IP3 and increases Ca release. Ca release causes TSH release from the thyrotrophs in the anterior piruitary.
TSH then causes TH release by activating GPCR linked to adenlyate cyclase which generates intracellular cAMP. Causing T3/T4 release.
Dopamine and Somatostatin exherts inhibitory effects on TSH release.
54
What is the adrenal glands made from and what do they secrete?
The Cortex is made from the mesoderm and has three layers: ( essential for life)
Zona glomerularis: aldosterone (Na.Salt balance) mineralcorticoid.
Zona fasciculata: glucocorticoids( response to sugar/glucose)
Zona reticularis: Androgens (DHEA and adrostenedione).
The medulla is made from the neural crest and secretes caletocholamines: NE, Epi. ( not life threatening)
55
Difference between mineralcorticoid and glucocorticoids?
| Name some analogues.
Mineralcorticoids respond to minerals such as sodium and potassium and is made in the zona glomerularis of the adrenal glands. Analogues: Aldosterone, Hydrocortisone
Glucocorticoids are the stress hormones that respond to stress by increasing sugar formation. It is formed in the zona reticularis. Analogue: Dexamethasone, Prednisone, Triamcinolone, Fludrocortisone acetae, hydrocortisone.
56
What is the rate limiting step of the synthesis of what type of hormones in the adrenal gland?
The cholesterol to pregenolone done by 20,22 desmolase ( P450 side chain cleavage enzyme)
57
How is Aldosterone (mineralcorticoids) synthesize?
It is synthesized from pregnenolone to progesterone via 3 B hyroxysteroid dehydrogenase in the cytosol.
Then it goes to 11-deoxycorticosterone via 21-hydroxylase
Then to corticosterone (gluccorticoid) via 11B hydroxylase and then ALDOSTERONE SYNTHASE in the mitochondria converts it to Aldosterone.
No 17 alpha hyroxylase in glomerulosa. No stage pool of aldosterone.Once secreted 37% remains free in plasma and the rest weakly binds to CBG and albumin
Aldosterone increases Na channels and increases sodium reabsorption and potassium secretion from distal nehprons segments.
58
How are Glucocorticosteroids ( cortisol) produced?
Glucocorticoids are produced in the fasciculata and contain 17 alpha hydroxylase ( also seen in reticuralris).
Pregnenolone by 17 alpha hydroxylase gets converted to 17 hydroxypregnenolone.
17 hydroxyprogesterone then uses 21 hydroxylase to form 11 deoxycortisol and then 11B hydroxylase is used to form cortisol.
Cortisol: 90% is bound to cortisol binding protein, 7% is bound to albumin and 3% circulates free
NO androgen synthase
59
How are androgens synthesized?
DHEA and androstenedione ( converted to testosterone) are less potent androgens.
Pregnenolone -(17 alpha hydroxylase)->17 hydorxylpregenolone.
17 hydroxylpregenolone -(17,20 desmolase)-> DHEA/Androsterendione.
DHEA peaks in 20s, lovers in early 30's. Important for sex drive after menopause.
60
How does cortisol act in the body?
Free cortisol (3%) enters the target cell by diffusion and binds to cytoplasmic receptor, migrates to nucleus and modulates gene transcription.
Cortisol inhibits transcription of POMC genes. It inhibits expression of CRH and ACTH in the anterior pituitary
61
What does Cortisol do?
It is a glucocorticoid. Stimulates gluconeogenesis in the liver, proteolysis in the muscle cells. Causes lipolysis in the peripheral but fat is deposited centrally. Decreases osteoblast activity and interferes with Ca absorption from gut. Blocks glucose uptake (except from the brain).
It inhibits cytokine (cytooxigenase and histamine inhibited) and production of chemoattractants, stabilizes lysosomal enzymes and contributes to vasoconstriction and decreased capillary permeability.
Immuosupressive: decrease lymphocyte proliferation and inhibits hypersensitivity reactions.
Emotional instability
62
How does ACTH and CRH work?
CRH ( peptide) is produced in the corticotroph (hypothalamus) to release ACTH by increasing cellular Ca. ACTH (peptide) is a trophic factor of adrenocortico cells and is required for adrenal cell survival. ACTH then increases cortisol synthesis via PKA in adrenal cortex cells.
PKA increases up regulating of several enzymes and P450.
63
What is POMC and how is it regulated?
POMC (pro-opiomelanocortin) is a large precursor protein that is ACTH is produced from in the anterior pituitary. The Melanocortin-2 receptor receives ACTH on the adrenal gland Cortisol inhibits POMC gene. It stimulates the rate limiting step of cortisol formation ( cholesterol > pregenolone).
POMC processing in the anterior pituitary gives rise to ACTH and Beta lipotropin.
During fetal life and pregnancy, intermediate pituitary lobe processes POMC to yield hormones : alpha- MSH and Beta-endorphin.
64
Explain how circadian rhythm affects cortisol secretion?
Cortisol undergoes diurnal variation with the highest levels present in the early morning, due to the need to increase gluconeogenesis in the morning. It lowers in the evening. ACTH is secreted in pulsatile secretions.
Physical, phychological and biological stressed enhance CRH secretion and thus enhanced ACTH secretion which results in increased secretion of cortisol.
65
What is 21 alpha hydroxylase deficincy?
Used to form aldosterone from progesterone to deoxycorticosteroid and CORTISOL. Both mineal and glucocorticoids not produced. Genetic mutation which is the most common form of congenital adrenal hyperplasia.
Decrease cortisol ( hypogylcemia) and aldosterone (loss of salt, hypotension, dehydration) production. Increase ACTH production due to no negative feedback. Since ACTH is a trophic factor, more ACTH means an increase in size. Adrenal hyperplasia and increased androgen (ambigous genetial in women, virilizing effects in males) production.
Check 17 hydroxylase before and after ACTH stimulation test. Treatment with glucocorticoids ( pednisolone/dexamethasone) and salt washing and elevated renin levls for mineralcorticoids. (fludrocortisone is the only mineralcorticoid drug).
66
What is 17 alpha hydroxylase?
Used in the production of Androgens and Cortisol. Reduced cortisol and androgren synthesis. Increased cortisterone (increase adrenal size) and aldosterone which cause hypertension and hypokalemia.
Clinical Symptoms: Hypertension, Hypokalemia, Sexual infantilism in genetic females and pseudohermaphroditism and sexual infantilism in genetic males.
Treat with glucocorticoid treatment. Estrogen/testosterone treatment.
67
What is Cushing Syndrome?
Hyperadrenal function: excessive levels of cortisol for long periods of time. Can be caused by prolonged use of immunosuppression drugs ( prednisone, adrenal tumors and tumors that increase ACTH).
Symptoms:
Moon face
Increase protein break down and increase fat deposits in the center of the body. Osteopenia. Skin thinning and fragility.
Diagnosis: Urinary or Salivary cortisol (hight at night) measurement:
Drexamethasone is a glucocoticoid analogue drug that sends negative feed back to CRH. A patient takes it at night and if the levels of cortisol are still high in the morning then the test is positive ( has an autonomous source of either cortisol or ACTH)
Treatment: Surgery to remove adrenal adenoma/ACTH producing adenoma. Replacement with hydrocortisone/prednisone if both removed. Inhibit cortisol synthesis using asketoconazole and metyrpone.
68
What is Addison Disease?
Hypoadrenal function.
Primary adrenal insufficiency ( classic): aldosterone hormone is deficient. Adrenaline usually decreased. Increased ACTH causes hyper pigmentation of skin an mucous membranes.
Lack of aldosterone leads to hypotension and hyperkalemia. Lack of cortisol results in hypoglycemia, weakness, weight loss and poor tolerance to stress.
Diagnoses by low cortisol response to ACTH injection. Usually due to autoimmune, TB targeting 21 hydroxylase.
Treatment with cortisol and fludrocortisone.
69
How much Ca is found in the Plasma?
1 kg Ca is found in the body. 99g is in the bone and 1g is found in the ECF and muscles.
Of the one gram: Half is ionized Ca (4.5-5.2) ( regulated by PTH). 40% is bound to protein ( albumin). 10% are complexed to Ion. They all equal the Total Ca which is measured (9-10.6 mg/dl).
False positive can be measured if the albumin is higher than normal but once the ionized Ca is normal then everything is good.
In acidosis, albumin decreases binding affinity to Ca and an increase in ionized Ca occurs.
70
Difference in symptoms between Hypercalcemia and Hypocalcemia?
Hypercalcemia ( above 12 mg): Fatigue, anorexia, headache, muscle weakness due to membrane polarization that reduces neural responses. Bradycardia, polydispia, polyuria, hypertension and calculi.
* Can be due to hyperparathyroidism or familial hypercalcelmia (FHH) but they don't have any symptoms.
Hypocalcemia: (below 7 mg): Learning retardation, apnea, low calcium reduces membrane polarization and increases hypersensitivity producing spasms, seizures and muscle cramps. Weak bone development and CO reduced. Long QT interval.
71
How is Ca maintained in the body?
Ca enters the body via the small intestine ( 80% is excreted in feces). The kidney filets and recaptures Ca. Bone stores Ca.
If Ca goes low then initially the kidneys can compensate but in the long run the bone reservoir will increase bone resorption which can cause osteoporosis.
Regulated by PTH and Vitamin D.
P04 can also reduced ionized Ca levels by binding to Ca.
72
How does PTH work?
Primarily on the Kidney and stimulates reabsoprtion of Ca in the distal tubule(9%). It stimulates PO4 excretion into the urine from proximal tubule and it also increases synthesis of vitamin D to its active form.
Secondary organ it affects is the bone. Activates osteoblasts receptors to increase osetoclast resorption. Increasing Ca and PO4 in ECF and plasma.
73
What stimulates PTH release
High PO4, Low Ca and Low Mg.
High Ca, High Vit D : decreases PTH
74
How does Vitamin D help and how is PO4 regulated by increased PTH?
Vitamin D aids by increasing Calbindin/Ca that helps with transporting Ca to the basal side of the kidney.
Po4 is usually increased due to GI absorption ( by vit D) and bone turnover which is up-regulated by PTH but due to the increase secretion in the kidney. PO4 is able to remain constant/low when Ca is being up-regulated.
75
What does Vitamin D Target?
The concentration of active form of vitamin D is upregulated by PTH. Vitamin D increases Ca and PO4 absorption from the GI and transports it to the plasma by increasinf the synthesis of the transporter calbindin. It also activates osteoblast receptors which promote the maturation and activation of osteoclasts. It also assists in the transport of Ca during reabsorption process. It also suppresses PTH secretion.
76
How is Vitamin D synthesized?
Primary source is from the sunlight and converted to cholicalciferol which migrates into the bloodsream. It is then converted in the liver to 25-OH-cholicalciferal and stored ( can be measured in plasma). PTH then increases the enzyme 1-aplha hydroxylase activity which is released from the tubular epithelium in the kidney. It converts 1-25 dihydroxy vitamin D3/calcitrol.
77
What is Rickets?
A chronic deficincy of vitamin D or Ca/Phosphorus leads to distubrances in bone development. Seen in children.
In adults, osteomalacia is seen.
78
What is primary Hyperparathyroidism?
PT gland secretes too much PTH that could be due to an adenoma. Causes High PTH and high Ca with a lower phosphorous. Increased Alkaline phosphatase which states bone is being turned over. Elevated Urinary Ca excretion. Treatment is remove nodule. Severe back pain and blood in urine.
Secondary: low Ca due to another factor such as renal failure, low D).
Pseudohypoparathyroidism: Genetic defect in G protein in PTH receptor in kidney.
79
What is Humoral Hypercalcemia of Malignancy?
Past history of lung cancer. The lung tumor cells release PTH related peptide which causes an increase in Ca release and bone resorption. High Ca is seen but a low PTH seen due to a negative feedback. Alkaline phosphatase elevated due to increase bone turnover. Normal albumin reassures us that the high total Ca is actually due to elevated ionized Ca.
80
What is an osteoid?
It is a mineralizing layer between osteoblast and the mineralized matrix that is a measure of the state of health of skeleton and the availability of Ca and PO4.
81
How is bone remodeled and turned over?
Trabecular bones and the spinal vertebrae are more subject to bone turnover due to the larger surface area to volume ratio in the trabecular bone. It is dissolved by osteoclats which are large multi nucleated cells (derived from monocyte) which secrete acidic molcules and dissolve the minerals. Proteases digest and phagocytize the collagen matrix.
RANKL from osteoblasts (stimulated by PTH, Vit D, Paracrine factors and Growth factors) activate ostoeclasts RANK and precursors.
OPG (osteoprotegrin) binds to Rank L and inhibits its activation : slowing down bone resorption.
Rate of bone remodeling controlled by OPG/RANK L ration.
82
What are regulators of bone remodelling?
```
PTH and Vit D increase resorption.
Estrogen decreases resoprtion
Calcitonin ( inhibitor of ostoclasts in kids)
Glucocorticoids: Inhibits Ca absorption
GH: stimulate fomration.
```
Mechanical Loading: bone mass is maintained and distributed in adults. Increase bone loading tends to stimulate bone formation and repair. Osteocyte and canaliculae most sensitive to response to mechanical loading, reducing the expression of sclerostin ( inhibitor of bone formation).
83
What is Graves Disease?
Also called thyrotoxicosis and is the most common form of hyperthyroidism. Patients have an elevated BMR, tacycardia, sweating, heat intolerance, nervousness, muscle wasting and weakness. Exophthalmos ( caused by antibodies). Onycholysis ( nail detachment). Patient develop toxic goiter/ Thyroid stimulating immunoglobulins (LATS) are present in circulation and cause the hypertrophy of thyrocytes resulting in the goiter. Increased T3/T4 causes decreased TSH release but the immunoglobulins continue to stimulate secretion of high amounts of TH.
84
Difference between Primary and Secondary Hyperthyroidism?
Primary: There is a defect in the thyroid gland causing high T3/4 but low TSH and TRH due to strong negative feedback.
Secondary: Defect in the anterior pituitary which secretes high TSH and causes high T4 and T3 but low TRH from hypothalamus.
85
What happens when you see patients who are taking thyroid extracts?
It directly up regulates T4 production in the plasma without affecting the thyroid. Therefore a small thyroid is seen and the high T4 has a strong negative feedback. Causing a low TSH.
86
Difference between primary and secondary hypothyroidism
Primary: Defect in he thyroid gland producind low T3/4 and therefore High TSH and TRH seen.
Secondary: Defect in the anterior pituitaty which cause a low TSH and a low T3/4. It causes high TRH due to low negative feedback.
87
What is Hashimoto thyroisitis?
Autoimmune disorder of antibodies against thyroid oxidase which destroys the gland ( antithyroid antibodies). Leads to increase TSH due to negative feedback. Treated with tyroxine.
88
Dietary iodine deficiency?
Leads to hypothyroidism and goiter. TH deficinecy is also called myxedema and a coma could occur in end stage untreated hypothyroidism.
89
Describe the ovarian cycle in three phases?
Follucular phase: occurs when FSH stimulates development of xfollicles until one follicle becomes dominant due to more FSH receptors. Estradiol rises.
Ovulatory phase: Estrogen begins to be secreted at higher level until the follicle matures, causing an increase in estrogen, positive feedback and LH surge. Rupture of Graafian follicle occurs.
Luteal phase: LH converts the ruptured follicle to a corpus luteum and progesterone begins to be secreted. Corpus albicans develops if fertilization does not occur.
90
What is the Graafian Follicle and what does it contain?
A Graafian follicle is a mature follicle. It contains Theca cells on the periphery and Granulosa cells centrally.
91
Name the three phases seen in the endometrial thickness in the ovarian cycle?
Proliferative phase: The endometrium thickness increases from 1-2 mm to 8-10 mm which is promoted by estradiol
Secretory phase ( luteal phase): Uterus becomes secretory due to progesterone secretion. Has a fixed length of 14 days. Progesterone promotes accumulation of glycogen, increased glandular secretions and vascularity.
Menstrual phase: prostaglandin mediated vasoconstriction of spiral arteries and local ischemic injury. Corpus luteum regression.
92
How does positive and negative feedback regulate the ovarian cycle?
During the late follicular and ovulatory phase. The hypothalamus initially secretes LH to the Theca cells which produce androgens to the Granulosa cells. FSH is then secreted to the Granulosa cells to secrete estrogen. Low levels of estrogen have a negative feedback until high estradiol occurs due to mature follicle. This causes a positive feedback and a LH surge.
In the luteal phase, the granulosa cell secretes progestins and estrogens and inhibins. The progesterone is also secreted by theta and has a negative feedback on hypothalamus and pituitary. The inhibins only inhibit FSH in the pituitary.
Activins and inhibins only act on the anterior pituitary. Progestin and estrogens act of both pituitary and hypothal ( negative feedback).
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What happens in the late follicular phase that causes the level of estrogen to cause a positive instead of a negative feedback?
High levels of estradiol enhances the sensitivity of the gonadotrophs in the pituitary due to increase in receptors. GnRH pulses remain the same strength and frequency.
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Where is FSH and LH secreted from?
Gonadotrophs from the anterior pituitary. LH affects Theca cells and FSH affects granulosa cells.
LH binds to theca cells and stimulates biosynthesis of progestins and androgens. Androgens enter granulosa cells where they are converted to estrogen.
The granulosa also has LH receptors that become active during the luteal phase.
FSH and LH are alphabeta dimers. The alpha subunits are identical but the B subunit determines specificity.
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How is Gonadotropin secretion regulated?
Binding of GnRH to a G protein linked receptor activates PLC pathway and releases Ca causing an increase in intracellular Ca. The IP3 and DAG pathway is activated which stimulates PKC which phosphorylates targets that indirectly upregulates gene transcription of FSH and LH.
The increase in Ca triggers exocytosis and release of the synthezied Gonadotropins.
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How is Estrogen and progesterone made?
They are derived from cholesterol. Aromatase is only found in the Granuloma cells and is used to create estrogen but needs androgens as a precursors.
In the follicular phase, LH primes the theca cells to convert cholesterol to androstenedione androgens, it diffuses to the granulosa which uses aromatase ( stimulates by FSH) to make estradiol.
In the luteal phase, LDL is available to theca cells since it is highly vascularized and LH makes it able to make progesterone. After the corpus luteum is open to vascular, LDL can also be taken up by the granulosa cells and progesterone can be made also.
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What are steroid hormone response elements?
Activated steroid hormones bind to these stretches of DNA and stimulate gene transcription. During the follicular phase estrogens induce endometial growth, stimulation of bone growth by inhibiting osteoclasts, increase fat deposition in subcutaneous tissues. Proliferation and development of mucosal lining of the fallopian tubes.
Progesterone in the luteal phase induces genes that converts the uterus to a secretory type (enhancing differentiation of epithelial and stromal cells). Decreases frequency and intensity of uterine contractions and increase fallopian tube secretions.
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How are gonadotropins inhibited before puberty?
The hypothalamus before puberty does not produce pulses of GnRH until puberty when it starts at night as pulsatile and continues during the day. The production of steroid hormones promotes the development of secondary sexual characteristics.
In childhood, low levels of estrogen are sufficient to fully suppress gonadotropin output, in adolescence, higher levels of estrogens are required and in adults estrogen must be high to suppress gonadotropin release.
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What happens during menopause?
Stop producing sex steroids due to no remaining ovarian follicles. No negative feedback causes a rise in gonadotropins. FSH has the most dramatic rise ( due to loss of inhibins) compared to LH.
Hot flashes, atrophy of the vaginal epithelieum, nigh sweats, mood changes, short term memory, loss of libido.
People with more adipose tissue have a less effect seen during menopause due to the pheripheral conversion from the adrenal gland to estrone. Providing postmenopausal source of estrogen
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What is the acrosome reaction?
Sperm weaves past follicular cells and binds to the zona pellucida. A rise in Ca inside the sperm triggers exocytosis of the acrosome which contains hydrolytic enzymes. It is triggered by the sperm binding to one of the three glycoproteins present on the zona pellucida. Sperm head then moves to oocyte
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What is the cortical reaction?
One the sperm releases its content into the oocyte. There is a second rise in Ca inside the egg. Triggers exocytosis of cortical vesicles that hardens the zona pellucida, preventing the entry of other sperms. Ca also causes completion of the second meiotic division of the oocyte. Second polar body is expelled.
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How is a zygote formed?
The sperm swells once it has enter the oocyte and becomes male pronucleus. The male and female pronuclei fuse to form the zygote
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What is the time course of fertilization and implantation?
7/6 days delay so that the uterus can develop for implantation because after LH surge it takes a couple days for progesterone to be secreted by the corpus luteum to change the uterus to the secretory phase. HCG is secreted by the blastocysts once implanted.
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How does the Corpus Luteum stay stable after the LH surge decreases?
HCG is produced by the syncytiotrophoblasts by the blastocysts. It sustains the corpus luteum by increasing sex steroid production. Immunosuppresive agent, promotes placental develoment and stimulates the tests of the male fetus to produce testosterone.
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What takes over the corpus luteum?
The placenta around 10 weeks. It secretes estrogen and progesterone. Progesterone needs to be higher because it keeps the uterine quiescent and without progesterone the uterine can contract and have an abortion.
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How the fetus nourished before the placenta?
Endometrial decidua
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Three important hormones secreted by the placenta?
Steroid hormones, HCG and Somatomammotropins ( Breast development and supports fetal metabolism).
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What is used to measure the health of the placenta?
Estriol ( E3). All other estrogen and progesterone are secreted by the placenta around 8-10 weeks of gestation.
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What is the maternal-fetal-placental unit?
The placenta lacks the enzyme needed for synthesis of estrone and estradiol and also a third enzyme needed for synthesis of estriol(17 aplha hydroxylase and 17,20 desmolase, 16 alpha hydroxylase). Mother provides loads of LDL for progesterone synthesis.
The fetus lacks 3 beta hydroxysteroid dehydrogenase and aromatase. Fetal adrenal gland and liver supply the three enzymes that the placenta lacks and forms estrogen that moves to the placenta. It lacks the final step that catalyzes the final step of estrogen synthesis.
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What is the Maternal Response to Pregnancy?
1) Increased blood volume ( meet demands of enlarged uterus and store for possible hemmorage)
2) MAP decreases during midpregnancy and rises during the third trimester. Low BP
3) Increase CO primarily in the 1st trimester
4) Increase alveolar ventilation due to increase pCo2 from baby ( goes from 40 - 46).
5) Increase demand for dietary protein/ iron and folic acid
6) Uterus and breast increase in size
7) BMR increases and weight gain ( 25-35) lbs.
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How is parturition initiated?
Might be due to an increase in cortisol near tern which increases the estrogen to progesterone ration and stats uterus contractions.
Prostaglandins initiate contractions and they are sustained by oxytocin and more prostaglandins. During pregnancy, estrogen increases the number of oxytocin receptors on myometrial tissue.
Relaxin is produced by corpus luteum and helps to soften/dilate the cervix.
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What can help with expelling the placenta?
Feeding the baby after delivery which increases oxytocin and increases muscle contractions to help expel the placenta.
Pitocin is an analougue of oxytocin and is used to induce labor.
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What does oxytocin and prolactin do?
Oxytocin causes uterine contraction and promotes milk let down.
Prolactin promotes milk synthesis
Both released in response to suckling.
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What cant you produce milk while pregnant?
Because estrogens and progesterone inhibit prolactin during pregnancy. There is the growth of the breast but no active milk production. After birth of the placenta, prolactin stimulates milk production.
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What is an alveolus?
It is the functional secretory unit of the breast an the lobular and alveolar systems are needed for milk production. Drains into ductules.
Myoepithelial cells surround each alveolus and adipose cells and promote milke let down in response to oxytocin.
Secretory epothelial cells comprise of alveolus and secrete milk in response to prolactin and permissive hormones.
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Mammogenic, Lactogenic, Galactokinetic, Galatopoietic
Mammogenic: Promote cell proliferation ( progesterone)
Lactogenic: Promote initiation of milk production (prolactin)
Galactokinetic - promote milk ejection/let down (oxytocin)
Galactopoietic - maintain milk production (prolactin)
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Sucking causes inhibition and increased stimulation of what hormones?
1) It inhibits Dopamine since Dopamines usually travels via the portal system to inhibit prolactin release. Causes increase of prolactin release.
2) Release of oxytocin from the posterior pituitary
3) Inhibition of GnRH which stimulates LH and FSH. Therefore inhibition of GnRH also inhibits LH and FSH and inhibits the ovarian cycle in lactating females.
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What are the four unique shunts present in fetal circulation?
Umbilical vein: Gad exchange occurs in the placenta and highly oxygenated blood goes to the umbilical vein
Ductus venosus: Bypassing the liver to the IVC via this duct. The blood becomes mixed as it enters the right atrium.
Foramen ovale: In the R Atrium the pressure is very high and 40% blood moves into the L atrium via this ovale. Blood pools fro SVC,IVC and Coronary Vessels into RA.
Ductus arteriosus: bypasses the lung from R Ventricle into the descending aorta due to increase Pulmonary vascular resistance.
Both L/R ventricle pump into the descending aorta and their output is parallel rather than in series.
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What is the first breathe by the fetus triggered by?
Loss of placental circulation requires newborn to breathe on its own. Triggered by mild hypoxia, hypercapnia,tactile stimuli and cold skin.
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What happens to pulmonary vascular resistance and the shunts after birth?
Pulmonary vascular resistance drops due to the inspired air into the lungs. Allowing blood to flow through and increasing P02 causing vasodilation. Local prostaglandins cause vaodilation.
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Four essential functions of placenta:
Lungs: Gas Exchange, GI: Nutrition, Liver: nutrition and waste removal, Kidney: fluid and electrolyte balance, waste removal.
Placenta insufficiency causes type 2 intrauterine growth restriction. Baby growth affected.
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Where does gas exchange occur in the placenta?
Mature chorionic villus ( covered with syncytiotrophoblast). Spiral arteries from the mother enter directly into the intervillous space which is over the MCV.
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Why is the fetal HB saturation 50% higher than the mother?
In the umbilical vein the heart in the fetus beats twice as fast as the mother. Fetal Hb has a high 02 affinity due to the gamma chains. Ensure Sufficient O2 supply to fetus.
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What happens with the placental ciruclation when it is removed after birth?
There is no more flow into the umbilical vein which causes less pressure into R atrium an decreases the pressure. The lungs expand and reduce the pulmonary arterial pressure that backed up into the R A which now causes decrease in RA pressure.
The L pressure increases due to backflow from the placenta ( umbilical artery). Lung inflation allows a large amount of blood to enter the LA therefor increasing its pressure.
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How does the foramen ovale close?
Due to the reversal of right and left atrial pressure. Seal forms fossa ovalis and if it does not close it causes patent foramen ovale.
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How does the ductus venosus close?
It forces the portal blood to perfuse the liver. Reduced prostaglandins from the placenta and increase 02 causes vasocontriction of the vessels forming the ligamentum venosum. 1-3 hours.
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How does the ductus arteriosus close?
Increase in P02 and decrease in circulating prostaglandin cause constriction. Bradykinin from the lungs causes contraction.
Ductus Arteriosus stays open due to:
Circulating prostaglandins are 5x that of adults because of placenta keeps it open. Lower level of P02 maintains it open. Lungs have high resistance due to hypoxic vasoconstriction and therefore blood is shunted through ductus arteriosus.
Adult circulation is obtained when this closes.
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What is Persistent Fetal Circulation?
Seen when you deliver babies at a higher altitude where the P02 is low. Hypoxia causes vasoconstriction and increase resistance in the lungs which doesnt allow the ductus arteriosus to close. Endometesin is used to treat this since it inhibits prostaglandin synthesis.
Also called Patent Ductus Arteriosus: Difficulty breathing, feeding poor, HR and sweating elevated. Weight is low. Endocarditis.
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Coarctation of the aorta is?
Smooth muscles of the ductus arteriosus invade the descending aorta and constricts the following birth since the SM of the ductus arteriosis constrict in respond to High O2 levels. High BP in regions perfused by the aorta above constriction.
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Ventricular Septal Defects are?
Most common of birth defects due to a hole in wall between ventricle. Small ones usually close on its own which large one can cause congestive heart failure.
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Atrial Septal Defects?
Hole large enough for movement from L and R atria, leading to volume overload in the R heart. Can lead to pulmonary hypertension, R heart enlargement and heart failure.
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Tetralogy of fallot is?
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Pulmonary Stenosis ( improper pulmonary valve development) causing hypertrophy of the RV wall. Dextroposition of the aorta so it is located more on the Right. Ventricular septal defect.
Blue Baby syndrome.
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Why is there an increase in FSH seen in menopause?
Due to the lack of inhibin secreted due to the lack of graffian follicle proliferation seen in menopause.
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What is hypothalamic amenorrhea?
Pituitary hypothalamic GnRH secretion is diminished by weight loss, exercise and stress. No LH,FSH and no ovulation seen. There would be an increase in FSH and LH release after injection of exogenous GnRH
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What is Polycystic ovary syndrome/
No dominant follicle emerges and ovulation does not occur. There is a decrease in estrogen seen due to no dominant follicle and a decrease in progesterone due to corpus luteum. There is an increase in androgen from the theca cells since granulosa cells are not using them. Androgens causes hair and acne. High LH will be seen.
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What is endometriosis?
Endometrial tissue gets into peritoneal space causes pelvic pain with menses
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What is ectopic pregnancy?
Pregnancy worse if found in the interstitial area ( since that is where all the vasculature comes into the uterus).
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What causes Male Sexual Development?
SRY gene encodes the testis determining factor (TDF). Gonads become testes and germ cells develop into spermatogonia.
The hormones produced by the gonads determine phenotypic sex: accessory organs, external genetalia (DHT) and secondary sex characteristics.
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How does an XX male occur?
Translocation of SRY gene onto the X chromosome from a sperm. Normal testes never are produced.
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How is the testes differentiated?
When the gonad is indifference it is closely associated with mesonephros and excretory ducts(wolffian and mesonephric duct) that lead to the uritogenital sinus.
Androgens produced by the Leydig cells promote Wolffian differentiation and prostate development (DHT).
mesonephros: epididymis
Wolffian duct: vas deferens, seminal vesicles and ejaculatory duct. Requires testosterone.
Mullerian ducts degenrate.
External genetalia requires DHT.
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During Puberty what happens to the hypothalamus?
Secretes pulsatile GnRH which causes LH and FSH pulsatile release which induce Leydig cells to produce testes. Testes have a negative feedback on the hypothalamus which is less sensitive than before puberty.
Constant supply of GnRH downregulates receptors and fails to induce LH and FSH secretion. This is used to treat prostate cancer to lower testosterone production.
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What happens to the Leydig Cells before puberty?
Make up more that half the testes by 60 days of gestation. It increases due to maternal chorionic gonadotropin. Hypothalamus and pituitary is very sensitive to negative feedback by androgens.
Spermatogonia exist in diploid, undifferentiated form in basal component of testes
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What does GnRH stimulate in males?
| KNOW
LH and FSH from the anterior pituitary. FSH stimulate the Sertoli cells which produce inhibins that work on the anterior pituitary. LH acts on the Leydig cells that produce testosterone. Testosterone also activates the sertoli cells and has a negative feedback on both the anterior pit and hypothalamus.
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How do the Leydig and Sertoli Cells work?
Leydig Cells respond to LH which has Gs coupled receptors. Activating cAMP and PKA. It stimulates the rate limiting step of cholesterol to pregnenolone increases cholesterol transport proteins to increase testosterone production.
Sertoli Cells: respond to FSH and have similar signaling pathway. It increases androgen binding protein transcription which keeps local testosterone high (for sperm production). Increase in P450 aromatase to produce estradiol from the testosterone that comes in via leydig cells. Growth factors that support sperm production.
Leydig cells produce inhibins/B endorphins that inhibit sertoli cell proliferation. Sertoli cells generate growth factors to increase LH receptors on Leydig.
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What is kallman Syndrome?
Caused by mutations in KAL 1,FGFR1,PROK2, PROKR2 due to failure in GnRH cell migration and development.
These patients lack FSH and LH and have congenital anosmia ( inability to smell). Both GnRH and olfactory receptors develop in the olfactory epithelium. The GnRH cells migrate along extended axons into the brain and hypothalamus. The mutations prevent the neurosensory neurons from extending their axons into the brain and prevent migration of GnRH neurons into the hypothalamus. Treatment include hormone replacement therapy.
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How are androgens synthesized?
Cholesterol is converted to pregnenolone by desmolase ( P450 cleavage enzyme).
Testosterone produces DHT from 5 alpha reductase ( 95% produced in testes)
Testosterone with aromatase produces estradiol
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What is male pseudohermaphoroditism?
defect in male androgen production. Could be due to five alpha reductase deficiency which makes DHT. DHT levels are reduced and testosterone levels are ok. No prostate or external genetalia developed.
Adrogen receptors are absent or defective with regular DHT and testosterone levels. Appears female.
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What are the androgenic effects on the body?
1) Promote protein synthesis and muscle bulking, muscle strenght.
2) Increase bone density and strength
3) Development of voice, beard, axillary hair.
4) larger organs
5) increases erythropoeitin expression on the kidneys leading to higher hematocrit in men
Estrogen has a dominant effect on long bone growth and maturation. This is why girls have growth spurts sooner and quicker.
Only 2% of testosterone is free and this is biologically active form. the rest is bound to albumin and sex hormone binding globulin.
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What is Kennedys Disease/Spinobulbar Muscular Atrophy?
Mutation in the androgen receptor causes CAG triple repeat and expansion of androgen receptor. Toxic gain of function that leads to nerve cell loss. Weakness of Tongue, mouth mucles and progressive weakness of the limbs.
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What can high testosterone cause and what is Finasteride?
Testoserone can worsen sleep apnea, severe benign prostatic hypertrophy, CHF and high RBC erythrocytosis. Significant hair loss.
Hair loss can be treated with finasteride (propecia) which blocks production of DHT.
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What does anabolic steroid abuse cause?
Reduced sperm count, shrinkage of testicles since testsosterone is needed 200 fold or higher in testes for sperm production. permanent liver damage, heart liver.
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When does spermatogenesis occur?
it is initiated by the Sertoli Cells via FSH. They then move to the rete testis and epididymis it takes 70 days to mature.
Seminal plasmid contains sugar and ions and are derived from seminal vesicles ( fructose), prostate gland and bulboutethral glands. Semen is only 20% sperm.
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Nervous System Control on Male Reproductive System?
Sympathetic: Responsible for emission and ejaculation and maintains detumescence ( flacidity). Reaches the genetials via the inferior mesenteric, hypogastric and pelvic plexuses and hypogastric and cavernous nerves.
Parasym: Responsible for corporeal vasodilation and corporeal smooth muscle relaxation leadin to tumescence/erection.
Somatic: Fibers travel via the pudenal nerve. contributes to tumescence.
Sensory: activates spinal cord circuits that lead to automonic reflexes and CNS involvement.
Blood supply primarily from pudendal artery.
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How does an erection occur?
Parasym: increases Acetyclcholine which causes the endothelial cells to increase NO and vasodilation of arteries. NO causes smooth muscles to relax. and increases intracellular cGMP.
Increase blood flow into cavernosal spaces and venous outflow drops as the tunica albuginea presses on the veins.
Viagra inhibits phosphodiesterase type 5 which inhibits cGMP. Therefor cGMP remains high and so does vasodilation
155
How does ejaculation occur?
sympathetic stimulation of hypogastric causes contraction of SM of distal epidydmis, vas defens and accessory glands. internal sphincter of bladder prevents retrograde flow of sperm. Semen is propelled into prostatic urethra.
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How does cortisol exhert a feedback on the hypothalamus/pituitary axis?
Cortisol exerts a negative feedback on both the release of CRH and ACTH. Cortisol inhibits POMC genes and inhibits releases of ACTH in anterior pituitary. Hypthalamus: cortisol decreases CRH levels.
