Physiology Flashcards
<p>Difference Between Peptide and Steroid Hormones?</p>
<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>
<p>Thyroid Hormones T3/T4 are what kind of hormone and how do they act on target cells?</p>
<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>
<p>What is Hypoparathyroidism: </p>
<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>
<p>What is Pseudohypoparathyroidism:</p>
<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>
<p>What regulates the Adrenal Medulla?</p>
<p>SNS. Adrenal secretes NE and Epi in the Medulla of the Adrenal Gland.</p>
<p>Where is Growth hormone is produced and how is it regulated? </p>
<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>
<p>What does the Parathyroid Secrete?</p>
<p>It Secretes PTH which causes Increase in Ca and decrease in Phosphorus</p>
<p>When you have a meal high in protein, how does that affect
glucagon, insulin and growth hormone?</p>
<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>
T/F: Is GH chronically present in the plasma?
F : GH is Released in a cyclical fashion. Strenuous exercise to build muscle releases GH. Peaks at Midnight
What is the cellular origin of the Anterior/Posterior Pituitary?
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.
Types of Hormones Released in the Hypothalamus to the Anterior Pituitary:
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)
Types of Hormones Released in the Hypothalamus to the Posterior Pituitary:
AVP: AVP ( water permeability)
OT: Oxytocin ( Uterus and Breast)
Example of long loop negative feedback in males and females? Name a positive feedback example?
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.
Describe how prolactin is regulated?
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.
What happens to prolactin if the infundibular stalk is severed?
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.
What does Oxytocin do?
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.
What does ADH do?
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
What is Central Diabetes insipidus?
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).
What is Hypopituitarism?
Insufficiency of pituitary to release hormones or Insufficiency of hypothalamic releasing hormones. Caused by tumors, TBI, subarachnoid hemorrhage.
How is GH regulated?
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
Excess GH during puberty and after puberty results in which two clinical conditions?
During Puberty: Gigantism.
After Puberty: Acromegaly ( enlarged hands and feet and increased in tongue size).
How is GH expressed in the plasma?
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).
Name 8 factors that stimulate GH Secretion
Deep sleep, Exercise, Amino Acid, Hypoglycemia/Fasting, Sex steroids, Stress, alpha adrenergic agonists ( constrict blood vessels) and dopamine agonist ( suppress in acromegaly).
Name 7 factors that inhibit GH secretion
Obesity ( decreases GH pulses) GH IGF 1 Beta Adrenergic ( Dilate) Hyperglycemia Free Fatty Acids Glucocorticoids ( steroid hormones)
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).
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).
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.
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.
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.
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).
Difference between insulin, IGF 1 and 2.
Insulin cleaves peptide C where as it is not cleaved in IGF 1 or 2
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.
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.
What is Laron Syndrome?
GH receptor mutation causing low IGF 1 and normal/elevated GH hormone. Mild Growth Retardation. No acne/diabetes.
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.
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.
GH is approved for use in which GH deficiency diseases?
Prader Willi, Chronic renal insufficiency, small for gestational age.
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).
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.
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.
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.
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
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.
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)
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.
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.
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.
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.
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.
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
TH deficiency in infants results in?
Mental retardation( cretinism) and Growth Retardation
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.
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.
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)
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.
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)
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.
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
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.
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
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
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.
