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74 Cards in this Set
- Front
- Back
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What roles does the Ca2+ ion play?
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-Essential structural component of the skeleton
-Normal blood clotting -helps maintain transmb potential with Na+ and K+ -Important in excitabililty of nervous tissue -release of H and NT |
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What is the [Ca2+] in cellular and extracellular fluid?
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10mg/100ml
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How does Ca2+ circulate the body?
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50% is free
50% is bound to albumin (major blood ptn) |
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Where is most of the body's calcium stored?
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99% is in the bone
-part of this Ca2+ is loosely bound --> Bone = Ca2+ reservoir |
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How is plasma Ca2+ lvl maintained?
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By exchange btw the bone and plasma under the influence of H
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What other organs do H affect Ca2+ lvls in?
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Absorption of Ca2+ in intestine
Excretion of Ca2+ in the kidneys |
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What are the 3 important H in Ca2+ lvls? What do they do?
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1) Parathyroid H (PTH): ptn produced by parathyroid glands.
->INC circulating lvls of Ca2+ 2) Calcitonin: ptn, produced by the parafollicular ("C") cells of the thyroid gland. -> Lowers Ca2+ lvls 3) Vitamin D: steroid ->INC circulating lvls of Ca2+ |
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How do we obtain Ca2+?
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In our diet: milk, cheese, eggs, butter...
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Where does Ca2+ absorption take place? What influences it?
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-Takes place in the duodenum and jejunum
-Inc absorption due to Vit D and PTH |
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What is the Ca2+ cycle in the plasma?
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-some Ca2+ is deposited in the bone or other tissue cells (calcitonin inc Ca2+ deposition in the bone)
-some Ca2+ goes through the kidney and is excreted in the urine' (calcitonin inc Ca2+ loss) -if [plasma] is less then 10mg/100ml, PTH stimulaes reabsorption of Ca2+ from kidneys and remove Ca2+ from bone (Bone Resorption) |
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What does calcitonin do?
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Inc deposition of Ca2+ in bone
Inc Ca2+ excretion in the urine |
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Which cells secrete PTH?
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Chief cells of the parathyroid gland
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What is the structure of PTH?
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-84 aa polypeptide
-only the N-terminal 34 aa are imp for full activity -Made as part of a larger ptn (prepro-PTH) which is proteolytically cleaved to make PTH -very short 1/2 lif: 3-18 min |
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Where ae the parathyroid glands located? How many are there?
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-On the backside of the thyroid gland
-4 |
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What are the fcts of PTH?
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Increase [Ca2+] in the plasma:
1)Bone Resorption: inc bone demineralization and inc in body fluids 2)Kidney:inc the reabsorption of Ca2+ in the poximal convulted tubules 3) Vit D activation: stimulates conversion of 25-hydroxyvitamin D3 to 1,25-dihydroxyvitamin D3 (active form of the vit) mainly in the kidney 4) Gut: PTH and 1,25D3 help absorption of Ca2+ from the gut |
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How is PTH release controlled?
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Directly by the circulating concentration of Ca2+
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What is the mechanism of PTH activity?
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-Binds to cognate receptor on target cell
- Stimulates adenylyl cyclase and increase the production of cyclic AMP -GPCR |
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What is the hypofct of parathyroid gland fct?
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Hypothyroidism: low lvls of PTH in circulation
Symptoms: -low plasma Ca2+ (Hypoalcemia) **-Prod'n of biologically active vit D is DEC -Tetany, convulsions ->Ca2+ <7mg/100ml: increased neural overexcitabiloty, muscle spasms, muscles contract spontaneuosly and don't relax -> spasms of laryngeal muscles can lead to asphyxiation Treatment: admin of vit D and Ca2+ supplements (expensive to make PTH .: use vit D) |
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What is the hyperfct of parathyroid gland fct?
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Hyperthyroidism: often caused by adenoma of parathyroid glands (1ry parathyroidism)
-High lvls of PTH **-High prod'n of 1,25-D3 -high PTH .: Bone resorption and Ca2+ reabsorption from the kidneys -1,25D3 inc Ca2+ absorption from the intestines -elevated Ca2+ in circulation -can have kidney stone formation (Ca2+ deposition) Severe cases: Cardiac arrythmias, depressed neuromuscula excitability, Ca2+ deposition on walls of bld vessels and cartilagenous regiokns of bones Treatment: surgery to remove parathyroids and prelacement therapy of 1,25D3 and Ca2+ |
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Why is vit D not really a vitamin?
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Can be synthesized from a cholesterol metabolite
(synthesis involves several tissues) |
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Where can vit D be found in our diet?
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Cod liver oil
Fatty fish |
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How is Vit D synthesized?
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1) UV light + 7-dehydydrocholesterol
2) 25-hydroxylation in liver 3) 1-hydoxylation in kidney and several peripheral tissues to get 1,25-dihydroxyvitamin D3 |
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What are the physiological fct of Vit D?
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**1) Primary fct: Inc Ca2+ absorption from the intestines
2) Regulates immune system: anti-inflammatory 3) Anticancer properties 4)Cardio protective |
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How is synthesis of Vit D in the kidney regulated?
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-Vit D inc in low Ca2+ (also when PTH is inc) (PTH stimulates conversion of enz to make vit D active)
-Depressed by high Ca2+ |
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How is Vit D related to geography?
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Farther north you go, more likely to have vit D deficiency, because of absence of UV
->Get deficient bone mineralization (more severe in dark-skinned people) --> Ricketts in growing ppl |
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How does renal failure affect vit D?
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Might have defective Vit D synthesis
-deficient in 1-hydroxylation |
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What happens when adults have low vit D?
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Osteomalacia (soft bone)
Insufficient Ca2+, weaker bones |
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What is Ricketts? Why do ppl get it?
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Ricketts: Deficiency in bone growth
Due to: 1-Nutritional: from diet or UV 2-Genetic: ->Lack of prod'n of hormonal 1,25D3 (treat with 1-hydroxy) ->No fct of Vit D receptor: can't give them 1,25D3: end up with baldness cuz only go through 1 hair cycle (this fct of vit D receptor has nothin todo with Vit D) |
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What is the structure of calcitonin? Where is it made? How does it act?
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32 aa Ca2+ lowering peptide hormone (requires all 32 aa)
-made by parafollicular (C) cells of thyroid gland -Lowers plasma Ca2+ by promoting the transfer of Ca2+ from blood to bone and incrasing the excretion of Ca2+ |
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How does plasma Ca2+ lvls influence calcitonin?
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-Inc in plasma Ca2+: inc calcitonin
-Dec in plasma Ca2+: dec cacitonin |
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Is calcitonin more or less important then PTH and Vit D?
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Less important
Absence of calcitoni does not compromise Ca2+ homeostasis in man (its biological importance must be limited) |
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What are some characteristics of the adrenal glands?
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-Locatded adjacent to the upper surface of kidneys
-Heavier (larger) in males -2 distinct types of tissue: Cortex and medulla |
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Compare histological appearance of cortex and medulla.
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Cortex: Large, lipid containing epithelial cells
Medulla: Chroffamin cells. Fine brown granules when fixed with potassium bichromate |
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What is the origin of the cortex and the medulla?
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Cortec: mesoderm
Medulla: Neural crest |
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Compare the fct of cortex and medulla.
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Cortex: Produces steroid H, glucocorticoids (cortisol), mineralocorticoids (aldosterone) and progestins
Medulla: Produces catecholamines nor/epinephrine and some peptide H enkephalins, dynorphins and atrial natriuretic peptides) |
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How many zones does the adrenal cortex have?
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3
each zone is morphologically different (zona glomerulosa): mostly mineralocorticoids (zona fasciculata): produces mostly glucocorticoids (zona reticularis): makes glucocorticoids, progestins androgens and estrogens |
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What does ACTH do?
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-Glucocorticoid secreting
-Pituitary H -controls activity of 2 zones |
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How is 18-hydroxylase synthesized?
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From aldosterone
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What happens under hyperplasia conditions?
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Can't get higher lvls of aldosterone and cortisol
There are genes that encode the enzymes required for the biosynthesis of this steroid |
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What are the molecular mechanisms of action of steroid hormones?
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Function to regulate (inc/dec) the transcription of hormone/receptor-specific target genes
**genes regulated vary with each target tissue and relate specifically to those fuctions regulated by each steroid hormone and the physiological function of the tissue |
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Why can steroid H pass through the PM?
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Looks like cholesterol
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What is an example of a mineralocorticoid?
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Aldosterone
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What does aldosterone do?
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Sodium metabolism: increases the reabsorption of Na+ by the kidney
->also affects the [plasma] of K+ and H+ (balance Na+ reabsorption by losing K+ and H+ in urine) |
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Where are glucocorticoids made?
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Humans: Cortisol
Rodents: Corticosterone |
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What are the 5 functions of glucocorticoids?
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1) Salt retention
2) Effects on protein and carbohydrate metabolism 3) Lipid metabolism 4) Anti-inflammatory and immunosuppresive actions of glucocorticoids 5)Effects of glucocorticoids on bone |
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How do glucocorticoids affect salt retention?
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Less effective than mineralocorticoids (aldosterone)
Can be important under pathological conditios when plasma cortisol remains elevated |
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What effects do glucocorticoids have on protein and carb metabolism?
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-Stimulate synthesis of gluconeohenic enzymes in hepatocytes and enzymes that breakdown proteins in muscle and other tissues (released aa go to liver where they can be made into glucose and glycogen)
-Decrease glucose uptake by the cells and decreased gycolysis (glucose oxidation) -Lead to increased blood glucose levels (inc insulin secretion) |
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Wht is adrenal diabetes?
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Increased blood glucose because of excess glucocorticoid activity
->Increased production of fuel |
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What happens if adrenal diabetes is prolonged?
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Can lead to teh destruction of beta-cells of pancreas
->Diabetes mellitus |
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What effect to glucocorticoids have on lipid metabolism?
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Maintain or increase the levels of lipolytic enzymes in adipose tissue cells
Increase lipolytic activity of other H (i.e. epinephrine) |
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What happens to lipid metabolism if there's excess glucocorticoids?
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Hyperlipidemia
Hypercholesterolemia |
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What are the anti-inflammatory and immunosuppressive actions of glucocorticoids?
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-Reduce inflammatory response (ex:at injury site)
-Cause atrophy of the lymphatic system (lymph nodes, thymus, spleen) -Decreased leves of circulating lymphocytes and reduced antibody formation (can use glucocorticoids to facilitate organ transplant) -Decrease histamine formation and .: decrease allergic reactions |
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What effects do glucocorticoid have on bone?
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Use protein catabolic effect to decrease the protein matrix of the bone
Increased loss of Ca2+ from the bone leading to osteoporosis (2,,3 and 5 go together: ptn/cab/lipid metab and effect on bone) |
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What is osteoporosis?
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Loss of protein matrix of the bone
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What controls glucocorticoid secretion?
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Pituitary adrenocorticotropin (ACTH)
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What is ACTH?
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39 aa polypeptide (made as part of a larger ptn: POMC, proopiomelancortin)
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What allows for feedback control of cortisol secretion?
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Hypothalamus
Anterior pituitary *In humans, only cortisol has this negative fdbk for ACTH release |
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What is congenital adrenal hyperplasia?
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Present at birth
Enzyme deficiency (11B-hydroxylase) ->Cortisol is not produced and ACTH secretion is unchecked (no negative feedback) |
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How are enzyme deficiencies for cortisol production treated?
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Administration of cortisol
-> Corrects the deficiency -> Normalizes the ACTH secretion |
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What is the mechanism of action of ACTH?
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-Binds to specific ACTH receptors
-Stimulates adenylyl cyclase -> make more cAMP -activates steroidogenic enzymes --> increased synthesis and release of steroid H |
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What is the daily rhythm of plasma cortisol and ACTH?
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**Diurnal rhythm of ACTH and cortisol secretion: minimu at midnight and max in the morning
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What happens to the diurnal rhythm in jet lag?
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It gets messed up
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What can bolish the diurnal rhythm?
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-Can be independent of sleep
->Stopped by stress and Crushing's disease |
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What effect does stress have on glucocorticoids?
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Induces glucocorticoid release
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What happens to glucocorticoids under stress stimuli (physical/physiologcal)?
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Increased synthesis and release of:
CRH ACTH Cortisol |
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What are some examples of stress?
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Pain
Fear Exercise Hunger Cold Hemorrhage |
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Why are the advantages of releasing cortisol under stressful conditions?
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Provides energy
Provides aa through the breakdown of tissue proteins ->Leads to fight or flight response |
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What is the main disadvantage to cortisol release under stressful conditions?
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Cortisol inhibits wound healing (immune response)
->Immunosuppressive and anti-inflammatory* |
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What would happen under conditions of prolonged stress?
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Constant high levels of glucocorticoids
Lead to increased blood glucose (true diabetes mellitus) Lead t decreased immune responses (more susceptible to infection) Loss of bone |
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What is Addison's Disease?
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Hypofunction
-Failure of the adrenal cortex to make adrenocorticoid H -May involve total detruction of the glands -Mostly due to atrophy of the adrenal glands due to tuberculosis and involves medulla and cortex |
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What is Cushing's disease?
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Hyperfunction
-Hyperplasia of adrenal cortex due to increased circulating levels of ACTH -Excessive production of glucocorticoids -Increased production of mineralocorticoids |
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What can happen to sex H in hyperplasia?
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Increased sex H and androgens
Masculinzation |
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What is the diagnosis of hyperplasia?
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Puffiness of face
Masculizing efect Hypertension Increased blod glucose Increased steroid metabolits in urine |
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What is the treatment for hyperplasia?
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Surgery:
Subatomal removal of the adrenal cortex |
