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39 Cards in this Set
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- Back
- 3rd side (hint)
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Where is calcium stored in the body? How much is stored? How does it get there/leave?
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-calcium is stored both in bone and extracellular fluid
-about 1 kg of calcium stored in bone -more mobile store in the ECF: plasma and soft tissue -calcium enters pool through GI tract and leaves through the kidneys. |
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Hormones that control calcium metabolism
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Hormones:
1. Vitamin D 2. Parathyroid hormone 3. Calcitonin -also note that FGF-23 is important in controlling phosphate metabolism |
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What organs are involved in maintaining normal calcium metabolism?
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-parathryoid glands
-skin -liver -kidney -small intestine -bone |
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The role of vitamin D is to __. What does it do? What does it act on?
The stimulus for synthesis of vitamin D is ___. |
The role of vitamin D is to increase plasma calcium (whole body action).
-Essential for serum calcium homeostasis -Excess or deficiency is associated with disease states -Exerts effects directly on the gastrointestinal tract -NO direct action on kidneys or bones The stimulus for synthesis of vitamin D is lowering of calcium level. -Synthesized sequentially in the skin, liver, and kidneys |
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What is synthesis of vitamin D in the skin dependent on?
What affects your ability to make vitamin D? |
If you expose your arms and face to sun for about 10-15 min, you make about 200 IU of vitamin D
-Ability to synthesize vitamin D depends on a. Age (skin inefficient at over age 70 years) b. Length of sun exposure c. Strength of sun exposure (latitude) d. ethnicity is also a factor – some skin types less able to make vitamin D -Here is the US where we change from dark to light at 37* latitude - above 37* latitude its difficult to make vitamin D in the winter time -below this latitude can make vitamin D in the skin year round look at graph on right shows vitamin D concentrations v months of the year. -Vitamin d levels in these individuals fall as you get to winter time, go up in summer, fall again in winter *amount you can make in skin is affected by season |
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Dietary sources of vitamin D
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Dietary vitamin D is absorbed in the intestine
-Few foods contain vitamin D -Exception is fatty fish, fish oils, (dairy products, eggs) -Vitamin D (D2 or D3) fortified foods include milk, cereals, grains, dairy products |
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Vitamin D supplements
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-another way we can get vitamin D in our diet is through supplements
-vitamin d2 is an animal product that we use as a supplement -vitamin d3 -both are good sources of vitamin d -both are activated in liver and kidney to make activated vitamin d |
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How is vitamin D stored?
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- 25 hydroxyvitamin is the “storage form” of vitamin D. All the vitamin D you take in is converted to this
- Production of 25 hydroxyvitamin D is substrate-dependent and not hormonally regulated (enyzme = liver 25 hydroxylase) |
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What is the regulated step in active vitamin D synthesis?
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Conversion to 1,25 vitamin D by 1-alpha hydroxylase is an ACTIVELY REGULATED STEP
-1-alpha hydroxylase is stimulated by factors associated with low 25 hydroxyvitamin D and low calcium levels! -Enzyme Stimulated by: 1. Increased PTH 2. Low phosphate |
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Vitamin D synthesis (pathway time!)
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Starting with cholesterol like structure in skin --> vitamin d in liver --> 25 hydroxyvitamin d --> active vitamin d in kidney (1,25 dihydroxyvitamin d)
1. In skin need UV radiation. Converts 7- dehydrocholestrol into Vitamin d Once the vitamin d is made in the skin its absorbed into the circulation -Dermal synthesis is major source -Synthesis is dependent on ultraviolet light -Synthesized non-enzymatically from 7-dehydro-cholesterol -Casual daily sun exposure of arms and face provides about 200 IU per day -Ability to synthesize vitamin D depends on a. Age (skin inefficient at over age 70 years) b. Length of sun exposure c. Strength of sun exposure (latitude) d. ethnicity is also a factor – some skin types less able to make vitamin D -Can also take in vitamin D through foods from the diet or supplements (D2, D3) 2. Once you have vitamin d either made in skin or taken in by the diet (foods or supplements), the next step is to convert it in the liver to 25- hydroxyvitamin d3 - both vitamin d and 25-hydroxyvitamin d3 are INERT. Neither of these are the active hormone - Production of 25 hydroxyvitamin D is substrate-dependent and not hormonally regulated - 25 hydroxyvitamin is the “storage form” of vitamin D. All the vitamin D you take in is converted to this 3. Conversion to 1,25 vitamin D by 1-alpha hydroxylase is an ACTIVELY REGULATED STEP -1-alpha hydroxylase is stimulated by factors associated with low 25 hydroxyvitamin D and low calcium levels -Enzyme Stimulated by a. Increased PTH b. Low phosphate |
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Actions of vitamin D on the bone?
What does vitamin D deficiency cause? |
Despite the fact that vitamin d has no direct action on bone, it is still very important for bone health
Vitamin D deficiency causes: a. Decreased bone density b. Osteomalacia |
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Actions of vitamin D on the kidneys?
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-No direct action on kidney
-Vitamin D deficiency is associated with renal phosphate wasting because you get a compensated increase of PTH levels --> renal phosphate wasting |
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Actions of vitamin D on the gastrointestinal tract?
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-in the GI tract, vitamin D increases the absorption of calcium and improves the absorption of phosphate but to a lesser extent than calcium
-the way it acts in the intestine is basically it will stimulate intestinal calcium transport by inducing a number of proteins. A couple of steps within the intestinal cell where vitamin D will improve calcium transport: 1. There is a calcium transporter in the microvillus of the intestine. This is stimulated by vitamin D. 2. There is another calcium binding protein that is also stimulated by vitamin D. 3. Once calcium is in the cells it is actively transported into the blood stream and this step is also stimulated by vitamin D. |
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What is the relationship between PTH and Vitamin D ?
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-as vitamin d levels go down you tend to have an increase in PTH
- this is because both of these hormones are trying to defend your serum calcium levels - the PTH tries to compensate as the vitamin D levels go down |
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What is the role of PTH? What is the stimulus for its release? Where is it synthesized
What does it exert its effects on? |
Whole body role: increase plasma calcium
-Essential for calcium homeostasis Stimulus for release: decreased plasma calcium - Excess or deficiency associated with disease states - Synthesized in the parathyroid glands located in the neck -Exerts effects directly on the skeleton and kidneys -->Recall Vit d has direct effect on intestines ** Acts directly on bone Acts directly on kidney Acts indirectly on gastrointestinal tract |
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How is PTH secretion regulated?
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-PTH secreted by exocytosis in response to hypocalcemia
-->Signal is change in extracellular Ca++ -->Transmitted through a Ca++ sensing receptor -->Receptor present on parathyroid cell membrane -this is the calcium sensing receptor on the parathyroid cell -the amount of calcium that affects this receptor is going to control the level of PTH -not much calcium binding to this receptor, PTH levels will increase -a lot of calcium binding to this receptor, PTH levels will go down. |
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Relationship between calcium levels and PTH
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-as serum calcium goes down, PTH levels then increase
-steep change in range of normal calcium levels -parallel curves different set points for relationship between calcium and PTH |
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Relationship between calcium and vitamin d?
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-As vitamin d levels go down there is a bit of fall in calcium, but curve is not steep because as vitamin d levels fall, PTH levels rise and keep calcium up
-without PTH would see much steeper relationship here |
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What are the effects of PTH on the bone?
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-Increases bone resorption by stimulating activity of osteoclasts
-->Osteoclasts are cells that break down bone and release calcium -May be PTH receptors on osteoclasts -PTH also increases other factors which then stimulate osteoclast activity |
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What are the effects of PTH on the kidney?
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*decreases secretion of calcium, increases excretion of phosphate, stimulates 1-alpha hydroxylase
-increases renal absorption of calcium so less calcium is excreted in the urine, more is absorbed and that maintains serum calcium levels -also increases excretion of phosphate -other important action of PTH is that is stimulates enzyme (1-alpha hydroxylase) that converts 25 hydroxyvitamin d -> 1,25 hydroxyvitamin d |
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What are the effects of PTH on the gastrointestinal tract?
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*Indirect action only
-PTH stimulates production of 1, 25-dihydroxyvitamin D (active form) -Vitamin D then increases absorption of calcium, and to lesser extent absorption of phosphate |
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List 4 calcium disorders:
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1. Hyperparathyroidism
2. Vitamin D toxicity 3. Hypoparathyroidism 4. Vitamin D deficiency |
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Describe
a. serum calcium levels b. serum phosphate levels c. Vitamin D levels d. Serum PTH levels for Hyperparathyroidism |
hyperparathyroidism
-someone making too much PTH -high PTH levels mobilize calcium from bone, high serum calcium causes phosphate excretion so you have low phosphate -25- hydroxyvitamin D is normal BUT PTH stimulates the conversion of 25-hydroxyvitamin D-->1,25-dihydroxyvitamin D by 1-alpha hydroxylase so you get high levels of activated vitamin d because of high PTH |
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Describe
a. serum calcium levels b. serum phosphate levels c. Vitamin D levels d. Serum PTH levels for Vitamin D toxicity |
vitamin d toxicity
-Someone is taking too much Vitamin d (high 25-hydroxyvitamin D) -this causes a high serum calcium level, also high PO4 absorption -PTH goes down because you have a high serum phosphate level. -Because PTH is low, the formation of 1,25-dihydroxyvitamin D from 25-hydroxyvitamin D is DOWNREGULATED since you don’t have PTH to stimulate this conversion. -This prevents you forming high 1,25-dihydroxyvitamin d levels |
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Describe
a. serum calcium levels b. serum phosphate levels c. Vitamin D levels d. Serum PTH levels for Hypoparathyroidism |
hypoparathyroidism
-condition where you don’t have enough PTH so you can’t mobilize calcium from bones -low serum calcium, need PTH to secrete phosphate so you have high serum phosphate level -vitamin d levels normal but need PTH to stimulate enzyme, so you have low 1,25-dihydroxyvitamin d levels |
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Describe
a. serum calcium levels b. serum phosphate levels c. Vitamin D levels d. Serum PTH levels for Vitamin D Deficiency |
Vitamin D deficiency:
- low serum calcium -low phosphorus (not absorbing) -PTH tries to compensate stimulates conversion from 25-hydroxyvitamin d --> 1,25-dihydroxyvitamin d by stimulating 1-alpha hydroxylase |
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Signs and symptoms of hypocalcemia
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1. Neuromuscular manifestations: mild
-Circumoral numbness -Numbness around mouth -Paresthesias hands and feet (Numbness, tingling in hands and feet) -Muscle cramps 2. Neuromuscular manifestations: severe -QT prolongation (Changes in EKG) -Chvostek’s sign, Carpopedal spasm (Manifestations of neuromuscular iritability) -Laryngospasm (and Difficult breathing) -Tetany -Focal or generalized seizures Chvostek's sign: -This is outline of facial nerve: lip nose eye -get irritability of nerves and muscle -elicit sign by tapping nerve by lips and get twitching of mouth, nose, eye, get sign of hypocalcemia Carpopedal spasm -pump up blood pressure cuff and maintain at slightly high pressure to induce spasm of hand -this is more historical not used as much now -there are some genetic disorders where people have low PTH and calcium levels and they spontaneously develop carpopedal spasm |
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Symptoms of hypercalcemia
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-Fatigue
-Weakness -Polydipsia (excessive thirst) -Polyuria (excessive urination) -Nocturia (the need to get up in the night to urinate) -Constipation -Depression -Headache -Memory loss -Arthralgias (joint pain) -Myalgias (muscle pain) -Anorexia -Nausea -Heartburn -Vomiting |
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Signs of Hypercalcemia
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1. Hypercalcuria
-->Huge problem leads to kidney stone formation 2. Nephrolithiasis (kidney stones) 3. Nephrocalcinosis -->Deposition of calcium in the kidney get renal insufficiency 4. Hematuria (from passage of stone) 5. Renal insufficiency ***If due to excess PTH a. Decreased bone density b. Fracture |
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Effects of vitamin D deficiency
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-Hypocalcemia
-Hypophosphatemia -Myopathy a.Weakness b. Muscle pain -Secondary hyperparathyroidism a. Compensatory increase in PTH levels -Inadequate bone mineralization a. Osteomalacia (softening of bones) b. Osteoporosis (low bone density) c. Rickets |
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Rickets
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-During childhood poor vitamin D
-bone is soft and not formed properly -uncommon in this country now -In early 1900s moving from rural areas --> cities people were not getting sun exposure and there was an epidemic of rickets |
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Osteomalecia
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-osteomalacia is SOFTENING of the bones
-Look at bone in vitamin d deficiency see area called osteoid where bone is trying to form normally but it cant because there is not enough calcium -normal bone in top , some ostoid formation occurring but then have excess osteoid formation in osteomalacia |
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Effects of excess vitamin D
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1. Hypercalcemia
-Confusion -Polydipsia -Polyuria -Anorexia -Vomiting 2. Hypercalciuria -Nephrolithiasis (kidney stone) -Renal calcinosis (calcinosis = calcium deposition) -Renal insufficiency 3. Hyperphosphatemia 4. Inhibition of PTH secretion |
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Effects of hypoparathyroidism
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1. Hypocalcemia
-Paresthesias -Muscle spasm -Tetany -Laryngospasm -Seizures 2. Hyperphosphatemia -->PTH responsible for allowing phosphate excretion in the kidney |
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Effects of hyperparathyroidism
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1. Hypercalcemia
-Confusion -Anorexia -Nausea, vomiting -Polydipsia (excessive thirst) -Muscle weakness 2. Hypophosphatemia 3. Osteoporosis 4. Nephrolithiasis (kidney stones) |
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Patient:
-65 year old nun with intolerance of dairy products -presents to her primary care physician complaining of a.Fatigue b. Painful muscles c. Extreme weakness d. Pain with movement Why is the PTH high? Why is the 1,25 hydroxyvitamin D normal? |
1. Look at 25-hydroxyvitamin d -- this is the storage form. Very low.
Calcium is low, cant absorb it from diet phosphate low for same reason then have 2ndary hyperthyroidism, up high, converting 25-hydroxyvitamin d to 1,25-dihydroxyvitamin d and maintaining its levels within normal range Why is the PTH high? -Vitamin d deficiency causing low calcium levels Why is the 1,25 hydroxyvitamin D normal? PTH is helping enzyme (1-alpha hydroxylase) convert 25-hydroxyvitamin d --> 1,25-dihydroxyvitamin d Source of problem is inadequate vitamin d causing low calcium level the parathyroid glands are kicking in Getting increased PTH, that’s going to try and mobilize calcium from the bone at the same time this high PTH level is going to act in the kidney to convert all the 25-hydroxyvitamin d available to 1,25-dihydroxyvitamin d Treatment? |
Treatment:
-Because vitamin d stores are so low you would need to load with very large doses of vitamin D |
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Patient:
60 year patient who is receiving treatment for osteoporosis mistakenly takes 50,000 IU D3 daily instead of weekly and develops a. Constipation, anorexia, nausea b. Anxiety, depression c. Polyuria, polydipsia Why is the PTH low? Why is the 1,25 hydroxyvitamin D not high? |
-Note 25 –hydroxyvitamin d levels are very high because she’s taking it too frequently. As a result, she has high serum calcium and high phosphate level at same time
-PTH has responded to the situation so it drops way down -1,25-hydroxyvitamin d is at the high end of the normal range but not significantly above --> this is because PTH helps to stimulate enzyme (1-alpha hydroxylase) that converts 25-hydroxyvitamin d --> 1,25-dihydroxyvitamin d and its not stimulating that step -not all the 25-hydroxyvitamin d is being converted to 1,25-dihydroxyvitamin d helps protect against hypercalcemia High vitamin d --> high serum calcium --> shut off PTH production --> little PTH, so there is not as much conversion of 25-hydroxyvitamin d --> 1,25-dihydroxyvitamin d Why is the PTH low? -->Feedback from high calcium Why is the 1,25 hydroxyvitamin D not high? -->Low PTH protecting against excessive levels of 1,25-dihydroxyvitamin d Treatment??? |
Treatment
1. Hydration --> patient dehydrated because of high serum calcium levels 2. Withhold vitamin D |
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Patient:
-22 year old patient underwent an eventful thyroidectomy and was discharged home. She then developed the following symptoms for which she presented to the emergency department a. Tingling in her hands and lips b. Cramping in her hands and feet c. Sensation of difficulty breathing d. Feeling of anxiety and impending doom Why is the 1,25 hydroxyvitamin D low despite a normal 25 hydroxyvitamin D? Why is the phosphate high? |
Low PTH, calcium is low, has normal 25-hydroxyvitamin d but low 1,25-dihydroxyvitamin d
Why is the 1,25 hydroxyvitamin D low despite a normal 25 hydroxyvitamin D? -->PTH deficiency! -->Not enough PTH being secreted, low PTH levels, no PTH to stimulate enzyme (1-alpha hydroxylase) even though 25-hydroxyvitamin d levels are normal you’re not getting much formation of 1,25-dihydroxyvitamin d, so that’s why 1,25-dihydroxyvitamin d is low (lack of PTH) Why is the phosphate high? -->phosphate is high because normally the PTH allows you to secrete phosphorus but in its absence you cant secrete it Why has this patient developed PTH deficiency? Treatment? |
Why has this patient developed PTH deficiency?
-->If glands get damaged during thyroid surgery or accidentally removed patient can develop severe hypocalcemia Treatment? --> A. Emergent - intravenous calcium -IV calcium push over minutes -IV calcium infusion over 6-12 hrs -Use IV if severe hypocalcemia associated with muscle cramps, tetany, EKG abnormalities, or mental status changes B. Long term therapy -requires calcium and 1,25 hydroxyvitamin D (alternative: calcium and PTH --> Don’t normally give PTH because it needs to be given by injection) |
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Patient:
65 year old female referred for hypercalcemia Complains of fatigue, confusion, and polyuria Previously hospitalized because of elevated serum calcium (14 mg/dl) Why is the phosphate low? Why is the 1,25 dihydroxyvitamin D high despite a normal 25 hydroxy-vitamin D? |
Problem?
-Shes making too much PTH -calcium being mobilized from bone, high calcium level -secreting lots of phosphate because of PTH effect on kidney -normal vitamin D but because of all the PTH converting all the 25-hydroxyvitamin d --> 1,25-dihydroxyvitamin d so there is a slightly high level. Why is the phosphate low? -->PTH stimulates phosphate excretion Why is the 1,25 dihydroxyvitamin D high despite a normal 25 hydroxy-vitamin D? -->High PTH mobilizing calcium from bone --> high serum calcium --> PTH stimulates conversion of 25-hydroxyvitamin d --> 1,25-dihydroxyvitamin d by 1-alpha hydroxylase What is the treatment? |
Surgical removal of over-active parathyroid gland!
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