Term
| A patient's Ca is measured as 7.0mg/dl. After treatment, his albumin increases 2g/dl. What's his new Ca level? |
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Definition
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Term
| What is most of Ca bound to? |
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Definition
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Term
| What %, where, and what regulates Ca abs? |
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Definition
| 99%, prox tubule along w/ Na, PTH dependent abs in the distal tubule |
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Term
| Where in GI tract is Ca abs? |
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Definition
| G.I. absorption is efficient, primarily in jejunum. Vitamin D regulated |
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Term
| 2 things that dec PTH and 1 thing that inc PTH sec |
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Definition
Major factor is plasma level of ionized calcium that bind to receptors on cheif cell membranes => PTH secretion is suppressed.
2) 1,25dOHVitD decreases the PTH secretory response to Ca
3) low phosphate => PTH secretion |
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Term
| 2 mechs by which Ca inhibits PTH |
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Definition
1) it goes through the PLC -> DAG -> PKC pathway to inhibit AC->cAMP
PLC also => IP3 to induce Ca release from ER
2) Ca enters directly and blocks PKA -> PTH |
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Term
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Definition
Decreases proximal tubular reabsorption of phosphate
Increases calcium reabsorption in the distal tubule
Increases 1-alpha hydroxylation of vitamin D
Effects are mediated through cAMP |
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Term
ACTIONS OF PTH ON BONE
breaking vs building? |
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Definition
Increases osteocytic and osteoclastic osteolysis, leads to increased release of Ca and PO4
Probably plays a role in bone remodeling
Intermittent administration increases trabecular bone density and reduces fracture risk |
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Term
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Definition
Promote absorption of Ca++
Effect is primarily mediated through increased levels of 1,25-dihydroxycholecalciferol |
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Term
| after administering PTH what happens to urine Ca and PO4 |
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Definition
Ca: dec and then inc
PO4: inc and then dc
due to changed serum levels => affects filtered load |
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Term
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Definition
7-dehydrocholesterol stored in skin in large amounts
7-dehydrocholesterol in skin is converted to vitamin D3 by UV light
Vitamin D2 added to milk, cereal, etc |
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Term
| stages of VitD hydroxylation |
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Definition
| skin (vitD), liver converts to 25OHVD, and kidney conv to 1,25 OH2 VitD which is the only thing that actuall y regulates GI tract |
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Term
| Pth and hypophosphatemia role in regulation of VitD hydroxylation/metabolism? is there negative feedback? |
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Definition
1 alpha-hydroxylase is the regulated step
Pth and hypophosphatemia both increase 1-alpha hydroxylase activity
1,25 dihydroxy D inhibits activity |
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Term
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Definition
Gut - stimulate calcium and phosphate absorption
Bone - in higher doses, stimulate resorption. Allows effect of Pth.
Parathyroid gland – suppress Pth secretion |
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Term
| CALCITONIN role in calcium metabolism? |
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Definition
no role in Ca metabolic disorders...
but it does inhibit osteoclastic activity
32 amino acid peptide produced in the C cells of the thyroid |
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Term
| therapeutic use of calcitonin? |
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Definition
| used therapeutically in hypercalcemia, Paget's disease, and osteoporosis |
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Term
| characteristic Ca level in PTH adenoma...what type of primary PTHism most common and if you have the other type what should you suspect? |
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Definition
elev calcium that post operatively gets markedly reduced and requires calcium infusions.
Common disorder occurs more commonly in women and in older individuals
Most commonly due to a single benign adenoma. Less often due to hyperplasia |
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Term
| Which symptoms are common to all patients with hypercalcemia and which is unique to primary hyperPTHism? |
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Definition
Most people are asymptomatic
THESE OCCUR IN HYPERCALCEMIA OF ANY CAUSE!!!
Bone changes only occur with high PTH though…
Renal - Kidney stones, hyposthenuria (inability to conc the urine), renal failure
Bone - Pain, pathologic fractures (frx without expected trauma)
GI - Anorexia, nausea, vomiting, constipation
Neurologic - Lethargy, weakness, depression |
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Term
| PRIMARY HYPERPARATHYROIDISM LABORATORY ABNORMALITIES |
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Definition
Increased calcium
Decreased phosphate
Increased alkaline phosphatase
Increased serum parathyroid hormone
Sometimes this dx has mostly all normal levels…
PTH sometimes inappropriately high…should be undetectable with normal levels of calc |
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Term
| Your patient has an inc serum calcium and PTH level, and normal urine Ca level. what should you exclude when making a dx of primary PTH before going in for surgery? |
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Definition
familial hypercalcinemia
make sure that urine Ca is NOT low.... |
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Term
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Definition
| Calcium receptor agonist therapy (cinacalcet) is available, but has not been approved for use in primary hyperparathyroidism |
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Term
| A patient with squamous cell carcinoma presents to you with a pathologic fracture. What should you be concerned about and what's the etiology of this? |
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Definition
PARATHYROID HORMONE RELATED PEPTIDE (PTHrP)
MOST common cause of hypercalcemia…
Diff from PTH but 8 of first 13 aas are the same…homology => 100% agonist though!
Some homology with PTH, binds to PTH receptors, and mimics all known actions of PTH
Levels are commonly elevated in patients with squamous cell carcinoma of lung and head and neck
Many other tumors may also overproduce PTHrP |
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Term
| Which cancers should alert you to CYTOKINE MEDIATED HYPERCALCEMIA |
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Definition
Occurs most commonly in patients with multiple myeloma and lymphoma
Breast cancer may activate both local and systemic mechanisms |
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Term
| What clinical course/symptoms do you expect to see in hypercalcemia of malignancies? |
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Definition
Because of the rapid onset, CNS and GI symptoms tend to predominate
With mild to moderate hypercalcemia, symptoms are similar to those of hyperparathyroidism
With severe hypercalcemia (>15 mg/dl) patients may develop obtundatation, disorientation, coma
Volume depletion is uniformly present and serves to worsen hypercalcemia |
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Term
| What bisphosphonates are good for treating severe hypercalc? Other therapies? |
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Definition
Hydration with saline
Intravenous Pamidronate or Zoledronic acid
Other therapies
Gallium nitrate
Calcitonin
Loop diuretics |
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Term
| A patient has read on the news that she should take lots of vit D so she's been loading up on pills as much as she can. Now she presents with nausea, vomiting, anorexia and constipation and dec mental status. In other patients with her presenting condition, what things should you be concerned about? |
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Definition
Granulomatous diseases
Lymphoma
Inadvertent VitD overdosage in hypoparathyroidism or renal failure |
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Term
| What's the mech of her dz? |
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Definition
Macrophages and lymphocytes have l-alpha hydroxylase activity
When there is a marked increase in macrophages, increased 1, 25 dihydroxy D is secreted
Modest overdosage causes no abnormalities.
Massive doses result in enough active vitamin D generation to cause increased calcium absorption.
When 1,25 dihydroxy D (calcitriol) is used in therapy, modest overdoses are more likely to cause abnormalities |
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Term
| What would her PTH levels be? |
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Definition
With moderate hyperabsorption of calcium, Pth levels are suppressed and hypercalciuria occurs, maintaining normal serum calcium
With severe hyperabsorption, renal excretory capacity is exceeded, and hypercalcemia ensues |
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Term
Which of the following are expected in Hypercalcemia?
Renal disease and stones
GI symptoms
CNS dysfunction
Bone disease
All of the above |
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Definition
| All except bone dz b/c only High PTH casuses this |
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Term
| HYPERVITAMINOSIS D TREATMENT |
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Definition
Treat granulomatous disease or remove vitamin D excess
Saline infusion to enhance calcium excretion
Glucocortioids to decrease GI calcium absorption |
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Term
| Positive Chvostek and Trousseau sign is assoc with what labs? |
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Definition
| Low Ca, high PO4, and high PTH |
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Term
| what could explain these lab values? |
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Definition
PSEUDOHYPOPARATHYROIDISM
Symptoms: increased neuromuscular irritability, twitching, tetany, convulsions
Laboratory abnormalities
Low serum calcium
High phosphate
If hypoparathyroidism, Pth is low
If pseudohypoparathyroidism (end organ resistance) Pth is high |
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Term
| Tx for HypoPTH or pseudohypoPTH? |
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Definition
| metadoses of VitD/Calcium |
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Term
Man with 15ft small intestine resection has pathologic fractures, but 8.6 Ca and low PO4 (1.2) and Hgb, carotene, chol all low. but alk phos is very high.
What's his PTH?
What do you expect to see on bone biopsy?
Dx? |
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Definition
| Serum 25 hydroxyvitamin D levels were unmeasurable. Bone biopsy showed increased osteoid seams (place in bone w/ collagen laid down but not mineralized. Vit D def px don’t have mineralization). |
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Term
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Definition
Inadequate intake and sunlight – even if u use too much sun screen!
Malabsorption – can’t get into the system
Severe liver disease
Renal failure |
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Term
| VITAMIN D DEFICIENCY PATHOGENESIS |
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Definition
Decreased absorption of calcium by the GI tract.
As serum calcium starts to fall, secondary hyperparathyroidism occurs.
Elevated Pth levels may maintain serum calcium in the normal range, but at the cost of phosphaturia, hypophosphatemia and increased bone reabsorption |
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Term
A patient who uses way too much sun screen all the time for fear of skin cancer comes in and is hypocalcemic...what's the problem?
What other things will you find? |
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Definition
In severe cases, secondary hyperparathyroidism is not adequate to maintain serum calcium levels, and hypocalcemia occurs (A LATE EVENT)
Bone pain and pathologic fractures
Decreased bone density
Hypophosphatemia, increase in alkaline phosphatase and serum PTH levels
Late hypocalcemia |
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Term
| VITAMIN D DEFICIENCY TREATMENT |
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Definition
Vitamin D replacement
Patients with renal failure need 1,25 dihydroxycholecalciferol b/c can’t convert precursors
Patients with malabsorption may need high doses |
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Term
| After 6 months of darkness in Alaska, what can you be expected to be low in? |
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Definition
During the past several years, routine measurements of 25-hydroxyvitamin D have been obtained by many physicians
Low levels of 25-hydroxy-D are exceptionally common, especially in places with limited sunlight. |
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Term
Renal failure predisposes you to what type of PTHism?
What Sx in the diabetic man with this? |
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Definition
secondaryhyperPTHism
Increased parathyroid hormone secretion in response to decreased plasma calcium level
Commonly occurs in renal failure and vitamin D deficiency
Serum calcium may be low or normal, prolonged PTH secretion may result in bone resorption
Sx:
He had weakness, anorexia, vomiting, dyspnea and pleuritic chest pain. He also complained of several months of diffuse bone pain. |
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Term
| SECONDARY HYPERPARATHYROIDISM TREATMENT |
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Definition
Treat underlying cause
Phosphate binders for renal failure
Calcitriol
Paracalcitol
Cinacalcet
Parathyroidectomy |
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