Flashcards in Calcium Metabolism Deck (36):
4 ways parathyroid hormone (PTH) increases serum calcium?
1) Increases bone resorption (activates osteoclasts).
2) Production of Active form of Vitamin D (adds 2 hydroxy groups)
3) Increased kidney reabsorption of Ca++.
4) Increased gut absorption of Ca++ (by calcitriol)
Mnemonic for hyperparathyroidism (hyper-PTH) effects?
What significant problem isn't included in this mnemonic?
Bones, groans (GI stuff), stones, and psychic moans.
There is also kidney dysfunction (increase in urinary phosphate), and increased BP
Most common etiology of primary hyper-PTH?
Less common causes?
Solitary adenoma - 85%
Diffuse hyperplasia - 15%
Parathyroid carcinoma - <1% - really rare.
What happens to phosphate in hyper-PTH?
More is absorbed from bone, but even more is excreted in the kidney.
Net result: decreased serum phosphate (with decreased ECF phosphate).
2 GI effects of hyper-PTH?
1) Constipation, GI distress
2) Stomach ulcers, pancreatitis
What are the "psychic moans" of hyper-PTH?
Can cause depression and/or psychosis, fatigue and malaise.
Stones of hyper-PTH?
Kidney stones - from increased Ca++ in urine.
What's the term for the pattern of bone demineralization seen in hyper-PTH? What 3 bone findings define it?
Osteitis fibrosa cystica.
1) Generalized demineralization of bone
2) Subperiosteal bone resorption
3) Bone cysts
What type of bone does hyper-PTH most effect? (What's a good place to x-ray... or DXA??... that has a lot of this type of bone?)
Mostly affects cortical bone.
(the distal radius is often looked at - femoral neck too. Not vertebrae.)
How do most patients with hyper-PTH present?
With high Ca++ in screening bloodwork. They're often caught before they're symptomatic.
When would you do surgery on an asymptomatic patient with hyper-PTH? (there are 4 criteria)
When younger than 50.
Reduced creatinine clearance (impaired kidney function).
(also want to make sure it's not Familial Hypocalciuric Hypercalcemia)
- Only need to meet 1 of these criteria to go to surgery
Parathyroid adenoma looks histologically like...
increased cellularity... making lots of PTH.
- Clustering of cells--> can lead to atrophy of the parathyroid glands
3 causes of secondary hyper-PTH?
It's all about decreased Ca++ due to...
1) Renal insufficiency.
2) Calcium malabsorption.
3) Vitamin D deficiency.
What is tertiary hyper-PTH?
Starts off as secondary PTH, but then some of the parathyroid becomes autonomous -> primary PTH.
What is Familial Hypocalciuric Hypercalcemia (FHH)? Sequelae?
There's a mutation in the calcium sensor such that the set-point for PTH is shifted: PTH is secreted at a higher level of Ca++, so serum Ca++ stays higher than normal.
It's a completely benign condition.
They have LOW URINE CALCIUM
DON"T SEND THEM TO SURGERY
Where is the mutated Ca++ sensor in FHH? Why does this matter?
In both the parathyroid and the kidney.
It matters that it's in the kidney because excess Ca++ is NOT excreted into the urine because the kidney doesn't think Ca++ is high.
Ca++ is kept at a higher set point both at the level of PTH and resorption in the kidney.
How do you differentiate primary hyper-PTH from FHH?
In primary hyper-PTH, urine Ca++ will be elevated (also causing kidney stones).
In FHH, urine Ca++ will be normal (low)
3 types of causes of hypoparathyroidism (hypo-PTH)?
1) Post-surgery following total thyroidectomy
2) Infiltrative disease.
2 infiltrative diseases that cause hypo-PTH?
Hemochromatosis, Wilson's disease.
2 congenital cause of hypo-PTH?
1) DiGeorge syndrome.
2) Autosomal recessive autoimmune polyglandular syndrome Type 1.
2 signs of hypocalcemia?
1) Cardiac arrhythmias.
2) Neuromuscular irritability. (paresthesias, tingling, tetany)
2 tetany signs associated with hypocalcemia? What is each?
Chvostek's sign: tapping angle of jaw cause muscles innervated by the facial nerve to twitch.
Trousseau's sign: carpal spasm (wrist flexion in response to prolonged brachial a. occlusion)
Tx for hypo-PTH?
Replace the downstream effects of PTH:
Give Vitamin D.
What is the target calcium level for a patient with hypo-PTH? Why?
You're not replacing PTH's effect on kidney to reabsorb Ca++, so lots will spill into urine, and you don't want to cause kidney stones.
How can someone give his or herself prolonged hypercalcemia accompanied by nausea, vomiting, weakness, and altered mental status?
Taking too much Vitamin D (>10,000 IU/d).
Why does Vitamin D toxicity last so long?
Because it's Vit D is fat soluble.
4 etiologies of Vitamin D deficiency?
1) Not enough sunlight.
2) Not enough intake / absorption.
3) Defects in metabolic activation of Vit D.
4) GI disease (Celiac, Crohn's)
(Fun fact: Lighter-pigmented skin is thought to have evolved when early humans migrated north out of Africa to latitudes with less direct sun exposure in order to better make Vit D.)
What's the weird rough measure for how much Vit D you make in response to UV radiation?
Minimum Erythema (or something) Dose (MED) = enough UV to make your skin just a little red.
1 MED -> 10,000 to 20,000 IU Vit D in 24 hours.
...and then calculate how much Vit D you made based on how much of your skin is red....
Not very useful.
2 disease of Vit D deficiency?
1) Rickets in kids.
2) Osteomalacia in adult
What is the role of Vitamin D in bone formation/health?
Mineralization of the osteoblasts--> lays down calcium
Classic presentation of Rickets?
Kids' legs bowed because they can't support weight.
Fraying of distal radius and ulna.
WIDENED OSTEOID SEAMS AND IMPAIRED MINERALIZATION
Characteristic symptoms of osteomalacia?
Diffuse bone pain and tenderness (in hips/pelvis)
Proximal muscle weakness.
WIDENED OSTEOID SEAMS AND IMPAIRED MINERALIZATION
What is the parathyroid sensitive to?
- Low Ca2+ levels--> works to increase serum Ca2+
- High Ca2+--> will shut down production of PTH (negative feedback loop)
Basic difference between primary and secondary hyperparathyroidism?
Primary: High PTH AND HIGH calcium
Secondary: LOW calcium--> High PTH (revved up to increase serum Ca2+)
- Secondary is NOT pathological (it's the appropriate response to low Ca2+)
How does vitamin D cause hypercalcemia?
It increases calcium absorption from the gut?