Nephrology - Calcium

Nephrology

[DISORDERS OF CALCIUM]

Introduction and Physiology Calcium is regulated by Calcitonin (“calci-tone-down”) and by parathyroid hormone. The main level of function is at the  parathyroid gland via PTH. Calcium’s detected by calcium sensing receptors on secretory cells of the parathyroid. Increased Calcium inhibits PTH release. Thus, decreased levels permit release. PTH has three effects: it 1) activates osteoclasts to clear bone, ! Ca and ! P  2) directly reabsorbs Ca and excretes P  in the kidney, and 3) indirectly absorbs Ca and P from the gut via Vitamin D. Calcium in the blood travels mostly as bound calcium (inactive) with a small proportion as ionized calcium. We measure total calcium routinely so it must  be adjusted for albumin levels and alkalotic states. For every one point of albumin below four correct the calcium by 0.8.

!Ca

CaSR PTH

PTH

i. 1o Hyperparathyroidism A single autonomous gland secretes PTH without effective feedback. Calcium is absorbed (! Ca) while Phos is lost ( "P). An additional bone finding is found here - fibrosa cystica (aka “brown tumor”) - from overstimulated osteoclasts creating large bone lesions. The treatment is resection. Use a radionucleotide scan to identify which gland is autonomous / hypertrophied. Monitor for signs of hypocalcemia after surgery (hungry bone syndrome ).

Albumin "1

= Calcium "0.8

! Ca ! P

! Ca " P

! Ca ! P

Pt has ! Ca Bones, Stones Groans, Moans  Present Treatment IVF, Calcitonin, Bisphosphonates, Furosemide Treatment IVF

Onset Rapid

Furosamide Calcitonin Bipshos phonates

Rapid Immediate Chronic

 Normal  Normal

 No

Recheck

 No

o

iii. 3  Hyperparathyroid If renal failure continues, eventually parathyroid glands  become autonomous -  just like in primary hyperparathyroidism. This is an autonomous gland in the presence of existing renal disease. Although resection is required, there’s no risk of cancer.

Stop

Diagnose PTH P Ca

Effect Dilutes Calcium, !Prerenal Excretion via diuresis !Diuresis = !Ca excretion. Use only after IVF Effect fades quickly, gets you through a crisis Puts the calcium back on bone, risk of jaw osteonecrosis, good for fractures only

 Adenoma with atrophied normal  glands

 After Resection, atrophied glands are unable to produce enough PTH 

Over Time  Recovery

o

ii. 2  Hyperparathyroid While we’re here let’s talk about some other PTH diseases. In early renal failure  Vit D isn’t made. This produces a hypocalcemia that then causes !PTH and parathyroid gland hypertrophy . PTH increases in order to maintain a normal calcium.

0.1% Free

Vit D

For every disease you’ll use the PTH, Ca, and P levels to make a diagnosis. 1) Hypercalcemia A high calcium may be nothing. If increased on ambulatory screening and asymptomatic, redraw it. Further investigation’s required if it’s still increased on the redraw or there are symptoms. Symptoms of hypercalcemia are: bones (fracture, osteopenia), stones (calcium Nephrolithiasis), abdominal groans (nausea vomiting, abdominal pain), and psychic moans (altered mental, severe hypercalcemia only, Calcium of 13-15). Diagnosis is less important if there are symptoms, so treat first. Intravenous Fluid is always the first line therapy. Furosemide is added to increase naturesis and calcium excretion, but only AFTER volume status is corrected (dehydration from early administration of furosemide is actually HARMFUL). If more aggressive therapy is required (because symptoms are severe), start Calcitonin (acts fast, fades fast) and Bisphosphonates (long term therapy).

99.9% Bound

1o Hyper PTH PTH

2oHyperPTH "Vit D

!!Ca, "P

"Ca !PTH PTH

!Ca "P

3oHyper PTH ! PTH !!PTH

PTH !!Ca, "P

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Nephrology

[DISORDERS OF CALCIUM]

iv. Familial Hypocalciuric Hypercalcemia Caused by an abnormal calcium sensing receptor, there’s a new “set point.” There’s an !Ca and !PTH, but the body is just maintaining its “normal.” They’re asymptomatic and require no treatment . There’s caution with stenotic aortic disease as they age. v. Malignancy Cancer can cause hypercalcemia. It can do it in two ways. Either metastasis goes to the bone and actively destroys it (releasing Ca and P) or a cancer can produce PTH-rp (parathyroid like hormone), turning the cancer into a 1 0  hyperparathyroidism but with a “low” blood PTH (our tests only captures the real PTH; special tests are required to measure levels of PTH-rp). Treat the cancer and the condition goes away.

2) Hypocalcemia Albumin  plays a bigger role in Hypocalcemia. Poor nutrition, cirrhosis, or nephrosis will cause a "  Albumin. Adjustment for albumin usually reveals a normal calcium. Potentially, checking for signs and symptoms is important as it could lead to catching a life-threatening emergency before it gets there. Look for perioral tingling (usually comes first) then signs of tetany (both Chvostek’s and Trousseau’s sign). Treatment is to replace the calcium. Use PO Calcium and Vitamin D for nonemergent , IV if emergent.

i. Hypoparathyroidism Typically iatrogenic , either from an “oops” Thyroidectomy or from a parathyroidectomy of an adenoma (hungry bone syndrome ) secondary to decreased PTH production of atrophied glands. ii. Vitamin D Deficiency Whether it’s from renal failure or sunlight / diet deprivation, having too little Vitamin D leads to secondary hyperparathyroidism. Initially, there’s decreased calcium. iii. Calcium Sequestration An acute condition that’s often in the setting of pancreatitis.

! Ca ! P

"PTH

! Ca " P

"PTH

Cancer Osteoclasts + Kidneys

PTH-rp

vi. Immobilization For some reason (we think it’s " impact stress) patients who are bed-ridden have an asymptomatic increase in calcium secondary to bone turn over. Get them out of bed and walking the condition will improve. vii. Vitamin D excess Granulomatous disease (Sarcoid, TB) can turn on Vitamin D independently of kidneys, which increases calcium, turning off PTH, resulting in P being unable to be renally excreted. Use steroids to treat the underlying disease.

Bone Destruction

Metastasis

Perioral Tingling Chvostek or Trousseau Asx Low Ca

Check Calcium

Critical

 Normal Check Albumin  Albumin Corrects Calcium Monitor 

PTH !!  !  " !!  ! " 

IV Calcium

 Albumin Ø Correct Treat PO Ca + Vit D

Ca

Emergency

Disease Hyperparathyroidism FHH Malignancy Mets Malignancy PTH-rp Immobilization Vit D Excess Pseudohypoparathyroidism Vit D Deficiency Chronic Renal Failure Pancreatitis

Hypoparathyroidism

PTH Phos Ca

Diagnosis

PO4  " " ! " ! ! ! " ! "

Path ! PTH = ! Ca ! PTH = ! Ca !Ca = " PTH !Ca = " PTH !Ca = " PTH !Ca = " PTH

"

" PTH = " Ca

“Ø PTH” " Ca = !PTH " Ca = !PTH " Ca = !PTH

iv. Pseudohypoparathyroidism An awfully named disease that means PTH-end organ resistance . There’s a high PTH but everything works normally. Ignore it.

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