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MS2 Endocrine > 10/12- Diseases of Mineral Metabolism > Flashcards

10/12- Diseases of Mineral Metabolism Flashcards

1
Q

What are the 3 main bone minerals?

  • Hormones involved?
  • Organs involved?
A

Minerals:

  1. Ca
  2. Phosphate
  3. Mg

Hormones:

  1. PTH
  2. 1,25(OH)VitD3
    - Aka 1,25 dihydroxycholecalciferol
  3. Calcitonin

Organs:

  1. Intestine
  2. Kidney
  3. Bone
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2
Q

How is serum calcium distributed (what forms)

A

Non-diffusable

  • Globulin
  • Albumin (most)

DIffusable

  • Complexed
  • Ionized (free)
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3
Q

What form(s) of Ca is/are monitored and regulated by the body?

A

ONLY ionized Ca!

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4
Q

How are ionized Ca levels affected by acid-base status?

A

Acidosis -> Ca displaced form albumin -> increased ionized Ca

(alkalosis decreases iCa)

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5
Q

Serum Ca levels must be corrected for what?

A

Plasma protein changes

  • Hydration
  • Excess production/loss of protein (liver or kidney disease)

Corrected serum Ca for albumin: Serum Ca* + 0.8 (4 - albumin**)

*Serum Ca in mg/dL

**Albumin in g/dL

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6
Q

Correct the serum Ca for albumin of 2.5 and Serum Ca of 8.2

A

Corrected Ca = Serum Ca + 0.8 (4 - albumin)

Corrected Ca = 8.2 + 0.8 (4-2.5)

Corrected Ca = 9.4

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7
Q

What are the effects of PTH?

A

Increase serum Ca

  • Increase bone resorption
  • Increases renal production of calcitriol
  • Increase renal Ca reabsorption

Decrease serum PO4

  • Increases PO4 excretion
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8
Q

What are the effects of calcitonin?

  • Secreted by what cells/organ
A

Lower serum Ca (not very significant role)

  • Produced by parafollicular cells (C-cells) of thyroid
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9
Q

Describe the parathyroid glands

  • Number
  • Location
A

Usually 4/person

  • 5% have more, 5% have fewer

Found posterior to thyroid or in upper mediastinum

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10
Q

Describe the Ca sensing receptor?

  • Expressed by what cells
  • Mechanism (in parathyroid)
A

CaSR

  • Expressed by: parathyroid, kidney, bone marrow, osteoclasts, breast, C-cells, stomach gatrin cells

Mechanism:

  • GPCR (7 TM segments)
  • Ca binds receptor when levels are high
  • Stimulates PLC-beta -> IP3 -> high cytosolic Ca
  • Blocks secretion of PTH from parathyroid
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11
Q

What stimulates PTH secretion?

A
  • Low Calcium
  • High Phosphate
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12
Q

Describe Vitamin D synthesis

A
  • D3 generated in the skin (UV-B rays)
  • Diet (cholecalciferol/ergocolciferol)
  • Animals: fish oils, eggs, fortified milk/cereal
  • Plants (Vit D2- ergo)
  • D3 and D2 need to be metabolized into active hormones; this is regulated by PTH (1a-OHase activity)
  • Active Vit D works on intestine and bone
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13
Q

What are effects of active Vitamin D?

A

Increase Ca AND PO4 in ECF

  • Increase gut uptake of Ca and phosphate
  • Bone:
  • Increase osteoblast activity to increase matrix protein synthesis
  • Increase osteoclast activity (via OB release of OAFs) to increase Ca release
  • Increase renal reabsorption of Ca and phosphate
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14
Q

What can cause hypercalcemia?

A
  • Primary hyperparathyroidism (#1)
  • Malignancy (#2)
  • Small cell carcinoma (mostly squamous!)
  • Renal cell carcinoma
  • Breast
  • Multiple myeloma
  • Mets
  • Familial Hypercalcemic Hypocalcuria (AD)

Also:

  • Excess Vitamin A/D
  • Milk of magnesia (tums)
  • Immobilization
  • Infection (TB, coccidio, histo)
  • Sarcoid
  • Drugs
  • Renal failure (3’ hyperparathyroidism)
  • Thyrotoxicosis
  • Addison’s
  • Padget’s of bone (in conjunction w/ immobilization)
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15
Q

What drugs may cause hyeprcalcemia?

A
  • Thiazides
  • Theophylline
  • Lithium
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16
Q

What are the most common causes of primary hyperparathryoidism?

A
  1. Adenoma (90%)
    - Autonomous secretion of PTH by parathyroid adenoma
  2. Hyperplasia (7%)
    - Typically occurs in hereditary syndromes (MEN1 and MEN2a have component of this)
  3. Carcinoma (3%)
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17
Q

What will you see in labs with primary hyperparathryoidism?

A
  • High PTH
  • High Ca
  • Low phosphorus
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18
Q

What are the clinical manifestations of 1’ hyperparathryoidism?

A
  • Height loss
  • Osteitis fibrosa cystica
19
Q

What is Osteitis Fiborosa Cystica

  • Associated with what conditions
  • Histologically
  • Grossly
  • Radiologically
  • Clinically
  • Treatment
A
  • Associated with severe 1/2’ hyperparathyroidism
  • Increased numbers of osteoclasts and fibroblasts
  • Accumulation of “hemosiderin” in tumor gives them the name “brown tumors”

Radiologic findings:

  • Subperiosteal resorption
  • Bone cysts

Clinical:

  • Severe hypercalcemia
  • Bone pain

Treatment:

  • Surgical resection of parathyroid tumor
  • Causes rapid reversal of clinical findings!
20
Q

What is seen here?

A

Resorption of distal phalanx (symptom of 1’ hyperparathyroidism?)

21
Q

What is seen here?

A

Bone cysts in primary hyperparathyroidism

22
Q

What is secondary hyperparathyroidism

  • Causes
  • Labs
A

Causes:

  • Renal insufficiency:
  • Hyperphosphatemia
  • Hypocalcemia (due to decreased 1,25(OH)Vita D production)
  • Intestinal malabsorption
  • Hypocalcemia (from Vit D deficiency)

Labs:

  • High PTH
  • Low Ca
  • High (renal) or low (malabsorption) phosphorus
23
Q

What are consequences of 2’ HPT?

A

Osteitis fibrosa cystica

  • Cysts/nodules
  • Sub-periosteal resorption of bone
24
Q

What is teritary hyperparathyroidism?

  • Causes
  • Labs
  • Treatment
A

Causes

  • Autonomous PTH secretion
  • PTH gland hyperplasia

Labs:

  • High Ca
  • Variable phosphorus
  • High PTH

Treatment:

  • Parathyroidectomy
  • Calcimimetic (bind CaSR and suppress PTH)
25
Q

How is malignancy related to hypercalcemia (mechanisms, 4)?

A
  • PTH related protein (PTHrP) that mimics PTH (amino terminus binds normal PTH receptor)
  • Osteoclast activating factors (i.e. cytokines)
  • Osteolytic bone lesions (myeloma, breast carcinoma)
  • Ectopic production of calcitriol (lymphoma)
26
Q

What tumors produce PTHrP

  • Mechanism of action
  • Lab values
A

Solid tumors:

  • Squamous cell carcinomas (lung, esoph, H/N, skin, cervix)
  • Renal, bladder
  • Breast
  • Ovarian

Lymphoma due to HTLV-1

Action: mimics PTH

Labs:

  • Low PTH
  • High C
  • Low PO4
27
Q

What is the effect of an inactivating mutation of the CaSR?

In what condition(s) is this seen?

A

(Calcium sensing receptor)

  • Inactivating mutation -> failure of activation by calcium
  • Ca levels falsely perceived as low
  • PTH is still released (hyperparathyroidism)

This occurs in Familial Hypocalciuric Hypercalcemia

28
Q

Describe Familial Hypocalciuric Hypercalcemia

  • Distinct from 1’ hyperparathryoidism
  • Genetics
  • Mechanism
  • Symptoms
  • Diagnosis
  • Treatment
A
  • 1’ hyperparathryoidism typically has normal/high urine Ca, while it is low in FHH (FEca under 1%)
  • Autosomal dominant; heterozygous mutation (overall disease manifestation is less severe)
  • Increased “set point” for Ca-regulated PTH secretion (PTH released even when Ca not that low; CaSR is inactivated and PTH continues to be secreted even when Ca is high)
  • Symptoms: mild, asymptomatic, found incidentally on labs (PTH normal/high but serum Ca is not low)
  • FHx of hypercalcemia
  • No treatment needed
29
Q

What are signs/symptoms of hyperalcemia?

A

Bones, stones, moans, and groans

  • Bones: osteoporosis, fractures, osteitis fibrosa cystica, brown tumor of jaw, bone pain/arthralgias
  • Stones: nephrolithiasis, renal failure
  • Moans (abdominal): nausea, constipation, peptic ulcer disease, acute pancreatitis
  • Groans (psychiatric): altered mental status, lethargy, coma, psychosis, decreased concentration, depression

ALSO:

  • Band keratopathy (corneal calcification)
  • HTN, cardiac arrhythmia, shortened QT interval
30
Q

What is acute management of hypercalcemia?

A

1. Hydrate aggressively with IV saline

2. Loop diuretic (furosemide) after* adequate hydration

3. Decrease bone resorption

  • Bisphosphonates IV (pamidronate/zoledronate once)
  • Later onset (2-3d), but longer sustained duration of action
  • Calcitonin (4 to 8 IU/kg sc q12h)
  • Earlier onset (1/2-1d), but short duration of action (2-3d)

4. Glucocorticoids when indicated

  • Vit D intoxication, granulomatous diseases or hematologic malignancies mediated by Vit D

5. Gallium nitrate or plicamycin

  • For refractory hyperCa
  • Beware of toxicities (renal, bone marrow, hepatic)

6. Dialysis (against low Ca bath)

31
Q

Is QT long or short in hypercalcemia?

A

Short QT (Long QT in hypocalcemia)

32
Q

What are indications for surgery in 1’ hyperparathryoidism?

A

Symptomatic:

  • Nephrocalcinosis, nephrolithiasis, osteitis fibrosa cystica
  • Altered mental status

Asymptomatic:

  • Corrected serum Ca > 1 mg/dL above normal
  • Renal: Decreased Creatinine Clearance (CrCl under 60%)
  • 24 hr urinary calcium > 400 mg, increased stone risk or presence of nephrolithiasis or nephrocalcinosis by radiograph, ultrasound, or CT
  • Skeletal: T-score
33
Q

What are major/minor causes of hypocalcemia?

A

Major:

  • Vitamin D deficiency
  • Exhaustion of skeletal Ca stores with repeated pregnancies
  • Hypoparathryoidism (surgical, idiopathic)

Minor:

  • Pseudo-hypoparathyroidism-PTH resistance
  • “Hungry bones” following surgery for primary hyperparathyroidism
  • Activating mutation of CaSR**
  • Mg++ deficiency (severe)
  • Pancreatitis (chelation effect)
34
Q

Rickets and osteomalacia may result from what?

A

Hypocalcemia

35
Q

What is rickets? Osteomalacia?

  • Effects/observations
  • Causes
A

Rickets occurs in kids and osteomalacia in adults

  • Impaired mineralization of new bone matrix (osteoid)
  • Surfaces of cortex and trabeculae have thickened layer of unmineralized osteoid
  • Disorganized bone susceptible to deformity/fracture

Causes:

  • Inadequate exposure to sunlight
  • Culture
  • Latitude
  • Sunscreen (SPF 8)
  • Decreased dietary intake
  • Liver/kidney disease
  • Malabsorption
  • Genetic defects in Vit D receptor (resistance)
36
Q

What is seen in nutritional rickets (example)?

A
  • Cupping and fraying of distal metaphysis of radius and ulna
  • Gen varum (bowing of legs)
37
Q

What is seen here?

A

Rachitic rosary

  • Seen in hypocalcemia
38
Q

Difference between Vitamin D:

  • Deficiency
  • Insufficiency
A
  • Deficiency (under 20)
  • Insufficiency (under 30)
39
Q

What are clinical features of Osteomalacia?

A
  • Low serum calcium or phosphorus, or both
  • Key point: Low calcium X phosphorus product
  • Elevated level of serum alkaline phosphatase
  • Bone pain
  • Proximal muscle weakness
  • Deformity
  • Pseudofractures (“Looser’s Zone” or Milkman’s fractures):
  • Indicative of severe osteomalacia
  • Weak site predisposed to traumatic fracture
40
Q

What is seen here?

A

Looser’s zone (pseudofractures)

  • Seen in osteomalacia
41
Q

What are signs and symptoms of hypocalcemia?

A

Symptoms (Ca under 7 mg/dL)

  • Perioral, tongue and extremity paresthesias
  • Facial spasms
  • Myalgias
  • Muscle cramps (back, legs)

Signs:

  • Tetany
  • Carpopedal spasm
  • Chvostek’s sign
  • Trousseau’s sign
  • Arrhythmia
  • Prolonged QT interval
42
Q

What is Chvostek’s sign?

A

Neuromuscular irritability seen in hypocalcemia

  • Tap the facial nerve in front of the ear (below the zygomatic arch)
  • Positive sign is contraction of the ipsilateral facial muscles
43
Q

What is Trousseau’s sign?

A

Seen in hypocalcemia

  • Inflate BP cuff above systolic (10 mmHg) and hold; results in:
  • Carpal spasm
  • Muscular contraction at wrist and MCP joints
  • Hyperextension at fingers
  • Flexion of thumb
44
Q

How to treat acute/severe hypocalcemia?

A

1. Calcium - PO (“elemental”)

  • IV infusion

2. Normalize Mg

  • Will allow for normal PTH secretion

3. 1,25(OH)Vit-D3

  • Especially useful if hypoparathryoid
  • Calcitriol

4. Thiazide diuretic

  • Increases renal reabsorption of Ca
  • Include amiloride to avoid hypokalemia

MS2 Endocrine (25 decks)

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