Calcium Phosphate Flashcards
1. Describe the main actions of PTH and vitamin D in the maintenance of calcium and phosphorus homeostasis. 2. Define the following diseases/disorders to include the pathophysiology, epidemiology, risk factors (if any), clinical presentation, physical findings, diagnostic evaluation, differential diagnoses, and management plan. • Hyperparathyroidism and hypoparathyroidism • Paget disease • Osteoporosis 3. Discuss screening and treatment decisions in people with osteoporosis based on the F
1
Q
How much of serum calcium is bound to a protein?
A
45%
2
Q
What protein is calcium most commonly bound to?
A
Albumin
3
Q
Because albumin levels will alter the serum calcium levels, in order to measure ionized Calcium effectively, one must
A
Correct for Calcium
0.8 * (4.0 - Pt’s Albumin) + Serum Calcium
4
Q
Alkalosis is indicated by what in reference to calcium?
A
Increased binding to albumin
5
Q
Acidosis is indicated by what in reference to calcium?
A
Decreased binding to albumin
6
Q
Calcium is regulated by
A
Parathyroid Hormone (PTH)
Vitamin D
7
Q
Negative inhibition can be caused by acting what receptor?
A
Calcium Sensing Receptor (CaSR) to stop release of PTH
8
Q
Where are the Calcium Sensing Receptors?
A
Parathyroid Gland
9
Q
By inhibiting the release of PTH, what will happen in the kidneys?
A
Calcium will be excreted due to decreased Calcium reabsorption
10
Q
PTH does what to the kidneys?
A
- Increases Calcium Reabsorption
- Increases Phosphate Excretion
- Activates Vitamin D
11
Q
What triggers PTH release?
A
Low blood calcium detected by the Parathyroid
12
Q
Where are the parathyroids located?
A
Snake eyes on the thyroid gland (4)
13
Q
When PTH is released, it affects which two things directly?
A
- Bones
- Kidneys
14
Q
When Vitamin D is activated by the Kidney, it will affect what organ?
A
Small Intestine
15
Q
Vitamin D causes what to happen in the Small Intestine?
A
Increases absorption of calcium from the diet
16
Q
When PTH acts on the Bone, what does it do?
A
Stimulates osteoCLAST activity
– Bone is resorbed which releases calcium into the blood stream
17
Q
The overall affect of PTH release is to?
A
Increase Serum Calcium
18
Q
High levels of Calcium in the blood will do what to the thyroid gland?
A
Stimulate to release Calcitonin
19
Q
When Calcitonin is released from the thyroid (due to high Ca2+ levels in the blood), what happens?
A
Calcitonin will inhibit osteoclasts.
This will decrease blood Calcium levels.
20
Q
When there is a decreased Calcium level in the blood, this will stimulate what to do what?
A
Stimulate the Parathyroid Gland to release more PTH
21
Q
What in the parathyroid released PTH?
A
Chief cells
22
Q
What is the form of Vitamin D released from the kidneys by PTH activation that acts on the Small intestines to increase dietary calcium absorption?
A
Calcitriol
23
Q
Increased blood calcium can cause what to the bone?
A
Calcification
24
Q
Common Symptoms with Hypercalcemia
A
- Dehydration
- Anorexia/Weight Loss
- Pruritus
- Fatigue
- Weakness
- Hypotonia (low muscle tone)
- Myopathy (proximal)
- Mental status change
- Seizure/Coma
- Bradycardia
- Atrial or Ventricular Arrhythmia
- Nausea Vomiting Constipation
- Ileus
- Pancreatitis
- Dyspepsia
- Polyuria
- Nephrocalcinosis
25
Two broad causes of Hypercalcemia
1. PTH Dependent
2. PTH Independent
26
PTH Dependent causes of Hypercalcemia could be due to?
1. Primary Hyperparathyroidism (ademona, 4 gland hyperplasia)
2. Familial Hypocalciuric hypocalcemia
3. Tertiary Hyperparathyroidism
27
PTH Independent causes of Hypercalcemia could be due to?
1. Malignancy (direct bone invasion, PTH rp release, Increased 1,25 Vitamin D synthesis)
2. Vitamin D Intoxication
3. Medications (thiazides, Lithium)
4. Granulomatous Dz
5. Hyperthyroidism
6. Vitamin A intoxication
28
Granulomatous Diseases
TB
Fungal Diseases
Sarcoidosis
29
Granulomatous Diseases & Vitamin D Intoxication cause
Increased 1,25 Vitamin D, which causes increased absorption of Ca2+ from the intestines
30
Thiazides and Familial Hypocalcemic Hypercalcemia cause
Increased reabsorption of Ca2+ in the kidneys
31
Immobolization, Malignant Tumor, and Hyperthyroidism
Stimulated increased resorption of bone (osteoclast)
32
Hyperparathyroidism will cause increased PTH, which will stimulate
Increased resorption of bones (osteoclast)
Increased reabsorption of Ca2+ in kidneys
33
Causes of Primary Hyperparathyroidism
1. Single Adenoma (85%)
2. Hyperplasia (15%)
3. Carcinoma (<1%)
4. Multiple Endocrine Neoplasia (family hx!!!)
34
Causes of Secondary Hyperparathyroidism
1. Results from Hypocalcemia
2. Normal physiological response
35
Causes of Tertiary Hyperparathyroidism
1. Autonomous Production
2. Often Assc with Renal Diseases
36
Stones, Bones, Abdominal Groans, and Psychic Moans
Primary Hyperparathyroidism
37
Symptoms of Stones
Renal stones
Nephrocalcinosis
Polyuria
Polydyspia
Uremia
38
Symptoms of Bones
1. Osteitis fibrosa (subperiosteal resorption, osteoclastomas, bone cysts)
2. Radiologic Osteoporosis
3. Osteomalacia or rickets
4. Arthritis
39
Symptoms of Abdominal Groans
1. Constipation
2. Indigestion
3. Nause
4. Vomiting
5. Peptic Ulcer
6. Pancreatitis
40
Symptoms of Psychic Moans
1. Lethargy, Fatigue
2. Depression
3. Memory Loss
4. Psychoses-paranoia
5. Personality change - neuroses
6. Confusion
41
Other symptoms with Primary Hyperparathyroidism
1. Proximal muscle weakness
2. Keratitis/Conjunctivitis
3. Hypertension
4. Itching
42
Most common location for Bone Mass Density loss?
Lumbar Spine > Femoral Neck > Radiu
43
If you find hypercalcemia in a patient, you should first check?
PTH levels
44
67% of women with hyperparathyroidism experience what during pregnancy?
Exacerbated symptoms: pancreatitis, nephrolithiasis, hyperemesis, muscle weakness, cognitive changes, hypercalcemic crisis.
45
Are fetuses affected by hypercalcemia?
80% of fetuses DO! Includes fetal demise, preterm delivery, low birth weight, postpartum neonatal tetany, and permanent hypoparathyroidism
46
The hallmark of primary hyperparathyroidism is hypercalcemia, with the serum adjusted total calcium
as > 10.5 mg/dL
47
Patients with low bone density who have an elevated serum PTH but a normal serum calcium must be evaluated for
Causes of secondary hyperparathyroidism (e.g., vitamin D or calcium deficiency, hyperphosphatemia, renal failure).
48
In the absence of secondary hyperparathyroidism, patients with an elevated serum PTH but normal serum calcium are determined to have
Normocalcemic hyperparathyroidism
49
Normocalcemic hyperparathyroidism should be _____ because ______ can occur.
Monitored because hypercalcemia can occur.
50
Is imaging a useful technique in diagnosing hyperparathyroidism?
No, imaging is not useful for the diagnosis of hyperparathyroidism, which must be made by serum calcium and PTH determinations.
51
Imaging is useful for patients who have had previous neck surgery
Fun fact? Idk I'm tired.
52
DDx for Hyperparathyroidism
1. Artifact Finding (Lab error or medication alteration; Always repeat blood work)
2. Hypercalcemia due to Malignancy (Multiple Myeloma)
3. Sarcoidosis and Other Granulomatous Diseases
4. Calcium or Vit. D Ingestion
5. Familial Benign Hypocalciuric Hypercalcemia
6. Vitamin D Deficiency
7. Adrenal Insufficiency
8. Immobilization of Hypercalcemia
9. Other causes of Hypercalcemia
53
Treatment for Asymptomatic Primary Hyperparathryoidism
No therapy really needed
Stay active, avoid immobilization, and drink adequate fluids.
Avoid thiazide diuretics, large doses of Vit. A.
Post-menopausal women Hormone Therapy to rebuild bones
Monitor at least twice a year.
54
When is parathyroidectomy needed?
Parathyroidectomy is recommended for patients with symptomatic hyperparathyroidism, kidney stones, bone disease, and pregnancy.
55
Treatment of Severe Hypercalcemia
Treat Ca2+ > 14mg/dL
- IV hydration
- Diuresis with Lasix (with fluid overload)
- Calcitonin*/bisphosphonates*
- Calcimimetics* (inhibits PTH release)
- Dialysis?
- Glucocorticoids when indicated
*Calcitonin: IV or SQ osteoclast inhibitor/increases renal excretion of Ca2+ → rapid reduction in Ca2+ (4-6hr) but short-lived effect
*Bisphosphonates: IV, osteoclast inhibitors → Ca2+ reduction in 24-36hr w/ variable duration (dotn use in cretanin cleareance <30 – can disrupt renal function)
*Cinacalet: calcimimetic, increases sensitivity of CaSR to extracellular Ca2+
(for parathyroid cancer, 2* HPTH, non-surgical 1* HPTH with hypercalcemia)
56
What is a common cause of hypoparathyroidism?
Post-surgery
57
Low serum calcium
Hypocalcemia
58
Causes of Hypoparathyroidism
1. Post surgical
2. Autoimmune
3. Congenital
4. Familial
59
Causes of Hypocalcemia
1. Hypoparathyroidism
2. Infiltrative Dz (hemochromatosis, amyloidosis, Wilson's Dz)
3. Severe Mg deficiency
4. Hungry Bone Syndrome
5. Vitamin D Deficiency
6. Vitamin D Resistance
7. PTH Resistance
8. Acute Pancreatitis
etc etc.
60
What causes Pseudohypoparathyroidism?
1. Resistance to PTH action
2. Autosomal Dominant gene mutation of GNAS1 (alpha subunit of G protein)
3. G-protein becomes unable to activate downstream signaling and end organ response to PTH
*** Can get this from Maternal Transmission (biochemical and phenotypic: type 1A) or Paternal (phenotypes only)
61
What labs will we see in PTH resistant pseudohypoparathyroidism?
Elevated PTH level, because PTH is being created, but not being used on the receptors.
** This will also effect TSH, LH, FSH, and GH signaling
62
Most common type of pseudohypoparathyroidism?
Albright's hereditary osteodystrophy
63
Labs for Albright's Hereditary Osteodystrophy will show?
Increased PTH
Increased Phosphate
Low Calcium
Resistance to other G-protein coupled hormones
64
Symptoms of Albright's Hereditary Osteodystrophy
Short statue
Obesity
Round Face
Developmental Delay
Short metacarpals
65
Clinical Features of Hypocalcemia
Neuromuscular irritability
Paresthesias
Chvostek's Sign
Trousseau's Sign
Prolonged QT interval
Broncho, carpal or laryngeal spasm
Seizures
66
What is Chvostek's Sign? How do you test?
Ask patient to relax the face
Tap on the facial nerve and see if a twitch occurs on the lip (one extreme) or expanded to all over the facial nerve innervations.
Spasm intensity will be based on the degree of hypocalcemia
67
What is Trousseau's Sign?
To elicit the sign, a blood pressure cuff is placed around the arm and inflated to a pressure greater than the systolic blood pressure and held in place for 3 minutes. This will occlude the brachial artery. In the absence of blood flow, the patient's hypocalcemia and subsequent neuromuscular irritability will induce spasm of the muscles of the hand and forearm. The wrist and metacarpophalangeal joints flex.
68
If Symptomatic Hypocalcemia or Asymptomatic with a serum calcium of <7.5 mg/dL, history of Sz, or Abnormal EKG, treatment will be:
AKA Acute Treatment
1. IV Calcium Gluconate (less likely to cause tissue necrosis)
2. Cardiac Monitoring
69
Management of Chronic Hypocalcemia
Manage based on Etiology
1. Oral Calcium (1.0-1.5 g elemental Calcium/day)
2. Oral Vitamin D (Calcitriol 0.25-0.5 mcg/QD or BID
70
Inadequate mineralization of bone can result in:
Osteomalacia/Rickets
71
What is the difference between Osteomalacia and Rickets?
Osteomalacia - Adult bone (impaired mineralization)
Rickets - Children at the epiphysis of growing skeleton (unmineralized osteoid at the growth plate)
72
Cause of Osteomalacia/Rickets
Inadequate calcium, phosphate, or Vitamin D
73
Clinical Features of Osteomalacia
1. Bone Pain
2. Deformity
3. Fracture
4. Proximal Myopathy
5. Hypocalcemia
74
Clinical Features of Rickets
1. Growth retardation
2. Bone pain, fractures in unusual locals (scapulae, pubic rami)
3. Skeletal Deformity (Bowing, widening of growth plates)
75
Vitamin D Deficiency can be caused by
Decreased Skin Production (elderly, pigmented skin, sunscreen)
Obesity
Poor Nutrition (malabsorption)
Secondary Hyperparathyroidism (malabsorption, gastric bypass)
Drugs like phenytoin (increases metabolism of Vit D)
76
Vitamin D Deficiency Lab Findings
25 OH D <15-20 (100%)
PTH elevated (100%)
Elevated Alkaline phosphatase
Low calcium, phosphorus
Low urinary calcium
77
Symptoms of Vit. D Deficiency
Bone pain (lower extremities, pelvis)
Muscle weakness
Fracture/osteomalacia
Waddling gait
Muscle spasms, cramps
Symptoms are insidious in onset
78
Treating Vit D Deficiency
Ergocalciferol (D2)
Cholecalciferol (D3) **preferred
For every 100 units of Vit D added, serum 25 OH D should increased 1.0 ng/mL
If level is <20, would load once a week with 50, 000 IU x 6-8 weeks, followed by daily vit D to maintain
79
Repeat Vit D labs
1 month after initial treamtent, then 3-4 months after that.
80
Vit D levels should be
30-50
81
Pathophysiology of Paget's Dz
Unknown, commonly genetic.
82
Presentation of Paget's Dz
Disorganized osteoid formation, commonly in men more than women. 40+ years old
83
Symptoms of Paget's Dz
Asymptomatic
Bone pain = first symptom
Kyphosis, Bowed Tibia, Large Head, Deafness, Frequent Fractures
84
Risk Factors for Paget's Dz
Family Hx
85
Diagnostic Evaluation of Paget's Dz
Elevated Alkaline Phosphatase and Urinary Hydroxyproline
Serum Calcium and Phosphate Normal
86
DDx for Paget's Dz
Vitamin D Deficiency (inc. alkaline phosphatase and bone pain)
Paget's Dz
87
Management Plan for Paget's Dz
Asymptomatic: Observation and/or Biphosphonates
Biphosphonates used cyclically until alkaline phosphatase goes back to normal.
