Parathyroid Gland Flashcards
(56 cards)
1
Q
Calcium distribution in the body and types
A
- 99% in bones
- 1% in intracellular compartment as free Ca++ and protein bound
- 0.1% in interstitial fluid as free Ca++
- less than 0.5% in plasma:
- 50% of it as free Ca++
- 40% of it as protein bound Ca++
- 10% of it complexed to anions like phosphate and and citrate
Note: acidosis will increase free Ca++ by decreasing protein-bound Ca++, alkalosis will decrease free Ca++ by increasing protein-bound Ca++. Acidic environment will free Ca++ and phosphate from bones
2
Q
Bone Remodeling (Regulation and Indices)
A
- It is regulated by the balance in activity of both osteoblasts and osteoclasts
- Increased serum osteocalcin and alkaline phosphatase (ALP), and increased urinary excretion of hydroxyproline indicate high bone remodeling
3
Q
Osteoblasts
Secretory products
A
- Receptor Activator Nuclear Factor Kappa Beta ligand (RANK-L) which promotes bone resorption
- Osteoprotegerin (OPG) which is an endogenous blocker of RANK-L thereby inhibits bone resorption
4
Q
Osteoclasts
Regulators
A
- Osteoclast precursors are differentiated to mature osteoclasts by RANK-L that binds to RANK on them, also by IL-1, IL-6 and TNF-alpha secreted by T-lymphocytes
- This differentiation is blocked by OPG secreted from osteoblasts that blocks RANK-L and also by estrogen that inhibits the secretion of cytokines from T-lymphocytes
5
Q
Osteoblasts
Regulators
A
- Parathyroid hormone (PTH) induces them to secret RANK-L
- Estrogen induces them to secret OPG
Note: high glucocorticoids will increase RANK-L and decrease OPG inducing bone resorption
6
Q
Weight-bearing Stress
Effects
A
Increases the mineralization of bones through unwell-understood mechanism
7
Q
Weight-bearing Stress Absence
Effects and Lab findings
A
- Being sedentary, bedridden or weightless will promote demineralization of bones
- Plasma Ca++ in the upper range of normal, decreased plasma PTH, and increased urinary Ca++
8
Q
Bone Demineralization and Remodeling
Markers and Indices
A
- Increased serum osteocalcin and alkaline phosphatase (osteoblastic activity)
- Increased urinary hydroxyproline (breakdown product of collagen)
9
Q
Parathyroid Hormone (PTH) (Factoids)
A
- It is a peptide
- Works through cAMP
- It increases serum Ca++
- It needs adequate amount of serum Mg++ for release
10
Q
Parathyroid Hormone (PTH) (Effects on Kidneys)
A
- Increases Ca++ reabsorption at the DCT
- Decreases phosphate reabsorption at the PCT
- Increases excretion of cAMP and hydroxyproline
- Stimulates 1-alpha hydroxylase that will produce Calcitriol (active vitamin D) in PCT
11
Q
Parathyroid Hormone (PTH) (Effects on Bones)
A
- Induces bone resorption (not when given as bolus) by increasing RANK-L by osteoblasts leading to an increase in serum Ca++ and Pi
- Increases plasma alkaline phosphatase and osteocalcin
12
Q
Parathyroid Hormone (PTH) (Stimulants)
A
Decrease in serum Ca++ (parathyroid gland has CaSR which senses the calcium plasma levels)
13
Q
Parathyroid Hormone (PTH) (Source)
A
Chief cells of parathyroid gland
14
Q
Parathyroid Hormone (PTH) (Regulation)
A
- It will be increased by decreased serum Ca++ and Mg++ and increased serum phosphate
- It will be decreased by major decrease in serum Mg++
15
Q
Decreased serum Mg++
Common Causes
A
- Diarrhea
- Aminoglycosides
- Diuretics
- Alcohol abuse
16
Q
Vitamin D
Types and Sources
A
- D2 (ergocalciferol) from plants, fungi and yeasts
- D3 (cholecalciferol) from skin exposure to sun (UVB converts 7-dehydrocholesterol to D3 in keratinocytes of the 2 inner most epidermal layers [stratum basale and stratum spinosum]), fish and plants
- 25-hydroxycholecalciferol from hydroxylation of D2 or D3 by 25-hydroxylase in liver (best indicator of total body stores)
- 1,25-dihydroxycholecalciferol (calcitriol or active vitamin D) from hydroxylation of 25-hydroxycholecalciferol by 1-alpha-hydroxylase in renal PCT
17
Q
Vitamin D (Calcitriol) (Effects)
A
- Increase synthesis of calbindin proteins in small intestine which increase the absorption of dietary Ca++ and phosphate
- Enhances bone mineralization
- Enhances PTH action at renal DCT
18
Q
Vitamin D (Calcitriol) (Regulation)
A
- Increase in PTH, decrease in Ca++ and phosphate will increase calcitriol
- Calcitriol feedback inhibits its own production
19
Q
Vitamin D (Calcitriol) (Effects of High levels)
A
- Increases bone resorption and release of Ca++ and phosphate from bone
- It requires concurrent presence of PTH for this effect to tack place
20
Q
1-alpha hydroxylase
Regulation
A
- It will be increased by low phosphate and high PTH
- It will be decreased by high calcitriol
21
Q
Hypercalcemia
Effects
A
- Decrease neural excitability causing lethargy,confusion and constipation
- Muscle weakness (blocks fast Na+ channels)
- Reduced deep tendon reflexes
- Decrease QT interval and sometimes Osborn wave (as in hypothermia)
- Nephrogenic DI (inactivates ADH)
22
Q
Hypercalcemia
Causes
A
- Primary, Secondary and Tertiary hyperparathyroidism
- Lithium (decreases responsiveness of parathyroid gland to Ca++)
- Sarcoidosis and other granulomatous disorders (due to increased 1-alpha hydroxylase activity in granulomas)
- High bone turnover like in Thyrotoxicosis, Multiple myeloma, prolonged immobilization, Paget’s disease and vitamin A intoxication
- Ectopic hormonal activity due to PTHrP like in lung squamous cell carcinoma, breast cancer, ovarian small cell carcinoma, and renal cell carcinoma
- Milk-alkali syndrome
- Thiazide diuretics
- Aluminum intoxication
- Rebound hypercalcemia after rhabdomyolysis
- Adrenal insufficiency
- Zollinger-Ellison syndrome
23
Q
Primary Hyperparathyroidism
Causes
A
- Single parathyroid adenoma (80%)
- Primary parathyroid hyperplasia as in MEN 1 or MEN 2A (15%)
- Parathyroid carcinoma (rare)
- Familial Hypocalciuric Hypercalcemia (FHH)
24
Q
Hypercalcemia
Treatment
A
- Hydration (with saline), increased salt-intake and forced diuresis (using loop diuretics)
- Bisphosphonates like Etidronate, Pamidronate, Alendronate and Zoledronic acid (take 2-3 days for full activity)
- Calcitonin (works quickly)
- Prednisone if the cause is sarcoidosis or any granulomatous disease
25
Primary Hyperparathyroidism
| Lab Findings
- Hypercalcemia
- Hypophosphatemia
- Calciuria (polyuria)
- Increased phosphate excretion in urine
- Increased PTH
26
Primary Hypoparathyroidism
| Lab Findings
- Hypocalcemia
- Hyperphosphatemia
- Decreased PTH
- Low Ca++ and low phosphate in urine
27
Hypocalcemia
| Effects
- Tetany
- Increased neural excitability (convulsions)
- Hyperactive deep tendon reflexes
- Increased QT interval (intermittent) which predispose to Torsade de pointe
- Decreased cardiac output due to decrease in both heart rate and contractility
- Life threatening complications are laryngospasm and cardiac arrhythmias
28
Hypocalcemia
| Presentation
- On-off petechiae that later become confluent and appear as purpura in dependent parts of the body
- Oral, peri-oral, and acral parasthesias (the earliest symptoms)
- Carpopedal or generalized tetany
- Trousseau sign (carpal spasm by inflating a cuff around the arm and keep it above systolic pressure)
- Chvostek's sign (facial spasm by tapping the facial nerve just anterior to the ear lobe)
- Convulsions
- Cardiac arrhythmias
- Slit lamp examination shows early cataracts
29
Primary Hypoparathyroidism
| Causes
- Accidental surgical removal during thyroid surgery or when it is removed on purpose to correct hyperparathyroidism
- Autoimmune destruction of the parathyroid gland
- Hypomagnesemia
- DiGeorge's syndrome
30
Hypocalcemia
| Causes
- Primary hypoparathyroidism
- Pseudohypoparathyroidism
- Alkalosis (via hyperventilation)
- Transfusions of citrated blood
- Rhabdomyolysis or tumor lysis (subsequent hyperphosphatemia)
- Chronic renal failure (hyperphosphatemia)
- Vitamin D deficiency
- Eating disorders and prolonged vomiting
- Exposure to mercury and hydrofluoric acid
- Excessive dietary Mg++ and Zinc
- Prolonged use of laxatives or medications that contain magnesium
- Chelation therapy especially EDTA
- Bisphosphonates, Denosumab and Calcitonin
- Pancreatitis (one of the complications)
- Neonatal hypocalcemia (very low birth weight [less than 1500 gram] and/or gestational age less that 32 weeks)
31
Calcium in the blood
| Normal ranges
- Total Ca++ is 8.5-10.5 mg/dL
- Ionized Ca++ is 4.65-5.25 mg/dL
- You should either measure the ionized Ca++ or calculate what is called corrected Ca++ after measuring the total one depending on the albumin level
* Corrected Ca++ = Measured total Ca++ (mg/dL) + 0.8 * (4 - serum albumin [g/dL])
32
Secondary Hyperparathyroidism
| Lab Findings
- Hypocalcemia
- Hypophosphatemia
- Low Ca++ and High phosphate in urine
- High PTH
33
Secondary Hypoparathyroidism
| Lab Findings
- Hypercalcemia
- Hyperphosphatemia
- High Ca++ and Low phosphate in urine
- Low PTH
34
Secondary Hyperparathyroidism
| Causes
- Vitamin D deficiency
| - Malabsorption syndromes
35
Secondary Hypoparathyroidism
| Causes
- Vitamin D excess
| - Thiazide diuretics
36
Diagnosis of Parathyroid disorders
- If plasma Ca++ and Phosphate go in the opposite direction it is a primary disorder except chronic renal failure
- If plasma Ca++ and Phosphate go in the same direction it is a secondary disorder except chronic renal failure
37
Chronic renal failure
| Consequences on Ca++ homeostasis
- It is the most common cause of secondary hyperparathyroidism
- There will be impairment of phosphate excretion, this will lead to elevated plasma phosphate which in turn will lower free Ca++; therefore will increase PTH secretion
38
Hypocalcemia
| Treatment
- If acute and mild to moderate give 10% calcium gluconate
- If acute and severe give calcium chloride
- If chronic maintenance doses of both Ca++ and vitamin D (calcitriol) are given
39
Osteoporosis
| Definitions
- If bone density is more than 2.5 standard deviation (SD) below average, it is osteoporosis
- If bone density is 1 to 2.5 SD below average, it is osteopenia
40
Bone Mass
| Effectors
- Hereditary variations
- Physical activity
- Nutrition
- Estrogens
41
Secondary Osteoporosis
| Causes
- Thyrotoxicosis
| - High glucocorticoids
42
Osteoporosis
| Treatment
- Bisphosphonates is the mainstay of treatment
- Denosumab (RANK-L inhibitor)
- Teriparatide (synthetic PTH) given as intermittent boluses which stimulate osteoblastic bone formation
- Calcitonin
- Raloxifene (selective-estrogen receptor modifier)
43
Paget's disease
| Physical and Lab findings
- Skin overlying thighs, lower back and skull is warm to touch, with loss of hearing in 30-40% of cases involving the skull
- Increased serum alkaline phosphatase, but normal serum Ca++ and phosphate
- Increased urine hydroxyproline
44
Paget's disease
| Treatment
- Most patients are asymptomatic and require no treatment
- Bisphosphonates like Etidronate, Pamidronate and Alendronate
- Calcitonin
- NSAIDs and acetaminophen for pain management
45
Calcitonin
| Source
Parafollicular cells (C cells) of thyroid gland
46
Calcitonin
| Function
Decrease bone resorption of Ca++ (not important in normal Ca++ homeostasis)
47
Calcitonin
| Regulation
Increase in serum Ca++ will stimulate its release
48
Hypercalcemia
| Presentation
- Confusion, stupor, lethargy and constipation
- Osteoporosis
- Nephrolithiasis, DI, and renal insufficiency
- Short QT syndrome and Hypertension
- Acute pancreatitis
- Peptic ulcer disease (Ca++ stimulates gastrin)
49
Primary Hyperparathyroidism
| Imaging
- DEXA densitometry is better than x-ray to test bone effects of high PTH
- Neck sonography or nuclear scanning before surgery
50
Primary Hyperparathyroidism
| Treatment
- Surgical removal of the involved gland(s)
| - If surgery is not possible, give Cinacalcet (an inhibitor of PTH release)
51
Primary Hyperparathyroidism
| Presentation
- Most often asymptomatic,but may presents the same way as hypercalcemia presentation
- Osteitis fibrosa cyctica (cyctic bone spaces filled with brown fibrous tissue consisting of osteoclasts and deposited hemosiderin from hemorrhages and causes bone pain)
52
Tertiary Hyperparathyroidism
| Definition
Refractory hyperparathyroidism resulting from chronic renal disease (very high PTH with high Ca++)
53
Secondary Hyperparathyroidism due to renal insufficiency
| Treatment
- Treat the hypercalcemia
- Give oral phosphate binders like aluminum hydroxide, calcium salts, sevelamer hydrochloride, and lanthanum carbonate in addition to restriction of dietary phosphate
- Give Cinacalcet
54
Osteoporosis
| Diagnosis
- Checking the bone mineral density (BMD) using Dual-energy x-ray absorptiometry (DEXA) usually in vertebral bodies, proximal femur and distal radius
- Rule out secondary causes by doing CBC, TFTs, CMP,, 24-hour urine Ca++, serum 25-hydroxycholecalciferol, testosterone (in men), and SPEP/UPEP (to rule out multiple myeloma)
- X-rays: global demineralization is apparent only after > 30% of bone density is lost
55
Paget's disease
| Diagnosis
- Radionuclide bone scan in early disease (most sensitive)
- Plain x-ray films are critical with the classical signs being: thickened bone cortex, thickened trabeculae, and expansion of femoral head ("mosaic" lamellar bone pattern)
56
Paget's disease
| Complications
- Pathological fractures
- High-output cardiac failure
- Osteosarcoma (up to 1%)
