Growth Hormone and Hormones of Calcium-Phosphate Balance
GH EXCESS
- Before puberty = gigantism - After puberty = Acromegaly
Effect of GH and IGF
- Bone, cartilage and muscle growth - anabolic growth for protein synthesis - LIPOLYTIC - Gluconeogenic and hyperglycemia (opposite of insulin)
What are 3 effects the growth hormone (GH) can have?
- Causes hyperglycemia and tissue growth - Causes release of IGF-1 - Causes bone growth
Calcitonin
- Decreases bone resorption and stops osteoclasts (opposite of PTH) - Salmon Calcitonin can be used as treatment for Paget's disease to stop bone turnover
What is the main cause of primary hyperparathyroidism (PHPT)?
- From adenoma - Associated with Nephrolithiasis (kidney stones)—-> from hypercalciuria b/c you have so much Ca - Calcium can deposit in tissues or eyes - May be asymptomatic - Also look for Brown tumors occasionally- cluster giant cells (macrophages) and bone in mouth is substituted with connective tissue
Bone Formation is stimulated by what hormones?
1. GH 2. IGF-1 3. Calcitonin 4. Vitamin D (mineralization, osteoblasts) 5. Insulin 6. Sex steroids
What medication is used for treatment of osteoporosis?
Bisphosphonates = block osteoclasts - used for Paget's and Osteoporosis - side effect = JAW NECROSIS
What cells produce calcitonin?
C cells of the thyroid gland
Bone resorption is inhibited by what hormones?
Calcitonin Sex steroids
What are the physiological effects of GH & IGF (Insulin-like growth factor)?
Growth of: 1. Bone 2. Cartilage 3. Muscle growth
GH and IGF-1 stimulate growth of tissues and elevate plasma glucose. IGF-1 exerts negative feedback via...
Hypothalamus and pituitary gland on GH secretion
What is the distribution of plasma calcium?
Mostly free or ionized Ca++ and protein bound (albumin) The least amount is found complexed, mainly with phosphate
Low Vit. D = ?
Rickets in children —-> look for deformed bowing legs. - Treat with COD LIVER OIL - Key findings: Bowed legs, knock-kneed legs, Rib beading = Rachitic Rosary, Kyphosis/Lordosis, Enamel hypoplasia, wrist enlargement Osteomalacia in adults - Bone demineralization, pain, fragility - Fractures
When is PTH made?
With low calcium!
What are the actions of PTH?
- Increases calcium reabsorption in kidney - Stimulates production of Vitamin D——-> so you can reabsorb more calcium - Kicks out phosphate in the proximal tubule - Bone RESORPTION to increase calcium levels in blood (via osteoclasts)
Calcitriol
- It's the active form of vitamin D - Produced in KIDNEY. It increases calcium absorption in GI tract. - Calcitonin = promotes bone mineralization. It TONES down the calcium levels in blood
Osteoporosis
- Lots of bone resorption —-> spongy trabecular bone loss - Due to hyperthyroidism, low VIT D, parathyroid problems
GH
- Made in anterior pituitary - Tyrosine Kinase receptor (like insulin) - The actual resultant effects of growth are mostly mediated by IGF- 1 (from liver), but GH has some effects of its own too
What causes Vit D release?
- PTH (low calcium) and low plasma phosphate - Recall: It's a steroid! - It can cause bone resorption and mineralization simultaneously to help maintain healthy bone structure
What inhibits GH?
- Somatostatin - Negative feedback from IGF-1 and GH on GHRH - Hyperglycemia - Free Fatty Acids
What is Paget's disease?
- Super hyperactive osteoclasts —-> bone remodels a ton and gets disorganized - accelerated disorganized bone remodeling - CN compression —-> deafness, loss of facial sensation - SKULL ENLARGEMENT - Risk for osteogenic sarcoma b/c of the super high bone turnover - Risk for Cardiac hypertrophy and high output heart failure - Bowed Tibias - Hydrocephalus b/c of compressed cerebral aqueduct from thick skull bones - Chalk stick fractures
Hypocalcemia physical exam finding
- TROUSSEAU SIGN- hit your TRicep & contract - CHVOSTEK SIGN- hit your CHeek & contract
Bone growth
- What builds = osteoblasts - What is a "sleeping" osteoblast = osteocyte - What resorbs bones = osteoclasts
What causes release of GH?
- sleep - high plasma amino acid level - low plasma glucose - low insulin
What two hormones does the hypothalamus produce in order to regulate growth hormone release by the pituitary gland?
1. GHRH (stimulates release) 2. Somatostatin (stops release)
What controls the release of growth hormone (GF) from the anterior pituitary gland?
1. Hypothalamic growth hormone releasing hormone (GHRH) (simulates) and somatostatin (inhibits)
Negative feedback is provided to the hypothalamus to stop the secretion of GH by what two hormones?
1. IGF-1 2. GH on GHRH
Bone resorption is stimulated by what hormones?
1. PTH 2. Vitamin D (osteoclasts) 3. TH 4. Cortisol
Calcium & Phosphate Balance primarily depends on three hormones....
1. Parathyroid hormone (PTH) 2. Calcitriol- active form of vitamin D (regulation of ca uptake) 3. Calcitonin
Bone formation is inhibited by what hormones?
Cortisol
What are the clinical manifestations of hypercalcemia?
Decreased neuromuscular excitability, cardiac problems
Calcium _____ the opening of sodium gated channels.
Decreases - hence more Ca++ = less excitability
Dwarfism
GH deficiency with NORMAL proportions (epiphyseal plates close early)
Where is PTH made?
In the chief cells of the parathyroid gland
Where is calcium elimination regulated in the body?
In the kidney tubules *PTH major factor that controls Ca++ reabsorption in the kidney
What are the clinical manifestations of hypocalcemia?
Increased nerve and muscle excitability, tetany, cardiac arrhythmias
Osteocytes
Quiescent (dormant) osteoblasts