1) Why is calcium homeostasis important?

2) What is the normal calcium level in the body?

3) What are the 2 hormones associated with maintaining calcium homeostasis? 

1) All physiological process directly or indirectly involve calcium ions

2) between 9mg - 11mg/100cc of blood

3)Parathyroid hormone & Calcitonin

1) Where is the parathyroid hormone released from?

2) Where is calcitonin released from?

1) The parathyroid glands embedded in the posterior aspect of the thyroid hormone

2) The parafollicular cells (also known as "C" cells) in the thyroid gland 

1) What are the major stimuli that effect Parathyroid hormone (PTH) release?

2) What molecule does PTH release require?

3) When PTH binds to PTH receptors on target cells, what does it activate?

1) Hypocalcemia, hyperphosphatemia (too much phosphate in the blood)

2) Magnesium

3) cAMP dependent signal transduction mechanism

Describe what happens when:

1) Ca2+ blood levels rise

2) Ca2+ blood levels fall

1) Directly absorbs calcium and phosphate ions from the GI tract (from the diet) into the blood

2) Synergizes with PTH to stimulate calcium reabsorption from the kidneys

   a. In hypocalcemic conditions when PTH is present, 1,25 hydroxyvitD stimulates bone resorption

   b. In hypercalcemic conditions when PTH is absent, 1,25 hydroxyvitD activates the osteoblasts to stimulate bone tissue secretion and the mineralization of bone tissue

1) Bone breakdown

2) Osteoporosis 

Primary: Tumor of the parathyroid gland

Secondary: Ectopic production of PTH-related peptides (PTHrP) from cancers which act as agonists to stimulate PTH biological actions

1) Hypercalcemia due to excessive bone resorption which can cause osteoporosis

2) Increase in production of 1,25 (OH)2 VitD which synergizes with the high PTH to exacerbate bone resorption

1) Depressed nervous system activity especially at the neuromuscular junction resulting in the inability to sustain skeletal muscle contractions = muscle weakness

2) Formation of renal calculi

3) Polyuria 

4) Constipation and vomiting

5) Dehydration due to polyuria and vomiting

6) Depressed mental state due to reduced brain perfusion

1) Rehydration

2) Antiresorptive drugs - these inhibit osteoclastic bone resorption (Calcitonin, Bisphosponates such as palmidronate and etidronate)

3) Bone forming agents (Flouride - chelates calcium ions, Selective Estrogen Receptor Modulator [SERM] such as reloxifene)

4) Calcimimetics - drugs that bind and activate the calcium-sensing receptor to inhibit PTH release

5) Partial parathyroidectomy - surgical removal of two of the four parathyroid glands

1) Hypoparathyroidism

     a. Total thyroidectomy which results in total parathyroidectomy

     b. Damaged parathyroid glands

     c. PTH gene mutation - impaired synthesis

     d. Severe/chronic hypomagnesemia (in GI and renal disorders) hence, PTH release in inhibited

2) Pseudohypoparathyroidism

     a. Genetic disorder leading to dysfunctional PTH receptors (hence, blood PTH levels are actually elevated) 

1) Hyperphosphatemia

2) Hypocalcemia

1) Neuromuscular irritability

2) Paresthesia (an abnormal tingling/burning sensation)

3) Laryngospasm (spasmodic closure of the larynx)

4) Bronchospasm 

5) Tetany (spontaneous and sustained skeletal muscle contractions)

6) Seizures

7) Positive Chvostek Sign

8) Positive Trousseau Sign

9) Impaired Cardiac Function (due to this there is a decreased contractile force = decreased stroke volume)

When the facial nerve is tapped 2cm anterior to the earlobe

A positive response results in a hemifacial contraction/spasm

When a blood pressure cuff is inflated to about 20mmHg above the systolic BP for 3 mins and then released

A positive response results in muscular contraction including flexion of the wrist and metacarpophalangeal joints, hyperextension of the fingers, and flexion of the thumb on the palm, suggestive of neuromuscular excitability caused by hypocalcemia (this carpal spasm is refferred to as main d'accoucheur)

1) What are 5 clinical features of pseudohypoparathyroidism?

2) What are these features refferred to as:

1) Secondary hyperparathyroidism, short stature, short neck, round face, and brachydactyly (short digits)

2) Albright Hereditary Osteodystrophy

1) Exogenous intake of calcium AND VitD to raise the blood calcium levels

2) PTH replacement therapy

3) Calcilytics (drugs that block the calcium-sensing receptors on the chief cells in the parathyroid glands to promote PTH release.  They only work in intact parathyroid glands)

1) Where does VitD3 come from?

2) Where does VitD2 come from?

3) Hypofunction of VitD results in decreased absorption of (a) and (b) from the small intestine leading to (c) and hence, secondary (d)

1) Sunlight

2) VitD fortified dairy products

3)[a]calcium [b] phosphate [c] hypocalcemia [d] hyperparathyroidism

There are two types of Rickets found in children:

Rickets Type 1: due to (1)

Rickets Type 2: due to (2)

1) Due to lack of vitamin D

2) Due to resistance to vitamin D (vitamin D receptor dysfunction, hence VitD levels are high)

What are 9 clinical features of rickets?

1) Poor mineralization of bones

2) Bone resorption

3) Weakness, lethargy

4) Soft, misshapen head

5) Delayed teeth eruption/pitted teeth

6) Enlargement of costochondral junctions (rachitic rosary)

7) Hypotonia of muscle leads to a potbelly and a waddling gait

8) Poor mineralization results in thicker epiphyseal plates and wide epiphyses

9) Lower limbs bend and become bowed to accomodate the weight of the trunk

1) What is the name of vitamin D deficiency in adults?

2) What are 6 causes of this deficiency?

1) Osteomalacia

2) Inadequate sunlight exposure, diet poor in calcium and VitD2, malabsorption, liver disease (source of 25 hydroxylase), kidney failure (source of 1 alpha hydroxylase), hypophosphatemia

1) Bone fractures that happen with little injury

2) Bone pain, especially in the hips, pelvis, spine, and legs

3) Muscle weakness - difficulty standing/walking

1) It stimulates osteoblasts to secrete bone tissue which is mineralized with calcium phosphate crystals (the hydroxyapatites)

2) It inhibits osteoclasts from resorbing bone (note: in pharmacological doses, calcitonin acts as an antiresorptive drug in the treatment of hyperparathyroidism and osteoporosis)

1) Total thyroidectomy resultin in the complete absence of calcitonin is NOT associated with hypercalcemia

2) Medullary Thryoid Carcinoma - cancer of the parafollicular cells associated with high level of calcitonin does NOT result in hypocalcemia