Calcium, Phosphate and Parathyroid Gland

Question 1

What is the total body calcium?

Answer 1

Total body calcium - approximately 1000g

Question 2

Where is calcium located?

Answer 2

99% of body calcium is stored in bones as hydroxyapatite.
Skeleton strength and reservoir for calcium
1% located in blood, extracellular fluid and body tissue

Question 3

Calcium Blood levels

Answer 3

45% - free or ionised fraction and is biologically function portion of total Ca
45% - is bound to albumin in pH dependent manner
10% - exists as a complex with anions including phosphate and citrate
Total Ca in normal serum ranges between 2.18 to 2.62 mmol/L

Question 4

Physiological Functions of Calcium

Answer 4

Cell division
Cell adhesion
Plasma membrane integrity
Protein secretion
Muscle contraction including cardiac muscle
Neuronal excitability
Glycogen metabolism
Blood coagulation

Question 5

Daily Requirement & Sources of Ca

Answer 5

Daily requirement:
The infants and children - 350-550 mg/day
Teenage girls and boys: 800-1000mg/day
Adult men and women: 700 mg/day
Sources:
Milk, cheese and other daily foods
Green leafy vegetables - such as broccoli, cabbage and okra, but not spinach

Question 6

Calcium Balance

Answer 6

Because of its physiological importance ECF concentration of Ca is maintained within a narrow range.
Major role in Ca homeostasis are skeleton, gut and kidneys

Question 7

Hormonal Regulation of Ca homeostasis

Answer 7

Blood calcium concentration drops
Release of PTH: Chief cells of the parathyroid gland release parathyroid hormone (PTH)
Effects of PTH on bone: inhibits osteoblasts, stimulates osteoclasts, bone is broken down releasing calcium ions into blood stream
Effects of PTH on kidneys: PTH stimulates kidney tubule cells to recover waste calcium from urine, PTH stimulates kidney tubule cells to release calcitriol
Effects of calcitriol on intestine: Stimulates intestine to absorb calcium from digesting food
Blood calcium levels increase
Calcitonin release: high concentration of calcium stimulates parafollicular cells in the thyroid to release calcitonin
Effects of calcitonin on bone: Stimulates osteoblasts, inhibits osteoclasts, calcium is removed from blood and used to build blood.

Question 8

Phosphate

Answer 8

Phosphate 80% stored as hydroxyapatite in bones:
Skeletal integrity, primary reserve
Physiological functions
Intracellular processes including:
Nucleic acid synthesis
ATP production (provides energy at cellular level)
Kinase and phosphatase activity

Question 9

Daily Requirement and Sources of P

Answer 9

Adult needs 550mg of P a day
Sources:
Dairy
Red meat
Poultry
Bread

Question 10

Phosphate Balance

Answer 10

Blood level - 0.8-1.5 mmol/L
Systemic regulation is maintained through endocrine (PTH) feedback and vitamin D: intestines, kidneys and bones

Question 11

Disorders of Phosphate Homeostasis

Answer 11

Hypophosphataemia:
Decreased intestinal absorption
Increased renal wasting
Redistribution from ECF into cells
Hyperphosphataemia:
Decreased renal excretion
Acute exogenous phosphate load
Redistribution of intracellular phosphate to extracellular space

Question 12

Consequences of hypophosphataemia

Answer 12

Hypophosphataemia 5% of hospitalised patients (30% in alcoholics):
Poor growth in children
Fatigue, weakness, loss of appetite
Bone pain and fragile bones

Question 13

Consequences of hyperphosphataemia

Answer 13

Hyperphosphataemia:
Hypocalcaemia
Soft tissue calcification
Calcification of arteries and heart valves

Question 14

Parathyroid glands

Answer 14

4 small glands on the posterior aspect of thyroid gland
Parathyroid glands contains two main types of cells:
Chief cells - functional cells, responsible for synthesising and secreting parathyroid hormones
Oxyphil cells - no recognised physiological function

Question 15

Development of parathyroid gland

Answer 15

Development:
Develop from endoderm of the 3 and 4 pharyngeal pouches
Functional during gestation to control Ca balance of that state of development

Question 16

Parathyroid Hormone PTH

Answer 16

Pre-pro-PTH - 115 amino acids polypeptide.
Cleaved to pro-PTH - 90 amino acids polypeptide
Pro-PTH is cleaved further to active PTH - 84 amino acids

Question 17

PTH Physiological Actions

Answer 17

First of all, this stimulates the osteoclast cells. Osteoclast are cell which cause the resorption of the bone and that releases calcium into blood. It affects the kidneys, we have already seen that PTH increases the reabsorption of excreted calcium from the renal tubules. More importantly, PTH causes the release of calcitriol or the end product of vitamin D metabolism, which enhances the calcium absorption tremendously.

Question 18

PTH Action on Bones

Answer 18

PTH
Osteoblasts
RANKL - RANK ligand is a receptor activator for nuclear factor. This allows differentiation or change from osteoblasts to osteoclasts
Osteoclast
Resorption of bones
Release of Ca

Question 19

PTH Action on Kidneys

Answer 19

Increase serum Ca levels
Increase Ca resorption
Decrease phosphate reabsorption
Increase activation of vitamin D

Question 20

PTH Indirect effect on small intestines

Answer 20

No direct effect on intestines
The effect is due to increase in active vitamin D due to its action on kidneys
Vitamin D increases the absorption of Calcium and phosphate from the intestines

Question 21

Disorders of PTH-1 (excess parathyroid hormone)

Answer 21

Hyperparathyroidism (HPTH)
Primary (PHPT) - abnormality of gland itself. Adenoma, hyperplasia, rarely carcinoma
Secondary (SHPT) - compensatory over secretion. CKD (chronic kidney disease), Vitamin deficiency, malabsorption
Tertiary (THPT) - after SHPT is treated. Extremely rare

Question 22

Clinical Features of HPTH & Hyper Ca

Answer 22

Nausea and vomiting
Constipation
ECG changes - short QT interval
Kidney stones
Bone pain
Osteoporosis
Psychosis
Altered metal status

Question 23

Disorders of PTH (deficient parathyroid hormone)

Answer 23

Hypoparathyroidism
Hypoparathyroidism (low PTH & low Ca)
Surgical removal or damage
Auto-immune disorders
Pseudohypoparathyroidism (high PTH)
Target organ resistance to PTH - developmental disorder

Question 24

Clinical Features of Hypoparathyroidism & Hypo Ca

Answer 24

Muscles:
Weakness
Muscle cramps
Nerve function:
Peroral numbness and tingling
Chvostek’s sign - touching facial nerve results in spasm
Trousseau’ sign
Tetany