Endocrine system (Control of Blood Calcium Levels)
What influences calcium homeostasis?
Dietary intake, urinary and faecal losses (Normally very little calcium is excreted in the urine. Only occurs if levels are above normal.) Exchanges with the osseous tissue.
What is nephrocalcinosis?
The formation of renal calculi composed of Calcium Phosphate
Does a calcitonin deficiency cause a disease?
While calcitonin can be useful in lowering high levels of blood calcium, calcitonin deficiency does not cause any disease in humans
How many people between 45 and 79 are osteoporotic?
29% of women and 18% of men, The difference is because there is a fairly rapid decline in oestrogen production in females at this time
What percentage of the plasma concentration of Calcium is in the ionised form (Ca2+) which can diffuse through capillary walls and exert physiological effects?
45%
What is the plasma concentration of Calcium?
9.2 - 10.4 mg/dL (milligrams per 100ml) =approx. 2.5 mmol/Litre. Narrow margin of safety
What is the result of an insufficient amount of sunlight or Vitamin D?
Abnormal softness of the bones; Rickets in children and Osteomalacia in adults (softening of the bone - adult rickets)
How much calcium does the adult body contain?
About 1.1kg of Calcium
Calcium is a structural component of bone and teeth, where is calcium most often found?
About 99% of all body calcium is present in the skeleton - most is found in hydroxyapatite crystals
Of the 3 hormones involved in calcium regulation which is the most important?
Adult Calcium homeostasis is almost entirely under the control of parathyroid hormone (PTH)
Why can active vitamin D originating from the skin can accurately be called a hormone and the skin can be called an endocrine gland?
Because it can also be manufactured by a complex process involving the skin, U.V. radiation, the liver and the kidneys
What is the function of calcium in Blood clotting?
Calcium is needed for at least 4 of the steps in clot formation. Some in the intrinsic pathway and some in the extrinsic pathway and some on the common pathway
What are sources of Calcium?
Dairy products - cheese and milk, Egg yolks Fish with bones e.g. sardines, Leafy green vegetables - spinach and kale
What can a drop to 4mg/dL cause?
Fatal laryngospasm (Laryngospasm is tight constriction of the muscles of the larynx causing suffocation)
What is hyperparathyroidism?
Hyperparathyroidism causes the bones to become soft, deformed and fragile. Blood calcium concentrations become abnormally high as calcium salts in the skeleton are mobilised and bones are weakened. Most commonly results from a tumour of the Parathyroid gland.
What happens when the Parathyroid gland secretes inadequate or excessive amounts of PTH and calcium concentrations move outside normal homeostatic limits?
Hypoparathyroidism or Hyperparathyroidism
What is hypoparathyroidism?
Hypoparathyroidism with hypocalcaemia may develop after a thyroidectomy and especially if the blood supply to the parathyroid is restricted. Accidental removal of the parathyroid is the leading cause of hypocalcaemic tetany Hypocalcaemia leads to excessive neuromuscular irritability - muscular twitching, spasm and cramps can develop leading to tetany. Laryngeal spasm. Treatment with PTH is very costly as it can only be extracted from the blood of individuals with normal PTH levels so it is usually treated with Vitamin D and high doses of calcium.
What is the function of calcium as a second messenger and cofactor?
Important for enzymes and for water soluble (protein ) hormones
What is the role of non ionised calcium bound to plasma proteins and other solutes?
It serves as a reserve, from which calcium can be withdrawn as needed. Equilibrium exists. The plasma protein transporting calcium is mainly albumin. Other solutes are ions such as citrate or lactate
If you are over 65 and break your hip, there is a 25% chance that you will be dead within how long?
One year
Where is the steroid like hormone "Vitamin D" produced?
Produced by the coordinated action of the skin, liver and kidneys and then carried by the blood to other organs where it exerts its effect.
What does osteoporosis mean?
"porous bone" i.e. bone with holes in it! There is a reduction in bone density = bone mass as seen in bone density scan
What are the 3 ways PTH raises blood Calcium levels?
1.Direct effect: Dissolves bone matrix in the immediate vicinity, it also stimulates a rapid increase in the number of osteoclasts which dissolve osseous tissue at the bone surfaces. 2. Direct effect: This lowers the phosphate to a level that prevents the formation of hydroxyapetite. It lowers it by inhibiting phosphate reabsorption.PTH increases plasma calcium by increasing its reabsorption in the renal tubule.However, a more effective action of PTH in this connection is the increase in renal excretion of phosphate (HPO42-). Thus calcium remains dissolved in the plasma and is accessible to other organs. 3. Indirect effect: PTH stimulates the production of an enzyme in the kidneys that activates vitamin D. Since vitamin D is required for the absorption of calcium in the small intestine, PTH indirectly enhances calcium absorption.
What does the bone act as for Calcium & Phosphorous?
Bone is the storage "bank". Withdrawals and deposits can be made from this bank. In two reserves; Incorporated in Hydroxyapatite and not readily exchangeable with the blood and exchangeable calcium: 1% or less.
How does calcitonin reduce the plasma concentration of Calcium?
By 2 principal mechanisms; 1. Osteoclast inhibition. Osteoclasts release less calcium from the skeleton; decreased bone consumption within 15 minutes. (Remember clasts release calcium into bloodstream) 2. Osteoblast stimulation. Osteoblasts deposit Calcium in the skeleton; There is increased bone building within the hour. Remember blasts are the builders - moves calcium from blood to bone
How are Calcium levels controlled?
By hormones; Calcitonin (from the thyroid gland - the Parafollicular cells). Parathyroid Hormone (P.T.H.) - from the parathyroid glands. Calcitriol (= vitamin D) - from the diet/skin via the liver and kidney
How is secretion by the Parathyroid glands controlled?
By negative feedback control; The feedback signal is the Calcium concentration in the ECF (extracellular fluid) surrounding the Parathyroid cells. The concentration of calcium ions in the ECF is detected by calcium receptors in these cells. A decrease in calcium ions in the ECF leads to increased PTH secretion. Doesn't involve the nervous system, no hypothalamus - pituitary loop
Where is calcitonin released from?
By the "C cells" (parafollicular cells between the thyroid follicles) of the Thyroid gland when the plasma concentration of Calcium rises too high
What are the affects of hypocalcaemia on bone growth?
Calcium deficiency in children causes stunted growth, misshapen bones and enlarged wrists and ankles. In adults, such a deficiency may cause thinning of the bones and an increased risk of fracture
A general rule of digestive physiology is that the digestive tract absorbs all of a nutrient entering its lumen, rather than absorbing the amount needed by the body at the time. Which nutrient is an exception to this?
Calcium is an exception to this. The rate of calcium absorption is regulated and depends on the calcium level in the ECF (extracellular fluid). The control system that influences the rate of calcium absorption is mediated by Calcitriol (active vitamin D). When the level of calcium in the ECF is below a set point, increased amounts of vitamin D are activated and calcium absorption by the small intestine is enhanced via the parathyroid hormone.
What is the function of calcium in Acid -Base balance?
Calcium phosphate from the skeleton helps to correct the acid-base imbalances in the blood. In metabolic acidosis, when the pH drops, calcium phosphate is released from the skeleton to buffer the hydrogen ions. The mechanism by which this dissolution of bone crystal occurs involves two processes: -direct physiochemical breakdown of crystals in response to H+ -osteoclastic reabsorption of bone. The involvement of this process in buffering is independent of parathyroid hormone.
What is the function of calcium in muscle contraction?
Calcium released from the sarcoplasmic reticulum pushes tropomyosin out of the way and allows cross bridges to form between actin and myosin. This leads to muscle contraction.
What is the function of calcium in nerve impulse conduction?
Calcium triggers exocytosis of synaptic vesicles, allowing communication between adjacent neurons. Neurotransmitter release. Calcium ions are also needed to close sodium channels in nerve cell membranes. Important in the physiology of excitable cells.
What makes up 4it makes up 1.5% of the human body?
Calcium, Ca2+ is the most abundant mineral in the body
What are the affects of hypocalcaemia on spontaneous impulses to the skeletal muscles?
Causes tremors, spasms or tetany. Tetany is a sustained contraction in which the muscle cannot relax. One of the warning signs of hypocalcaemia is carpo-pedal spasm of the hands and feet (Trousseau's sign) - a characteristic tetany in which the wrists and fingers are spasmodically flexed. This is treated with calcium salts and high doses of vitamin D. Extra calcium demands in pregnancy can cause cramps
Why are blood Calcium levels critical?
Changes can be serious, even fatal. Causing Hypercalcaemia and Hypocalcaemia
What is the function of calcium in Exocytosis (E.g. with synaptic vesicles) and other membrane transport processes?
In a neuron, synaptic vesicles (or neurotransmitter vesicles) store various neurotransmitters that are released at the synapse. The release is regulated by a voltage-dependent calcium channel. Ca2+ enters the cell by the propagation of an action potential to the presynaptic membrane. Ca2+ binds to specific proteins, one of which is synaptotagmin, in neurons which triggers the joining together of the vesicle with the target membrane
Vitamin D obtained from the diet (vit. D3) is not the active form of vitamin D that promotes intestinal absorption of Calcium. Where must it be converted?
In the liver and then the kidney to the biologically active form Calcitriol, which can then trigger intestinal calcium absorption. The process in the kidney is the one which is stimulated by PTH
What are the affects of hypocalcaemia on the nervous System?
It becomes hyperexcitable. There is abnormal nerve impulse transmission as calcium ions are needed to close sodium channels in the nerve cell membranes. Compare this with hypercalcaemia where the N.S. is depressed. A marked reduction below the critical limits (hypocalcaemia) increases the excitability of nerve fibres but decreases the release of neurotransmitters at the synapses and the neuromuscular junctions. The net result of hypocalcaemia is spastic contractions in muscles (tetany).
What are Hypercalcaemia symptoms?
It is rare. Symptoms begin to appear at about 12mg/dL.(normal 9.2 -10.4 mg/dL). Depression of the nervous system - slowing of nerve impulse transmission, Emotional disturbances, Muscle weakness, Sluggish reflexes, Possible cardiac arrest - abnormal nerve and muscle function affects the heart.
What does Vitamin D deficiency lead to?
Leads to rickets because inadequate calcium absorption from the intestine and deposit in the bone results in soft bones which bend.
What are hypocalcaemia symptoms?
More common and can result from such things as: vitamin D deficiency, diarrhoea, thyroid tumours, under active parathyroid glands, pregnancy and lactation
Osteoclast activity is reduced in geriatric years for women, why is this? (Osteoclasts are the cells that degrade bone to initiate normal bone remodelling)
Reduction in Oestrogen and progesterone due to menopause
Where do parathyroid hormones come from?
Secreted by four tiny parathyroid glands on the posterior surface of the Thyroid gland. There is no anatomical or physiological connection between the thyroid and the parathyroid. Each parathyroid gland is about the size of a lentil
What would be the result from a small 1% drop in the level of blood calcium?
The secretion of PTH would be doubled; very sensitive and responsive to changes in calcium concentration.