LECTURE 5 (Parathyroid) Flashcards
How is calcium present in the body?
- combined with plasma proteins (non-diffusible through the capillary membrane)
- combined with anionic substances of plasma and interstitial fluids [IONISED] (diffusible through capillary membrane)
- diffusible through capillary membrane AND ionised
Which forms does inorganic phosphate exist in the plasma?
- HPO4+
- H2PO4-
Explanation: When the total quantity of phosphate in the extracellular fluid rises, so does the the quantity of each type of phosphate
What happens when the pH of the extracellular fluid becomes more acidic?
A relative increase in H2PO4- and a decrease in HPO4+
Explanation: This is to react with the increase in H+ in order to maintain the acid-base balance. The opposite occurs when the ECF becomes too alkaline.
What happens in Hypocalcemia?
ECF concentration of calcium ions falls below normal -> nervous system becomes progressively more excitable since it causes increased neuronal membrane permeability to Na+ -> allows for easy initiation of action potentials
MANIFESTATIONS:
- Tetany
- Carpopedal spasm (tetany in the hand)
- Dilation of heart
- Increased membrane permeability in some cells
- Impaired blood clotting
What happens in Hypercalcemia?
Calcium in ECF rises above normal -> nervous system becomes depressed and reflex activities of the CNS are sluggish -> increased Ca2+ concentration decreases the QT interval of the heart and causes lack of appetite and constipation (due to depressed contractility of the GI muscle walls)
What does Vitamin D promote?
calcium absorption by the intestines
Describe the organic matrix of bone
- 90-95% collagen fibers (extend along lines of tensional force + give bone its powerful tensile strength)
- ground substance (ECF, proteoglycans- chondroitin sulphate + hyaluronic acid)
- bone salts (calcium + phosphate) “hydroxyapatite”
______________ inhibits the precipitation of hydroxyapatite crystals in normal tissues except for bone despite supersaturation of the ions
Pyrophosphate
Describe the process of bone calcification
1) Osteoblasts secrete collagen molecules and ground substance and the collagen monomers POLYMERISE rapidly to form collagen fibers forming an OSTEOID (a cartilage-like material differing from cartilage in that Ca2+ salts readily precipitate in it)
2) Some osteoblasts become entrapped in osteoid and become quiescent and become OSTEOCYTES
3) Calcium salts begin to precipitate on the surfaces of collagen fibers and rapidly multiply to form HYDROXYAPATITE CRYSTALS
Where do calcium salts precipitate under abnormal conditions?
- Arterial walls (forming arteriosclerosis)
- Degenerating tissues
- Old blood clots
What is the importance of exchangeable calcium?
It provides a rapid buffering mechanism to keep calcium ion concentration in the ECF from rising to excessive levels or falling to low levels under transient conditions of excess or decreased availability of calcium
What are osteoclasts?
Large, phagocytic, multinucleated cells that are derivatives of monocytes or monocyte-like cells in the bone marrow that absorb bone
Describe the process of bone absorption
1) Osteoclasts send out villus-like projections towards the bone, forming a ruffled border adjacent to the bone
2) The villi secrete PROTEOLYTIC ENZYMES (released from lysosomes of osteoclasts) and SEVERAL ACIDS (like citric acid and lactic acid released from the mitochondria and secretory vesicles) -> enzymes digest or dissolve organic matrix of bone and acids cause dissolution of bone salts
3) Osteoclastic cells also phagocytose minute particles of bone matrix and crystals, dissolving these and releasing the products into the blood
How does parathyroid hormone (PTH) stimulate osteoclast activity and bone resorption?
1) PTH binds to receptors on adjacent osteoblasts causing them to release cytokines including OSTEOPROTEGERIN LIGAND/RANK LIGAND
2) OPGL activates receptors on preosteoclast cells causing them to differentiate into mature multinucleated osteoclasts
3) Mature osteoclasts develop a ruffled border and release enzymes and acids that promote bone resorption
What is Osteoprotegerin?
Osteoprotegerin (OPG), also called “osteoclastogenesis inhibitory factor”, is secreted by osteoblasts and prevents OPGL from interacting with its receptor which inhibits differentiation of proteoclasts into mature osteoclasts that resorb bone
What is important about bone deposition and absorption?
The rates of bone deposition and absorption are equal to each other so the total mass of bone remains constant
Describe the process of bone remodelling
1) Osteoclasts eat away the bone and create a tunnel. Once the osteoclasts disappear, the tunnel is invaded by osteoblasts and new bone begins to develop.
2) New bone being laid down in successive layers of concentric circles (lamellae) on the inner surfaces of the cavity until the tunnel is filled
3) Deposition of new bone stops when the bone begins to grow blood vessels to supply the area (canal is called the HAVERSIAN CANAL)
What is the importance of bone remodelling?
- bones ordinarily adjust its strength in proportion to the degree of bone stress (bones thicken when subjected to heavy loads)
- shape of bone can be rearranged for proper support
- old becomes become brittle and weak (new bone is needed when old bone degenerates)
What does “bone stress” cause?
- stimulates osteoblastic deposition and calcification of bone
- determines shape of bones
Describe the activation of Vitamin D3 to form 1,25-dihydroxycholecalciferol
1) Vitamin D3 (CHOLECALCIFEROL) is formed in the skin as a result of irradiation of 7-DEHYDROCHOLESTEROL (from UV rays)
2) Vitamin D3 is converted in the liver into 25-HYDROXYCHOLECALCIFEROL (limited since has an inhibitory feedback to be converted back to Vitamin D3 to be stored in liver for months)
3) 25-HYDROXYCHOLECALCIFEROL is converted to 1,25-DIHYDROXYCHOLECALCIFEROL in the kidneys in the presence of PTH (absence of kidneys or PTH -> cannot happen)
What is the importance of the inhibitory feedback mechanism of Vitamin D3 to 25-hydroxycholecalciferol?
- It regulates the concentration of 25-hydroxycholecalciferol in the plasma (high degree of feedback control prevents excessive action of vitamin D when intake is high)
- Conserves the vitamin D stored in liver for future use (25-hydroxycholecalciferol lasts for several weeks but vitamin D in the liver can stay for months)
