The Endocrine System, Parathyroid Hormone, Calcitonin, Calcium and Phosphate Metabolism, Vitamin D, Bone, and Teeth

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There are 2 regulatory hormones, Parathyroid Hormone and calcitonin.


CALCIUM AND PHOSPHATE IN THE EXTRACELLULAR FLUID AND THE PLASMA FUNCTION OF VITAMIN D.


  1. CONTROL OF VITAMIN D FORMATION
    1. The active form of Vitamin D 1,25-dihydroxycholecalceferol is regulated via the following steps
      1. In the skin: 7-dehyrocholesterol is conveted by UV light to Vitamin D3
      2. In the liver:  Vitamin D3 is converted to 25-hydroxycholecalciferol
      3. In the cortex of the kidney: 25-hydroxycholecalciferol is converted to 1,25-dihydroxycholecalceferol in reaction stimulated and controlled by PTH.
    2. PTH formation is stimulated by a reduction in ECF Calcium concentration, formation of 1,25-dihyroxycholecalcepherol also increases when Calium concentration in the ECF drops
  2. GASTROINTESTINAL CALCIUM ABSORPTION - 1,25-DIHYDROXYCHOLECALCIFEROL
    1. stimulates the intestinal epithelium of the small intestine to form calcium binding protein, calcium stimulated ATPase and Alkaline phosphatase, all which promote absorption of calcium ions out if the lumen to the intestine.
    2. Calcium cant cross cell membranes - calcium absorption occurs at a rate determined by 1,25-dihydroxycholecalceferol.
    3. Phosphate absorption is not regulated
  3. Calcium and Phosphate in the Extracellular Fluid and Plasma
    1. Accurate regulation of calcium ion concentration is essential to normal function of the neuromuscular system and the skeletal system
      1. Calcium concentrations less than 50% result in neuromuscular dysfunction, Intitially hyperreflexivity and finally tetenic contractions  
      2. If calcium concentration raises to 50% greater than normal, CNS depression will occur, along with slowing contractions of smooth muscle of the GIT
      3. Phosphate concentrations can vary widely with limited physiological impact.
  4. Bone and its relation to Extracellular Calcium and Phosphate
    5. most of bone is large salts - hydroxyapatite
    1. Bone is composed mostly of calcium and phosphate salts along with organic matrix
      1. most of bone is large salts - hydroxyapatite
    2. Formation of collagen fiber matrix precedes calcification
      1.  
      2. Bone formation begins with secretion collagen fibers by osteoblast cells
      3. the uncalcified collagen structure is referred to as osteoid  
    3. Bone is continually deposited by osteoblasts and absorbed by osteoclasts, a dynamic process referred to as remodeling:
      1. Mechanical Stress
      2. PTH and 1,25-dihydroxycholecalcepherol stimulate osteoclast activity and formation of new osteoclasts
      3. Calcitonin - decreases the absoptive capacity of osteoclasts and decreases the rate of formation of osteoclasts 
    4. The calcium and phosphate present in bone serve as resivoirs for the ions in the ECF
  5. Parathyroid Hormone
    1. PTH secretion increases in response to a reduction in extracellular calcium concentration
      1. formed in the CHIEF CELLS of the parathyroid gland
      3. If the low calcium levels persist - the parathyroid hormones will hypertrophy, as occurs in pregnancy and rickets, disease that is characterised by low calcium absorption from the GIT.
    2. Increase in PTH concentration decreases renal calcium Excretion.
      1. pH
        1. Metabolic acidosis - Increase Calcium Excretion
        2. Metabolic alkalosis - Decreases Calcium Excretion
      2. Increased PTH decreases Calcium Excretion 
    3. Increases in PTH concentration elevate phosphate excretion
  6. Calcitonin
    1. Calcitonin secretion increases in response to elevation of extracellular calcium concentration.
      1.  Secreted from the parafollicular cells found in the interstitial tissue of the thyroid
      2. Opposing effects to PTH
      3.    
  7. Overall control of Calcium Concentration
    1. Regulation of Calcium Distribution between Bone and Extracellular Fluid
    2. Regulation of Absorption from the GIT. When calciumcncentration in the ECF falls:
      1. PTH causes a higher rate of formation of 1,25-dihydroxycholecalceferol
      2. 1,25-dihydroxycholecalceferol stimulates the formation of calcium-binding protein in the epithelium of the small intestine that increase the rate of absorption of calcium from the lumen of the Gut.
    3. Regulation of Renal Calcium and Phosphate Excretion
      1. Low Calcium
        1. PTH formation increases
          1. Calcium absorption from collecting duct increases, and excretion of calcium decreases
          2. Phosphate reabsorption from the proximal tubule decreases, and phosphate excretion increases
  8. Physiology of Parathyroid Hormone and Bone Disease
    1. Hypoparathyroidism decreases extracellular calcium concentration
      1. Osteoclasts become inactive and the formation of 1,25-dihydrocholecalceferol declines to very low levels. 
        1. Transfer of calcium from the bone to the ECF decreases
        2. GIT lumen absorption decreases
        3. Kidney excretion is greater than the rate of absorption from the GIT lumen
      2. Treat with large doses of Vitamin D - 1,25-dihydroxycholecalciferol
    2. Excessive formation of PTH by the parathyroid gland (hyperparathyroidism) causes loss of calcium from bone and increase extracellular calcium concentration
      1. Stimulates excessive osteoclast activity, renal retension of calcium and excretion of phosphate, and increased formation of 1,25-dihydroxycholecalceferol.
      2. Calcium is elevated and the phosphates are low.
      3. Bony fractures is a complication
    3. Rickets is caused by inadequate absorption of calcium from the GIT
      1. Inadequate dietary calcium of failure to form adequate 1,25-dihydroxycholecalciferol.
      2. Kidney damage or absent kidneys - 1,25-dihydroxycholecalciferol cannot be formed.
      3. PTH is elevated - secondary to the chronic calcium ion deficiency 
        1. PTH causes renal calcium retension and potassium excretion
        2. weakening of the bone
    4. Osteoperosis is caused by depressed deposition of new bone by osteoblasts
      1. The rate of osteoblast deposition of new bone is less than the osteoclastic resorption of bone - caused by
        1. Loss of anabolic sex steroids, estrogen and testosterone, which strongly stimulate the activity of osteoblasts
        2. Calcium supplimentation post menopause is not effective as the condition is not caracterised by a shortage of calcium but a suppression of the osteoblastic activity
  9. Physiology of the Teeth - four parts: enamel, dentine, cementum and pulp 
    1. Enamel makes up the outer layer of the crown of the tooth
      1. Large and dense crystals of hydroxyapatite in a tight mashwork of protein fibers
      2. Hard and resistant
    2. Dentine makes up the main Body of the Tooth
      1. Hydroxyapatite crystals 
    3. Cementum is the bony substance that lines the tooth socket
      1. secreted by the peridontal membrane
    4. Pulp is the tissue that fills the pulp cavity of the tooth







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