1. Unit Fourteen: Endocrinology and Reproduction
Chapter 79: PTH, Calcitonin, Calcium and
Phosphate Metabolism, Vitamin D,
Bone, and Teeth
Guyton and Hall, Textbook of Medical Physiology, 12 edition

2. Overview of Ca and P Regulation in ECF and Plasma
Calcium in the Plasma and Interstitial Fluid
About 41% of the calcium is combined with the
plasma proteins and is non-diffusible through
the capillary membrane
About 9% of the calcium is diffusible but combined
with anionic substances
c. Remaining 50% is both diffusible and ionized

3. Overview of Ca and P Regulation in ECF and Plasma
Inorganic Phosphage in the ECF
Exists in two forms HPO4 (1.05 mmol/L) and
H2PO4 (0.26 mmol/L)
Increase in ECF phosphate and the two forms
increase proportionately
If pH becomes more acidic, H2PO4 increases
and HPO4 decreases

4. Overview of Ca and P Regulation in ECF and Plasma
Fig Distribution of the three forms of calcium

5. Overview of Ca and P Regulation in ECF and Plasma
Non-bone Physiologic Effects of Altered Calcium and Phosphate Concentrations in
the Body Fluids
Hypocalcemia causes nervous system excitement and tetany
Hypercalcemia depresses nervous system and muscle activity

6. Overview of Ca and P Regulation in ECF and Plasma
Absorption and Excretion of Ca and P
Fig Overview of calcium exchange between different tissue compartments
of a person ingesting 1000 mg calcium per day

7. Bone and Its Relation to Extracellular Ca and P
Organic Matrix of Bone
90-95% collagen fibers
Rest is a homogeneous ground substance
Ground substance-composed of ECF, proteoglycans, especially chondroitin sulfate and hyaluronic acid

8. Bone and Its Relation to Extracellular Ca and P
Bone Salts
Crystalline salts are primarily calcium and phosphate
Magnesium, sodium, potassium, and carbonate
ions are also present
c. Calcium salts have great compressible strength and collagen has great tensile strength

9. Bone and Its Relation to Extracellular Ca and P
Precipitation and Absorption of Calcium and
Phosphate in Bone-Equilibrium with the ECF
Mechanism of bone calcification
Initial stage in bone production is the secretion
of collagen molecules and ground substance by
osteoblasts
Collagen polymerizes to form collagen fibers and
forms the osteoid substance
Calcium salts ppt into the osteoid and eventually
the osteoid traps the osteoblasts which then are
referred to as osteocytes

10. Bone and Its Relation to Extracellular Ca and P
After a few days the ppt calcium forms hydroxy-
appetite crystals
Calcium exchange between bone and ECF-calcium
is in equlibrium between bone and ECF; provides a
rapid buffering system to keep the calcium ion
concentration in the ECFs from rising to excessive
levels or falling to low levels under transient conditions of excess or decreased availability of calcium

11. Bone and Its Relation to Extracellular Ca and P
Deposition and Absorption of Bone-Remodeling
Bone is continually being deposited by osteoblasts and being absorbed by osteoclasts; osteoclasts are found in bone cavities and on the outer surfaces
Absorption of bone-the function of osteoclasts; release proteolytic enzymes and organic acids
PTH stimulates osteoclast activity and bone resorption

12. Bone and Its Relation to Extracellular Ca and P
Deposition and Absorption of Bone-Remodeling
Bone deposition and absorption are normally in equilibrium (except in growing bones where deposition exceeds absorption)
Value of continual bone remodeling-bone adjusts in strength in proportion to the degree of bone stess; replacement of old bone with new bone keeps the bones tough but not brittle; allows for the proper support of mechanical forces by deposition and absorption in accordance with growth patterns

13. Bone and Its Relation to Extracellular Ca and P
Deposition and Absorption of Bone-Remodeling
Repair of a fracture activate osteoblasts-in a fracture osteobalsts are formed from osteoprogenitor cells; fracture maximally activates peristeal and intraosseus osteoblasts involved in the break; eventual formation of the callus (bony ridge surrounding the break)

14. Bone and Its Relation to Extracellular Ca and P
Fig Osteoblastic and osteoclastic activity
in the same bone

15. Bone and Its Relation to Extracellular Ca and P
Fig Bone resorption by osteoclasts

16. Bone and Its Relation to Extracellular Ca and P
Fig Structure of bone

17. Vitamin D
Cholecalciferol (Vitamin D3) is Formed in the Skin-
as a result of irradiation of 7-dehydrocholesterol,
a substance normally in the skin, by uv light rays
from the sun
Cholecalciferol is Converted to 25-Hydroxychole-
calciferol in the Liver

18. Vitamin D
Fig Activation of vitamin D3 to form 1,25-dihydroxycholecalciferol
and the role of vitamin D in controlling the plasma calcium
concentration

19. Vitamin D
Fig Effect of increasing vitamin D3 intake on the plasma concentration of
25-hydroxycholecalciferol.

20. Vitamin D
Fig Effect of plasma calcium concentration on plasma concentration
of 1,25-Dihydroxycholecalciferol

21. Vitamin D
Formation of 1,25-Dihydroxycholecalciferol in
the Kidneys and Its Control by PTH
Calcium Ion Concentration Controls the Formation
of 1,25-Dihydroxycholecalciferol
Actions of Vitamin D
Vitamin D receptors are present in most cells of
the body and are located in the nuclei of the
target cells.

22. Vitamin D
Actions of Vitamin D
Vitamin D has a “hormonal” effect promoting
intestinal calcium absorption
Promotes phosphate absorption by the intestines
Decreases renal calcium and phosphate
excretion
Extreme quantities cause absorption of bone
Small quantities promote bone calcification

23. Parathyroid Hormone (PTH)
Physiologic Anatomy of the Parathyroid Glands
Normally there are four glands located
immediately behind the thyroid gland
Removal of two of the glands generally causes
no major physiologic abnormalities (removal of
the third causes a transient hypoparathyroidism)

24. Parathyroid Hormone (PTH)
Physiologic Anatomy of the Parathyroid Glands
Fig The four parathyroid glands lie immediately behind
the thyroid gland.

25. Parathyroid Hormone (PTH)
Chemistry of Parathyroid Hormone
First is a preprohormone, the prohormone, and finally
the active hormone; MW 9500
PTH increases calcium and phosphate absorption
from the bone and decreases calcium excretion
by the kidneys

26. Parathyroid Hormone (PTH)
Chemistry of Parathyroid Hormone
Fig Approximate changes in calcium and phosphate concentrations during the
first 5 hours of PTH infusion at a moderate rate

27. Parathyroid Hormone (PTH)
Osteolysis-Rapid Phase of Ca and P Absorption
From Bone
In the presence of large quantities of PTH, removal
of bone salts occurs from two areas (1) from the bone
matrix in the vicinity of the osteocytes, and (2) near
the osteoblasts along the bone surface
Activation of the Osteoclasts-Slow Phase of Bone
Absorption and Calcium Phosphate Release
Occurs in two phases (1) immediate activation of
the osteoclasts already formed and

28. Parathyroid Hormone (PTH)
(2) formation of new osteoclasts
Several days of excess PTH usually cause the osteoclastic
system to become well developed, but can continue to
growth for months under the strong stimulus of PTH
After a few months, osteoclastic resorption can lead to
weakened bones and a secondary stimulation of
osteoblasts to correct the condition

29. Parathyroid Hormone (PTH)
PTH Decreases Calcium Excretion and Increases
Phosphate Excretion by the Kidneys
Causes rapid loss of phosphate due to a decrease in
proximal tubular reabsorption
Increases the renal absorption of calcium, magnesium,
and hydrogen
Decreases the absorption of sodium and amino acids
PTH is necessary otherwise there would be a continual
loss of calcium from the ECF and bones

30. Parathyroid Hormone (PTH)
PTH Increases the Intestinal Absorption of Ca and P
Cyclic AMP mediates the effects of PTH
Slightest decrease in calcium concentration in ECF
causes the parathyroid gland to increase the rate of
secretion within minutes
If decreased calcium concentration continues, the
parathyroid glands will hypertrophy (i.e. ricketts,
during pregnancy, and lactation)

31. Parathyroid Hormone (PTH)
Fig Approximate effect of plasma calcium concentration on the plasma
concentrations of PTH and calcitonin

32. Parathyroid Hormone (PTH)
Fig Summary of the effects of PTH on bone, the kidneys, and the
intestine in response to decreased extracellular fluid calcium
ion concentration

33. Calcitonin
Increased Plasma Calcium Concentration
Stimulates Calcitonin Secretion
Synthesis and secretion of calcitonin occur in the parafollicular or C cells of the thyroid gland
Calcitonin is a 32 amino acid peptide with a
MW 3400

34. Calcitonin
Calcitonin Decreases Plasma Calcium Levels
The immediate effect is to decrease the absorptive activities of the osteoclasts
The second and more prolonged effect is to decrease the formation of new osteoclasts
Calcitonin has only minor effects on calcium handling in the kidney tubules
Calcitonin has a weak effect on plasma Ca levels in the adult human

35. Summary of Control of Ca Ion Concentration
The First Line of Defense: Buffer Function of
the Exchangeable Calcium in Bones
The Second Line of Defense: Hormonal Control of Calcium Ion Concentration

36. Pathophysiology of PTH, Vitamin D, and Bone Disease
Hypoparathyroidism
Primary Hyperparathyroidism
Secondary Hyperparathyroidism
Ricketts
Osteoporosis

37. Physiology of the Teeth
Functions of Different Parts of the Teeth
Fig Functional parts of
a tooth

38. Physiology of the Teeth
Functions of Different Parts of the Teeth
Enamel-covers the outer surface of the crown of the tooth; once the tooth has erupted no more enamel is formed; extremely hard
Dentin-main body of the tooth and is composed of hydroxyapatite crystals embedded in collagen fibers; deposited and nourished by a layer of cells called odontoblasts

39. Physiology of the Teeth
Functions of Different Parts of the Teeth
Cementum-bony substance secreted by cells of the periodontal membrane which lines the tooth socket; collagen fibers and cementum hold the tooth in place; increases in thickness and strength with age
d. Pulp-fills the pulp cavity and is composed of connective tissue with nerve fibers, blood vessels, and lymphatics

40. Physiology of the Teeth
Dentition
Two sets of teeth: the deciduous or milk teeth and the permanent teeth
Deciduous-erupt between the 7th month and the second year of life, and last until the 6th to the 13th year of life; 20 in number
Permanent-replaces each deciduous tooth and an additional 8-12 molars appear posteriorly for a total of 28-32

41. Physiology of the Teeth
Formation of the Teeth
Fig A: Primordial tooth organ
B: Developing tooth
C: Erupting tooth

42. Physiology of the Teeth
Metabolic Factors Influence the Development
of the Teeth
Rate of development and speed of eruption can be accelerated by both thyroid and growth hormones
Deposition of salts is affected by the amount of calcium and phosphate in the diet, the amount of vitamin D, and the rate of PTH secretion

43. Physiology of the Teeth
Metabolic Factors Influence the Development
of the Teeth
Rate of development and speed of eruption can be accelerated by both thyroid and growth hormones
Deposition of salts is affected by the amount of calcium and phosphate in the diet, the amount of vitamin D, and the rate of PTH secretion
Mineral exchange-new salts replace old salts, similar to what occurs in bone

44. Physiology of the Teeth
Dental Abnormalities
Caries-result from the action of bacteria on teeth (most common Streptococcus mutans); begins with the formation of plaque; fluoride makes the teeth 3x more resistant to caries as teeth without fluoride
Malocclusion-usually caused by hereditary abnormality; the teeth do not interdigitate properly and therefore cannot perform their normal grinding or cutting action.