Transcript Unit One: Introduction to Physiology: The Cell and General

Chapter 79: PTH, Calcitonin, Calcium and
Phosphate Metabolism, Vitamin D,
Bone, and Teeth
Guyton and Hall, Textbook of Medical Physiology, 12 edition
Overview of Ca and P Regulation in ECF and Plasma
• Calcium in the Plasma and Interstitial Fluid
a. About 41% of the calcium is combined with the
plasma proteins and is non-diffusible through
the capillary membrane
b. About 9% of the calcium is diffusible but combined
with anionic substances
c. Remaining 50% is both diffusible and ionized
Overview of Ca and P Regulation in ECF and Plasma
• Inorganic Phosphage in the ECF
a. Exists in two forms HPO4 (1.05 mmol/L) and
H2PO4 (0.26 mmol/L)
b. Increase in ECF phosphate and the two forms
increase proportionately
c. If pH becomes more acidic, H2PO4 increases
and HPO4 decreases
Overview of Ca and P Regulation in ECF and Plasma
Fig. 79.1 Distribution of the three forms of calcium
Overview of Ca and P Regulation in ECF and Plasma
• Non-bone Physiologic Effects of Altered
Calcium and Phosphate Concentrations in
the Body Fluids
a. Hypocalcemia causes nervous system
excitement and tetany
b. Hypercalcemia depresses nervous system and
muscle activity
Overview of Ca and P Regulation in ECF and Plasma
• Absorption and Excretion of Ca and P
Fig. 79.3 Overview of calcium exchange between different tissue compartments
of a person ingesting 1000 mg calcium per day
Bone and Its Relation to Extracellular Ca and P
• Organic Matrix of Bone
a. 90-95% collagen fibers
b. Rest is a homogeneous ground substance
c. Ground substance-composed of ECF,
proteoglycans, especially chondroitin sulfate
and hyaluronic acid
Bone and Its Relation to Extracellular Ca and P
• Bone Salts
a. Crystalline salts are primarily calcium and
phosphate
b. Magnesium, sodium, potassium, and carbonate
ions are also present
c. Calcium salts have great compressible strength and
collagen has great tensile strength
Bone and Its Relation to Extracellular Ca and P
• Precipitation and Absorption of Calcium and
Phosphate in Bone-Equilibrium with the ECF
a. Mechanism of bone calcification
1) Initial stage in bone production is the secretion
of collagen molecules and ground substance by
osteoblasts
2) Collagen polymerizes to form collagen fibers and
forms the osteoid substance
3) Calcium salts ppt into the osteoid and eventually
the osteoid traps the osteoblasts which then are
referred to as osteocytes
Bone and Its Relation to Extracellular Ca and P
4) After a few days the ppt calcium forms hydroxyappetite crystals
b. 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
Bone and Its Relation to Extracellular Ca and P
•
Deposition and Absorption of Bone-Remodeling
a. Bone is continually being deposited by osteoblasts
and being absorbed by osteoclasts; osteoclasts are
found in bone cavities and on the outer surfaces
b. Absorption of bone-the function of osteoclasts;
release proteolytic enzymes and organic acids
c. PTH stimulates osteoclast activity and bone
resorption
Bone and Its Relation to Extracellular Ca and P
•
Deposition and Absorption of Bone-Remodeling
d. Bone deposition and absorption are normally in
equilibrium (except in growing bones where
deposition exceeds absorption)
e. 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
Bone and Its Relation to Extracellular Ca and P
•
Deposition and Absorption of Bone-Remodeling
f. 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)
Bone and Its Relation to Extracellular Ca and P
Fig. 79.4 Osteoblastic and osteoclastic activity
in the same bone
Bone and Its Relation to Extracellular Ca and P
Fig. 79.5 Bone resorption by osteoclasts
Bone and Its Relation to Extracellular Ca and P
Fig. 79.6 Structure of bone
Vitamin D
• Cholecalciferol (Vitamin D3) is Formed in the Skinas 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-Hydroxycholecalciferol in the Liver
Vitamin D
Fig. 79.7 Activation of vitamin D3 to form 1,25-dihydroxycholecalciferol
and the role of vitamin D in controlling the plasma calcium
concentration
Vitamin D
Fig. 79.8 Effect of increasing vitamin D3 intake on the plasma concentration of
25-hydroxycholecalciferol.
Vitamin D
Fig. 79.9 Effect of plasma calcium concentration on plasma concentration
of 1,25-Dihydroxycholecalciferol
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
a. Vitamin D receptors are present in most cells of
the body and are located in the nuclei of the
target cells.
Vitamin D
• Actions of Vitamin D
b. Vitamin D has a “hormonal” effect promoting
intestinal calcium absorption
c. Promotes phosphate absorption by the intestines
d. Decreases renal calcium and phosphate
excretion
e. Extreme quantities cause absorption of bone
f. Small quantities promote bone calcification
Parathyroid Hormone (PTH)
•Physiologic Anatomy of the Parathyroid Glands
a. Normally there are four glands located
immediately behind the thyroid gland
b. Removal of two of the glands generally causes
no major physiologic abnormalities (removal of
the third causes a transient hypoparathyroidism)
Parathyroid Hormone (PTH)
• Physiologic Anatomy of the Parathyroid Glands
Fig. 79.10 The four parathyroid glands lie immediately behind
the thyroid gland.
Parathyroid Hormone (PTH)
• Chemistry of Parathyroid Hormone
a. First is a preprohormone, the prohormone, and finally
the active hormone; MW 9500
b. PTH increases calcium and phosphate absorption
from the bone and decreases calcium excretion
by the kidneys
Parathyroid Hormone (PTH)
• Chemistry of Parathyroid Hormone
Fig. 79.11 Approximate changes in calcium and phosphate concentrations during the
first 5 hours of PTH infusion at a moderate rate
Parathyroid Hormone (PTH)
• Osteolysis-Rapid Phase of Ca and P Absorption
From Bone
a. 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
a. Occurs in two phases (1) immediate activation of
the osteoclasts already formed and
Parathyroid Hormone (PTH)
(2) formation of new osteoclasts
b. 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
c. After a few months, osteoclastic resorption can lead to
weakened bones and a secondary stimulation of
osteoblasts to correct the condition
Parathyroid Hormone (PTH)
•
PTH Decreases Calcium Excretion and Increases
Phosphate Excretion by the Kidneys
a. Causes rapid loss of phosphate due to a decrease in
proximal tubular reabsorption
b. Increases the renal absorption of calcium, magnesium,
and hydrogen
c. Decreases the absorption of sodium and amino acids
d. PTH is necessary otherwise there would be a continual
loss of calcium from the ECF and bones
Parathyroid Hormone (PTH)
•
PTH Increases the Intestinal Absorption of Ca and P
a. Cyclic AMP mediates the effects of PTH
b. Slightest decrease in calcium concentration in ECF
causes the parathyroid gland to increase the rate of
secretion within minutes
c. If decreased calcium concentration continues, the
parathyroid glands will hypertrophy (i.e. ricketts,
during pregnancy, and lactation)
Parathyroid Hormone (PTH)
Fig. 79.12 Approximate effect of plasma calcium concentration on the plasma
concentrations of PTH and calcitonin
Parathyroid Hormone (PTH)
Fig. 79.13 Summary of the effects of PTH on bone, the kidneys, and the
intestine in response to decreased extracellular fluid calcium
ion concentration
Calcitonin
• Increased Plasma Calcium Concentration
Stimulates Calcitonin Secretion
a. Synthesis and secretion of calcitonin occur in
the parafollicular or C cells of the thyroid
gland
b. Calcitonin is a 32 amino acid peptide with a
MW 3400
Calcitonin
• Calcitonin Decreases Plasma Calcium Levels
a. The immediate effect is to decrease the
absorptive activities of the osteoclasts
b. The second and more prolonged effect is to
decrease the formation of new osteoclasts
c. Calcitonin has only minor effects on calcium
handling in the kidney tubules
d. Calcitonin has a weak effect on plasma Ca
levels in the adult human
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
Pathophysiology of PTH, Vitamin D, and Bone Disease
• Hypoparathyroidism
• Primary Hyperparathyroidism
• Secondary Hyperparathyroidism
• Ricketts
• Osteoporosis
Physiology of the Teeth
• Functions of Different Parts of the Teeth
Fig. 79.14 Functional parts of
a tooth
Physiology of the Teeth
• Functions of Different Parts of the Teeth
a. Enamel-covers the outer surface of the crown of
the tooth; once the tooth has erupted no more
enamel is formed; extremely hard
b. 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
Physiology of the Teeth
• Functions of Different Parts of the Teeth
c. 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
Physiology of the Teeth
• Dentition
a. Two sets of teeth: the deciduous or milk teeth
and the permanent teeth
b. 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
c. Permanent-replaces each deciduous tooth and an
additional 8-12 molars appear posteriorly for a
total of 28-32
Physiology of the Teeth
• Formation of the Teeth
Fig. 79.15 A: Primordial tooth organ
B: Developing tooth
C: Erupting tooth
Physiology of the Teeth
• Metabolic Factors Influence the Development
of the Teeth
a. Rate of development and speed of eruption
can be accelerated by both thyroid and growth
hormones
b. 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
Physiology of the Teeth
• Metabolic Factors Influence the Development
of the Teeth
a. Rate of development and speed of eruption
can be accelerated by both thyroid and growth
hormones
b. 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
c. Mineral exchange-new salts replace old salts,
similar to what occurs in bone
Physiology of the Teeth
• Dental Abnormalities
a. 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
b. Malocclusion-usually caused by hereditary
abnormality; the teeth do not interdigitate
properly and therefore cannot perform their
normal grinding or cutting action.