DR.

RODINA GOROSPE - Ca-bound to cell surfaces has a role in stabilization of

CALCIUM DISTRIBUTION:
•Body of young adult cont. 1100g or 27.5 mmol
•99% skeleton
- Skeleton- also storage depot of phosphorus and
contains 80% of total body phosphorus
- Bone- 3rd line defense in acid base regulation
because it contains CO3, HCO3, PO4
•1% ECF and ICF
membrane and intracellular adhesion.
- Excitable membrane contain Ca channels
- HYPERCALCEMIA-NS depression
- HYPO: NS Excitation
- Calcium from outside to inside: 10,000-1
3. Ca essential in all excretion-secretion processes.
- Release of hormone
- Release of other end products by exocrine cells
- NT release

•Calcium conc: 4. Ca essential for muscle contraction

- ECF: 2.5X10-3 mol/L 5. Milk production
- ICF: 10-7 mol/L
- Normal plasma concentration: 9.4mg/dl or 2.4 B. SKELETAL CALCIUM-structural
mmol/L (9-11mg%) Ca++ formation of teeth and bone.

•HYPOCALCEMIEA: RENAL HANDLING OF CALCIUM:

6mg/dl- tetany (+)chvostek’s sign
4mg/dl- lethal (+)trousseau’s sign •98-99% of filtered is reabsorbed
•90% proximal tubule and rest in ascending limb of LH and
DISTRIBUTION (mmol) of Calcium in normal distal tubule.
PLASMA: •distal tubule- regulated by: PTH
Total Ionized 45% 1.18
diffusible Complexed 10% 0.16 GIT HANDLING OF CALCIUM:
1.34 HCO3,
citrate, etc •Active and some passive transport in upper small intestines
Total Albumin 0.92 •active transport is facilitated by: 1,25 dihydrocholecalciferol
non- bound via: Ca++H+ATPase
diffusible Globulin 0.24
1.16 bound
Total 2.5
plasma
CALCIUM POOLS:
•not readily exchangeable
- The larger Ca++ pool: 99%
- Stable mature bone
•readily exchangeable
- It is in physicochemical equilibrium with ECF
- Consist of Calcium Phosphate salts
(immediate reserve for sudden, changes in blood
calcium concentration)
Labile bone

ROLE OF CALCIUM IN PHYSIOLOGIC PHOSPHATE DISTRIBUTION:

PROCESSES: •total body phosphorus: 500-800g (16.1-25.8mol)
A. NON SKELETAL: •total plasma- 12mg/dl
1. Homeostasis: Ca activation of clotting •body PO4 distribution
enzymes in plasma - Bones 85% - ECF 1%
2. Ca controls membrane excitation: - Cells 14-15%
•organic compounds- 2/3
•inorganic HPO4, H2PO4, PO4

H E R N A N D O 1
 PHOSPHATE RENAL HANDLING: OSTEOCYTE, OSTEOCLAST OSTEOBLAST:

•85-90% of filtered is reabsorbed by active transport in the •originate in bone marrow

proximal tubule which is inhibited by PTH. 1. Osteoblast: BONE FORMING
- Derived from stromal cell precursors in bone marrow
PHOSPHATE-GIT ABSORPTION - Secrete large quantities of type 1 collagen, other bone
matrix proteins and alkaline phosphatase
•duodenum and small intestines 2. Osteocyte- differentiate from osteoblast
•active transport and passive transport - Round, multi nuclear cells surrounding bone matrix
•PO4 is found in: that are found in bone lacunae
- ATP - Have osteolytic activity, w/c is stimulated by PTH
- Camp
- 2,3 diphosphoglycerate FACTORS AFFECTING OSTEOBLAST AND
•phosphorylation and dephosphorylation of proteins are OSTEOCLAST:
involved in regulation of cell functions.
Stimulate osteoblast:
BONE PHYSIOLOGY: - PTH
- 1,25 dihydrocholecalciferol
•Special form of CT made up of crystals of phosphates of - IL-1
calcium within the matrix of collagen - T3/T4
•large surface area (100acres or 405,000 sq.m)- - HGH
microcrystalline structure - PGE2
•protects vital organs - TNF
•permits locomotion - Estrogens
•total blood flow 200-400ml/min - Insulin
•protein- type 1 collagen - Calcitonin
•bone crystals- hydroxyapatites. Inhibit osteoblast:
•(+)sodium, magnesium, and carbonate - Corticosteroid
Stimulate osteoclast:
BONE CHEMISTRY: - PTH
- 1,25 dihydrocholecalciferol
•calcium hydroxyapatite crystals - IL 6,IL 11
- Ca10(PO4)6(OH)2 - Sex hormones
- Flouride ion can replace OH group to form - Adrenal cortex
fluoroapatite Inhibit osteoclast:
- Ca – PO4 ratio= 1.7:1 - Calcitonin
•dry, fat free- 2/3 mineral and 1/3 oraganic (90% collagen) - Estrogen
- TGF- beta
TYPES OF BONE: - IFN alpha
- PGE2
1. Compact: outer layer, surrounding trabecular
(spongy) which is made up of spicules separated BONE FORMATION:
by space.
- 75% bone is compact 1. Elaboration of extracellular collagen matrix by
- Nutrient provided by haversian canal with blood osteoblastic layer of cells (osteoid)
supply. 2. Mineralization
3. Mineral accretion of matrix
2. Trabecular- nutrient diffuse from bone ECF into
the trabeculae. BONE RESORPTION:

1. From deep, older apatite crystals

2. A. dissociation of organic matrix
B. Breakdown of bone crystal- Ca & PO4 released

H E R N A N D O 2
 -2 pairs- embedded behind thyroid gland
2 TYPES OF CELLS:
1. PRINCIPAL/ CHIEF CELLS:
Secrete PTH
2. OXYPHIL CELLS
Non secretory

PTH
•polypeptide hormone
•MOA: thru Camp
•oral administration is INEFFECTIVE
•Difficult to acquire

PTH SYNTHESIS AND SECRETION

CALCIUM-PHOSPHORUS PRODUCT

•(Ca)(PO4)=k
30-40 adults
40-55 children
•Ca and PO4 reciprocal relationship
•altered K, Ca and PO4 precipitate- deposit to soft tissue

CALCIUM METABOLISM

•1,25 dihydrocholecalciferol- a steroid hoemone from

vitamin D by successive hydroxylations in the liver and
kidney

•PTH- secreted by Parathyroid glands

HORMONE PROFILE:
- MOA: Mobilize calcium from bone and increase
VIT D, PTH CALCITONIN
urinary phosphate excretion
HYDROXY
CHOLE
•calcitonin- A calcium lowering hormone
CALCIFEROL
REGULATION OF CALCIUM METABOLISM: CHEMISTRY Closely related Linear 32Amono acid
to sterols, poly MW 3400
HORMONES: produced by Peptide
- PTH UV light MW-
- Calcitonin 9500,
- Vit D 84
- Parathyroid related protein (PTHrP): Acts as one Amino
of the PTH receptors and is important in skeletal acid,
development in utero synth as
prepro
TARGET ORGANS PTH
- Bone
- Kidney TRANSPORT Bound to Albumin
- GIT Globulin globulin
binding protein
PARATHYROID GLANDS: Moves vitD3
-Smallest endocrine gland- 6mm diameter from skin to
circulation

H E R N A N D O 3
 3 RECEPTORS:
1. HPTH/PTHrP
2. PTH2- does not bind PTHrP, found on brain,
placenta, pancreas
3. CPTH- reacts with carboxyl terminal of PTH
1& 2 Activate adenylyl cyclase and increase in
intracellular Camp
1 activates phospholipase C increasing ICP
calcium.

CALCITONIN:
- Synthesized by parafollicular or C cells
Transport:
T1/2: 10 mins

MOA:
Receptors:
-BONE: decrease bone resorption
-KIDNEYS: decrease in Ca and PO4 reabsorption
Increase renal excretion of Ca and PO4
-GI- decrease Ca absorption

VIT. D CALCITRIOL- is the mediator hormone for intestinalaction of

- Produced in the skin (epidermis by non enzymatic PTH and CALCITONIN.
photoactivation) of mammals from
7dehydrocholesterol VIT / HYDROXYCHOLECALCIFEROL:
- Liver- Vit D3 is converted to 25
hydroxycholecalciferol (calcidiol) •MRNA produced dictate formation
- Converted to kidney: to calcitriol, can be ingested •actions:
on diet as well - Increase calcium transport
- Transport: - GIT absorb
Calcidiol: 30ng/mol - RENAL reabsorb
Calcitriol 0.02ng/mol - BONE: increase bone resorption
Increase mature osteoclast but the net effect is Ca
MOA: mobilization.
Calcitriol plus receptor regulation of gene MOA: increase Ca transport increase Ca H ATPase into the
expression, increased transcription os some and interstitium
inhibition of transcription to others.
PTH:
PTH
- PreproPTH enters the ER, a leader sequence is - BONE: increase bone resorption and mobilize Ca
removed from the amino acid terminal to form 90 Stimulates both osteoclast and osteoblast with
amino acid, proPTH, 6 additional are removed osteoclastic effectpredominating
from pro PTH in GA to form 84 amino acid - RENAL:
package 1 granules and released by chief cells. Increase:
Transport: Ca reab in DT
PTH- 10-55pg/ml PO4 secretion/ excretion
T1/2-10 mins Decrease:
PO4 reab
MOA: Plasma PO4

H E R N A N D O 4
CALCITONIN:
True hypoparathyroidism:
- BONE: Decrease PTH,
decrease circulating Ca and PO by inhibiting bone Causes:
resorption. - hypoplasia/absence of parathyroids, accidental removal
Decrease osteoclastic activity - absence or renal failure or malabsorption.

- RENAL: Normal creatinine, alk phosphatase

Increase urinary excretion of Na, Ca, PO
Decrease Ca, PO reabsorption Decrease PTH: low serum Ca, and Increase Serum
Inhibit: renal alpha hydroxylase activity which Phosphate.
leads to the synthesis of calcitriol

- GIT: Pseudohypoparaythroidism:
Inhibit gastric motility and secretion, stimulates Associated with genetic defects.
interstitial secretion. - Normal PTH
Inhibit jejunal reabsorption of Ca and PO - Kidneys don’t respond to PTH
- PTH fails to inh reabs of PO4
- Inc serum PO4
- Decrease calcium due to reciprocal relationship of
BONE RENAL GIT BLOOD calcium phosphate.
RESORP CL ABS CONC
CA PO CA PO CA PO CA PO Pseudopseudohypoparathyroidism
- Normal PTH
PTH
- Normal Ca PO4 in serum
CAL
- Only genetic defects present:
CIT
Short stature
ONIN
Round face
VIT D
Short metacarpals
Ectopic bone
Knuckie knuckie dimple dimple sign
DISORDERS OF CALCIUM METABOLISM:
HYPERPARATHYROIDISM:
HYPOCALCEMIA: Causes:
►SERUM CALCIUM= below 8mg% - Adenomas/ carcinomas
►SERUM IONIZED CALCIUM= 4.1-5.1mg% Symptoms:
-increase serum Ca, dec serum PO
►syndromes associated with hypocalcemia -Increase urinary Ca, PO4
1. Hypoparathyroidism -DECALCIFICATION: all bones due to increase
2. Pseudohypoparathyroidism osteolytic activity
3. Osteomalacia or rickets -Renal lesions:
-malabsorption NEPHROLITHIASIS- renal pelvis
-vit D def NEPHROCALNOSIS- renal substance
-Renal insufficiency -Von Recklinghaussen’s disease
-Renal tubular acidosis
SECONDARY HYPERPARATHYROIDISM:
4. Hypomagnesemia Compensatory enlargement of parathyroid glands due
Decr PTH sec dec Ca to decd serum Ca for long period of time
(-) PTH 7 vitD action on Bone Causes:
-chronic renal disease
5. Acute pancreatitis -ricketts
Intraabdominal precipitation of calcium soaps -osteomalacia
leading to decrease calcium -pregnancy and lactation

H E R N A N D O 5
 CHRONIC RENAL DISEASE:
-failure to excrete PO4
-Increase serum PO4
-Decrease serum Ca
+Parathyroids
-Increase PTH secretion

RICKETTS(CHILDREN)/
OSTEOMALACIA(ALDULTS):
Alimentary Ricketts:
- Vit D def in Children
- Dec Ca from Gut
- Dec serum Ca
- (+) parathyroids
- Inc PTH secretion

Renal Ricketts
- Excessive loss of Ca/ PO thru urinary tract
- Decrease serum Ca
- (+) parathyroids

PREGNANCY AND LACTATION:

- Increase transfer of Ca to fetus/ milk
- Dec serum Ca
- (+) parathyroids

H E R N A N D O 6
H E R N A N D O 7