Lecture 15: Calcium Balance Flashcards
T/F Ca is the most abundant element in the body
true
~99% of body Ca is found where
skeletal bone and teeth
0.9% is cytoplasmic (soft tissue)
0.1% in blood and exctracellular fluid (10mg/dl)
what is the second most abundant mineral in the body
Phosphate
0.1% in blood and ECF
hydroxyapatite
biological apatite that makes bone (Ca+Phosphate)
how can plasma ionized Ca be altered?
- increases in plasma proteins increases total bound Ca w/ minimal changes to ionized Ca
- increases in anions (phosphate) increase anion or complexed Ca and decrease ionized Ca
- acid base fluxes: protons compete w/ calcium for albumin binding sites
how can plasma ionized Ca be altered?
- hormonally mediated exchange b/w intestine, bone, kidney
Ca+ balance in the body (b/w ECF/bone/intestine/kidney) is slow compared to Ca+ balance in the
ECF (B/w ECF + bone fluid)
Ca and phosphate levels in the blood are regulated by ______ and vitamin _____
Parathyroid Hormone (PTH) and Vit D
calcitonin opposes …..
PTH
What conditions stimulate PTH
- low plasma Ca
- high plasma phosphate
what is the main regulator of Ca metabolism
PTH
what conditions stimulate Vit D and what does it do
- low plasma Ca
- increases absorption of Ca from the inteestine
- mainly balances Ca metabolsim via absorption in the gut
______ is not essential for the homeostasis or balance of Ca but does correct symptoms of hypercalcemia
Calcitonin
stimulates bone resorption of Ca
most domestic animals have how many pair of parathyroid glands
4
what is the plasma half life of PTH
2-5 min
PTH is a _____ hormone
peptide
high Ca levels inhibit the release of ….
PTH
majority cell type in the Parathyroid gland, they detect extra cellular Ca levels
Chief cells
*HUMORAL RESPONSE
bone is a living tissue composed of mineral components called the ______
matrix
osteoblasts
bone builders
deposite the matrix
osteocytes
former osteoblasts that are now internalized in the bone
osteoclasts
bone demolition
resorb the matrix
they are dervied from modified macrophages
what are the 2 calcium pools
Labile pool:in bone fluid, allows for rapid exchange of Ca w/ blood
Stable pool: in bone matrix, allows for storage and slow exchange of Ca, site of bone resorption
bone organization
osteon w/ central canal
lamellae canaliculi
the osteoblast-osteocyte network is a pool of living tissue that has a ______ reserve of Ca+
labile
PTH activates membrane bound _____ in the osteobalsts and osteocytes to take in Ca
Ca pumps
* Ca then transferred from these cells to the central cancal and into the blood
* phosphate left behind
PTH receptors are located in….?
osteoblasts
NOT osteoclasts
In fast exchange, Ca is moved from the _____ pool in the bone fluid into the ____ by PTH-activated Ca+ pumps located inside the osteocytic-osteoblastic membrane
labile pool into the plasma
In slow exchange, Ca is moved from the _____ pool in the mineralized bone into the _____ through PTH induced dissolution of the bone by ______
stable pool to the plasma, osteoclasts
PTH inhibits the bone formation activity of _______
osteoblasts
Long term slow exchange of Ca+ causes a _______ in osteoblast activity and a ________ in osteoclast activity
decreased osteobalst activity
increased osteoclast activity
osteoblasts release _______ (a ligand) that binds its receptor to cause macrophages to differentiate into osteoclasts
RANKL (binds to RANK)
Osteoclasts release ______ and _____ to dissolved the matrix and release Ca and phoshpate
Hcl and hydrolytic enzymes
what are the 2 direct effects of PTH in the kidney
- Conserves Calcium
- Eliminates Phosphate
how do the kidneys conserve calcium when stimulated by PTH
- resorb more filtered Ca
- increase Na/Ca cotransport in the DT
- urine Ca decreases
how do the kidneys eliminate phosphate
- phosphate resobsorption decreases
- inhibits Na/PO43- cotransport in the PCT
- urine phosphate increases
** Phosphate elimination is necessary to avoid cation-anion complexes and apatite formation in blood**
how does PTH activate Vit D
by stimulating 1α hydroxylase within the kidney, which converts vit D precursor into its active form
how is Vit D obtained
through diet or dervied from precursor in skin w/ UV light exposure
what are the 3 steps of VIT D synthesis
- UV dependent proteolysis of 7-dehydrocholesterol to vitamin D3 (Can also come from diet)
- Activation : in liver, CYP27A1 adds OH group to carbon 25
- PTH dependent activation: in kidney, CYP27B1 adds OH group to Carbon 1
effects of Vit D in the kidney
promotes Ca reabsorption form the DT and promotes PT resorption of phosphate
in bone, Vit D synergizes w/ PTH to stimulate ________ and bone remodeling
resorption
osteomalacia in adult animals
- impaired ability to absorb Ca and Phosphate in the intestine
- usually results from interstinal surgery that causes decreased Vit D absorption
- malabsorption syndrome, malnutrition, renal failure, celiac disease
- bones become demineralized and soft, fracture easily
Phosphate is regulated directly by _____ in the intestines
vit D
Phosphate is regulated indirectly by….
the inverse relationship bw plasma phosphate and Ca
* a fall in phosphate increases Ca, resulting in decreased PTH
* PTH decrease increases renal phosphate reabsorption
calcitonin is produced in _____ cells of the thyroid gland
Parafollicular C cells
hypercalcemia stimulates calcitonin release to decrease_________
ECF Ca
* this decreases bone resportion by limiting the activity of osteoclasts via the cAMP pathway
* inhibits Ca and phosphate reabsorption in kidney
calcitonin has no effects in the intestine or on ________
vit D
malignant cell clusters secrete _______ and bind to the PTH receptor
PTH-related peptide (PTH-r)
an antagnosit to the PTH receptor
what is the effect of PTH-rp bindng to PTH receptor
- increases bone resorption
- increases renal Ca reabsorption
- inhibits renal phosphate reabsorption
** most common cause of hypercalcemia and dogs and is common in cats**
2 main effects of excessive PTH-rp secretion
- hypercalcemia
- hypophosphatemia
clinical signs of hypercalcemia
- weakness, lethargy, difficulting getting up
- hyporexia, nausea, V+, constipation
- hypertension, arrythmia
- polydipsia, polyuria, urolithiasis, UTIs
the main effects of Vit D occur where
small intestine
* increases Ca and phosphate absorption by increasing the expression of Ca binding protein, Calbindin
Rickets in juveniles
insufficient Vit D, Ca and phosphate to mineralize bone
* growth failure, skeletal abnormalities
primary hyperparathyroidism results in excess _______, and subsequently _______ and _______
PTH
- hypercalcemia
- hypophosphatemia
physiological effects of PTH Hypersecretion
- elevated urine levels of PO43- and Ca
- increase in ca-containing kidney stone
- impaired renal functioning
- reduces the excitability of muscle and nerves
- thinning of bone, increased risk for fracture
- osteoporosis, osteomalacia
commonly caused by PTH-secreting parathyroid adenoma
horses lack _______ and thus don’t form calcitriol
1α-hydroxylase
for horses, intstinal absorption of Ca is ________ of Vit D signaling
independent
they absorb more Ca in the GI tract than any other species
main mechanism of removing excess dietary calcium (equine)
renal excretion
equine chronic failure may be indicated by ________ due to decreased excretion
hypercalcemia
neoplasia, hyperparathyroidism and Vit D toxicity may also cause hypercalcemia
What causes equine hypervitaminosis D
latrogenic (Dr caused) or by ingetion of calcinogenic plants
* hypercalcemia
* hyperphosphatemia
physiological symptoms of hypoparathyroidism
- low PTH
- hypocalcemia
- hyperphosphatemia
- increased neuromuscular excitability
- cataracts
- cognitive changes
what might cause hypoparathyroidsim
- damage from surgical thyroidectomies
- treatment for cancers
- Grave’s disdease
