Calcium And Phosphate Homeostasis Flashcards
Ca+ in the body is found Where
99% bone and teeth 1% ICF Rest in ECF and Plasma
Ca+ is found HOW in what form
ACTIVE= Ca+2 (50%) 40% protein bound 60% ultra-filterable——10% anions attached to another ion , 50% Ionized ca+2
During Aging Ca+
Ca+2 absorption is decreased from food and such
=BONE gets reabsorbed faster then new bone can be made since Ca+2 is needed and not taken in sufficiently from food= osteoporosis, osteopenia
Hypocalcemia:
And symptoms
and signs
low Ca+2 in plasma
hyperreflexia, spntaneous twitching, muscle cramp, tingling and numbness
Chnostek sign=facial muscels twitch, when tap on facial nerve
Trousseau Sign= spasm of wrist and forarm when BP cuff is put on arm
Hypercalcemi:
Symptoms
high plasma Ca+2
shorter QT interval, constipation, low appetite, polyuria, muscle weakness, hyporeflexia, lethargy
Plasma Ca+2
ECM Ca+2
Low Ca+2 plasma
lowers threthhold for activation of NA+ channels to open
easier to get AP
=spontaneous AP made
=Hopocalcemic TETANY
(tingling, numbness-sensory neurons, spontaneous muscle twitches-motor neurons)
High Ca+2 plasma
harder to get AP , farther from threshold
Depressed NS and refelxes are slowed
Change form of Ca+2 found how:
- change [plasma protein] =increase plasma proteins-> increase Ca+2
- change [anion] = increase phosphate concentration –> lower ionized Ca+2
- change acid base abnormalities =change amount of Ca+-ALBUMIN–> ionized Ca+2 changes
Acidemia
high amounts of free ionized Ca+2 due to lower amounts of ALBUMIN
Alkalemia
decrease in free ionized Ca+2 due to high ALBUMIN, and usually due to HYPOCALCEMIA
HOW CA+2 ENTERS ECF
HOW CA+2 LEAVES ECF
(in GI, Bone, Kidneys)
GI: absorbed with VitD
(also secreated into the GI, and excreted)
BONE: resoption by osteoclasts, VitD +PTH
(Deposited also on bone)
KIDNEY:
Reabsorption with PTH
(Filtered into the kidney also)
Bone remodeling
no net gain or loss of Ca+2, deposited=resopted
Kidneys EXcrete how much Ca+2
as much as absorbed by the GI
P and Ca+2 relationship
inversily related
high P = low Ca+2
P: highest in bone85%, then ICF15%, then Plasma1%
PTH Cycle/Pathways of Ca and P
- parathyroid glands make and secrete PTH by chief cells
- PTH = DECREASE Ca+2
PTH = INCREASE P
(high ECM Ca+2—-I PTH synthesis) since Ca+2 binds to CaSR and signals inhibition if PTH synthesis and secretion
when is PTH secreted
low Ca+2 in plasma
PTH H. characteristics
peptide
pre-pro-PTH—-> Pro-PTH—–> PTH in the GOLGI—> packaged into secratory granules
INCREASE RANKL, and DECREASE OPG
Binds to a GPCR
PTH in chronic Hypercalcemia
very low amounts of PTH synthesis and storge
=higher breakdown of stored PTH fragments released into the blood
PTH in chronic hypocalcemia
hgih levels of PTH made
= hyperplasia of parathyroid glands
= hyperparathyroidism
- During Low Ca+2, there is an increase in PTH, this causes WHAT
- Bone: incresed resorption of Ca+2 to ECF
- Kidney: decreased P reabsorption
increased Ca+2 reabsorption to ECF
increased cAMP in urine
- GI: increase absorption of Ca+2 with Vit D also to ECF
- CA+2 INCREASES TO NORMAL
VITAMINE D
increases P and Ca+2 in ECF = mineralization of new bone
decreases PTH
Vit D =STERIOID H.
(Cholecalciferon)- prohormone from diet and modified from sun
1, 25= active
24.25 = inactive
Kidney 1alpha-hydroxylase
inhibited by ca+2 and Vit D
Where are PTH receptors located
Osteoblasts
short-term, intermittent PTH
binds to osteoblasts to cause BONE FORMATION
for osteoporosis Tx
Long-term or continuous PTH
increase BONE RESORPTION causing osteoblasts to activate Osteoclasts
+ VIT D does the same
Bone resorption by PTH mechanism
- PTH or Vit D binds to Osteoblasts (PTHR)
- Osteoblasts secrete RANKL (also made by apoptotic osteoclasts + inhibits OPG secretion
- RANKL —> RANK receptor on osteoclasts
- Bone resorption
OPG
secreted by osteoblasts
—–I RANKL by binding to it and preventing it from binding to RANK receptor
=Bone formation
PTH in the kidney mechanism
- PTH binds to GPCR
- ATP—> cAMP
- cAMP activates protein kinase + excreted in urine
- protein kinase phosphorylates NPT (nephron Phosphate Transporter)
- —-I Pi reabsorption into the tubule
(+ increase Ca+2 reabsorption)
- excess P excreted in the urine
Vit D action in SI, Bone, Kidney, parathyroid Gland
SI= Increase Ca+2, and P
Bone = increase affintiy of PTH to osteoblasts (increase RANKL)
regulates calcification
Kidney= increase P reabsorption by NPT
Parathyroid Gland= —-I PTH gene
activate CaSR gene (increase ICF CA+2)
low Ca+2, how does PTH and Vit D act
Increase PTH
increase CYP1-alpha
increase:
- 1,25(OH)2 VIT D (slowest)
- Bone turnover
- Ca+2 reabsorption in bone and P excretion in the kidneys
- VIT D will increase: Ca+2 absorption by SI and P reabsorption by Kidneys
Calcitonin mechanism
“RISING CA+2 STIMULUS”
- HIGH Ca+2 stimulated calcitonin
- increase ca+2 bone deposition
decrease kidney uptake (reabsorption) of Ca+2
- lowers Ca+2 in blood
“FALLING CA+2 STIMULUS”
- low Ca+2
- PTH is released from the parathyroid gland
- *increase Ca+2 resorption from bones
*increase reabsorption of Ca+2 in kidneys
+ activate Vit D
- Vit D absorption of Ca+2 in SI
Calcitonin role
lower blood Ca+2 and P
binds to Osteoclasts to inhibit them
LONG TERM REGULATION of plasma CA+2
Thyroidectomy vs Tyroid tumors
X calcitonin= however no effect on Ca+2 reuptake
HIGH Calcitonin= however no effect on Ca+2 excretion or bone formation
calcitonin functions
and where does it bind
- —–I bone resorption= decrease Ca+2 and P
- binds to Osteoclast to inhibit their function
it is stimulated when Ca+2 is high
ACUTE
Estradiol-17B function
CA+2 absorption in GI
CA+2 Reabsorption in Kindey
SURVIVAL of osteoblasts
bone formation in bone
Adrenal Glucocorticoids (cortisol) function on Ca+2
Bone resporption
Ca+2 excretion in kidney
Ca+2 inhibited absorption in GI
can cause osteoporosis if prolonged steriod of cortisol is used
Primary Hyprtparathyroidism
Hypercalcinuria stones= increased PTH-> increased bone resorption—> stones and constepation groans
Tx: parathyroidectomy
(also increases P excretion, Ca+2 absorption and reabsorption, increased activation of VIT D)
HIGH, Vit D, Ca+2, PTH
Secondary Hyperparathyroidism
prolonger PTH =
- Renal Failure: low vit D, high P
- Vit D deficiency (low P)
—-> LOW CA+2
Hypoparathyroidism
Causes
and Tx
low PTH= low vitD activation, low Ca+2, high P
(Thyroid/parathyroid surgery, Autoimmune disease)
Tx: oral Ca+2 with active VitD
where is Vit D activated
Kidneys
25(OH)D3——> 1,25(OH)2D3
Hypoparathyroidsim
Sx:
Sx: muscel cramp, spasm
numbness or tingling, buring, around mouth
mental deficiency
poor teeth
seizures
Albright Hereditary Osteodystrophy (Psudohypoparathyroidism type 1a)
cause
Gs of the PTH R. is defective in bone and kindey
no cAMP
No bone resorption, no CA+2 reabsorption
LOW CA+2 HIGH P, PTH
=Hypoparathyroidism and Hyperphosphatemia
Albright Hereditary Osteodystrophy (Psudohypoparathyroidism type 1a)
Sx:
Sx: short neck, obesity, subcutaneous calcification, short finges
Humoral Hypercalcemia of malignancy
PTHrP(PTH related peptide) made by tumors
= similar to PTH —> type 1 PTH R.
HIGH Ca+2 reabsorptiona, resorption, absorption,
LOW P, PTH, vitD
same only slightly different from hyperparathyroidism
Familial Hypocalcinuric Hypercalcemia (FHH)
mutation inactivate CaSR in parathyroid = no inhibition of PTH exocytosis
LOW CA+2
Hypocalcinuria (low in urine)
Hypercalemia (high in blood)
Vit D inhibits what and activates what in the parathyroid
—–I PTH
—–> CaSR
Rickets- Osteomalacia
X: VitD metabolism
active vitD cant be formed (no 1-alpha-hyroxylase)
GI problems, Renal failure, LOW P and CA+2
Growth failure skeletal probs(children)
Xnew bones+ soft bones: Osteomalcia (adults)
Psudovitamin D-deficient rickets TYPE 1 vs TYPE 2
TYPE 1: X in 1-alpha-hydroxylase
TYPE 2: X in vitD receptor
Osteomalacia
LOW VIT D
GI disorder or bad nuttrition or low sun exposure
bone pain after gastric bypass surgery
Muscle weakness, fractures, cramps, + Chevostek’s sign, tingling and numbness
HIGH PTH, LOW Ca+2, P, cAMP
+ Chevostek’s sign
CN7 causes muscle twitching
=Hypocalcemia
When bone mass increases and decreases
steap increase: 0-30yo
men—> slow decrease
women—-> high decrease at 50yo
male is higher at all times
Osteoporisis Tx:
PTH anabolic therapy
Antiresorptive therapy: Bisphosphonated, ESTROGEN, CALCITONIN, DENOSUMAB (RANKL inhibitor)
Vit D cycle
