PHYS - Calcium and Phosphate Metabolism Flashcards
What are the symptoms of hypocalcemia?
Decreased plasma calcium levels causes:
- Hyperreflexia
- Spontaneous twitching
- Muscle cramp
- Tingling
- Numbness
What is Trousseau Sign?
When a hand becomes hyperflexed at the wrist as a result of the use of a blood pressure cuff.
Positive Trosseau Sign indicates hypocalcemia
What is Chvostek sign?
Twitching of facial muscles when tapping on the facial nerve
Positive Chvosek sign indicates hypocalcemia
What are the symptoms of hypercalcemia?
Increased plasma calcium levels cause:
- Diarrhea
- Reduced appetite
- polyuria (excessive urination)
- Polydipsia (excessive thirst)
- Muscle weakness
- Hyporeflexia
- lethargy (lack of energy/enthusiasm)
- Coma
How does hypocalcemia affect membrane excitability?
Hypocalcemia = Decreased extracellular [Ca2+]
Decreased extracellular Ca2+ causes a reduction in activation threshold, causing an increase in membrane excitability
Causes spontaneous Action Potentials, leading to tetany, tingling, numbness, spontaneous muscle twitching
How does hypercalcemia affect membrane excitability?
Hyperycalcemia = Increased extracellular [Ca2+]
Increased extracellular Ca2+ causes an increase in activation threshold potential, making it more difficult to achieve an Action Potential (reducing cell membrane excitability)
Causes nervous system to become depressed and reflex responses are slowed
How do changes in plasma protein concentration affect Ca2+ concentration?
Increased plasma protein concentration increases total Ca2+ concentration
But causes no change in ionized Ca2+
How does anion concentration affect Ca2+ concentration?
Increased anion concentration (such as phosphate) will cause a decrease ionized Ca2+
Ca2+ cations will become complexed with Phosphate anions
How does acid-base abnormalities affect Ca2+ concentration?
Acid-Base affects Ca2+ binding to Albumin
Albumin prefers binding to H+, which compete for binding sites with Ca2+
When pH is low, there is a large concentration of H+ competing for Albumin binding sites, meaning there are less available for Ca2+. Therefore, acidic conditions will promote an increase in free Ca2+ and a reduction in protein-bound Ca2+
When pH is high, there is a low concentration of H+ competing for Albumin binding sites, meaning there are more sites available for Ca2+. Therefore, basic conditions will promote a decrease in free ionized Ca2+ and an increase in protein-bound Ca2+
What are the three organ systems, and three hormones involved in calcium homeostasis?
Bone, Intestines, Kidneys
PTH, Calcitonin, Calcitriol (AKA vitamin D)
How does PTH affect Ca2+ and Phosphate homeostasis?
- Promotes renal reabsorption of Ca2+ from nephron lumen
- Promotes bone resorption of Ca2+
(increases blood Ca2+ levels)
- Inhibits renal reabsorption of Pi from nephron lumen
- Promotes Bone resorption of Pi
PTH activates Clacitriol (Vitamin D) - which promotes intestinal absorption of both Ca2+ and Pi
PTH increases urinary cAMP levels (due to Gs signaling, which increases intracellular cAMP levels)
How does Calcitriol (vitamin D) affect Ca2+ homeostasis?
Calcitriol promotes absorption of Ca2+ from the GI tract
Calcitriol promotes bone resorption of Ca2+
How does calcitonin affect Ca2+ homeostasis?
Calcitonin inhibits bone resorption of Ca2+
How is PTH gene expression and secretion regulated?
CaSR receptors detect extracellular Ca2+
When Ca2+ binds to CaSR receptors, it activates Gi and Gq signaling cascades, resulting in the inhibition of PTH gene expression and inhibition of PTH secretion
VItamin D (steroid hormone) diffuses through the parathyroid cell membrane and inhibits PTH gene expression, while also stimulating CaSR receptor gene expression
What affect does Magnesium have on PTH secretion?
In cases of severe hypomagnesemia (which can be caused by alcoholism) PTH synthesis and secretion is inhibited
What secondary messenger cascade does PTH utilize at its targets?
PTH binds to GPCRs that utilize a Gs signaling cascade
G-alpha S subunit acivates adenylyl cyclase
Adenylyl cyclase converts ATP into cAMP
cAMP activates PKA
PKA phosphorylates target proteins
How is Calcitriol production regulated?
PTH, decreased Ca2+ levels, and decreased Pi levels each promote activity of 1 - alpha - hydroxylase ezyme (AKA CYP1-alpha)
1-alpha-hydroxylase is the enzyme responsible for the final step in Vitamin D synthesis
How does PTH work on bone?
PTH binds with receptors on osteoblast cells (cells that build bone)
Short-term action of PTH causes buildup of bone
Activates osteoblasts secrete cytokines, which activate osteoclasts (bone mineralizing cells)
Long-term action of PTH causes bone mineralization indirectly
What cell does Vitamin D act on in the bone?
Osteoclasts
What is M-CSF?
Macrophage Colony Stimulating Factor
Induce stem cells to differentiate into osteoclast precursors, then into mononuclear osteoclasts, then into multinucleated mature osteoclasts
What is RANKL?
Receptor Activator for NF-kB Ligand
cell surface protein on osteoblasts that is the PRIMARY MEDIATOR OF OSTEOCLAST FORMATION
Binds with RANK, which is a cell surface receptor found on precursor osteoclast cells
What is OPG?
Osteoprotegerin
It is a decoy receptor for RANKL, produced by Osteoblast cells in order to inhibit RANKL/RANK interaction
How do PTH and Vitamin D help regulate RANKL and OPG?
PTH promotes RANKL, inhibits OPG
Vitamin D also promotes RANKL
How does PTH conduct its actions on the kidney, and where does it occur?
PTH acts on the Proximal Tubule by interacting with a Gs GPCR
- Causes inhibition of the Na+/Phosphate cotransporter on the apical membrane (facing the nephron lumen)
- cAMP generated from this interaction enters the Urine
THINK PPP - PTH blocks PHOSPHATE reabsorption in the PROXIMAL TUBULE
PTH acts on the Distal Convoluted Tubule to promote Ca2+ reabsorption from the nephron lumen into the blood stream
