Regulation of Calcium and Phosphate Metabolism Flashcards
(42 cards)
Where is most calcium stored?
In bones and teeth
The extracellular calcium concentration has a dramatic effect on the ? of cells
Excitability (particularly nerve fibers)
What are symptoms of hypocalcemia?
Hyperreflexia, spontaneous twitching, muscle cramps, tingling, numbness
What is Chvostek sign?
Twitching of facial muscles elicited by tapping on facial nerve when patient is hypocalcemic
What is Trousseau sign?
Carpopedal spasm upon inflation of BP cuff
What are symptoms of hypercalcemia?
Decreased QT interval, constipation, decreased appetite, polyuria (excess dilute urine), polydipsia (thirst), muscles weakness, hyporeflexia, lethargy, coma
What causes hypocalcemic tetany?
Hypocalcemia reduces activation threshold for Na+ channels = increased membrane excitability = easier to evoke APs (aka spontaneous APs occur)
How do acidemia and alkalemia alter ionized Ca2+ concentration?
Acidemia = more H+ bound to albumin (-) so less Ca2+ bound = more free Ca2+
Alkalemia - more Ca2+ bound to albumin (-), decreased free Ca2+ concentration (usually accompanied by hypocalcemia)
To maintain Ca2+ balance, kidneys must excrete ___ Ca2+ that is absorbed by the GI tract
The same amount
What is the relationship between Ca2+ and phosphate?
Inverse relationship
Extracellular [Pi] is regulated by?
The same hormones that regulate [Ca2+]
What is the normal range of extracellular Pi?
2.5-4.5 mg/dL
Where is most Pi located?
Bone (85%) and ICF (15%). <1% in plasma
Explain the regulation of PTH gene expression and secretion
High levels of Ca2+ bind to calcium sensing receptors (CaSR) which are Gi GPCRs in parathyroid cell membranes. The downstream effects of these GPCRs = inhibition of PTH gene in parathyroid cells and inhibition of PTH secretion
What does chronic hypercalcemia cause?
Decreased synthesis/storage of PTH (chief cells) and increased breakdown of stored PTH
What does chronic hypocalcemia cause?
Increased synthesis/storage of PTH and hyperplasia of parathyroid glands (secondary hyperparathyroidism)
What does hypomagnesemia cause?
Inhibition of PTH synthesis, storage, and secretion
seen in…. you guessed it….ALCOHOLISM (aka: what med school is slowly driving us to)
The PTH in humans can be pretty long, how much of a molecule is actually involved in it’s activity?
the first 34 amino acids
-apparently the rest is just for shits and gigs
What are some of the main actions PTH likes to do when plasma [Ca2+] is low?
- Increase bone resorption (bone)
- Decrease Pi reabsorption, Increase Ca2+ reabsorption, and increase urinary cAMP (kidney)
- Increase Ca2+ absorption indirectly via vitamin D…1,25-dihydroxycholecalciferol (Intestine)
all just to increase the [Ca2+] in plasma
(more than Natalie will ever do for me) ):
How good is Vitamin D?
Good enough to raise both Ca2+ and Pi plasma concentrations—> which promotes mineralization of new bone
Is regulated by Neg feedback (aka: “dr. that’s too rough”)
What is the main form of vit D in circulation?
and what is the active form?
25-OH-cholecalciferol = main circulating, low activity
1,25-(OH)2-cholecalciferol (active)
–converted by the 1alpha-hyroxylase (CYP1a) enzyme in proximal renal tubule
What are the short and long-term effects of PTH on bone?
Short term: Bone formation (direct osteoblast action)- basis for osteoporosis treatment (synthetic PTH administration)
Long-term: Increased bone resorption (via indirect action of osteoblast cytokines on osteoclasts)
What is M-CSF role in bone formation/resorption?
induces stem cells–>osteoclast precursors….all the way to matured osteoclasts
What are RANKL’s roles?
RANKL: (receptor activator for NF-kappaB)
- produced by osteoblasts
- primary mediator of osteoclast formation
- binds to RANK receptor on osteoclast precursors
