"Medical Physiology Parathyroid Hormone Joseph Spadaro" 3/23 Flashcards
(32 cards)
How does acidosis increase free ionized calcium?
The lower pH blocks Ca binding to albumin.
Conversely, alkalosis may bind too much ionized calcium.
PO4 also binds to calcium and can lower free ionized calcium levels, acting like a buffer.
Why does higher than normal albumin suggest a falsely positive hypercalcemia?
Total calcium may be higher, because there is more albumin to bind to, but ionized calcium, the true indicator for hypercalcemia, may be normal.
T/F: Patients with FHH, familial hypercalcemic hypocalcuria have high serum calcium but no symptoms of hypercalcemia.
True.
Patients with FHH have higher than normal calcium serum levels, but this does not effect their PTH secretion, which remains normal.
What are the symptoms of hypocalcemia?
Learning retardation, apnea (children)
Tetany, siezure, muscle cramps, numbness, spasms
Long QT interval, reduced cardiac output
Weak bone development, osteomalacia
What are the symptoms of hypercalcemia?
Fatigue, anorexia, delirium, coma
Headache, intracranial pressure, muscle weakness
Hyperpolarization leading to reduced neural responses
Bradiacardia, short QT internal
Polydipsia, Polyuria, HTN, calculi
In normal physiology, when is PTH high?
PTH secretion from the parathyroid gland (chief cells) increases when serum calcium is low.
The targets are (1) the kidney (fast), and (2) the bone (slow).
What are the 3 effects of PTH on the kidney?
PTH:
- increases Ca absorption from the distal tubule
- inhibits PO4 absorption from the proximal tubule
- increases vitamin D synthesis (to its active form)
In general, PTH effects on bone are slow. What is the fast effect of PTH on bone?
Osteocytic osteolysis
How does PTH influence osteoclast activity?
PTH’s main effect is on cells of osteoblastic lineage. These cells secrete paracrine agents is RANK-L that cause their maturation into active multi-nucleated osteoclasts, which resorb bone on the surfaces. This process slows in response to normalizing calcium levels.
How does the calcium sensor on the parathyroid gland function?
The calcium sensor on the parathyroid gland is a GPCR. Other inputs for PTH maintenance include high PO4 and low Mg, which both increase PTH release.
Would high active vitamin D increase or decrease PTH release?
Decrease
Where does the majority of calcium re-absortion occur in the kidney?
60% of daily calcium re-absorption occurs in the proximal tubule, via active transport, but this is not where PTH exerts its main effect on calcium. PTH affects the 9% of calcium normally re-absorbed in the distal tubule, through a channel.
Low PTH would have what effect on the proximal tubule?
Low PTH would allow more re-absorption of PO4 in the proximal tubule.
How does vitamin D act to support calcium reabsorption in the DCT?
Vitamin D acts on the basolateral side to put re-absorbed calcium into the blood, so that there is a gradient for movement of more calcium from the lumenal side. Calcium moves through the calbindin transporter.
Why is it important for PTH to decrease PO4 re-absorption from the PCT?
Ultimately, PTH increases result in both high serum calcium and phosphate due to bone resorption and calcium/PO4 absorption from the small intestine. Therefore wasting PO4 in the PCT keeps the PO4 from getting too high.
The two major targets of vitamin D are:
The two major targets of vitamin D are:
- small intestine
- bone
In both instances, vitamin D (active) acts to cause calcium and phosphate to travel from the lumen into the plasma.
What is the effect of vitamin D on the parathyroid gland?
Vitamin D negatively feeds back to the parathyroid gland to reduce PTH release, acting as a “buffer” to low calcium levels.
How does vitamin D affect osteoclast activity?
It acts on osteoblast receptors, and induces cell signaling to convert blasts to clasts.
Cholecalciferol, a vitamin D precursor, is also known as:
Vitamin D3, and is inactive until it becomes 1,25-OH2-vitamin D aka calcitrol.
D3 comes from cholesterol in the skin, and needs UV light to proceed down the path of vitamin D synthesis. Vitamin D synthesis occurs most notably in the kidney,but there is redundancy of this system in other tissues. The enzyme critical to this conversion to active vitamin D is 1-alpha-hydroxylase, the activity of which in creased when PTH acts on the kidney.
How does vitamin D increase calcium and phosphate absorption from the small intestine?
Vitamin D increases the synthesis of the calbindin transporter.
Technically the increase in phosphate absorption is not needed or desirable.
How does Rickets cause bone malformation?
Rickets is a chronic deficiency of vitamin D and/or the dietary deficiency of calcium/phosphorous during early development. The poor mineralization of bone results in bowing due to gravity of body on top of the legs. Children also have abnormal growth plates.
In adults, poor mineralization results in osteomalacia.
The following symptoms and labs suggest what dx? high serum calcium low serum phosphate high serum PTH high alk phos hypercalciuria kidney stone
Primary hyperparathyroidism, such as that from a PTH secreting adenoma. Too much calcium resulted in the precipitation of calcium in the form of a kidney stone.
PTH secretion in response to low calcium has what effect on urinary cAMP?
Increases urinary cAMP
The following symptoms and labs suggest what dx? Serum calcium high serum phosphate low serum PTH low alk phos very high lethargy ongoing cancer
Humoral hypercalcemia of malignancy. The tumor cells are secreting a PTH analog (PTH-rp). The real PTH was inhibited by the high calcium.
