Calcium & Phosphate Metabolism - Kovesdy Flashcards
Does dialysis represent a significant risk in the increase of calcification?
yes, coronary arter calcium was 2.5-5 times higher in dialysis pts
what is the importance of increased coronary arter calcium scores?
they are associated with high cv risk
T of F: Young dialysis pts were able to avoid increased coronary artery calcification
False
How do calcified/elderly stiff arteries affect pulse wave conduction of the heart?
in a young compliant artery, the normal pulse wave velocity is 8m/sec, returning during disatole
in calcified, old arteries, increased velocity of 12m/s, returning during systole, leading to abnormal heart beat
what does the abnormal heart beat due to calcification lead to?
increases vascular afterload with a propensity to develop lvh
decresaes coronary perfusion pressure
increases myocardial oxygen demand and subendocardial ischemia
increases endothelial dysfunction and atherogenesis
Where is the majority of phosphorus in the body? the minority?
85% in bone
ECF has less than 1%
What are the functions of phosphorus in the body?
key component of bony skeleton
important for metabolic processes (formatino of atp)
component of nucleic acids
important blood and urinary pH buffer
What is the normal concen in plasma of phosphorus?
3-4.5 mg/dl
How is phosphorus primarly present in the plasma?
hpo4 and h2p04
What is the ratio of hpo4 to h2po3 at a pH of 7.4?
4:1
Where is the majority of phosphorus excreted?
900 mg in urine/day
500 mg in fecal matter/day
Does a lower phosphate diet in dialysis pts help with their positive phosphorus balance in the body?
No, so they must use phosphate binders
What does the majority of the reabsorption of phosphate occur in the nephron?
pct (because mass quantity
what transporter does phosphate use?
uses Na-Phosphate transporter
What is TmP?
tubular maximum reabsorption of phosphate
As you increase GFR, what happens to TmP?
It increases as well.
What is the overall goal of Parathyroid Hormone?
To increase the serum calcium
How does PTH work through the kidney?
It stimulates the activation of vit d. which increases phosphate excretion and increases calcium reabsorption
How does PTH prevent phosphate reabsorption
it inactivates the na-p04 transporter in the pct
what happens to calcium when you have excess amounts of phosphate in the blood
the phosphate traps the calcium, preventing the active ion form from being highly available
What effect does the increases vit d due to increased PTH have on the small intestine
It increases vit d excretion which then leads to calcium and phosphate reabsorption, leading to increased calcium levels but also phosphate
What effect on the bone does increased PTH have?
it causes the efflux of Ca and Phosphate, enhancing bone turnoever
What occurs in response to PTH when you have kidney damage?
You lose the vitamind d production, which prevents phosphate excretion from occurring and calcium reabsorption from occurring. Also, the stomach decreases phophate reabsorption and calcium reabsorption. All thisleads to a decreased calcium concentration. Significance in the lost ability to regulate.
Is hyperphosphatemia common or uncommon in mild to moderate kidney disease?
no
What is the cutoff for hyperphosphatemia?
> 6 mg/dL, a strong predictor of death
Is hypophosphatemia or hyper considered life threatening?
hyperphosphatemia
How does kidney disease affect calcium and phosphate levels?
When you have kidney disease, you have a decrease in functioning nephrons. As such, each nephron takes on an additional load and you also secrete more PTH (attempting to lower phosphate levels and raise calcium levels). However, at a certain point, PTH being elevated isn’t enough to compensate for the renal failure, leading to hyperphosphatemia due to decreased phosphate excretion in the urine.
Where is majority of calcium excreted? The next largest amount?
Most in fecal loss 700
Urine 300
what happens to calcium levels in ckd?
you have less vit d. so the kidney reabsorbs less calcium and small intestine lowers calcium reabsorption, leading to hypocalcemia
as ckd progresses, phosphate levels increase or decrease?
calcium levels?
calcium levels decrease
phosphate levels increase
in ckd, can you see hypercalcemia?
yes, however it’s not as common or extreme as seeing hypocalcemia
What percentage of calcium is bound to albumin, and thus inactive?
40%
In CKD, you have less of what plasma protein, which could give you a decreased calcium level as well.
less albumin, leading to underestimating the amount of ionized calcium. you may have ionized calcium and see a decreased total calcium duet o loss of albumin-bound calcium
what calcium is typically measured?
both the albumin-bound and the ionized. this is how numbers can be misleading in ckd. may have a decreased level of albumin leading to artificially low Ca levels
What are the two main roles of calcium in the body?
rapidly fluctuating intracellular messenger
integral part of skeletal structure
Does hypocalcemia increase or decrease neuromuscular excitability?
increase
what are risks associated with hypercalcemia?
cv risk and soft tissue calcification
in normal kidneys, how is a vitamin d deficiency compensated for?
decreased vitamin d decreases calcium levels, which increases PTH (loewr phosphate levels). Increased PTH triggers kidney 1alpha-hydroxylase, which is stronger than tissue 1alpha-hydroxylase. This makes up for vitamin D deficiency
How does increased PTH in ckd lead to bone disease?
when you have low vit d, you get low calcium which activated and increases PTH levels. When increased PTH can’t activate kidney 1alpha-hydrxylase (bc ckd), you have decreased active vit. d and then increased po4, which feeds back to increase PTH further. Also, decreased active vit D increases PTH. PTH though is also enhancing bone turnover for calcium, which is where you get the bone disease.
What is FGF23?
A circulating heparin-indpt mcul and inactivity 1alpha-hydroxylase activity
What hpapens in fgf23 excess?
hereditary/acquired hypophosphatemic rickets
low serum phosphate
aberrant vitamin d metabolism
rickets osteomalacia
what happens in fgf23 deficiency?
hereditary tumoral calcinosis
hyperphosphatemia
elevated1,25(0H)2d production
soft tissue calcifications
hyperosteosis
