Renal Physiology VIII Flashcards
The function of Calcitriol is to maintain plasma levels of
Ca2+ and PO4
To accomplish this, calcitriol targets the renal tubules
and does which two things?
- ) Stimulates Ca2+ reabsorption
2. ) Blocks PO4 excretion
Calcitriol augments PTH-dependent Ca2+ reabsorption in the
Distal nephron
A powerful stimulant of Ca2+ and PO4 absorption from the small intestine (CaHPO4)
Calcitriol
In addition, Calcitriol induces Ca2+ and PO4 reabsorption from
Bone
During renal failure, the lack of calcitriol may play into the condition of
Secondary hyperparathyroidism
The overwhelming majority (approximately 99%) of body Ca2+ stores are housed within
Bone
There is a modicum of Ca2+ existing predominantly in bound form within the
ICF and ECF
Upon filtration from the glomeruli, Ca2+ reabsorption from the renal tubules follows the same general pattern as that of
Na+
The vast majority of the filtered load of Ca2+ is reabsorbed from the
Proximal tubule
Within the proximal tubule, this process is coupled to
Na+ and H2O reabsorption
However, Ca2+ moves mainly via the
Paracellular route
Within the TAL, Ca2+ reabsortion is again coupled to Na+ through the membrane potential gradients that are generated by
NKCC
Thus loop diuretics that block Na+ reabsorption also impair Ca2+ reabsorption from the
TAL
Within the distal tubule, Ca2+ reabsorption is stimulated by PTH and augmented by
Calcitriol
Hence, elevated PTH will induce
Hypocalciuria
Promote Ca2+ reabsorption from the distal tubule
Thiazide diuretics
To summarize, in response to depressed blood [Ca2+], PTH is secreted by the parathyroid glands in order to do what two things?
- ) Mobilize Ca2+ stores form bone
2. ) Thwart Ca2+ excretion by promoting reabsorption
Targets the proximal tubule to impair PO4 reabsorption and facilitates Ca2+ reabsorption from the distal tubules
PTH
In response to a PTH challenge, what would happen to the urinary concentrations of PO4 and Ca2+
Urine [PO4] would increase and urine [Ca2+] would decrease
Secondary hyperparathyroidism is known as
High bone turnover renal osteodystrophy
During chronic renal disease, Ca2+ reabsorption from the tubules is impaired; this results in
Hypocalcemia
Recall that hypocalcemia is the predominant stimulus for
PTH secretion
Since calcitriol is also produced within the kidney, chronic renal disease results in
Impaired calcitriol synthesis
Without calcitriol, Ca2+ reabsorption from the kidney and GI tract is
Blunted (exacerbates hypocalcemia)
Recall that calcitriol can block PTH secretion; therefore, diminished calcitriol production can exacerbate
Hyperparathyroidism
Finally, as renal function is lost, we see the retention of
PO4
Can directly induce hypocalcemia and has been shown to cause parathyroid hyperplasia
Hyperphosphatemia
Note that extra-skeletal calcifications (metastatic calcification) may occur within the
Heart, skeletal muscle, lungs, and large blood vessels
Myopathy and severe muscle weakness often occur with
Advanced renal failure
A condition of inadequate production of, or resistance to PTH
Hypoparathyroidism
As has been discussed, within the kidney PTH stimulates the production of calcitriol as well as the
reabsorption of Ca2+ from the
Distal nephron (more specifically the distal convoluted tubule)
Clinical signs of hypoparathyroidism are
Hypocalcemia, hyperphosphatemia, and low urinary Ca2+
In hypoparathyroidism, we see a disruption in calcitriol production, this leads to which 2 tings?
- ) Reduction in the ability to absorb dietary Ca2+ in small intestines
- ) Reabsorption of Ca2+ in DCT is prevented
Maintenance treatment of hypoparathyroidism involves the use of a form of
-goal is to restore serum Ca2+ to just below normal
Vitamin D
Why do we want to restore serum Ca2+ to just below normal levels when treating hypoparathyroidism?
Prevents symptoms of hypocalcemia while avoiding potential complications of elevated serum Ca2+
Since PTH enables the reabsorption of Ca2+ from the distal nephron, low-normal serum Ca2+ must be maintained in order to prevent
Hypercalciuria and the resultant nephrolithiasis
The kidney can
- ) Concentrate urine approximately
- ) Dilute urine approximately
- ) 4-fold
2. ) 10-fold
The kindeys concentrating urine maintains body free H2O and is called
NEgtive free clearance
The dilution of urine eliminates body free H2O and is called
Positive free H2O
This process relies upon the
Countercurrent multiplier mechanism
A key structure because of its ability to balance the concentrations of lumenal versus medullary interstitial NaCl and urea: the osmotic gradient
The loop of Henle
Can the loop of Henle maintain the necessary osmotic gradients without help?
No
A microvascular network that is intertwined among the loop of Henle
Vasa recta
Establishes the so called counter-current exchange mechanism that maintains the hypertonicity of the medullary interstitium
Vasa Recta
The vasa recta recycles NaCl, H2O, and a modicum of urea from the medullary interstitium back into
Systemic Circulation
What are the three key properties of the vasa recta?
- ) It’s looped structure
- ) Its relatively low blood flow
- ) Its inability to perform active transport
As blood descends the vasa, H2O loss from the plasma is initially
Robust
H2O loss then declines precipitously toward the
Deep Medullary Zone
Gradually increases from the more superficial to deep medullary zones
The influx of both NaCl and urea
The diffusion of H2O and solutes occurs because of the medullary interstitial osmotic gradient that is supported by the
Nephron (counter-current multiplier)
As blood ascends the vasa, solute loss (filtration) from the blood decreases because of the
Interstitial osmotic gradient
However, as blood ascends the vasa, we see the promotion of
H2O reabsorption from the interstitium
Does the blood leaving the vasa have more or less H2O and solutes than the blood that entered?
More (especially NaCl)
Through this mechanism with the vasa recta, NaCl is translocated from the interstitium, back into
Systemic circulation
The functional nephron operates as two looped tubes flowing in
Parallel
The delivery system is the selectively permeable
Nephron proper (proximal tubule)
Receives H2O, NaCl, K+, urea, etc. (as filtrate from glomerular blood); most of which is reabsorbed into the interstitium BECAUSE the interstitium contains osmotic gradients
Proximal Tubule
Assists in maintaining the interstitial osmotic gradients by recycling H2O, NaCl, etc. back into systemic circulation
Vasa Recta
Recall that changes in renal perfusion (i.e. renal BP) represent an immediate and profound signal to trigger alterations in renal
H2O and Na+ Handling
