---start 2.20.97 physio----

renal physio continued
phosphate reabsorption.

the hard stuff is over, we're just adding new solutes to it now.

phosphate is an integral electrolyte, many fxs. kidney regulates plasma 
[phosphate] but there are other metabolites influencing itas well. 

we call this serum inorganic phosphage. normal plasma conc is 3-6 mg/dl 
and it is present as ultrafilterable form, a free form - 80-90% of it, 
and 10-20% is protein bound, and not filtered. we are just pretending it 
is all free,since most of it is. free form exists as HPO4 and H2PO4, 
mostly HPO4. 

extrarenal factors: bone stores, intestinal absorption. these also 
regulate phosphate concentration. diet gives us about 20 mg/kg/day. about 
7 mg is excreted into feces. so about 13 is absorbed by intestines. it 
finally gets into plasma and then goes to kidney or to bone. the kidney 
and bone constantly see phosphate. bone is constantly remodeled so it 
uses phosphate and releases stored phosphate all the time. see handout 
"phosphorous pool" is plasma phosphate.

how does kidney regulate this? tubular reabsorption is the key process. 
no tubular secretion of phosphate exists. reabsorption of PO4 is in 
proximal tubule - see fig 10-17 showing that most of it is removed there. 
a bit is removed in loop of henle, and a tiny bit more in distal tubule. 
about 10% of filtered load of phosphate remains in urine. pretty much 
regardless of the load, 90% of the load is absorbed and 10% is excreted. 
this doesn't change much without a major change in PTH (parathyroid 
hormone). reabsorption mechanism is seen in fig 10-15. related to sodium: 
active pumps on brush border side, and passive movement of phosphate 
related to sodium movement. this phosphate is same phosphate used to 
excrete H+ in titratable acid system. before we had NHPO4, remember. the 
phosphate that picks up an H (H2PO4) is mostly excreted into urine, and 
carries H+ out with it.again most of this occurs in proximal tubule. 
Reabsorption of phosphate is classical "tubular maximum" TM system.

factors influencing reabsorption: table 10-6. PTH is the prime factor.
look at that table...very little handled in distal tubule, just forget 
that part ad remember the proximal tubule part which is mroe important. 
hypercalcemia increases HPO4 reabsorption if acute, chronic hypercalcemia 
DECREASES phosphate reabsorption. volume expansion decreases abs. of 
phosphate (and sodium.- the absorptions are linked.). acidosis causes 
minor decrease in phosphate reabsorption. alkalosis causes minor 
increase. PTH is overriding factor ofall. it decreases phosphate 
reabsorption. think of it as being the factor reducing phosphate 
reabsorption from 99% like sodium down to that fixed 90% level. Vitamin D 
acts like PTH, pretty much, but is minor compared to PTH. insulin and 
glucose have slightincreasing effect, and other stuff decreases it but 
these are all minor effects.     to show relationship between PTH and 
urinary handling of phosphate see slide:

plasma PTH and plasma phosphate and phosphate excretion are compared. 
there's a diurnal cycle of greater/lesser excretion of phosphate into 
urine. primary event leading to change in phosphate handling intubule is 
due to change in plasma phosphate concentration. if that changes, then 
PTH changes. PTH gland is sensitive, very sensitive to changes in plasma 
phosphate. so if you eat, and ingest phosphate, there is a slight change 
in plasma phosphate concentration which stimulates release of PTH, and 
PTH level will double or triple, increasing phosphate excretion (reducing 
phosphate reabsorption). so these three curves all pretty much parallel 
each other. 

so your body goes through these modulating phases minute to minute...

role of thyrocalcitonin is unclear, conflicting data.

growth hormone raises the TM for phosphate reabsorption. TM = maximal amt 
of phosphate that can be reabsorbed. thismakes sense: during growth, 
rapid bone development, need more phosphate to build bone. then you can 
save almost all of filtered load. 

reabsorption in animals in rapid growth phase, eg dog up to year old, 
serum phosphate is more like 6-9, not 3-6. cats elevated til about 9 mos, 
horses 2 yrs, people about 17 yrs.

tubular handling of calcium: 

usually discussed w/phosphate since both stored in bone. Ca++ is a 
different electrolyte in that the plasma concentration is divided equally 
between a free and a protein bound component. the normal concentration is 
9-11 mg/dl in plasma. slide shows that about half of that isin form of 
free ions (47%) and the rest is almost all protein bound. about 5 or 6% 
is CaPO4, CaCitrate, and other complexes. but we can call it half and 
half. only free calcium is filtered at the glomerulus. [tripp interrupts 
to find out what a dl is. why doesn't this seem surprising? :)]

moving on...
calcium is not well absorbed by GI tract. a lot goes out in stool. if 15 
mg/kg is eaten, 11 mg/kg is excreted in stool. we absorb less than half 
our ingested Ca++. absorption is strongly influenced by vit D. 

animals w/diarrhea can lose lots of calcium.

anyway...calcium in plasma is equilibrating w/calcium in bone due to 
remodeling...a relatively small amt calcium is presented to kidney and 
kidney tries to conserve it. normally, bet 95-99% of filtered load is 
reabsorbed. 

fig 10-4 note similarity to phosphate chart- just conserving a bit more 
of it.
in tubule, site of transport is proximal tubule, primarily. fig 10-2 
shows both prox and distal tubule - DT sees only small % of filtered 
load. there's a Ca++ ATPase pump on basolateral border. Ca++ is passively 
pulled in from the filtrate across the brush border in conjunction 
w/sodium. if you turn down sodium pump, you reduce Ca++ reabsorption (and 
vice versa)

distal tubule similar, but handles much smaller load and main factor 
influcing ca atpase pump is PTH. PTH INCREASES reabsorption of Ca++. 
recall it decreases HPO4 reabsorbtion.

fig 10-3 -two ways to consider serum calcium...

total serum calcium - mg/dl - normal 6-15. 
serum ultrafilterable Ca++ - normal 3-7.5 (half, remember)

kidney only sees filterable part. when we measure clinically, we measure 
total and assume that filterable part is 50%. UNLESS albumen is low, then 
we need to do a free (ionized) calcium level.

also, there are hypoparathyroid and hyperparathyroid patients on the 
chart. hyperparathyroidism is common in pets. these animals have a higher 
serum ca++. the increased PTH turns up Ca++ reabsorption, causing 
increased Ca++ levels. low levels of PTH (have had injury to gland or 
something) cause patient to not be able to reabsorb calcium. they get 
hypocalcemic.

don't worry about pathophysiology, just understand that PTH does the 
regulation here.

table 10-3 is summary of factors affecting ca++ reabsorption. primarily 
in proximal tubule...ignore stuff in loop of henle,that's not well 
understood, andignore distal tubule, it only handles a small amt.

hypercalcemia will decrease Ca++ absorption, as will phosphate depletion, 
volume expansion, hypermagnesemia, acidosis. he just said that PTH is the 
lone thing fighting to increase absorption, but the chart said alkalosis 
will too. hmmm.

slide: blood calcium pool communicates w/bone storage of Ca++ and PTH 
gland which is sensitive to changes in serum Ca++. if something happens 
to reduce plasma [Ca++], like in phosphate situation, PTH gland will make 
more hormone and the hormone will go to affect bone, kidney and gut, 
trying to increase plasma [Ca++]. in terms of kidney, it would increase 
calcium reabsorption. also directly affects production of vit D. kidney 
and liver will make more of it which will go to gut and increase Ca++ 
absorption. this is vitamin d's major effect. vit d is made in response 
to lowered ca+= - liver makes protovitamin, kidney finisihes it off, then 
it goes to gut.

mechanism of bone turnover is continual and can cause destruction of bone 
and this has to be balanced by keeping Ca+= available, which must be done 
to avoid osteopenia.


Magnesium: a relatively minor electrolyte: see fig 10-7. numbers are 
different but pattern similar to calcium. usually you eat about 4 
mg/kg/day Mg, and excrete about 2 mg/kg/dayin stool. the Mg pool 
communicates w/bone and soft tisue stores. renal mechanism for regulation 
is identical to that of calcium. fig 10-8 shows transport system for mg 
and it's same as for ca++ - active pump on basolateral membrane, also 
influenced byNa+ reabsorption. medically it's a  minor lyte, seldom out 
of normal range and doesn't cause a lot of problems.

renal reabsorption of glucose: glucose is a substance that is integral to 
all metabolism, major energy source. need to keep plamsa concentration 
between 80-120 mg/dl. is freely filtered, and about 99% of it is 
reabsorbed in proximal tubule. only about 1% gets out of proximal tubule. 
this is good only up to a point. the quantity presented to thekidney...

there's a carrier mediated transport system, so beyond a point, no more 
glucose can be reabsorbed. tubules are set so they will reabsorb almost 
all filtered glucose until plasma conc reaches 180-200. then you see 
glucose in urine. tubular load of glucose == filtered load: amt of 
glucose in plasma * GFR. if that stays normal, we reabsorb almost all 
glucose and see no glucose in urine. once above 180 mg/dl in plasma, we 
saturate the transport system, and we can't absorb any more, and lose it 
in the urine. as we increase the load, past that point, there's more and 
more glucose lost to the urine.

fig 7-2. 
at 100 mg/dl in plsma, no glucose lost in urine. at180-200 you see some 
excretion. you keep seeing that . excretion rate keeps going up as you 
exceed TM for glucose. assumption is that GFR stays normal. so. this TM 
system is classiclaly represented by glucose. 


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