Jackson 7 Flashcards
volatile acids - these by-products of
metabolism can be exhaled or dissipated by the lungs; re: CO2 is an acid because it produces H+ in the water of body fluids.
nonvolatile acids – arise from
metabolism or the diet; examples include phosporic, lactic, and sulfuric acids and ketones
nonvolatile acids
must be neutralized with
HCO3-
nonvolatile acids
are regulated by the
renal system
nonvolatile acids
neutralization requires
continual replenishment of HCO3-
In theory, the amount of acid in the urine should equal the
nonvolatile acid load
The kidney accomplishes this by reabsorbing all of the filtered bicarbonte, and then producing
enough new bicarbonate to neutralize acids produced by the body.
However, lowest possible pH for urine is ~4.4 which represents very little free H+, and this pH of the urine is not sufficient to
excrete the nonvolatile acid load. Therefore, the kidney must excrete more acid than can be held in a solution with pH=4.4
Buffers provide the solution to this dilemma
buffers bind to excess or free H+ to increase acid carried in urine without decreasing pH
Several molecules serves as physiological buffers. The kidney can produce HCO3- to act as a buffer, but it also adds
phosphate and ammonium to the filtrate to increase the amount of H+ excreted
Kidney
phosphate used
first but supply is limited
Kidney
ammonium production within ———- eliminates H+ and produces an
tubular cells
HCO3- that is reabsorbed (more on this mechanism later)
Net acid excretion (NAE) should remove all nonvolatile acid
3 components or forms excreted are free
H+, HPO4-2, and NH4+
Urine contains both titratable acids and NH4+. H+ and HPO4- are the titratable acids and can be measured by titration with a base to a pH=7.4. NH4+ is not
titratable (pKa ~9)
Acid secretion and bicarbonate reabsorption along the nephron
The kidney regulates the acidity of the urine by regulating
HCO3- reabsorption. Under normal conditions, the kidney excretes acid equal to the nonvolatile load and replenishes the HCO3- lost due to neutralizing the nonvolatile acids
the collecting duct is not significantly involved with
Ca2+ reabsorption
in distal tubule – transcellular reabsorption of
calcium
transport here can be regulated because expression of Ca2+ transporters is regulated by PTH
The are three options for renal regulation of body pH that will produce urine with different pH
- decrease body pH by not reabsorbing all HCO3- ; produces an alkaline urine and acidifies body fluids
- no effect on body pH by reabsorbing all HCO3- ; urine has a neutral pH
- increase body pH by reabsorbing all and producing more HCO3- (typical); produces an acidic urine and alkalinizes body fluids
A critical point to remember is that
HCO3- is not directly transported from tubular fluid into blood so HCO3- production and reabsorption results in H+ secretion.
Bicarbonate reabsorption begins in the
proximal tubule, and 80% of filtered HCO3- is reabsorbed here.
——- in the tubular epithelium produces H+ and HCO3-
CA activity
H+ is secreted via
Na+ / H+ antiporter
also have H+ ATPase pumps and H+/K+ ATPase pumps operating to
secrete H+ (not illustrated)
HCO3- is transported/reabsorbed across
basolateral membrane
Some HCO3- is reabsorbed in the thick ascending limb of the loop of Henle in manner similar to the mechanism used in the
proximal tubule.
In the late distal tubule and the collecting duct
CA activity in the intercalated cells produces H+ and HCO3-
H+ is secreted via an
H+ ATPase pumps and an H+/K+ ATPase pump (not illustrated)
the last of all filtered HCO3- is reabsorbed in the
late distal tubule and collecting duct.
A less common type of intercalated cell reverses the position of the
H+ and HCO3- transporters to the basolateral and apical membranes, respectively. These cells reabsorbs H+ and secretes HCO3- ; activity of this cell type is normally very low.
If the body is alkaline, the kidney must produce alkaline urine which requires
incomplete reabsorption of HCO3- (figure on right)
increase excretion of HCO3- by not neutralizing all the HCO3- that is in the tubular fluid
Cells of the proximal tubule detect
intracellular pH and can alter CA activity accordingly.
If the body is acidic, use
phosphate (HPO4- ) as an additional buffer to increase excretion of H+
After all HCO3- has been reabsorbed and
HPO4- is depleted, the kidney will produce ammonium as a third buffer to increase the amount of H+ that can be excreted.
note that is important to keep NH4+ from entering body where it would be converted to
urea and produce H+ as a result
NH4+ is produced in the ———– by metabolism of ———.
proximal tubules
glutamine
The NH4+ that is produced is transported into the
tubular fluid and the HCO3- moves into blood.
Production of NH4+ in the proximal tubule cells is regulated by
systemic pH.
Acidosis upregulates synthesis of enzymes for
glutamine metabolism, but note that this takes time (as does all protein synthesis).
More NH4+ can be added to the urine by
diffusion trapping.
Much of the NH4+ leaving the proximal tubule is reabsorbed by the
ascending limb of the loop of Henle (note that the orientation of the tubule cell is reversed in the proximal tubule diagram below)
NH4+ substitutes for
K+ in the Na+K+2Cl- symporter and enters the interstitial fluid in the medulla where it is in equilibrium with NH3
Because it is a polar molecule, NH4+ is “trapped” in the interstitial fluid, but NH3
(being nonpolar) can diffuse into the lumen of nearby collecting ducts
Because there is excess H+ in the fluid, NH3 in lumen is protonated to NH4+ , is once again
trapped, and gets eliminated with the urine
• Respiratory system keeps PCO2 ——, kidneys regulate ==———
constant
bicarbonate
• Net acid excretion occurs after all
filtered bicarbonate is reabsorbed
• New bicarbonate can be produced in the proximal tubule by production of
NH4+ from glutamine
• NH4+ produced in the proximal tubule facilitates
H+ excretion in the collecting duct as a consequence of diffusion trapping.
Respiratory acidosis – low pH due to
CO2 build-up
Respiratory acidosis
causes include -
impaired pulmonary function
Respiratory acidosis
renal compensatory response—–>
produce new HCO3-
Respiratory alkalosis – high pH due to low
PCO2
Respiratory alkalosis;
causes include
hyperventilation, anxiety, altitude, fever, drugs
Respiratory alkalosis;
renal compensatory response —–>
excrete HCO3-
Metabolic acidosis - low pH due to low
HCO3-
Metabolic acidosis
causes include
diabetic ketosis, diarrhea, renal failure
Metabolic acidosis
respiratory compensatory response —->
hyperventilate
Metabolic acidosis
renal compensatory response——>
produce new HCO3-
Metabolic alkalosis – high pH due to excess
HCO3-
Metabolic alkalosis
causes include
vomiting, antacids, hemorrhage
Metabolic alkalosis
respiratory compensatory response –
hypoventilate (how does this work?)
Metabolic alkalosis
renal compensatory response —–>
excrete HCO3-
Calcium is found in the body in
intracellular fluid
extracellular fluid
bone
only a little more than—— of ECF calcium is free or complexed with anions, and, therefore, can be filtered in the glomerulus
½
Calcium (and phosphate) are important for many
cellular processes, and are regulated by renal and digestive systems so that gastrointestinal absorption is balanced by renal excretion.
Why is it important to regulate calcium?
hypocalcemia increases excitability of neural and muscle tissue; tetany
hypercalcemia can cause cardiac arrhythmia and disorientation; can lead to death
Note that a decrease in plasma pH will increase the amount of
free Ca2+ which can be filtered and excreted, so alkalosis can lead to hypocalcemia.
Calcium reabsorption in the nephron
in proximal tubule –
mostly by paracellular transport/solvent drag
Calcium reabsorption in the nephron
in thick ascending limb –
transcellular and paracellular transport (paracellular not solvent drag)
• calcitonin
released in response to
hypercalcaemia
calcitonin
increases
bone deposition
Calcium is regulated by three hormones all of which are regulated by a
calcium sensing receptor (CaSR)
found in plasma membrane of cells in parathyroid gland, thyroid parafollicular cells, and cells of the proximal tubule.
• parathyroid hormone (PTH)
released in response to
hypocalcaemia
Calcium is regulated by three hormones
Parathyroid hormone
calcitonin
calcitriol
Parathyroid hormone
increases
bone resorption, increases renal Ca+ reabsorption, and stimulates calcitriol production
• calcitriol (1,25 dihydroxyvitamin D)
metabolism of
vitamin D to calcitriol is stimulated by hypocalcaemia and/or hypophosphatemia (and further stimulated by PTH, see above)
Calcitriol
stimulates
active transport mechanism for Ca2+ absorption in the small intestine
Calcitriol
facilitates action of
PTH and increases renal Ca2+ transport
