Jackson 7 Flashcards by Tyler Brown

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.

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nonvolatile acids – arise from

metabolism or the diet; examples include phosporic, lactic, and sulfuric acids and ketones

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nonvolatile acids

must be neutralized with

HCO3-

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nonvolatile acids

are regulated by the

renal system

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nonvolatile acids

neutralization requires

continual replenishment of HCO3-

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In theory, the amount of acid in the urine should equal the

nonvolatile acid load

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The kidney accomplishes this by reabsorbing all of the filtered bicarbonte, and then producing

enough new bicarbonate to neutralize acids produced by the body.

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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

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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

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Kidney

phosphate used

first but supply is limited

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Kidney

ammonium production within ———- eliminates H+ and produces an

tubular cells

HCO3- that is reabsorbed (more on this mechanism later)

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Net acid excretion (NAE) should remove all nonvolatile acid

3 components or forms excreted are free

H+, HPO4-2, and NH4+

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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)

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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

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the collecting duct is not significantly involved with

Ca2+ reabsorption

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in distal tubule – transcellular reabsorption of

calcium

transport here can be regulated because expression of Ca2+ transporters is regulated by PTH

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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

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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.

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Bicarbonate reabsorption begins in the

proximal tubule, and 80% of filtered HCO3- is reabsorbed here.

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——- in the tubular epithelium produces H+ and HCO3-

CA activity

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H+ is secreted via

Na+ / H+ antiporter

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also have H+ ATPase pumps and H+/K+ ATPase pumps operating to

secrete H+ (not illustrated)

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HCO3- is transported/reabsorbed across

basolateral membrane

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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.

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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

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