Renal & Acid/Base Physiology

Question 1

Describe fluid compartments of the body.

Answer 1

total body water is approximately 60% of body weight

ICF: 40% of body weight (2/3 of total body water); ECF: 20% of body weight (3/4 of ECF is interstitial fluid; 1/4, plasma)

Question 2

Describe changes in volume and osmolarity of body fluids following:
isoosmotic volume expansion, isosmotic volume contraction, hyperosmotic volume expansion, hyperosmotic volume contraction, hypoosmotic volume expanison, and hypoosmotic contraction (Give examples)

Answer 2

isotonic sodium chloride infusion: increase in ECF volume (No change in ICF volume or ECF osmolarity)

diarrhea (isotonic loss): decrease in ECF volume (No change in ICF volume or ECF osmolarity)

high sodium chloride intake: increase in ECF volume, decrease in ICF volume, and increase in ECF osmolarity

sweating, fever, diabetes insipidus: decrease in ECF volume, increase in ICF volume, and increase in ECF osmolarity

SIADH: increase in ECF volume, increase in ICF volume, and decrease in ECF osmolarity

adrenal insufficiency: decrease in ECF, increase in ICF volume, and decrease in ECF osmolarity

Question 3

What is the equation for renal clearance?

Answer 3

(urine concentration multiplied by urine volume) divided by plasma concentration

Question 4

Describe changes in renal blood flow.

Answer 4

Vasoconstriction of renal arterioles, which leads to a decrease in RBF, is produced by activation
of the sympathetic nervous system and angiotensin II. At low concentrations,
angiotensin II preferentially constricts efferent arterioles, thereby “protecting” (increasing)
the GFR. Angiotensin-converting enzyme (ACE) inhibitors dilate efferent arterioles and produce
a decrease in GFR; these drugs reduce hyperfiltration and the occurrence of diabetic
nephropathy in diabetes mellitus.

Vasodilation of renal arterioles, which leads to an increase in RBF, is produced by
prostaglandins E2 and I2, bradykinin, nitric oxide, and dopamine.

autoregulation:
Myogenic mechanism, in which the renal afferent arterioles contract in response to
stretch. Thus, increased renal arterial pressure stretches the arterioles, which contract
and increase resistance to maintain constant blood flow.

Tubuloglomerular feedback, in which increased renal arterial pressure leads to
increased delivery of fluid to the macula densa. The macula densa senses the increased
load and causes constriction of the nearby afferent arteriole, increasing resistance to
maintain constant blood flow.

Question 5

What is filtration fraction? filtered load?

Answer 5

is the fraction of RPF filtered across the glomerular capillaries (GFR/RPF)

filtered load = GFR x plasma concentration

Question 6

What is the Starling equation?

Answer 6

PBS = hydrostatic pressure in Bowman’s space; PGC = hydrostatic pressure in the
glomerular capillary; πGC = colloid osmotic pressure in the
glomerular capillary.

Question 7

Constriction of afferent arteriole causes what changes to GFR, RBF, and filtration fraction?

Answer 7

decreased GFR (decreased glomerular capillary hydrostatic pressure); decreased RPF, and no change to filtration fraction

Question 8

Contriction of efferent arteriole (by angiotensin II) causes what changes to GFR, RPF, and filtration fraction?

Answer 8

increase GFR (increased glomerular capillary hydrostatic pressure), no change to renal plasma flow, and increase in filtration fraction

Question 9

Increase plasma protein causes what changes to GFR, RPF, and filtration fraction?

Answer 9

decrease in GFR, no change in RPF, and decrease in filtration fraction

Question 10

T/F: if the filtered load is greater than the excretion rate, then net secretion of the substance has occurred?

Answer 10

F

Question 11

At what glucose plasma concentration does reabsorption of glucose plateau (saturation)?

Answer 11

350 mg/dL

Question 12

What substances have high renal clearance? low? clearance = GFR?

Answer 12

PAH (filtered and secreted);

sodium, glucose, amino acids, bicarbonate, and chloride (either not filtered or subsequently reabsorbed into peritubular capillary blood)

inulin (freely filtered, but not reabsorbed or secreted)

Question 13

Describe diffusion of weak acids and bases.

Answer 13

at acidic pH, HA form of weak acids predominates and diffusion occurs (uncharged and lipid-soluble)

at alkaline pH, the B form of weak bases predominates and diffusion occurs (uncharged and lipid-soluble)

Question 14

Describe renal sodium reabsorption.

Answer 14

proximal tubule (isosmotic):
early PT: Na/Glu, AA, PO4, lactate; Na+ is also reabsorbed by countertransport via Na+–H+ exchange, which is linked directly to the reabsorption of filtered HCO3−.
late proximal tubule: reabsorbed with chloride

TAL: sodium/potassium/2 chloride transporter (impermeable to water)

Distal tubule and collecting duct:
cortical diluting segment: sodium chloride cotransport (impermeable to water)
late distal tubule and collecting duct: principal cells reabsorb sodium and water secreting potassium (site of aldosterone action)

Question 15

Describe glomerulotubular balance.

Answer 15

Increases in GFR and filtration fraction cause the protein concentration and πc
of peritubular capillary blood to increase. This increase, in turn, produces an
increase in fluid reabsorption. Thus, there is matching of filtration and reabsorption,
or glomerulotubular balance.

Question 16

Describe potassium regulation.

Answer 16

filtered, reabsorbed, and secretion by the nephron (balance: intake equals excretion)

reabsorption: osmotic drift in PT; Na/K/2Cl cotransport in TAL; alpha intercalated cells via H/K ATPase
secretion: through principal cells

increased distal secretion caused by high potassium diet, hyperaldosteronism, alkalosis, thiazide and loop diuretics, and luminal anions

decreased distal secretion caused by low potassium diet, hypoaldosteronism, acidosis, and potassium-sparing diuretics

Question 17

What causes hyperkalemia?

Answer 17

insulin deficiency, beta adrenergic antagonists, acidosis (exchange of extracellular protons for intracellular potassium), hyperosmolarity (osmotic drift), inhibitors of Na/K pump (digitalis), exercise, and cell lysis

Question 18

What causes hypokalemia?

Answer 18

insulin, beta-adrenergic agonsits, alkalosis, and hyposmolarity

Question 19

Describe renal regulation of urea, phosphate, calcium, and magnesium.

Answer 19

urea: passively reabsorbed in the proximal tubule (distal tubule, cortical collecting ducts, and outer medullary collecting ducts are impermeable); ADH increases the urea permeability of inner medullary collecting ducts (urea reabsorption from IMCD contributes to urea recycling and to the development of renal osmotic gradient
phosphate: reabsorbed in the proximal tubule with sodium; PTH inhibits reabsorption; buffer for protons in urine
calcium: reabsorbed by proximal tubule and TAL (linked to sodium transport and affected by loop diuretics); PTH increases distal tubule reabsorption
magnesium: reabsorbed in proximal tubule, TAL, and distal tubule (competes for reabsorption in the TAL with calcium)

Question 20

Describe concentration and dilution of urine.

Answer 20

regulation of plasma osmolarity is accomplished by varying the amount of water excreted relative to the amount of solute excreted

concentrated urine is produced when circulating ADH levels are high (in situations of water deprivation, hemorrhage, and SIADH); increased water permeability of the principal cells of the collecting ducts

dilute urine is produced when circulating levels of ADH are low (in situations of high water intake and central diabetes insipidus); in the absence of ADH, the cells of the late distal tubule and collecting ducts are impermeable to water

Question 21

What generates the corticopapilalry osmotic gradient?

Answer 21

countercurrent multiplication, urea recylcing, and is maintained by countercurrent exchange in the vasa recta

augmented by ADH

Question 22

Describe response to water deprivation.

Answer 22

increased plasma osmolarity stimulates osmoreceptors in anterior hypothalamus and increases secretion of ADH from posterior pituitary

ADH: increases water permeability of late distal tubule and collecting duct (increases water reabsorption; increases urine osmolarity and decreases urine volume)

Question 23

Describe free-water clearance.

Answer 23

Urine that is isosmotic to plasma has a free-water clearance of zero; occurs in patients treated with loop diuretics when dilution of urine is hampered

urine that is hyposmotic to plasma has a positive free-water clearance

urine that is hyperosmotic to plasma (high ADH), has a negative free-water clearance

Question 24

What is the action of PTH on the kidney?

Answer 24

decreased phosphate reabsorption in the proximal tubule, increased calcium reabsorption in distal tubule, and stimulation of 1alpha-hydroxylase

Question 25

What are stimuli for ADH? aldosterone?

Answer 25

increase in plasma osmolarity or decrease in blood volume

decrease in blood volume (angiotensin II) and hyperkalemia

Question 26

What is the only volatile acid? Describe reactions it participates in.

Answer 26

carbon dioxide

reacts with water to form carbonic acid which dissociated into a proton and bicarbonate

carbonic anhydrase catalyzes this reaction

Question 27

When are buffers most effective?

Answer 27

within 1.0 pH unit of the pK of the buffer (linear portion of titration curve)

Question 28

What is the pK of the carbon dioxide/bicarbonate buffer pair?

Answer 28

6.1

Question 29

What is the Henderson-Hasselbach equation?

Answer 29

pH = pK + log (base/acid)

Question 30

Describe renal acid-base physiology.

Answer 30

reabsorption of filtered bicarbonate occurs in the proximal tubule (proton and bicarbonate are produce in the cells from carbon dioxide and water; bicarbonate leaves via basolateral membrane and proton leaves apically via Na/H exchange); in the lumen, secreted protons combine with filtered bicarbonate to form carbonic acid to start the cycle again

increases in carbon dioxide partial pressure results in increased rate of bicarbonate reabsorption because the supply of intracellular proton for secretion is increased (renal compensation for respiratory acidosis)

protons can be excreted as a titratable acid (H2PO4-); the amoutn of protons excreted this way is determined by the amount of urinary buffer and the pK of the buffer

the amount of protons excreted as ammonium is dependent on the amount of ammonia synthesized by renal cells and by the urine pH; ammonia is produced from glutamine and diffuses into the lumen; the lower the pH of hte tubular fluid, the greater the excretion of protons as ammonium; in acidosis, an adaptive increase in ammonia synthesis occurs and aids in the excretion of excess protons

Question 31

Describe metabolic acidosis.

What causes it?

Answer 31

overproduction or ingestion of fixed acid or loss of base; bicarbonate is used to buffer the extra fixed acid and arterial bicarbonate concentration decreases (primary disturbance)

causes hyperventilation (Kussmaul breathing)

increased excretion of excess fixed protons as titratable acid and ammonium (in addition ot increased reabsorption of new bicarbonate)

ketoacidosis, lactic acidosis, chronic renal failure, diarrhea, and methanol intoxication through formation of formic acid

Question 32

Describe metabolic alkalosis.

What causes it?

Answer 32

loss of fixed proton or gain of base; arterial bicarbonate increases

compensation is hypoventilation

correction of metabolic alkalosis consists of increased excretion of bicarbonate (because the filtered load exceeds the ability of the renal tubule to reabsorb it)

vomiting, hyperaldosteronism, and loop or thiazide diuretics

Question 33

Describe respiratory acidosis.

What causes it?

Answer 33

caused by decrease in respiratory rate and retention of carbon dioxide

causes an increase in proton and bicarbonate concentration by mass action (there is no respiratory compensation)

renal compensation consists of increased excretion of proton as titratable acid and ammonium and increased reabsorption of new bicarbonate

in acute respiratory acidosis, renal compensation has not yet occurred.

opiates, sedatives, anesthetics, Guillan-Barre syndrome, poli, ALS, multiple sclerosis, airway obstruction, COPD, and adult respiratory distress syndrome (inhibition of medullary respiratory center or weakening of respiratory muscles; decreased carbon dioxide exchange in the lungs)

Question 34

Describe respiratory alkalosis.

What causes it?

Answer 34

caused by an increase in respiratory rate and loss of carbon dioxide.

causes a decrease in proton and bicarbonate concentration by mass action (there is no respiratory compensation)

renal compensation consists of decreased excretion of protons as titratable acid and ammonium and decreased reabsorption of new bicarbonate

symptoms of hypocalcemia may occur (less free ionized calcium in plasma)

pneumonia, pulmonary embolus, high altitude, and psychogenic response (hypoxemia)