Renal Anatomy/Physiology

Question 1

Is the fluid flowing out of the loop of Henle into the
distal convoluted tubule hypertonic or hypotonic?
What is responsible for this?

Answer 1

Unlike the descending limb and thin ascending limb of the loop
of Henle, the thick ascending portion is permeable to solutes,
but not water. This means that solutes can be reabsorbed
(taken out of the loop of Henle) while water remains inside the
lumen of the tubule. This results in hypotonicity of the fluid
within the tubule (100-200 mOsm/L).
Butterworth JF, Mackey DC, Wasnick JD. Morgan & Mikhail’s
Clinical Anesthesiology. 5th ed. New York, NY: McGraw-Hill;
2013: 636.

Question 2

Where in the nephron is sodium reabsorbed?

Answer 2

Sodium is reabsorbed throughout the nephron but the majority
of it is reabsorbed in the proximal convoluted tubule. The
distribution is as follows: 60-75% of sodium is reabsorbed in the
proximal convoluted tubule, 15-20% is reabsorbed in the loop of
Henle, 5% in the distal convoluted tubule, and 5-7% in the
collecting tubule.
Butterworth JF, Mackey DC, Wasnick JD. Morgan & Mikhail’s
Clinical Anesthesiology. 5th ed. New York, NY: McGraw-Hill;
2013: 632.

Question 3

How does the release of renin by the juxtaglomerular
apparatus translate into an alteration in systemic
blood pressure?

Answer 3

When released by the juxtaglomerular apparatus, renin enters
the bloodstream where it acts on a protein synthesized by the
liver called angiotensinogen, converting it into angiotensin I.
This inert peptide is then rapidly converted into angiotensin II in
the lungs by a chemical called angiotensin-converting enzyme.
Angiotensin II activates AT1 receptors to produce intense, direct
arteriolar constriction which increases the systemic vascular
resistance and ultimately, the systemic blood pressure.
Butterworth JF, Mackey DC, Wasnick JD. Morgan & Mikhail’s
Clinical Anesthesiology. 5th ed. New York, NY: McGraw-Hill;
2013: 638-639.

Question 4

What structure in the nephron secretes renin and
what are the three primary stimuli that cause its
release?

Answer 4

Renin is secreted by the juxtaglomerular apparatus in the
nephron and it responds to Beta-1 stimulation, changes in
afferent arteriolar wall pressure, and changes in chloride flow
past the macula densa.
Butterworth JF, Mackey DC, Wasnick JD. Morgan & Mikhail’s
Clinical Anesthesiology. 5th ed. New York, NY: McGraw-Hill;
2013: 638-639.

Question 5

Where in the nephron are principal cells and
intercalated cells located and what function do they
serve?

Answer 5

Principal cells and intercalated cells are found in the collecting
tubule. Principal cells are responsible for the secretion of
potassium and they are also involved in the aldosteronemediated
reabsorption of sodium. Intercalated cells are
primarily responsible for acid-base regulation.
Butterworth JF, Mackey DC, Wasnick JD. Morgan & Mikhail’s
Clinical Anesthesiology. 5th ed. New York, NY: McGraw-Hill;
2013: 637.

Question 6

Where in the nephron does antidiuretic hormone

work and what function does it serve?

Answer 6

Antidiuretic hormone (ADH), also known as arginine
vasopressin, works in the medullary portion of the collecting
tubule. ADH is secreted in response to dehydration and
renders the lumen of the collecting tubule permeable to water
through the expression of water channel proteins called
aquaporin-2 channels. Adequate hydration suppresses the
release of ADH, rendering the lumen of the collecting tubule
impermeable to water.
Butterworth JF, Mackey DC, Wasnick JD. Morgan & Mikhail’s
Clinical Anesthesiology. 5th ed. New York, NY: McGraw-Hill;
2013: 638.

Question 7

Beginning at the aorta, name the vessels and

branches that supply blood to the glomeruli.

Answer 7

Each kidney is supplied by a single renal artery that arises from
the aorta and divides at the level of the renal pelvis into
interlobar arteries. At the junction of the renal cortex and
medulla the interlobar arteries divide into arcuate arteries which
further divide into interlobular arteries that eventually divide into
single afferent arterioles that supply each glomerulus.
Butterworth JF, Mackey DC, Wasnick JD. Morgan & Mikhail’s
Clinical Anesthesiology. 5th ed. New York, NY: McGraw-Hill;
2013: 639.

Question 8

Where in the nephron does aldosterone exert its

action?

Answer 8

The late distal tubule and the cortical portion of the collecting
tubule participate in aldosterone-mediated sodium reabsorption.
Butterworth JF, Mackey DC, Wasnick JD. Morgan & Mikhail’s
Clinical Anesthesiology. 5th ed. New York, NY: McGraw-Hill;
2013: 636.

Question 9

What are the values for normal renal plasma flow

and normal renal blood flow?

Answer 9

Normal renal plasma flow is about 660 mL/min and normal renal
blood flow is about 1200 mL/min.
Butterworth JF, Mackey DC, Wasnick JD. Morgan & Mikhail’s
Clinical Anesthesiology. 5th ed. New York, NY: McGraw-Hill;
2013: 639.

Question 10

What limits the amount of sodium that can be
reabsorbed in the thick, ascending segment of the
loop of Henle?

Answer 10

Normally, in the loop of Henle, solute and water reabsorption
occurs passively and follows concentration and osmotic
gradients. In the thick, ascending portion of the loop of Henle,
however, sodium and chloride are reabsorbed more than
water. Also, the reabsorption of sodium is directly coupled to
the reabsorption of potassium and chloride in this segment.
Because of this coupling effect in the thick, ascending loop of
Henle, the amount of sodium that can be reabsorbed is limited
by the chloride concentration in the tubular fluid.
Butterworth JF, Mackey DC, Wasnick JD. Morgan & Mikhail’s
Clinical Anesthesiology. 5th ed. New York, NY: McGraw-Hill;
2013: 635.

Question 11

What is the major function of the proximal

convoluted tubule of the nephron?

Answer 11

The primary function of the proximal convoluted tubule is
reabsorption of sodium. The cells of the proximal tubule
actively transport sodium out via membrane-bound Na-KATPase
which results in a low intracellular concentration of
sodium. Thus, sodium naturally passes down its gradient from
the fluid in the proximal convoluted tubule into the cells of the
tubule.
Butterworth JF, Mackey DC, Wasnick JD. Morgan & Mikhail’s
Clinical Anesthesiology. 5th ed. New York, NY: McGraw-Hill;
2013: 632-633.

Question 12

What percent of plasma is normally filtered through

the glomerulus?

Answer 12

Under normal conditions, about 20% of plasma is filtered as
blood passes through the glomerulus.
Butterworth JF, Mackey DC, Wasnick JD. Morgan & Mikhail’s
Clinical Anesthesiology. 5th ed. New York, NY: McGraw-Hill;
2013: 640.

Question 13

How does glomerular filtration pressure relate to
efferent and afferent arteriolar pressure in the
nephron?

Answer 13

Glomerular filtration pressure is directly proportional to efferent
arteriolar pressure and inversely proportional to afferent
arteriolar pressure.
Butterworth JF, Mackey DC, Wasnick JD. Morgan & Mikhail’s
Clinical Anesthesiology. 5th ed. New York, NY: McGraw-Hill;
2013: 632.

Question 14

What is the normal glomerular filtration pressure in

the nephron and what two forces oppose it?

Answer 14

The normal glomerular filtration pressure is about 60% of the
mean arterial pressure or about 60 mmHg. It is opposed by
plasma oncotic pressure which exerts a pressure of about 25
mmHg and renal interstitial pressure which exerts about 10
mmHg.
Butterworth JF, Mackey DC, Wasnick JD. Morgan & Mikhail’s
Clinical Anesthesiology. 5th ed. New York, NY: McGraw-Hill;
2013: 632.

Question 15

What separates the endothelial cells of glomeruli
from the epithelial cells of Bowman’s capsule in the
nephron and in what major way do these cells differ?

Answer 15

The endothelial cells of the glomeruli and the epithelial cells of
Bowman’s capsule are separated only by their basement
membranes. A major difference between these two cells are
that the glomerular endothelial cells have fairly large (70-100
nm) pores while the epithelial cells of Bowman’s capsule are
tightly fused and contain only small filtration slits (25 nm). The
fusion of these two cell types provide an effective filtration
barrier preventing the passage of large molecular weight
substances and cellular debris.
Butterworth JF, Mackey DC, Wasnick JD. Morgan & Mikhail’s
Clinical Anesthesiology. 5th ed. New York, NY: McGraw-Hill;
2013: 632.

Question 16

Where in the nephron do parathyroid hormone and

vitamin D act and what function do they serve?

Answer 16

Parathyroid hormone and vitamin D mediate the reabsorption of
calcium in the distal tubule of the nephron.
Butterworth JF, Mackey DC, Wasnick JD. Morgan & Mikhail’s
Clinical Anesthesiology. 5th ed. New York, NY: McGraw-Hill;
2013: 636-637.

Question 17

How can sevoflurane potentially result in renal

damage?

Answer 17

Sevoflurane can potentially result in an alteration in renal
function by two methods: 1) sevoflurane may possibly degrade
into significant amounts of fluoride which can lead to a
decreased ability of the kidneys to concentrate urine, and 2)
compound A, a breakdown product of sevoflurane can
accumulate when low flows are used. Compound A has been
associated with the development of renal damage in laboratory
animals and fresh gas flows of at least 2 L/min are
recommended when using sevoflurane.
Butterworth JF, Mackey DC, Wasnick JD. Morgan & Mikhail’s
Clinical Anesthesiology. 5th ed. New York, NY: McGraw-Hill;
2013: 643.

Question 18

What creatinine clearance values are associated

with mild, moderate, and severe renal failure?

Answer 18

Creatinine clearance values between 40-60 mL/min represent
mild renal impairment, 25-40 mL/min indicates moderate renal
dysfunction, and levels less than 25 mL/min indicate severe
renal dysfunction.
Butterworth JF, Mackey DC, Wasnick JD. Morgan & Mikhail’s
Clinical Anesthesiology. 5th ed. New York, NY: McGraw-Hill;
2013: 655.

Question 19

How is creatinine produced, what are its normal
laboratory values, and how is it related to muscle
mass and glomerular filtration?

Answer 19

Creatinine is produced when creatine, a normal byproduct of
muscle metabolism undergoes non-enzymatic degradation.
The normal creatinine concentration in men is 0.8-1.3 mg/dL
and 0.6-1.0 mg/dL in women. Creatinine concentration is
directly related to body muscle mass and inversely related to
the glomerular filtration rate. Because muscle mass is typically
fairly constant, the creatinine concentration is a relatively
reliable indicator of glomerular filtration rate.
Butterworth JF, Mackey DC, Wasnick JD. Morgan & Mikhail’s
Clinical Anesthesiology. 5th ed. New York, NY: McGraw-Hill;
2013: 656.

Question 20

What BUN level would typically be associated with
renal disease? What are some other non-renal
causes of increased BUN?

Answer 20

Elevations in the BUN above 50 mg/dL are typically associated
with renal disease. Other causes of an increased BUN include
increased protein catabolism due to trauma or sepsis,
degradation of blood within the gastrointestinal tract, resorption
of a large hematoma, or heavy protein intake.
Butterworth JF, Mackey DC, Wasnick JD. Morgan & Mikhail’s
Clinical Anesthesiology. 5th ed. New York, NY: McGraw-Hill;
2013: 656.

Question 21

What is Blood Urea Nitrogen (BUN) and what

conditions can cause derangements in its values?

Answer 21

Blood Urea Nitrogen refers to the amount of urea present in the
bloodstream. Ammonia is produced by the deamination of
amino acids. The liver metabolizes the potentially toxic
ammonia into urea and provides the primary source of urea in
the body. The normal BUN is 10-20 mg/dL. Low values can be
caused by starvation or liver disease. Elevated values can
result from decreases in glomerular filtration rate or increases in
protein catabolism. The BUN value is therefore directly related
to protein catabolism and indirectly related to glomerular
filtration.
Butterworth JF, Mackey DC, Wasnick JD. Morgan & Mikhail’s
Clinical Anesthesiology. 5th ed. New York, NY: McGraw-Hill;
2013: 656.

Question 22

The administration of cyclosporine and radiocontrast
dye have both been associated with renal
dysfunction. What are some methods that have
been shown to reduce the renal damage associated
with these drugs?

Answer 22

Pretreatment with acetylcysteine has been shown to protect
against renal dysfunction due to radiocontrast media. The
administration of calcium channel blockers such as diltiazem
have been shown to reduce the incidence of cyclosporineinduced
nephrotoxicity.
Butterworth JF, Mackey DC, Wasnick JD. Morgan & Mikhail’s
Clinical Anesthesiology. 5th ed. New York, NY: McGraw-Hill;
2013: 644.

Question 23

What percentage of cardiac output is directed

towards the kidneys?

Answer 23

Blood flow to both kidneys normally accounts for 20-25% of
cardiac output.
Butterworth JF, Mackey DC, Wasnick JD. Morgan & Mikhail’s
Clinical Anesthesiology. 5th ed. New York, NY: McGraw-Hill;
2013: 639.

Question 24

Which intravenous induction agent would be most
likely to preserve renal function in the patient with
hemorrhagic hypovolemia?

Answer 24

Although most intravenous induction agents appear to exert
mild decreases in renal function, ketamine has been shown to
have minimal effect on renal function. Ketamine also preserves
renal function to a greater degree than other agents in the
presence of hemorrhagic hypovolemia.
Butterworth JF, Mackey DC, Wasnick JD. Morgan & Mikhail’s
Clinical Anesthesiology. 5th ed. New York, NY: McGraw-Hill;
2013: 644.

Question 25

What is the normal renal tubular threshold for

glucose?

Answer 25

Glycosuria is usually due to a decrease in the renal tubular
threshold for glucose (which is normally 180 mg/dL) or
hyperglycemia.
Butterworth JF, Mackey DC, Wasnick JD. Morgan & Mikhail’s
Clinical Anesthesiology. 5th ed. New York, NY: McGraw-Hill;
2013: 657.

Question 26

How do general and regional anesthesia affect renal

function?

Answer 26

Both regional and general anesthesia result in reversible
decreases in renal blood flow, glomerular filtration rate, urinary
output, and sodium excretion, but the effects are not as
dramatic in regional anesthesia.
Butterworth JF, Mackey DC, Wasnick JD. Morgan & Mikhail’s
Clinical Anesthesiology. 5th ed. New York, NY: McGraw-Hill;
2013: 642.

Question 27

How does stimulation of alpha-1, alpha-2, and
dopamine receptors affect the function of the
nephron?

Answer 27

Stimulation of alpha-1 adrenergic receptors results in increased
sodium reabsorption in the proximal tubules. Alpha-2 receptor
stimulation results in decreased sodium reabsorption and
increased excretion of water. Dopamine, which is formed in the
proximal tubules as well as released from nerve endings
reduces proximal reabsorption of sodium and dilates afferent
and efferent arterioles.
Butterworth JF, Mackey DC, Wasnick JD. Morgan & Mikhail’s
Clinical Anesthesiology. 5th ed. New York, NY: McGraw-Hill;
2013: 641.

Question 28

Sympathetic outflow to the kidneys arises from what

spinal cord levels?

Answer 28

Sympathetic outflow to the kidneys arises from the T4-L1 spinal
cord levels and travels through the celiac and renal plexuses.
Butterworth JF, Mackey DC, Wasnick JD. Morgan & Mikhail’s
Clinical Anesthesiology. 5th ed. New York, NY: McGraw-Hill;
2013: 641.

Question 29

What is renal filtration fraction (FF) and how do

changes in arteriolar tone in the nephrons affect it?

Answer 29

Filtration fraction is the ratio of the glomerular filtration rate to
renal plasma flow and it is normally about 20%. The glomerular
filtration rate is dependent on the relative tone of the afferent
and efferent arterioles in the nephron. An increase in the
diameter of the afferent arteriole (vasodilation) or a decrease in
the diameter of the efferent arteriole (vasoconstriction) will
increase the filtration fraction and vice versa. The changes in
the tone of these arterioles can maintain a steady glomerular
filtration rate between mean arterial pressures of 80 and 180
mmHg.
Butterworth JF, Mackey DC, Wasnick JD. Morgan & Mikhail’s
Clinical Anesthesiology. 5th ed. New York, NY: McGraw-Hill;
2013: 641.

Question 30

What is creatinine, why is it important, and how is

creatinine clearance calculated?

Answer 30

Creatinine is a product of phosphocreatine breakdown in
muscle and is normally completely filtered by the kidneys.
Because creatinine is not reabsorbed and is secreted in very
small amounts, it provides an easy way to assess the
glomerular filtration rate by measuring the amount of creatinine
in the blood and the amount in the urine. The formula for
creatinine clearance = (Urinary Creatinine) X (Urinary Flow
Rate)/Plasma Creatinine.
Butterworth JF, Mackey DC, Wasnick JD. Morgan & Mikhail’s
Clinical Anesthesiology. 5th ed. New York, NY: McGraw-Hill;
2013: 656-657.

Question 31

What percentage of renal plasma flow is the normal
glomerular filtration rate (GFR) and what are normal
GFR values?

Answer 31

The normal GFR is about 20% of renal plasma flow. The
normal values in men are about 120 mL/min (+/- 25 mL/min)
and for women the value is 90 mL/min (+/- 20 mL/min).
Butterworth JF, Mackey DC, Wasnick JD. Morgan & Mikhail’s
Clinical Anesthesiology. 5th ed. New York, NY: McGraw-Hill;
2013: 639.

Question 32

Which drugs typically administered in the
perioperative period can impair the ability of
dopamine to increase renal function? What other
drugs administered in the perioperative period can
adversely affect renal function?

Answer 32

Drugs such as metoclopramide, phenothiazines, and droperidol
that have antidopaminergic effects can interfere with the ability
of dopamine to increase renal function. Other drugs such as
aminoglycosides, amphotericin B, immunosuppressive drugs,
and radiocontrast dyes can impair renal function, especially in
the face of pre-existing renal damage.
Butterworth JF, Mackey DC, Wasnick JD. Morgan & Mikhail’s
Clinical Anesthesiology. 5th ed. New York, NY: McGraw-Hill;
2013: 644.