Renal clearance - Advances in Physiology Education

Adv Physiol Educ 40: 458–461, 2016;
doi:10.1152/advan.00059.2016.
Illuminations
Renal clearance: using an interactive activity to visualize a tricky concept
Kerry Hull
Department of Biology, Bishop’s University, Sherbrooke, Quebec, Canada
Submitted 20 April 2016; accepted in final form 31 July 2016
METHODS
Study design. The study population consisted of 44 students in their
third or fourth year of a B.Sc. program specializing in biology,
neuroscience, or biochemistry. The course was the second in a series
of two animal physiology courses required of the biology and biochemistry students but optional for neuroscience students and had two
cell biology courses as prerequisites. The class format was somewhat
“flipped” in that students were first exposed to the material via a
directed reading (8) and an online video and quizzing engine (Mastering A & P Dynamic Study Modules; Pearson Education). Students
Address for reprint requests and other correspondence: K. Hull, Dept. of
Biology, Bishops University, 2600 College St., Sherbrooke, QC J1M 1Z7,
Canada (e-mail: [email protected]).
458
completed these out-of-class activities during the 4-day period separating the final lecture of one week and the first lecture of the
subsequent week. They were thus acquainted with renal structure and
the basics of renal handling. Although both the reading and the online
materials discussed renal clearance, students were very vocal in their
request that class time be devoted to this concept.
The first half of the class (40 min) utilized the peer instruction
method to discuss renal handling; students used a personal response
system (“clicker”) to record an answer to each multiple choice
question (10). If a significant portion of the class chose an incorrect
answer, students were instructed to discuss their answer with a
classmate prior to repeating the answer selection process. Each of the
five questions was followed by an instructor’s explanation of the
correct and incorrect response options. Clicker questions addressed
the equation “excretion rate (E) ⫽ filtration rate (F) ⫹ secretion rate
(S) ⫺ reabsorption rate (R),” the cellular mechanism of sodium
reabsorption, substances transported by secondary active transport,
the mechanism of potassium reabsorption in the proximal tubule, and
the distinction between tubular maximum and the renal threshold. For
instance, the last concept was addressed by this question: “Which of
these statements is true about the tubular maximum but not the renal
threshold?” Answer choices included the following:
A. It is measured in mg/min.
B. It reflects the number of carriers available for a particular solute.
C. Above this value, the substance begins to appear in the urine.
D. None of these statements correctly answers the question.
The clearance simulation activity took up the rest of the class (⬃40
min), including a 10-min debriefing. The activity was performed too
late in the semester to be included in the general in-class survey of
class activities administered in the 8th wk of term. Instead, students
were asked to complete an optional online survey one week after the
last class of the semester. Student perceptions of the clearance activity
were compared with those of two previously validated activities
examined in the in-class survey: peer instruction (10) and a roleplaying simulation in which students acted out the events of inhalation
and exhalation (2). Results are presented as means (SD).
Student mastery of the concepts of renal clearance and handling
was examined using quantitative questions on the final exam. The
questions asked students to calculate renal clearance based on renal
blood flow and the solute concentrations in the renal artery and the
renal vein; the solute filtration rate and the glomerular filtration rate
based on the plasma solute concentration, the solute excretion rate,
and the solute reabsorption rate; and renal clearance from the urine
production rate and the solute concentrations in urine and plasma.
The study was approved by the Research Ethics Board of Bishop’s
University.
Description of the activity. This simulation is informed by the
clearance figure, Fig. 19.13 from the course textbook (see Fig. 1) (8),
but refers to a “hypothetical mammal” because the concentrations and
filtration fraction differ significantly from those of real animals.
Student pairs were provided with a full-page game board large enough
to allow student pairs to work together, a small amount of blue
modeling clay to represent water, and four beads to represent solute
(Fig. 2). The activity instructions were provided on a separate sheet.
Both the full-page game board and the student handouts are available
upon request from the author.
First, students were asked to label the renal tubule, peritubular
capillaries, glomerulus, and renal capsule and to add labeled arrows
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RENAL CLEARANCE, that is, the volume of blood cleared of a
substance in a particular time period, is commonly recognized
as one of the most difficult concepts in physiology (9). This
difficulty may in part reflect the quantitative nature of renal
clearance since many life sciences majors perceive that mathematics is irrelevant to their discipline (1, 12). Moreover,
students must apply the general model of mass balance to
events occurring within the kidney (5). Wenderoth et al. (11)
observed that most (75%) students were able to correctly
answer a question about mass balance, but only 40% of
students were able to apply this model to a situation in renal
physiology. Richardson and Speck (7) attributed the problem
to misconceptions about virtual volume. Students may infer
from the clearance definition that, in blood leaving the kidney,
the blood volume corresponding to the clearance will be
completely free of the substance, but the remainder of the
blood volume will contain the original concentration. The
authors use a simple demonstration to show that blood leaving
the kidney is homogeneous.
Thus, renal clearance is difficult for students to master both
qualitatively and quantitatively. A variety of excellent case
studies have been developed to address the quantitative aspect;
these provide opportunities to practice calculating clearance
and other indicators of renal handling (3, 4, 6). However,
although students may become proficient at slotting clinical
values into memorized formulae, personal experience suggests
that these activities do not always result in conceptual understanding, even when coupled with well-designed diagrams and
videos. This activity was developed to improve student understanding by modeling the renal handling of different solutes in
a quantifiable manner. Using clay droplets to represent water
volumes (50 ml/droplet) and beads to represent solutes (10
mg/bead), students trace the path of solutes and water as they
enter the glomerulus, are exchanged between the tubule and
peritubular capillaries, and eventually leave the kidney in urine
or in the renal vein. The simulation thus allows students to
visualize and enact dynamic processes in a way that cannot be
done with data sets, images, or videos.
Illuminations
RENAL CLEARANCE
B. The solute is too big to be filtered. It is not reabsorbed or
secreted (clearance ⫽ 0 ml/min).
C. The solute is filtered and not reabsorbed nor secreted (clearance ⫽
50 ml/min).
D. The solute is filtered and not reabsorbed. Any nonfiltered solute
is secreted (clearance ⫽ 100 ml/min).
E. The solute is filtered and 50% reabsorbed but not secreted
(clearance ⫽ 25 ml/min).
This activity could theoretically strengthen the misconception involving virtual volume discussed earlier (7), since the solute may be
cleared of the filtered water droplet but not the other. Students should
thus be reminded that solutes diffuse freely through a volume of fluid
and that they should redistribute the solute after the calculation, but
before the blood or urine leaves the kidney. Preceding the activity
with the thought problems outlined by Richardson and Speck (7) may
also help to prevent this misconception.
Following the activity, the instructor modeled each situation on the
board. Students were then asked to predict which trial could be used
to measure renal blood flow (trial D), and which could be used to
measure GFR (trial C).
RESULTS AND DISCUSSION
representing filtration (F), reabsorption (R), and secretion (S). They
then created two flattened teardrop shapes from the modeling clay that
were large enough to accommodate two beads each yet small enough
to fit on the game board’s blood vessel and renal tubule. The
parameters of the simulation were outlined as follows:
• The game board represents all of the nephrons of the kidney of a
hypothetical mammal.
• Each bead represents 10 mg of solute, and each water droplet
represents 50 ml of water.
• It takes 1 min for the two droplets (representing 100 ml) to pass
from one side to the other (i.e., through the kidney).
• 50% of the fluid arriving at the glomerulus is filtered (i.e., 1
droplet).
Based on these parameters, students were asked to determine the
glomerular filtration rate (GFR; 50 ml/min) and the renal blood flow
(100 ml/min). They were then asked to model renal handling of water
by following these steps:
1. Ignore the solute for now (put your beads aside).
2. Place your two droplets in the blood.
3. As the droplets enter the glomerulus, one droplet is filtered into
the tubule (remember, 50% filtration). The other continues in the
blood.
4. As the droplet passes through the tubule, most of it gets reabsorbed into the blood. The amount varies widely, but in our
simulation we will reabsorb 48 ml of the droplet. Break off a
small piece of the filtered droplet to represent the small amount
of water that forms the urine, flowing to the renal pelvis and then
to the bladder.
5. Calculate the urine flow rate (V; 2 ml/min). What percentage of
the filtered water is reabsorbed (96%)?
Before proceeding with the other trials, the instructor modeled the
movement of water on the board and confirmed that all students
understood the basic principles of the simulation and arrived at the
correct value for V.
The additional trials addressed various types of solutes. For each,
students were asked to model what will happen to the solute (beads)
and the water (droplets) and then to use the model to determine the
clearance (Table 1). They were reminded that the GFR (50 ml/min)
and the urine flow rate (2 ml/min) are the same in all trials. If desired,
examples can be given of solutes handled in each manner.
A. The solute is filtered, completely reabsorbed, and not secreted
(clearance ⫽ 0 ml/min).
Instructor and student observations. The students divided
themselves into 12 groups of three or four students each. All
students effectively engaged in the activity, and there was a
considerable amount of lively discussion both within groups and
between groups. Requiring only minimal instructor intervention,
all student groups were able to predict the clearance of each solute
using the model. Moreover, students were confronted with and
were largely able to correct several misconceptions. For example,
the simulation only produced correct results if students realized
that 1) water is handled differently from solute (that is, the
droplets and the solute do not always move together), 2) each
solute is handled differently, and 3) the GFR applies to all solutes
and water passing through the kidney at a particular time.
Twenty-one students completed the optional online survey
of the activity, and 42 students completed the earlier in-class
survey of the other class activities. In response to the question
“Did the activity using play dough and beads help you understand the concept of renal clearance?”, only three students
ranked the activity “not useful” or “a bit useful”; the mean
score was 3.43 (SD 1.00) (Fig. 3). For comparison, the average
scores for peer instruction and the ventilation simulation were
3.9 (SD 1.02, n ⫽ 42) and 3.38 (SD 1.13; n ⫽ 40), respectively. Some student comments were very positive, such as,
“I loved it! I didn’t understand clearance at all, and then
after the activity, I felt like a master of clearance.” Students
Fig. 2. The game board, with labels added. Each droplet represents 50 ml of
water, and each bead represents 10 mg of solute. The filtration fraction is 50%,
and the renal blood flow is 100 ml/min. This image depicts a filtered solute
before any reabsorption of water or solute has occurred. F, filtration; R,
reabsorption; S, secretion.
Advances in Physiology Education • doi:10.1152/advan.00059.2016 • http://advan.physiology.org
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Fig. 1. The textbook figure upon which the activity was based (8). Used with
permission. GFR, glomerular filtration rate.
459
Illuminations
460
RENAL CLEARANCE
Table 1. Expected results from each trial
Handling*
Trial
%F
%R
%S
Example
Clearance, ml/min
Us, mg/100 ml
Filtration Rate, mg/min
Excretion Rate, mg/min
A
B
C
D
E
100
0
100
100
100
100
NA
0
0
50
0
0
0
100
0
Glucose
Albumin
Inulin
PAH
Urea
0
0
50
100
25
0
0
1,000
2,000
500
20
0
20
20
20
0
0
20
40
10
Us, urine solute concentration; F, filtered; R, reabsorbed; S, secreted; NA, not available; PAH, para-aminohippurate. *Handling: %maximum. The 3 right
columns describe the results of the extension activity.
Fig. 3. A: Results of an anonymous online
survey. Students were asked if the activity
helped them understand renal clearance
(hatched bars) and if they enjoyed the activity
(gray bars) (n ⫽ 21). Scores ranged from 1
(strongly disagree) to 5 (strongly agree). B:
means (SD) of the survey results for the clearance activity (light gray bars). For comparative
purposes, results are also included from an
earlier survey examining student perceptions
of peer instruction (clickers; dark gray bars;
n ⫽ 42) and a role-playing simulation examining ventilation (open bars; n ⫽ 40).
A
ute. They can compare values obtained using the model with
those obtained with formulae (F ⫽ PS ⫻ GFR; E ⫽ Us ⫻ V).
See Table 1 for a summary of the expected values for each
trial. Other measures of renal handling can also be explored.
For instance, students can calculate the fractional tubular
reabsorption (TRP; for trials A and E) by dividing the number
of beads “reabsorbed” by the number of beads that were
“filtered” and compare this observed value with the calculated
value [TRP ⫽ (F ⫺ E/F) ⫻ 100%].
Conclusion. The power of this renal clearance model is its
ability to link conceptual understanding with quantitative problems, especially if time permits the inclusion of the extension
activity. Many students consider the clearance formula as a
black box; they input clinical values and magically obtain the
clearance. By modeling the renal handling of various substances using quantifiable amounts of clay and beads, students
can logically deduct the value for clearance (as well as other
measures of renal handling) and compare their “observed”
values with their calculated values.
GRANTS
This work was supported by the Senate Research Committee of Bishop’s
University.
DISCLOSURES
K. Hull is a contributing author to Anatomy and Physiology textbooks
published by Wolters Kluwer Health, but the article discusses a concept that is
not discussed in the author’s textbooks.
AUTHOR CONTRIBUTIONS
K.H. conception and design of research; K.H. performed experiments; K.H.
analyzed data; K.H. interpreted results of experiments; K.H. prepared figures;
K.H. drafted manuscript; K.H. edited and revised manuscript; K.H. approved
final version of manuscript.
B
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mentioned that “it was very helpful to be able to see a
concept and not just imagine it,” and that they liked the
“visual and hands-on aspect.” Four students noted that
including additional problems to solve using the game sheet
would have rendered the activity more useful, and two
students stated that they understood clearance already and would
have preferred to spend the time doing more difficult problems.
The extension activity described below was designed to address
these comments. In response to the question “Was the clearance
activity interesting and/or enjoyable?”, all students ranked the
activity at 3 or higher, with a mean score of 4.10 (SD 0.61). For
comparison, the average scores for peer instruction and the ventilation simulation were 3.88 (SD 0.95, n ⫽ 42) and 3.23 (SD
1.23, n ⫽ 40), respectively.
Free response quantitative problems relating to renal clearance and handling constituted 8% of the final exam. The
average overall score on these questions was 78.7% compared
with 73% for the entire exam.
Extension activity. If students will be expected to use laboratory values to calculate clearance and other measures of renal
handling, the model can be used quantitatively to prepare
students for this task. For each trial, ask students to determine
the urine solute concentration (US) by counting the solute
beads in urine (each representing 10 mg) and dividing this
number by the urine volume (2 ml). Multiplying this number
by 100 results in the most useful unit of measurement (mg/100
ml) for later calculations. Students can use this calculated value
for US along with the values for plasma solute concentration
(PS; always 40 mg/100 ml) and V (always 2 ml/min) to
calculate clearance (C ⫽ UsV/Ps) and to compare their calculated value with their theoretical value (see Table 1).
Students can also use the model to determine the filtered
load and the excreted load for each solute by determining the
number of beads filtered and excreted (respectively) per min-
Illuminations
RENAL CLEARANCE
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