Renal Physiology

I. Introduction

II. Functional Aspects of the Renal System

A. Renal Vasculature

--parallel vs. series arrangement

--relationship between pressure, flow and resistance
B. Glomerular Filtration

1. Determinants of filtration

EFP = Pc - Pt - IIc EFP = effective filtration pressure

2. Normal values

Pt = 10 mmHg *Pc = 45 mmHg

IIt = 0 mmHg *IIc = 27 mmHg

EFP = 45 - 10 - 27 = 8 mmHg

GFR = 120 ml/min

3. Materials filtered

- the following are easily filtered:

a. electrolytes
b. metabolic waste products like urea, creatinine, and organic acids
c. glucose and inulin
d. amino acids
e. lower weight proteins and peptides like growth hormone and inulin

- albumin and other plasma proteins are not filtered

- negative charge on the filtering membrane inhibits the filtering of anions

**fluid entering the tubule is an ultrafiltrate of plasma, i.e., filtrate has the same
concentration of dissolved substances as plasma except proteins – 300 mOsm

4. Factors affecting GFR and filtration fraction (FF)

FF = GFR RPF = renal plasma flow

RPF FF = 20%

- 2 main factors
1. filtration pressure
2. renal blood (plasma) flow

- effects of afferent arteriole constriction

⇓ filtration pressure
⇓ plasma flow
⇓ GFR

- effects efferent arteriole constriction

⇑ filtration pressure
⇓ plasma flow
GFR?
⇑ FF
⇑ capillary II
⇑ net reabsorption pressure of peritubular capillaries

- effects of sympathetic system (afferent and efferent constricted)

⇓ GFR
⇑ FF
 6. Filtration and filtered load

The filtration rate (load) of a freely filtered substance is equal to:

GFR X Px Px = plasma concentration of substance

Question: Given the following information:

GFR = 120 ml/min

plasma glucose = 100 mg/100ml
plasma sodium = 140 mM
plasma potassium = 5 mM
plasma bicarbonate = 24 mM

What is the filtration rate (load) of the preceding substances?

Questions 1-2. Select all the correct answers.

1. Which of the following would tend to increase glomerular filtration rate?

1. an increase in glomerular-capillary oncotic pressure

2. vasoconstriction of the afferent arteriole
3. an increase in hydraulic pressure in Bowman’s capsule
4. an increase in renal blood flow

2. Which of the following would be expected to cause a large reduction in glomerular filtration
rate?

1. a reduction in mean arterial pressure from 100 to 95 mmHg

2. a reduction in plasma oncotic pressure by one-half
3. a decrease in sympathetic activity
4. complete urethral obstruction

3. The glomerulus:

A. is permeable to all molecules with a molecular weight (M) over 5000

B. contains no active transport systems (“pumps”) that produce an important effect on the
composition of the glomerular filtrate
C. produces a filtrate with a lower concentration of amino acids than found in plasma
D. produces a filtrate with a higher concentration of urea than found in plasma
E. all of the above statements are correct
4. The glomerular filtration rate:

A. is greater than 50% of the plasma flow to the glomeruli

B. falls to approximately 25% of normal when mean arterial pressure changes from 100 to
25 mmHg
C. is decreased by a decrease in plasma colloid osmotic pressure
D. increases ipsilateral to a ureteral obstruction
E. none of the above statements are true

Question 5. Select all the correct answers.

5. Sympathetic stimulation of the renal arterioles causing a marked reduction in renal blood
flow results in:

1. increased reabsorption of fluid by the nephron

2. decreased glomerular filtration rate
3. decreased peritubular hydrostatic pressure
4. a decreased filtration fraction

6. Sympathetic stimulation of the renal arterioles results in:

A. a greater percentage of filtrate being absorbed by the renal tubule

B. a decreased renal filtration fraction
C. increased peritubular hydrostatic pressure in the kidney
D. an increased glomerular filtration rate

Question 7, true or false.

7. The filtration fraction of the kidney is normally about 20%, and is increased due to the
vasoconstrictor effects of angiotensin II.

8. In a healthy individual, what percentage of the effective renal plasma flow would you expect
to pass into the glomerular capsule?

A. less that 5%
B. between 15% and 20%
C. between 40% and 50%
D. between 70% and 80%
E. greater than 90%

C. Tubular Reabsorption and Secretion

1. Tubular reabsorption

- processes involved: diffusion, facilitated diffusion, primary active transport,

secondary active transport (co-transport, counter transport)

a. transport maximum (Tm) systems e.g., proximal tubule glucose

- carrier easily saturated
 - carrier high affinity for substrate
- low back leak

- everything filtered is reabsorbed until carrier saturated, then excess excreted

b. gradient time system e.g., proximal tubule sodium

- carrier never saturated
- carrier low affinity for substrate
- high back leak

- approximately a constant percentage of filtered sodium reabsorbed (70-75%_

- O2 consumption of the kidney α to sodium reabsorption in the proximal tubule

2. Tubular secretion
a. transport maximum systems e.g., PAH
b. secretion not exhibiting Tm e.g., potassium

3. Net effects of reabsorption and secretion

filtered load = CFR x Px

GFR = glomerular filtration rate (ml/min)

Px = plasma concentration of substance

excretion = Ux x V

Ux = urine concentration of substance

V = urine flow rate (ml/min)

net transport rate = filtration rate - excretion rate

= (0) no tubular modification

= (+) net reabsorption

= (-) net secretion

Question: Given the following information:

GFR = 120 ml/min

plasma glucose = 300 mg/100 ml
plasma sodium = 140 mM
plasma potassium = 5 mM
plasma bicarbonate = 24 mM

urine flow = 2 ml/min

urine glucose = 10 mg/ml
urine sodium = 180 mM
urine potassium = 8 mM
urine bicarbonate = 0

Calculate the reabsorption rate of the preceding.

1. The following data are obtained from a patient:

24-hour urine sample

total volume 1440 ml
sodium concentration 120 mEq/liter
potassium concentration 100 mEq/liter
creatinine concentration 200 mg/100ml
urea concentration 2050 mg/100 ml

plasma sample taken at the midpoint during the urine collection

sodium concentration 140 mEq/liter

potassium concentration 5 mEq/liter
creatinine concentration 1 mg/100 ml
urea concentration 25 mg/100 ml

What is the rate of potassium excretion?

A. less than 0.2 mEq/min

B. 0.2 mEq/min
C. 0.3 mEq/min
D. 0.4 mEq/min
E. more than 0.4 mEq/min

2. Toward the end of World War II, Karl Beyer and his associates noted that the injection of
PAH decreased the excretion of penicillin in the urine. What would you suggest was its
mechanism of action?
The PAH:

A. competes with penicillin for a site on a carrier molecule in one of the reabsorptive
mechanisms
B. prevents active reabsorption
C. either of the above could be correct
D. increases filtration
E. competes with penicillin for a site on a carrier molecule in one of the secretory
mechanisms

3. If a substance has a transport maximum (Tm) for absorption, this means:

A. reabsorption is only passive

B. only a constant fraction of the substance will be reabsorbed
C. statements A and B are both correct
D. below a threshold level, all of the substance will be reabsorbed
E. phlorhizin blocks reabsorption
4. Which one of the following substances does not have a Tm value: albumin, arginine, beta
hydroxybutyrate, glucose, hemoglobin, phosphate, sulfate, urea, uric acid?

D. Regional Transport along the Nephron

Proximal Tubule Cell

tubule blood

Summary of proximal tubule alterations

- approximately 75% of the sodium that is filtered is reabsorbed here (requires ATP)

- about 75% of the filtered H2O, K+, C1- follow sodium and the osmolarity of urine at the
end of the proximal tubule is 300 mOsm

- all CHO, protein, peptides, and aa reabsorbed here via secondary active transport (require
luminal sodium)

- all filtered bicarbonate reabsorbed here a loop of henle

Loop of Henle

- the mechanisms of the counter current multiplier produce the high interstitial
osmolarity in the medulla

- fluid leaving it hypotonic

- the vasa recta are counter current capillary loops, flow is slow
 Distal Tubule Cell

distal tubule-collecting duct

- sodium reabsorption-aldosterone

- K+ secretion

- acidification of urine = H+ lost as 2 forms

a. H2PO4 - titratable acid
b. NH4+ - nontitratable acid or ammonium

- water reabsorption - ADH

1. Increased blood flow through the vasa recta of the kidney allows less time for equilibrium
between the medullary interstitium and the blood. This would be expected to:

A. increase the solute concentration gradient between the medullary interstitial fluid and
collecting duct
B. concentrate the urine
C. facilitate the action of anti-diuretic hormone
D. reduce the osmolarity of the urine

2. The following description is most characteristic of which renal tubular segment:

A. proximal tubule
B. thick ascending limb of Henle’s loop
C. distal convoluted tubule
D. medullary collecting duct

Questions 3 - 7. Select all the correct answers

3. Which of the following describe glucose reabsorption by the kidney?

1. secondary active co-transport at the luminal membrane

2. characterized by a transport maximum of approximately 200 mg per 1200 ml of plasma
3. the filtered load and reabsorption rate are the same at plasma concentrations below
threshold
4. active extrusion of glucose across the contraluminal membrane by the Na+ - K+ ATPase

4. A person in previously normal potassium balance maintains neurotic hyperventilation for

several days.
During this period, what happens to potassium balance?

1. hyperkalemia is observed
2. aldosterone stimulates potassium reabsorption
3. renal excretion of potassium is unchanged
4. renal tubular secretion of potassium is increased

5. Potassium:

1. reabsorption occurs primarily in the late distal and collecting tubule

2. excretion would be expected to increase in response to a diuretic which inhibits
reabsorption of sodium chloride in the proximal tubule
3. secretion is under the control of aldosterone, by inhibiting sodium-potassium ATPase
activity in the renal proximal tubule
4. has a direct effect on cells of the zona glomerulosa of the adrenal cortex to secrete
aldosterone
6. Which of the following are co-transported with sodium in the renal proximal tubule?

1. phosphate
2. amino acids
3. glucose
4. potassium

7. An osmotic diuretic would be expected to:

1. increase urine flow

2. reduce net reabsorption of sodium in the renal proximal tubule
3. enhance sodium excretion
4. increase back-diffusion of sodium in the renal proximal tubule

8. Reabsorption of filtered bicarbonate:

A. contributes to excretion of titratable acid

B. is reduced during respiratory acidosis, resulting in increased excretion of bicarbonate
C. is accomplished by net secretion of sodium
D. is enhanced by carbonic anhydrase

9. Potassium:

A. reabsorption occurs primarily in the late distal and collecting tubule

B. excretion would be expected to increase in response to a diuretic which inhibits
reabsorption of sodium chloride in the proximal tubule
C. reabsorption in under the direct control of vasopressin, which stimulates sodium-
potassium ATPase activity in the renal proximal tubule
D. has a direct effect on cells of the zona glomerulosa of the adrenal cortex to prevent
secretion of aldosterone

Questions 10-13. Select all the correct answers

10. If renal tubular carbonic anhydrase were completely inhibited, you would expect increased
excretion of which of the following?

1. sodium
2. water
3. bicarbonate
4. potassium
11. Reabsorption of filtered bicarbonate:

1. contributes to excretion of titratable acid

2. is accompanied by net secretion of sodium
3. reduces the pH of the extracellular fluid
4. is enhanced by carbonic anhydrase

12. The renal countercurrent multiplier is characterized by:

1. a low water permeability in the thick ascending limb of Henle’s loop

2. permeability of the descending limb of Henle’s loop to water
3. active salt reabsorption in the thick ascending limb of Henle’s loop
4. tubular fluid in the thick ascending limb of Henle’s loop which is more concentrated than
the interstitial fluid at that level

13. An osmotic diuretic would be expected to:

1. enhance net reabsorption of sodium in the proximal tubule

2. increase urine volume
3. reduce potassium excretion
4. increase back-diffusion of sodium in the proximal tubule

14. Which of the following structures in the kidney would you expect to be most involved in
concentrating the urine?

A. superficial nephrons
B. the proximal tubule
C. Bowman’s capsule
D. the glomerulus
E. juxtamedullary nephrons

15. Potassium:

A. reabsorption occurs primarily in the late distal and collecting tubule

B. excretion would be expected to decrease in response to a diuretic which inhibits
reabsorption sodium chloride in the proximal tubule
C. reabsorption is under the control of anti-diuretic hormone, which stimulates sodium-
potassium ATPase activity
D. has a direct effect on cells of the zona glomerulosa of the adrenal cortex to secrete
aldosterone
E. Clearance concept and renal calculations

1. clearance definition

C = U x V U = urine concentration
P V = urine flow rate
P = plasma concentration

= ml/min

Clearance = the minimum volume of plasma at the prevailing plasma concentrations

that could have supplied the material appearing in the urine in the given time interval.

List the following from the least to the greatest clearance:

sodium
glucose
creatinine
inulin
PAH

2. GFR measurements

GFR = Cin = Uin x V

Pin

- inulin

- freely filtered, not metabolized, not secreted, not reabsorbed

- substances used instead of inulin: mannitol, sucrose, creatinine*
(*some secreted in humans*)

Cx > Cin - substance filtered and secreted (e.g., PAH)

Cx < Cin - substance filtered and reabsorbed or not freely filtered (e.g., glucose)

- concentration of inulin in the tubule is an index of water reabsorption

3. Renal blood flow measurement

PAH - filtered + completely secreted

Cpah = ERPF (effective renal plasma flow)

ERPF = Vpah x V
Ppah

renal blood flow = ERPF

(1 – Hct)

4. Filtration fraction (FF)

FF = GFR = Cin
RPF Cpah

5. Free water clearance

- denotes the volume of pure water that must be removed from or added to the flow
of urine to make it isosmotic with plasma

Cosm - Vosm x V
Posm

C
H2O = V - Cosm

C
H20 (+) = plasma being concentrated, dilute urine is formed

C
H20 (-) = plasma diluted, concentrated urine is formed

6. Fraction of filtered material excreted (Fractional excretion)

FE = Ux / Px = excretion = clearance of x
Uin / Pin filtered load clearance of inulin

> 1 = net secretion

< 1 = net reabsorption
1. Which of the following substances has the greatest renal clearance?

A. inulin
B. sodium
C. urea
D. creatinine
E. glucose

2. Determine the excretion of glucose given the following data:

urine glucose concentration 125 mg/100ml

urine inulin concentration 56 mg/100ml
plasma glucose concentration 90 mg/100ml
plasma inulin concentration 1 mg/100ml
urine flow rate 2 ml/min

A. 112 mg/min
B. 98.5 mg/min
C. 200 mg/min
D. 2.5 mg/min

3. The following data are obtained for a patient:

inulin clearance 170 L/day

plasma bicarbonate concentration 25 mmol/L
urine bicarbonate concentration 0 mmol/L
urine pH 5.8
titratable acid in urine 26 mmol/day
ammonium ion in urine 48 mmol/day

Calculate the total amount of hydrogen ions secreted:

A. 4250 mmol/day
B. 26 mmol/day
C. 74 mmol/day
D. 4324 mmol/day

4. Given the following data:

urine flow rate 0.5 liters/24 hours

urine osmolarity 600 mosmol/L
plasma osmolarity 300 mosmol/L

What is the free-water clearance?

A. 2 L/24 hours
B. -0.5 L/24 hours
C. -4 L/24hours
D. 1 L/24 hours
5. Given the following data:

urine concentration of sodium 1400 mEq/1

urine concentration of inulin 1 mg/ml
plasma concentration of sodium 140 mEq/1
plasma concentration of inulin .01 mg/ml

What is the fractional excretion of sodium?

A. 1.0
B. 0.5
C. 0.1
D. 0.25

6. Calculate the renal filtered load of sodium:

glomerular filtration rate: 100 ml/min

urine flow rate 2.4 ml/min
urine concentration of inulin 1 mg/ml
plasma concentration of sodium 0.12 mEq/ml

A. 20 ml/min
B. 100 mg/min
C. 12 mEq/min
D. 50 ml/min

7. Renal clearance of inulin provides a measure of:

A. renal blood flow

B. cardiac output
C. glomerular filtration rate
D. renal plasma flow

8. Calculate the free-water clearance in a patient with the following laboratory date:

urine output 1.5 L/24 hours

glomerular filtration rate 125 ml/min
osmolarity of the urine 150 m0smol/L
osmolarity of the plasma 300 m0smol/L

A. 2.25 L/24hours
B. 1.5 L/24 hours
C. 3.0 L/24 hours
D. 0.75 L/24 hours
9. calculate the bicarbonate reabsorption in a patient with the following data:

clearance in inulin: 175 L/day

plasma bicarbonate 25 mmol/L
urine bicarbonate 0
urine pH 5.8
titratable acid in urine 26 mmol/day
urine ammonium ion 48 mmol/day

A. 4449 mmol/day
B. 74 mmol/day
C. 26 mmol/day
D. 4375 mmol/day

10. How much new bicarbonate has been added to the blood of the above patient?

A. 48 mmol/day
B. 26 mmol/day
C. 4449 mmol/day
D. 74 mmol/day

11. Calculate the renal plasma flow of a patient given the data below:

effective renal plasma flow 585 ml/min

uncorrected measured hematocrit 45%
renal extraction of PAH 0.90
(i.e., 90% of PAH is removed from the plasma by the kidney
in a single passage)

A. 1064 ml/min
B. 961 ml/min
C. 1066 ml/min
D. 650 ml/min

Question 12. Select all correct answers.

12. Regarding the fractional excretion of a freely filtered susbstance:

1. a value greater than one suggests that net secretion of the substance has occurred
2. in hypernatremia (high sodium in plasma) the fractional excretion of sodium is greater
than one
3. the renal clearance of a substance X divided by the inulin clearance is a measure of the
fractional excretion of substance X
4. it is necessary to measure urine flow rate to determine the fractional excretion of a
substance
DIRECTIONS: (Questions 13-14). Answer true or false to the following statements by marking
A for true and B for false.

13. The renal clearance of glucose is less than that of inulin

14. Inulin is present at the same concentration in the glomerular filtrate and the final urine.

15. Which one of the following statements is most consistent with a filterable substance being
actively reabsorbed from the renal tubular lumen?

A. its renal clearance value is lower than that of inulin

B. its renal clearance value is higher than that of inulin
C. the ratio of its rate of urinary excretion/plasma concentration is the same as that for
glucose
D. the ratio of its rate of urinary excretion/plasma concentration is greater than that for
glucose
E. its concentration in the distal tubule is higher than that in plasma

16. During the infusion of PAH into a patient, the concentration of PAH in the cephalic vein
stabilized at 0.02 mg/ml of plasma (=PPAH). At this time, the two kidneys were producing 1
ml of urine per minute (=VU), and the concentration of PAH in the urine was 16 mg/ml
(=UPAH). What was the PAH clearance (=CPAH)? What was the effective renal plasma
flow (=ERPF)?

17. The renal clearance of (select the one best answer):

A. a substance is measured in mg/ml

B. a substance is measured in mg/min
C. sodium is decreased by the injection of aldosterone
D. inulin, at a plasma concentration of 60 mg%, is lower than at a plasma concentration of
120 mg%
E. para-aminohippurate (PAH) at a plasma concentration of 60 mg% is higher than at a
plasma concentration of 120 mg%
18. The clearance of substances f, g and h are studied at different concentrations in the blood.
The following data are obtained:

Which of the following statements best characterizes substance f ? Substance f in the nephron is:

A. secreted
B. reabsorbed
C. filtered
D. filtered and reabsorbed
E. filtered and secreted

19. Which one of the following statements best characterizes substance h in question18.
Substance h in
the nephron is:

A. filtered and actively secreted

B. filtered and passively reabsorbed
C. filtered, passively reabsorbed, and actively reabsorbed
D. filtered and synthesized
E. filtered, synthesized, and secreted

20. Which one of the following statements concerning curve h in question 18 is true? the plasma
concentration at point:

A. i represents the transport maximum

B. i represents the splay
C. i represents the threshold
D. j represents the splay
E. j represents the threshold
21. All of the following substances are filtered into the glomerular capsule. Indicate which ones
will produce a clearance curve in man similar to f, g or h in question 18. One of these
substances has a Tm value of 375 mg/min and another of 1 mg/min. Therefore, in making
your comparisons, concentrate on the shape of the clearance-concentration curve, not
absolute values of concentration.

_____inulin _____penicillin _____lysine

_____glucose _____albumin _____hemoglobin

_____PAH _____arginine _____diodrast

_____sulfate _____ketone bodies _____phosphate

_____ascorbic acid
 Answers to Renal Questions

Pages 4-5 Pages 19-23

1. 4 only 1. D
2. 4 only 2. D
3. B 3. D
4. E 4. B
5. A 5. C
6. A 6. C
7. T 7. C
8. B 8. D
9. D
10. D
Page 10 11. D
12. B
1. A 13. A
2. E 14. B
3. D 15. C
4. Urea 16. 800 ml/min
17. C
18. E
Pages 14-16 19. C
20. C
1. D
2. A 21. g f h
3. 1 & 3 hhh
4. 4 only fhf
5. 2 & 4 hhh
6. 1, 2, 3 h
7. all
8. D
9. B
10. all
11. 4 only
12.
13. 2 & 4
14. E
15. D