Overview of renal function

and the clearance concept

Prof Harbindar Jeet Singh

Faculty of Medicine
Universiti Teknologi MARA
Shah Alam
Objectives

1. Describe the structure of kidney and nephron

2. List the functions of the kidney

3. Describe clearance concept

4. Define renal clearance

5. Discuss the uses of the clearance concept in the measurement

of renal function, like g.f.r., renal blood flow etc.

6. Define glomerular filtration rate

7. Describe free water clearance

Major functions of the kidney

4. Water and electrolyte balance

6. Acid-base balance

3. Excretion of metabolic waste

4. Blood pressure regulation (RAAS)

5. Vitamin D metabolism

6. Secretion of erythropoietin
The human kidneys are bean-shaped organs lying behind the peritoneum on
each side of the vertebral column.

Each kidney weighs between 125 – 170 g in the male and between 115 – 155 g
in the female. They make up less than 0.5% of the total body weight.
The single functional unit of a kidney is the nephron.

The number of nephrons found in mammals varies, the number

increasing with increasing body mass

e.g. a mouse has 12,400 nephrons per kidney

human 1.2 million per kidney
an elephant has 7.5 million per kidney
a fin whale has 192 million per kidney

Most mammalian kidneys generally contain two types of nephrons

short-looped nephrons
long-looped nephrons

(except the dog, which has all long-looped nephrons and a mountain
beaver that has all short looped nephrons)
Although the division of nephrons according to the position of the
corpuscle does not coincide with the division based on the length
of their loops, generally superficial glomeruli give rise to short-looped
nephrons and mid-corticol and juxta-medullary glomeruli give rise
to long-looped nephrons.

Short-looped and long-looped nephrons differ in two

important aspects:

Short-looped nephrons turn near the inner-outer

medullary border and lack a thin ascending limb.

Thin ascending limbs are found only in the inner

medulla.

Generally there are more short-looped nephrons

than long-looped nephrons.
The long-looped nephrons tend to exhibit substantial variation in the
depth reached within the inner medulla.

Some mammalian kidneys, such

as human kidneys, also have
nephrons whose loops of Henle
do not reach into the medulla;
these nephrons are the cortical
(superficial) nephrons.
Structure of a nephron
Tubule segments of the nephron

Tubule segment Abbreviation

Proximal convoluted tubule - PCT

Proximal straight tubule - PST
Thin descending limb of loop of Henle - tDLH
Thin ascending limb of loop of Henle - tALH
Thick ascending limb of loop of Henle - TAL/TALH
Distal convoluted tubule - DCT
Cortical collecting duct - CCT
Outer medullary collecting duct - OMCD
Inner medullary collecting duct - IMCD
In 1842, William Bowman proposed that the glomerular capillaries
secrete water, which flushes out solutes secreted by the renal
tubules

In 1844 Carl Ludwig concluded that urine is formed by ultrafiltration

of plasma at the glomerulus, and that it merely passes down the
nephron without further alteration save for concentration of solutes
by passive reabsorption of water

In 1917 Arthur Cushny modified Ludwig’s view by proposing that

not only water but also solutes are reabsorbed by the tubules, in
proportions, which are determined by their normal values in the
plasma

In 1923 E.K. Marshall proved that tubular secretion also occurs

The process of urine formation involves a combination of ultrafiltration at
the glomerulus, followed by selective tubular reabsorption of water and
solutes, and selective tubular secretion of solutes.

Filtered Excreted Reabsorbed %

H2O L/d 180 1.5 178.5 99.2

Na+ mM/d 25,000 150 24,850 99.4

Cl- mM/d 18,000 150 17,850 99.2

HCO3- mM/d 4,500 2 4,498 99.9+

Glucose mM/d 800 0.5 799.5 99.9+

Urea g/day 46.8 23.4 23.4 50

The clearance concept is a central concept in renal physiology.

It is a concept or technique that allows us to assess renal function using only

analysis of urine and plasma.

Instead of talking about the rate of excretion of a substance in urine,

we talk about the rate of removal of this substance from the plasma.

Definition:

Renal clearance can therefore be defined as the volume of plasma in mls

passing through the kidneys that has been completely cleared of a substance
in a given period of time.
Thus, if the plasma contains 0.1 gm of a substance in 100 ml,

and 0.1 gm of the substance also passes into the urine each minute,

then, 100 mls of plasma is cleared of the substance per minute.

The equation for the calculation of plasma clearance is

Renal clearance (ml min-1) =

urine excretion rate of the substance (mg/min)

plasma concentration of the substance mg/ml
 Urine flow (ml/min) × Conc. of substance in urine (μmol/ml)

Conc. of substance in plasma (μmol/ml)

Or Uc × V

E.g.

Urine flow = 1 ml/min

Conc in plasma = 100 μmol/ml
Conc in urine = 12000 μmol/ml

12000 x 1
= 120 ml/min
100
Uses of the clearance concept.

1. In the measurement of glomerular filtration rate (gfr)

For the measurement of g.f.r., we need a substance that is

a) freely filtered
b) not secreted by the tubular cells,
c) not reabsorbed by the tubular cells.
d) should not be toxic
e) should not be metabolised
f) easily measurable.

An example of such a substance is inulin. It is a polysaccharide with a

molecular weight of about 5200 and it fits all the above requirements.
So, if we say,

Plasma conc. of inulin = 100μg/100ml

Urinary conc of Inulin = 12000 μg /100ml
Urine flow (UV) = 1 ml /min

then, the clearance of inulin will be

Ci = U×V = 12000 × 1
= 120 ml/ min
P 100

As inulin is neither secreted nor reabsorbed the clearance of inulin can be

taken as a measure of the glomerular filtration rate.

Other sugars that could be used include sorbitol, mannitol.

In clinical practice creatinine clearance is used as a measure of g.f.r.

2. For the measurement of Renal Blood Flow.

Inulin clearance or g.f.r. only reflects the volume of plasma that is filtered and
not that remains unfiltered and yet passes through the kidney.

It is known that only 1/5 of the plasma that enters the kidneys gets filtered.

To measure renal blood flow we will have to measure renal plasma flow first
and then from the hematocrit we calculate the actual blood flow.
For the measurement of renal plasma flow, we will again need a substance
that is

a) freely filtered
b) rapidly and completely secreted by the renal tubular cells
c) not reabsorbed
d) not toxic
e) and easily measurable.

An example of the substance is Para-aminohippuric acid (PAH).

So if the concentration of PAH in the urine and plasma and the urine flow
are as follows:

Conc. of PAH in urine = 25.2 mg/ml

Urine flow = 1.1 ml/min
Conc of PAH in arterial blood = 0.05 mg/ml

Then CPAH or Renal Plasma Flow = 25.2 × 1.1

= 560ml
0.05

Lets say the hematocrit is 45%, then renal blood flow will be

560 × 100
= 1018 ml/min
100 - 45
3. Clearance can also be used to determine renal handling of a substance.

Clearance values can also be used to determine how the nephron handles
a substance filtered into it.

In this method the clearance for inulin or creatinine is calculated and then
compared with the clearance of the substance being investigated.
Free water clearance

Free water refers to water that is free of solutes.

Free water clearance may be defined as the amount of distilled water that
must be subtracted from or added to the urine in order to render that urine
iso-osmotic with plasma.

CH20 = V - Cosm

where Cosm = the osmolal clearance

= U×V

P
e.g.

urine osmolality = 100 mOsm/kg H2O,

urine flow rate = 10 ml per minute,
plasma osmolality = 300 mOsm/kg H2O

Then,

100 × 10
CH2O = 10 - = 6.7 ml/min
300

When hyperosmotic urine of 1,000 mOsm/kg is formed, and

the urine flow is 0.5 ml per minute,

Then,
1000 × 0.5
0.5 ml - = -1.2 ml/min
300
When hypoosmotic urine is formed, the free water clearance has a positive
value,

and when hyperosmotic urine is formed this clearance has a negative

value

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