1. Plasma Clearance
Dr. Sai Sailesh Kumar G
Associate Professor
Department of Physiology
R.D. Gardi Medical College, Ujjain, Madhya Pradesh.
Email: dr.goothy@gmail.com

2. Case study
 A 45 year old man comes to the OPD with the complaints of
excessive thirst, urination, hunger and weakness from past two
weeks. Answer the following
1. What is the most likely condition
2. Explain symptoms
3. What tests you suggest to confirm
4. What are diet and life style modifications you suggest for this man

3. Introduction
 Of the 125 mL of plasma filtered per minute, typically 124 mL/min
are reabsorbed, so the final quantity of urine formed averages 1
mL/min.
 Thus, of the 180 liters filtered per day, 1.5 liters of urine are
excreted.

4. Introduction
 Urine contains high concentrations of various waste products
plus variable amounts of the substances regulated by the
kidneys, with any excess quantities having spilled into the urine.
 Useful substances are conserved by reabsorption, so they do
not appear in the urine.

5. Introduction
 A relatively small change in the quantity of filtrate reabsorbed
can bring about a large change in the volume of urine formed.
For example, a reduction of less than 1% in the total reabsorption
rate, from 124 to 123 mL/min, increases the urinary excretion rate
by 100%, from 1 to 2 mL/min.

6. Plasma clearance
 The plasma clearance of any substance is defined as the volume
of plasma completely cleared of that substance by the kidneys
per minute
It refers not to the amount of the substance removed but to the
volume of plasma from which that amount was removed.
Plasma clearance is actually a more useful measure than urine
excretion.

7. Plasma clearance
 it is more important to know what effect urine excretion has on
removing materials from body fluids than to know the volume and
composition of discarded urine.
Plasma clearance expresses the kidneys’ effectiveness in
removing various substances from the internal fluid environment.

9. Plasma clearance
 The plasma clearance rate varies for different substances,
depending on how the kidneys handle each substance.
Let us consider how three common patterns of renal handling
influence clearance rates for the involved substance.

10. Plasma Clearance Rate for a Substance Filtered But
Not Reabsorbed or Secreted
 No normally occurring chemical in the body has the characteristics of substance X.
All substances naturally present in the plasma, even wastes, are reabsorbed or
secreted to some extent.
However, inulin (do not confuse with insulin), a harmless foreign carbohydrate
produced abundantly is freely filtered and not reabsorbed or secreted—an ideal
substance X.
Inulin can be injected and its plasma clearance determined as a clinical means of
finding out the GFR.

13. Plasma Clearance Rate for a Substance Filtered But
Not Reabsorbed or Secreted
 Although determination of inulin plasma clearance is accurate and straightforward, it is not
very convenient because inulin must be infused continuously throughout the determination to
maintain a constant plasma concentration.
Therefore, the plasma clearance of an endogenous substance, creatinine, is often used
instead to find a rough estimate of the GFR.
 Creatinine, an end product of muscle metabolism, is produced at a relatively constant rate. It
is freely filtered and not reabsorbed but is slightly secreted.
Accordingly, creatinine clearance is not a completely accurate reflection of the GFR, but it
does provide a close approximation and can be more readily determined than inulin clearance.

14. Plasma Clearance Rate for a Substance Filtered and
Reabsorbed
 Some or all of a reabsorbable substance that has been filtered is returned to the
plasma.
The plasma clearance rate of a reabsorbable substance is always less than the GFR.
For example, the plasma clearance for glucose is normally zero. All the filtered glucose
is reabsorbed with the rest of the returning filtrate, so none of the plasma is cleared of
glucose.
 For a substance that is partially reabsorbed, such as urea, only part of the filtered
plasma is cleared of that substance. With about 50% of the filtered urea being passively
reabsorbed, only half of the filtered plasma, or 62.5 mL, is cleared of urea each minute

17. Clearance Rate for a Substance Filtered and Secreted
 Tubular secretion allows the kidneys to clear certain materials from
the plasma more efficiently.
 Only 20% of the plasma entering the kidneys is filtered. The
remaining 80% passes unfiltered into the peritubular capillaries.
The only means by which this unfiltered plasma can be cleared of
any substance during the trip through the kidneys before being
returned to the general circulation is by secretion.

18. Clearance Rate for a Substance Filtered and Secreted
 An example is H+.
Not only is filtered plasma cleared of nonabsorbable H+, but the
plasma from which H+ is secreted is also cleared of H+.
The plasma clearance rate for a secreted substance is always
greater than the GFR.

20. Clearance Rate for a Substance Filtered and Secreted
 Just as inulin can be used to determine the GFR, plasma clearance of another foreign
compound, the organic anion para-aminohippuric acid (PAH), can be used to measure
renal plasma flow.
Like inulin, PAH is freely filterable and nonreabsorbable.
It differs, however, in that all the PAH in the plasma that escapes filtration is secreted
from the peritubular capillaries by the organic anion secretory pathway in the proximal
tubule
The plasma clearance for PAH is a reasonable estimate of the rate of plasma flow
through the kidneys.

21. Clearance Rate for a Substance Filtered and Secreted
 Typically, renal plasma flow averages 625 mL/min, for a renal blood
flow (plasma plus blood cells) of 1140 mL/min—more than 20% of the
cardiac output.
If you know the rates of inulin clearance (GFR) and PAH clearance
(renal plasma flow) you can easily determine the filtration fraction,

23. Artificial Kidney
 Because chronic renal failure is irreversible and eventually fatal,
treatment is aimed at maintaining renal function by alternative methods,
such as dialysis and kidney transplantation.
The process of dialysis bypasses the kidneys to maintain normal fluid
and electrolyte balance and remove wastes artificially.
In the original method of dialysis, hemodialysis, a patient’s blood is
pumped through cellophane tubing that is surrounded by a large volume
of fluid similar in composition to normal plasma

24. Artificial Kidney
 After dialysis, the blood is returned to the patient’s circulatory
system.
During hemodialysis, about 250 mL of blood is outside of the body
at any given time.
Like capillaries, cellophane is highly permeable to most plasma
constituents but is impermeable to plasma proteins

25. Artificial Kidney
 As blood flows through the tubing, solutes move across the cellophane down their
individual concentration gradients; plasma proteins, however, stay in the blood.
Urea and other wastes, which are absent in the dialysis fluid, diffuse out of the plasma
into the surrounding fluid, cleaning the blood of these wastes.
Plasma constituents that are not regulated by the kidneys and are at normal
concentration, such as glucose, do not move across the cellophane into the dialysis
fluid because there is no driving force to produce their movement. (The dialysis fluid’s
glucose concentration is the same as normal plasma glucose concentration.)

26. Artificial Kidney
 Electrolytes, such as K+ and PO4-2, which are higher than their normal
plasma concentrations because the diseased kidneys cannot eliminate
excess quantities of these substances, move out of the plasma until
equilibrium is achieved between the plasma and the dialysis fluid.
 Because the dialysis fluid’s solute concentrations are maintained at
normal plasma values, the solute concentration of the blood returned to
the patient after dialysis is essentially normal.

27. Artificial Kidney
 Hemodialysis is repeated as often as necessary to maintain the plasma
composition within an acceptable level.
 Conventionally, it is done three times per week for up to five hours at
each session at a treatment center, but newer, more user-friendly, at-home
methods dialyze the blood up to six times per week during the day or at
night while the person is sleeping.
The more frequent methods maintain better stability in plasma
constituents than the less frequent methods do.

28. Artificial Kidney
 Another method of dialysis, continuous ambulatory peritoneal dialysis
(CAPD), uses the peritoneal membrane (the lining of the abdominal cavity)
as the dialysis membrane.
With this method, 2 liters of dialysis fluid are inserted into the patient’s
abdominal cavity through a permanently implanted catheter.
Urea, K+, and other wastes and excess electrolytes diffuse from the
plasma across the peritoneal membrane into the dialysis fluid, which is
drained off and replaced several times a day.

29. Artificial Kidney
 The CAPD method offers several advantages:
The patient can self-administer it,
the patient’s blood is continuously purified and adjusted,
and the patient can engage in normal activities while dialysis is
being accomplished.
One drawback is increased risk of peritoneal infections.

30. Artificial Kidney
 Although dialysis can remove metabolic wastes and foreign compounds and help maintain fluid
and electrolyte balance within acceptable limits, this plasma-cleansing technique cannot make
up for the failing kidneys’ reduced ability to produce hormones (erythropoietin and renin) and to
activate vitamin D.
One promising new technique under investigation incorporates living kidney cells derived from
pigs within dialysis like machine. Standard ultrafiltration technology like that used in
hemodialysis purifies and adjusts the plasma as usual. Importantly, the living cells not only help
maintain even better control of plasma constituents, especially K+, but also add deficient renal
hormones to the plasma passing through the machine and activate vitamin D.

31. Artificial Kidney
 For now, transplanting a healthy kidney from a donor is another option for treating
chronic renal failure.
Because 25% of the total kidney tissue can maintain the body, both the donor and the
recipient have ample renal function with only one kidney each.
The biggest problem with transplants is the possibility that the patient’s immune
system rejects the organ.
Risk of rejection can be minimized by matching the tissue types of the donor and the
recipient as closely as possible (the best donor choice is usually a close relative),
coupled with immunosuppressive drugs.

32. Artificial Kidney
 Another new technique on the horizon for treating end-stage renal
failure is a continuously functioning artificial kidney that mimics
natural renal function.
Using nanotechnology (very small-scale devices), researchers are
working on a device that contains two membranes, the first for
filtering blood like the glomerulus does and the second for
mimicking the renal tubules by selectively altering the filtrate.

33. Diuretics
 Substances that increase urine formation
Mainly by inhibiting the absorption of sodium, chloride, and water
Poly urea occurs
Two types of diuretics
1. Causes water diuresis
2. Causes osmotic diuresis

34. Water diuresis
 Failure of water absorption
Due to lack of ADH
Excess water ingestion
Alcohol ingestion
In the above both cases ADH secretion is inhibited

35. Osmotic diuresis
 Presence of large amounts of osmotically active substances in
tubular fluid
Increases excretion of water in urine
Poly urea in diabetes

36. Factors that cause Water diuresis
 Water
Alcohol
Antagonists of ADH – Lithium, Demeclocycline
Inhibits ADH secretion
Decrease water reabsorption
Increase urine formation

37. Factors that cause osmotic diuresis
 Water
Alcohol
Antagonists of ADH – Lithium, Demeclocycline
Inhibits ADH secretion
Decrease water reabsorption
Increase urine formation

38. Factors that cause osmotic diuresis
 Glucose
In diabetes mellitus causes osmatic diuresis
Mannitol also causes osmotic diuresis

39. Factors that cause osmotic diuresis
 K+ depleting drugs
Carbonic anhydrase inhibitor (acetazolamide)-
Acts on PCT
Increases K+, Na+, HCO3- excretion

40. Factors that cause osmotic diuresis
 K+ depleting drugs
Loop duuretics
Furosemide, bumetanide
Block Na+, Cl-, K+ co transport in ascending loop of henle
Increase in excretion of Na+, K+, Cl-

41. Factors that cause osmotic diuresis
 K+ depleting drugs
Chlorothiazide
Block Na+, K+, Cl- transport from early DCT
Stimulate Na+-Ca+2 exchanger
Increases excretion of Na+,K+
Decrease excretion of Ca+2

42. Factors that cause osmotic diuresis
 K+ sparing diuretics
Spiranolactone
Block effect of aldosterone on late DCT and CD
Increase in K+ retention
Increase in Na+ and Cl- excretion

43. Factors that cause osmotic diuresis
 K+ sparing diuretics
Amiloride
Block sodium channels in CD
Stimulate calcium absorption from CD
Increase in Na+ excretion
Decrease in Ca+2 excretion