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Renal Handling of water, salt

and Salicylate
Exercise 15
Objectives
• Estimate the rate of the urinary elimination of a person and relate
this to the volume of fluid and amount of sodium chloride intake;
• Discuss factors which influence the rate of urine formation, and;
• Describe how urinalysis is utilized in obtaining clinical
information about the body.
Chloride concentration

• 0.5 mL of urine
• add 50 l of 20% potassium
chromate

• 50 l portions of 2.9% silver nitrate


solutions, until the bright yellow
solution changes to brown color
Ferric chloride test
The presence of phenolic group
in a compound is indicated by
the formation of violet iron
complex

Aspirin
-negative result
-absence of phenolic group
Salicylic acid
-presence of phenolic group
What is the relationship of the volume and Cl concentration in urine with the amount of water
or salts ingested by an individual?

Subject 1 (0%)
Subject 2 (1%)
Subject 3 (6.7%)
KIDNEYS EXCRETE EXCESS WATER
BY FORMING DILUTE URINE

• excess water in the body and body fluid osmolarity is reduced


• the kidneys can excrete urine with an osmolarity as low as 50
mOsm/L, a concentration that is only about 1/6 the osmolarity of
normal extracellular fluid

• a deficit of water in the body and extracellular fluid osmolarity is high,


the kidneys
• can excrete highly concentrated urine with an osmolarity of 1200 to
1400 mOsm/L
What is the relationship of the volume and Cl concentration in urine with the amount of water
or salts ingested by an individual?

Subject 1 (0%)
Subject 2 (1%)
Subject 3 (6.7%)
KIDNEYS CONSERVE WATER BY
EXCRETING CONCENTRATED URINE

• water deficit in the body


• the kidneys form concentrated urine by continuing to excrete solutes
• while increasing water reabsorption
• decreasing the volume of urine formed
• human kidney can produce a maximal urine concentration of 1200 to
1400 mOsm/L, 4-5 X the osmolarity of plasma.
• Theoretically, for the next one hour, the volume of urine excreted will still
increase in patient 1 (0%) and decrease in patient 2 (1%) and 3 (6.7%) .
• Urine chloride ion concentration will decrease in patient 1 (0%) and increase
in patient 2 (1%) and 3 (6.7%) .
Biological Half-life
• biological half-life refers simply to how long it takes for half of the
dose to be metabolized and eliminated from the bloodstream (if
elimination rate is exponential)
• NaCl = 17 minutes
• Aspirin =13-19 minutes
• Salicylate= 3.5-4.5 hours
(Pubmed.gov)
Salicylates

• Salicylate is a monohydroxybenzoate that is the conjugate


base of salicylic acid
• Salicylates are a group of drugs, including aspirin.
• Relieves pain and inflammation and lowers fevers.
• Salicylates are ubiquitous agents found in hundreds of over-the-
counter (OTC) medications and in numerous prescription drugs,
making salicylate toxicity an important cause of morbidity and
mortality. 
• If exceeded approximately 360 mg

salicylates, elimination is zero-

order kinetics.

• At very small doses, salicylate

was found to proceed by first-

order kinetics.

(LEVY, 1965)
• In a low pH environment like the stomach (pH =2), aspirin is
predominantly unionized and crosses membranes into the
blood vessels readily by passive diffusion.

• Aspirin is a weak acid and it tends to ionize (give up a H atom)


in an aqueous medium at high pH (basic).

• Urine pH normal range: 4.5 to 8.0


Test for salicylates

Subject 20 mins 40 mins 60 mins 80 mins 100 mins 120 mins


1  - - -  -  -  - 
  +  + +   + + 
4 +        
Structure of
Glomerular Capillaries

The basement membrane


effectively prevents filtration
of plasma proteins, in part
because of strong negative
electrical charges associated
with the proteoglycans.
What is glomerular filtration rate? Name factors
that affect it.

Capillary Some diseases, lower Kf by reducing the


filtration number of functional glomerular
capillaries (thereby reducing the surface area
coefficient (Kf) for filtration) or by increasing
the product of the
the thickness of the glomerular capillary
permeability and
membrane and
filtering surface area
reducing its hydraulic conductivity.
of the capillaries
• Colloid osmotic
pressure (COP),
the osmotic
pressure exerted by large
molecules, serves to hold
water within the vascular
space. It is normally created
by plasma proteins, namely
albumin, that do not diffuse
readily across the capillary
membrane.
INCREASED GLOMERULAR CAPILLARY
HYDROSTATIC PRESSURE INCREASES GFR

• Glomerular hydrostatic pressure is


determined by three variables, each of
which is under physiological control:
(1) arterial pressure
(2) afferent arteriolar resistance
(3) efferent arteriolar resistance
INCREASED BOWMAN’S CAPSULE
HYDROSTATIC PRESSURE
DECREASES GFR
• “stones” that lodge in the
urinary tract
• raising Bowman’s capsule
pressure
• reduces GFR
• and can damage or even
destroy the kidney unless the
obstruction is relieved
Clearance Rate
Renal clearance is the volume of plasma that would be necessary to
supply the amount of substance excreted in the urine per unit of
time
• Cs is the clearance rate of a substance
• Ps is the plasma concentration of the substance
• Us is the urine concentration of that substance, and
• V is the urine flow rate
Plasma Clearance Rate (mL/min)
Plasma Clearance Rate (mL/min)
Creatinine clearance
• Urine test
• 24-hour urine collection
• Male: 97-137 mL/min
• Female: 88-128 mL/min
• Damaged kidneys: creatinine in urine goes down
Creatinine in blood goes up

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