RENAL

FUNCTION

Medical Laboratory Science Program

College of Allied Medical Professions
Lyceum of the Philippines University - Batangas
 FUNCTIONS OF THE
URINARY SYSTEM
Excretion of wastes
Maintenance of fluid balance
Maintenance of blood pH (acid-base balance)
Regulation of blood pressure
Secretion of erythropoietin important for
hematopoiesis
Activation of Vitamin D
DNEYS
Reddish-brown bean-shaped organ
located at the posterior wall of the
abdomen.
Nephrons are the structural and
functional unit of the kidney.
Each kidney contains approximately
1-1.5 million of nephrons.
Renal Blood Supply
Renal Blood flow
1200 ml/minute
Renal Plasma flow
600-700 ml/minute
PARTS OF THE NEPHRON
 Renal/Malpighian Corpuscles
 Glomerulus
 Bowman’s Capsule
 Renal Tubules
 Proximal Convoluted Tubule
 Descending Loop of Henle
 Loop of Henle
 Ascending Loop of Henle
 Distal Convoluted Tubule
 Types of Nephrons
1. Cortical nephrons (85%)
Renal corpuscle is located in the cortex
Loop of Henle is located in the renal medulla near its junction with the renal
cortex
Primary function: excretion of wastes and reabsorption of essential
nutrients
2. Juxtaglomerular nephrons (15%)
Renal corpuscle is located near the medulla (but still in the cortex)
Loop of Henle of juxtamedullary nephrons is located deep in the renal medulla
Primary function: concentration of glomerular filtrate

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Blood Vessels associated with the
Nephron
Renal Artery
Afferent arterioles
Glomerular Capillary
Efferent arterioles
Peritubular capillaries
Surrounds PCT and DCT
Allow immediate reabsorption of essential molecules,
secretion of unfiltered wastes and final adjustment of the
urinary composition
Vasa Recta
surrounds the loop of Henle

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Fig. 18.6
Fig. 18.4
Three Processes Involved in Urine
Formation

Glomerular Filtration
Tubular Reabsorption
Tubular Secretion
I. Glomerular Filtration
Glomerulus- Tuft of eight capillaries encircled or
located within the Bowman’s capsule (the
beginning of renal tubules)
The glomerulus is a nonselective filter of plasma
substances with molecular weights less than
70,000 Daltons (70kD)
Factors that Influence the Filtration Process

1. Hydrostatic pressure
results from the smaller size of the efferent arteriole compared to
the afferent arteriole that enhances the filtration process.
2. Oncotic pressure
due to presence of unfiltered proteins in the plasma
opposing force to capillary filtration pressure since it pulls water
into the capillaries
3. Cellularity of the capillary walls
4. Renin-Angiotensin-Aldosterone System
 Glomerular Filtration Barrier
 Plasma filtrate must pass through three cellular layers:
 Capillary wall membrane (endothelium)
- Consists of fenestrated pores (increasing
capillary permeability but does not allow the
passage of large molecules)
 Basement membrane (basal lamina)
 Visceral epithelium of the Bowman’s capsule
Consisting of PODOCYTES
 NOTE: Besides the glomerular filtration barrier, the shield of
negativity repels most plasma protein like albumin (66.5 KD) to
prevent their loss from the blood.
Influence of Blood Pressure on
Renal Arterioles
Maintenance of glomerular blood pressure is
critical to maintaining the normal filtration
process (increased pressure = enhanced
filtration)
Increased BP = afferent arterioles constricts and
efferent arterioles dilate to prevent overfiltration
and damage to glomerulus
Decreased BP = afferent arterioles dilates and
efferent arterioles constrict to prevent tissue
hypoxia (mediated by angiotensin II)

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Regulation of Blood Pressure
1. Kidney regulates blood pressure via secretion
of RENIN (angiotensinogenase) produced by
juxtaglomerular cells
Kidney is the first organ to respond to
decreasing blood pressure since it receives
approximately 25% of the total cardiac output.
Stimuli for the secretion of renin:
1. Decrease in arterial blood pressure (low
plasma sodium)
2. Decrease in intravascular volume

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Juxtaglomerular Apparatus is consist of:
Juxtaglomerular cells of the afferent arteriole
Macula Densa cells of the distal convoluted tubule (senses
changes in the plasma sodium)

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 Renin-Angiotensin-Aldosterone System
Decrease BP (low Na)
Decrease volume

Juxtaglomerular cells
secretes RENIN

ANGIOTENSINOGEN

Angiotensin I  lungs

Angiotensin Converting
Enzyme (ACE)
Angiotensin II- active form

Vasoconstriction of
efferent and vasodilation Na reabsorption Release of Aldosterone
of afferent arterioles In the PCT (Na-retaining hormone
of the adrenal cortex)
ADH secretion by the hypothalamus
(Water reabsorption Na reabsorption
in DCT and Collecting duct) In the DCT (in exchange of K+)
 Urine is an ultrafiltrate of plasma

Since glomerular filtration is non-selective, the only

difference between the composition of the filtrate and the
plasma is the absence of plasma proteins, protein-bound
substances and cells.
The specific gravity of the fluid leaving the glomerulus is
1.010 and confirms that it is chemically an ultrafiltrate of
plasma.
glomerulus
pct dlh Alh DCT COLLECTING DUCTS

glomerulus

1.010

PCT

DLH

ALH

COLLECTING DUCTS
DCT
RENALTUBULES
 II. TUBULAR
REABSORPTION
 This involves two cellular transport
mechanisms:
1. ACTIVE TRANSPORT
 movement of a substance across cell membranes
requiring the expenditure of energy.
 Requires ATP.
 Happens transcellularly- across the cell
Actively transported substances exhibit maximal
reabsorptive capacity
 II. Tubular Reabsorption
2. PASSIVE TRANSPORT
 movement of molecules across a membrane as a
result of differences in concentration or gradient
 Requires NO ENERGY (ATP-independent)
 Movement of substances is from higher
concentration to lower concentration
 Occurs paracellularly- between cells through
junctions or intracellular spaces
 II. Tubular Reabsorption
Mechanism Substance Site of reabsorption
1. Active Glucose, amino PCT
Transport acids, salts
Chloride ALH
Sodium PCT & DCT
2. Passive Water All except ALH (walls
Transport impermeable to water)
NOTE: water permeability in
the DCT and collecting ducts
is controlled by ADH

Urea PCT & ALH

Sodium ALH
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NOTE:

When the plasma concentration of a substance

that is NORMALLY completely absorbed
reaches an abnormally high level, the filtrate
concentration exceeds the maximal reabsorptive
capacity of the tubules and the substance begins
appearing in the urine.
Renal threshold - plasma concentration at which active transport stops.
e.g.
Glucose = 160-180 mg/dl
Sodium = 110-130 mmol/L

Increase Renal Glucose Diabetes

glucose in threshold is appear in mellitus
serum reached urine

Normal Renal Glucose Tubular

glucose in threshold is appear in damage
serum NOT reached urine
 Renal Concentrating
Mechanism
Ascending Loop of Henle
impermeable to water, highly permeable to salts
Descending Loop of Henle
impermeable to salts, highly permeable to water
The selective reabsorption process is called the
countercurrent mechanism and serves to maintain
the osmotic gradient (hypertonicity) of the medulla.
 III. TUBULAR
SECRETION
 Transfer of materials from peritubular
capillaries to renal tubular lumen
 Two major functions:
 Elimination of waste products not filtered by
the glomerulus. Many drugs are eliminated by
tubular secretion.
 Regulation of acid-base balance in the body
through secretion of H+ and NH3
III. Tubular Secretion

Foreign substance Peritubular

(medications, capillaries
drugs)

Bound to Strong affinity to tubular cells

plasma (dissociate from
proteins the carrier protein)

Can’t be filtered
by the Final removal- PCT
Glomerulus
Mechanism by which kidney
regulates pH:
1. Reclamation of bicarbonate (almost 100%)
in the PCT in the form of CO2

2. Excretion of acids in the form of ammonium

ions (NH4+), H2PO4 and titratable acids (free H+)
ammonia formed in the PCT are derived from
GLUTAMINE

3. ATP-dependent excretion of H+ in exchange

of sodium via Na+-H+ pumps
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 Regulation of Fluid Balance
Vasopressin/Antidiuretic Hormone (ADH)
 Function: prevents excessive loss of water in urine.
 The action of ADH takes place in the collecting ducts
and distal convoluting tubules which possess ADH receptors

Increased Body Decreased ADH Increased Urine

Hydration production Volume

Decreased Body Increased ADH Decreased Urine

Hydration production Volume
URETERS
Right and Left ureter
Passageway of urine
URINARY BLADDER
Temporary storage of urine
Capacity (1000 ml of urine)
Transitional epithelium
Small amount of urine: cuboidal
Full of urine: squamous
Urine volume higher than 1000 ml
 internal sphincters will open (involuntary)
External sphincters (voluntary)
 DISEASES
Urinary Incontinence
 One is unable to control the sphincters.
 Normal- < 2 years old
 Usually associated with some psychological disorders
Urinary Retention
 One is unable to expel the bladder’s contained urine.
Urinary stones (urinary calculi)
Surgery (takes some time for muscles to
regain activity)
Benign Prostatic Hyperplasia (BPH)
RENAL FUNCTION TESTS
 Renal Function Tests
I. GLOMERULAR FILTRATION TESTS
 Measure the excretory capacity of the kidney
1. Clearance Tests- measures the rate at which the
kidneys are able to remove a filterable substance
in urine.
a. Endogenous Clearance test- measures a substance
that is already present inside the body.
E.g. Urea, creatinine, beta-2-microglobulin, cystatin C
b. Exogenous- requires a substance to be infused inside
the body.
E.g. Inulin, radioisotopes
 Renal Function Tests

I. Glomerular Filtration Tests

 To ensure that glomerular filtration is being accurately
measured, the substance to be analyzed should neither be
reabsorbed nor secreted by the tubules.
 The best overall indicator of the level of kidney function
 Other factors include:
 Stability of the substance in a 24-hour urine
 Consistency of plasma level
 Substance availability to the body
 Availability of the tests for chemical analysis
 Glomerular Filtration Tests
 ENDOGENOUS CLEARANCE TESTS
1. Urea Clearance
 Earliest glomerular filtration test
 Normal value have to be readjusted that is why it is NOT
recommended for laboratory applications.
 In advanced renal failure, urea clearance approaches unity with
GFR, and is a better predictor of GFR than creatinine clearance
 As renal function declines:
 urea reabsorption decreases progressively
 creatinine secretion increases progressively
 The faster the rate of urine flow, the less urea is reabsorbed and vice
versa.
 Glomerular Filtration Tests
2. Creatinine Clearance
 Most commonly used clearance test for routine assessment of
Glomerular Filtration Tests
 NOT useful in detecting early renal disease
 Specimen of Choice: 24-hour urine sample
 Greatest source of error: Improperly timed urine sample
Formula: C = UV/P
C= crea clearance
U= urine creatinine in mg/dl
V= volume of urine in ml/minute
P= plasma creatinine in mg/dl

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Glomerular Filtration Tests
 DISADVANTAGES of using creatinine as a measure of
GFR:
1. Some creatinine is secreted by the tubules and secretion
increases as blood levels rises
 Cimetedine = drug of choice used to inhibit creatinine
secretion, enhance accuracy of the methodology
2. Chromogens present in human plasma react in the chemical
analysis
3. Bacteria will break down creatinine if stored at room
temperature for prolonged periods
4. A diet heavy in meat consumed during a collection of a 24-
hour urine specimen may influence the results if specimen is
drawn prior to the collection period.

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 Glomerular Filtration Tests
5. Measurement of creatinine clearance is NOT a
reliable indicator in patients suffering from muscle-
wasting diseases.
6. Medications, including gentamicin, cephalosporins,
and cimetidine (Tagamet), inhibit tubular secretion of
creatinine.
7. Accurate results depend on the accurate completeness
of a 24-hour collection.
8. It must be corrected for body surface area, unless
normal is assumed, and must always be corrected for
children
 Creatinine Clearance
Given:
Urine Creatinine= 120 mg/dl
Plasma Creatinine= 1.0 mg/dl
Urine volume= 1 ml/minute

C= UV/P
C= 120 (1)/1.0
C= 120 ml/minute- Normal Glomerular
Filtration Rate
 Creatinine Clearance
Given:
Urine Creatinine= 120 mg/dl
Plasma Creatinine= 1.0 mg/dl
Urine volume= 1440 ml/24hrs
Volume= 1440ml x 1 hr x 1440 ml = 1ml/min
24hr 60mins 1440 mins
C= UV/P
C= 120 (1)/1.0
C= 120 ml/minute- Normal Glomerular
Filtration Rate
 Creatinine Clearance
Given:
Urine Creatinine= 180 mg/dl
Plasma Creatinine= 2.0 mg/dl
Urine volume= 2500 ml/24 hours

Crea Clearance= 156.6 ml/minute

 Creatinine Clearance
Normal values vary in size and muscle mass of a person.
Normal body surface area= 1.73 m2
The laboratory receives a 24-hour urine sample from a 26
year-old (6’4” or a body surface area = 2.34 m2)
Specimen volume= 800 ml
Plasma Crea= 1.2 mg/dl
Urine Crea= 150 mg/dl
 Creatinine Clearance

C= U x V / P
V= 800 ml x 1 hr x 800 ml = 0.56 ml/min
24hr 60 mins 1440 mins.
C= U x V /P
C= 150 mg/dl x 0.56/min / 1.2 mg/dl
C= 70 ml/min

Corrected Crea Clearance= 70 ml/min x 1.73 m2

2.34 m2
Corrected Crea Clearance= 51.75 ml/min
N.V. (men) = 107-139 ml/minute
N.V. (women)= 87-107 ml/minute
 Crea Clearance
SAMPLE PROBLEM:
The laboratory receives a 24-hour urine sample from
a 24 year-old
(5’4” or a body surface area = 1.75 m 2)
Specimen volume= 3000 ml/24 hrs
Plasma Crea= 2.4 mg/dl
Urine Crea= 300 mg/dl
SOLUTION FOR THE SAMPLE
PROBLEM
 Creatinine Clearance
Gault and Cockcroft Formula
General equation:
Crea clearance= (140-age) x weight in kg
72 x serum crea (mg/dl)

Example- Age= 50
Weight= 90 kgs.
Serum Crea= 1.1 mg/dl
If female: Multiply by 0.85
 SAMPLE PROBLEM
Example: 73 y.o. Female patient
Weight= 120 kgs.
Serum Crea= 0.35 mg/dL

Solution:
Glomerular Filtration Tests
3. Cystatin C
Small protein (molecular weight 13,359) produced at a
constant rate by all nucleated cells
It is readily filtered by the glomerulus and reabsorbed and
broken down by the renal tubular cells. Therefore, no
cystatin C is secreted by the tubules
Monitoring levels of cystatin C is recommended for
pediatric patients, persons with diabetes, the elderly, and
critically ill patients.
An advantage of cystatin C is that it is independent of
muscle mass.
Specimen = SERUM

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 Glomerular Filtration Test
4. Beta 2 microglobulin
Constituent of MHC Class I molecule that
dissociates from it at a constant rate and removed
from plasma by glomerular filtration
Rise in the plasma level of beta2-microglobulin
has been shown to be a more sensitive indicator of
a decrease in GFR than creatinine clearance.
Not reliable in patients who have a history of
immunologic disorders or malignancy
 Glomerular Filtration Tests
EXOGENOUS CLEARANCE TESTS
Inulin Clearance- Inulin is a polymer of fructose;
an extremely stable substance that is NOT
reabsorbed nor secreted by the tubules. It is
considered the Gold Standard Glomerular filtration
test.
Radionucleotides (e.g. 125I-iothalamate)
Provides a method for determining glomerular
filtration through the plasma disappearance of the
radioactive material and enables visualization of
the filtration in one or both kidneys
Estimated Glomerular Filtration
Rates
Newer methods that do not require the collection of timed (24-
hour) urine specimens
Modification of Diet in Renal Disease (MDRD) formula
variables included: ethnicity, BUN and serum albumin (does not include body
weight)
National Kidney Disease Education Program (NKDEP)
recommends the MDRD-IDMS-traceable formula
Other formulas
CKD-EPI formula: more accurate than MDRD
Mayo Quadratic formula: for patients with preserved kidney function
Schwartz formula: exclusive for children

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Clinical Significance:
1. Assess the functional capacity of nephrons
2. Used to determine the extent of nephron damage
in known cases of renal disease
3. Monitor the effectiveness of treatment designed
to prevent further nephron damage
4. Determine the feasibility of administering
medications which may accumulate to toxic
levels if GFR is markedly decreased.

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 TUBULAR REABSORPTION
(CONCENTRATION) TESTS
First Function to be affected in a RENAL/KIDNEY
disease (GFR is not a useful indicator of early renal
disease)
Tests to determine the ability of the tubules to
reabsorb the essential salts and water that have been
nonselectively filtered by the glomerulus are called
CONCENTRATION TESTS
Urine concentration is largely determined by the
body’s state of hydration, thus control of fluid intake
is essential in measuring the concentrating ability of
the kidney.
 Tubular Reabsorption
(Concentration) Tests
A. Concentration Tests- Water deprivation Tests
1. Fishberg- The patient is deprived of fluid
for 24 hours before measuring urine specific
gravity.
2. Mosenthal- compare day and night urine in
terms of volume and specific gravity.
The final urine S.G. should be higher than
1.010.
These two tests are now obsolete.
 Concentration Tests
1. Specific Gravity
Simplest renal concentration test
Most useful as a screening procedure
Compared the weight of the fluid with that of distilled water at a
reference temperature
Measurement is affected by solute number and density, as
opposed to osmolality
Affected by HMW substance = x-ray dye, mannitol (high S.G >
1.040)
Fixation at 1.010 (isosthenuria) - indicates severe loss of
concentrating ability of the kidney
Specific gravity of the glomerular filtrate = 1.010 (same that of
protein-free plasma)
Concentration Tests
2. Osmolality
 Osmolarity is influenced only by the number of solute,
thus more accurate than specific gravity in assessing
renal concentration ability.
 Urine osmolality is primarily due to urea, serum
osmolality is primarily due to sodium and chloride
 Not affected by HMW substance like mannitol,
proteins and lipids
 Normal ratio of urine to serum osmolality = 1:1
 after a period of dehydration 3:1
 Normal urine osmolality reading after an overnight
dehydration = 800 mOsm

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Concentration Tests
3. Freezing Point Osmometers
 1 osm 0r 1000 mOsm of a nonionizing substance dissolved in
1 kg of water is known to lower the freezing point 1.86°C.
 Decrease Freezing Point= Increase Osmolarity
 Normal serum osmolality: 275-300 mOsm
 Calculates osmolarity by comparing the freezing point
depression of an unknown solution with that of a known
molal solution
 Serum water displacement by insoluble lipids produces
erroneous results
 Lactate may cause falsely elevated results
 Uses NaCl solutions as reference standards

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 Concentration Tests
4. Vapor pressure Depression
 Measures the dew point (temperature at which water vapor condenses
to a liquid)
 Do NOT detect the presence of volatile substances, such as alcohol
 Uses NaCl solution as standard
 Serum water displacement by insoluble lipids produces erroneous
results
 Lactate may cause falsely elevated results
Free Water Clearance
The volume of blood plasma that is cleared of solute-free water
per unit time.
Determine the ability of the kidney to respond to the body state of
hydration.
Urine and plasma osmolality is being compared
 Negative water clearance = water is being retained
(dehydration)
urine more concentrated than plasma
 0 = no renal concentration or dilution is taking place
urine and plasma osmolality is the same
 Positive water clearance = excess water is being
excreted
urine more dilute than plasma
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 Test for Tubular Secretion
1. Para-amino hippuric acid (PAH) Test (Diodras
test)
 Exogenous test that measures renal plasma flow
 PAH is a nontoxic substance that is loosely
bound to plasma proteins, which permits its
complete removal as the blood passes through
the peritubular capillaries
2. Phenolsulfonphthalein (PSP) Test: obsolete
 Measures excretion of dye proportional to renal
tubular mass
Test for Tubular Secretion
3. Titratable Acidity and Urinary Ammonia
Measures the ability of the kidney to secrete
ammonia (PCT and DCT) and H+ (PCT)
A normal person excretes 70mEq/day of titratable
acids in the form of H+, ammonium ions (NH4+)
and H2PO4-
Impaired secretion of H+ and ammonia will lead to
metabolic acidosis in the form of renal tubular
acidosis.

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