LESSON 3: RENAL FUNCTION

THE KIDNEYS AND THE PROCESS OF URINE FORMATION

FOUR MAIN COMPONENTS OF THE URINARY SYSTEM
1. Kidney this is where urine is formed.
2. Ureter- approximately 25 cm long. It is a muscular tube that connects the pelvis of the kidney to the bladder. Ureters
carry the urine to the bladder.
3. Urinary Bladder it stores the urine produced temporarily. Shaped like a three-sided pyramid
4. Urethrait delivers the urine for secretion.
● Urethra in women- approximately 4 cm long
● Urethra in man-approximately 24 cm long
Note:
❖ Renal Pelvis is a cavity area that is an expansion of the ureter
❖ The pelvis functions to collect urine from the calyces for transport from kidney to the ureter
KIDNEYS
● Bean-shaped paired organs located at the posterior wall of the abdomen→ we have 2 kidneys
● Each kidney weighs approximately 150 grams in adult male and 135 grams in adult female
● It measures about 12.5 cm in length, 6 cm in width and 2.5 cm in depth
FUNCTIONS OF KIDNEYS
1. The kidneys maintain homeostasis by regulating fluid balance, acid-base balance and electrolyte balance
● Homeostasismaintaining the steady state.
● How does kidney regulate fluid balance?
○ the kidney is the key organ for water balance. The kidneys ensures that the make up and volume of
the fluids in the body is correct
● How does kidneys regulate acid-base balance?
○ The kidneys regulate the acid-base balance in the body through the secretion of hydrogen ions.
● How does the kidney regulate electrolyte balance?
○ the kidney regulate electrolyte balance to make sure you have appropriate levels of electrolytes such
as sodium, calcium and potassium
2. The kidneys are primarily excreters of waste products
● They excrete nitrogenous waste such as creatinine, urea, and uric acid
● These nitrogenous waste substances are product of metabolism
3. The kidneys secretes hormones to maintain blood pressure and erythropoiesis
● Kidneys secrete renin, erythropoietin and vitamin D
a. Reninkapag nasense na ni macula densa and juxtaglomerular apparatus na low ang sodium content at
low ang blood pressure, the Raas will occur. Juxtaglomerular cells in the kidneys will secrete renin to
increase blood pressure.
b. Erythropoietin  it plays a role in the production of red blood cells
c. Vitamin D  most of the vitamin D that is in the blood is inactive and it is modified by the kidney
ANATOMY OF THE KIDNEY
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Renal Cortex
2. Renal Medulla
3. Calyx
Note:
● Bawat part andun andun ang nephrons
● 2 types of nephrons: Cortical Nephron, Juxtamedullary nephron
 ● When approximately 150 ml of urine accumulates or the bladder is full, a nerve reflex is initiated and urine is voided via
the urethra. The nerve reflex is called Micturition Reflex.
● The stretches in the bladder increases their firing rate as the bladder becomes more this causes the micturition reflex so
you need to urinate

ANATOMY OF THE KIDNEY

● 2 main regions of kidneys: Cortex and Medulla
1. Cortex
● about 1.4 cm thick and is granular in macroscopic appearance
● contains the glomeruli, Proximal Convoluted tubule and Distal Convoluted Tubule
● It is the exclusive site of the plasma filtration process because all the glomeruli is located in the outer cortex.
And it is in the glomeruli where the filtration process happens.
● Cortex contains glomeruli
2. Medulla
● inner layer and consists of renal tissue shaped into pyramids
● The medulla of the kidneys contains the loops of henle (ascending loops of henle and descending loops of
henle) and the collecting tubules.

3. Calyx
● area where the collecting tubules join together and empty freshly formed urine into renal pelvis
● From the calyx, the urine flows into the ureters then to the bladder and out to the urethra
4. Nephrons
● Considered as the functional units of the kidney
● Responsible for urine formation
● Each kidney contains 1- 1.5 million nephrons. Both kidneys contains 2- 3 million nephrons
● Nephrons contains glomerulus (filtering unit) and renal tubules which are 30-40 millimeter in length
TWO TYPES OF NEPHRON
1. Cortical nephrons
 Make up approximately 85 % of nephrons
 Primarily situated in the cortex of kidney
 Primary responsible for removal of waste products and reabsorption of nutrients
2. Juxtamedullary nephrons
 Have longer loops of henle that extends deep into the medulla of the kidney
 Primary function is concentration of urine
PARTS OF THE NEPHRON
1. Glomerulus/Glomeruli or Renal Corpuscle
 Composed of four distinct structural components:
a. Endothelial cells of the capillary walls
· Differ from those in other capillaries by containing pores or
fenestrated/fenestra (small window)
b. Visceral epithelial cells (podocytes)
· With intertwining foot processes that form filtration slits.
c. Mesangium
· Refers to mesangial cells together with the mesangial matrix
they produced. The mesangial cells provide structural
support to glomerular tuft.
d. Basement membrane
· Or basal lamina which restricts large molecules to be passed
 Filtering unit of kidney
 Consists of a coil of approximately 8 capillary lobes (also known as capillary tuft) that are formed in the afferent
and efferent arterioles
 Located within Bowman’s capsule which forms the beginning of renal tubule
 Bowman’s space is where the glomerulus is located.
 Non-selective filter of plasma substances with molecular weight of less than 70,000
2. Proximal Convoluted Tubule
 Has a convoluted portion and a straight portion; the latter becoming the loop of Henle after entering the renal
medulla.
 Located in cortex
3. Loops of Henle
 Composed of: Thin descending loop of Henle, U-shaped segment (also called hairpin turn), and thin and thick
ascending limbs (sometimes called the straight portion of distal tubule)
4. Distal Convoluted Tubule
  Begins at the juxtaglomerular apparatus with the macula densa; after two to three loops, it becomes the collecting
duct.
 Also located in cortex
5. Collecting Duct
 Site of final urine concentration
 Joins with other collecting duct and forming a papillary duct to carry urine into a calix of renal pelvis
5. Renal Tubule
 Includes the Bowman’s capsule, PCT, loops of Henle and DCT
7. Renal calyces
 Chambers of the kidney which through urine passes
RENAL FUNCTIONS
1. Renal Blood Flow
 Kidney require rich blood supply to execute their primary function of regulating the internal environment of the
body
 There is direct relationship between kidney functional ability and its blood supply so kidney receives 25% cardiac
output (blood that leaves the left ventricle of the heart)
 In normal adults, blood passes through kidneys at a rate of 1200 mL/min or 600 mL/min/kidney
 Average body size surface: 1.73 m2 of surface.
 Total renal blood flow is (volume of blood delivered to kidneys per unit time): approximately 1200 mL/min
(Depend on body size)
 Total renal plasma (volume of plasma delivered to kidneys per unit time) flow ranges from: 600 to 700 mL/min
a. Renal artery supplies blood to the kidney.
b. Human kidneys receive approximately 25% of the blood pumped through the heart at all times (cardiac
output).
c. Blood enters the capillaries of the nephron through the afferent arteriole.
d. It then flows through the glomerulus and into the efferent arteriole.
e. Varying sizes of these arterioles help to create the hydrostatic pressure important for glomerular filtration
and to maintain consistency of glomerular capillary pressure and renal blood flow within the glomerulus.
The smaller size(small do it constrict which increases glomerular capillary pressure) of the efferent
arteriole and the glomerular capillaries enhances filtration.
f. Before returning to the renal vein, blood from the efferent arteriole enters the peritubular
capillaries(provides immediate reabsorption of essential substances from fluid in PCT and final
adjustment of urinary composition in the DCT) that surrounds the proximal convoluted tubule and distal
convoluted tubule
g. After peritubular capillaries, blood goes to the vasa recta (located adjacent to the ascending and
descending loops of Henle in juxtamedullary nephrons) and flows slowly through the cortex and medulla
of the kidney close to the tubules. In this area, the major exchanges of water and salts take place
between the blood and the medullary interstitium. This exchange maintains the osmotic gradient (salt
concentration) in the medulla, which is necessary for renal concentration.
 Note: Afferent arteriole carries blood TO the glomerulus and the efferent arteriole carries blood FROM the
glomerulus. Peritubular capillaries surrounds the PCT and DCT.
 BLOOD FLOW IN KIDNEY: Renal artery---afferent arteriole---glomerulus---efferent arteriole---peritubular
capillaries---vasa recta---renal vein
 2. Glomerular Filtration
 In order to form and excrete urine, 3 processes function together:
1. Glomerular Filtration
2. Tubular Reabsorption
3. Tubular Secretion
 Glomerulus or Renal Corpuscles  filtering unit. It is where filtering of blood happens
o Nonselective filter of plasma substances with molecular weight of less than 70,000
o Functions as a semi-permeable membrane to make an ultrafiltrate of plasma that is protein-free
 Although glomerulus serves as a non-selective filter of plasma substances with molecular weight of less than
70,000, several factors influence the actual filtration process.
 This include :
o cellular structure of the capillary walls and bowman's capsule
o hydrostatic pressure and oncotic pressure,
o the feedback mechanisms of RAAS (Renin Angiotensin Aldosterone System

FACTORS AFFECTING FILTRATION PROCESS

1. Cellular Structure of the Glomerulus (Cellular Structure or the Filtration Barrier)
 composed of three layers:
o fenestrated (with pores) endothelium of the capillary wall
o basement membrane or the basal lamina
o visceral epithelium or the podocytes
 Endothelial cells / Capillary wall
o is unique compared to other capillaries because of the presence of pores.
o the pores increase capillary permeability, but do not allow the passage of large molecules such as
serum proteins and blood cells
 Basement membrane / Basal lamina
o composed of collagen and proteoglycans
o "proteo" – protein
o "glycans" – sugar
o the basement membrane restrict large molecules to pass
 Visceral Epithelium or Podocyte
o with intertwining foot processes that form filtration slits
 How do these 3 layers prevent proteins to be filtered?
o Proteins most especially albumin causes kidney or renal diseases if present
o There are two ways to prevent protein to be filtered
o Size
 the protein may be too big to get through the filtration slits
o Charge
 the three layers are negatively charged in nature
 the basement membrane is strongly negative charged because of proteoglycans
 the charge is needed for the shield of negativity
o Shield of Negativity
 is the term describing the impediment produced by negatively charged components of the
glomerular filtration barrier
 it repels molecules with a positive charge even though they are small enough to pass through the
three layers of the barrier
 it is present on both sides and throughout the filtration barrier
 NOTE : Shield of Negativity is very important because albumin, which is the primary protein
associated with renal disease, has a positive charge and would easily pass through the barrier
 albumin can easily penetrate because it is a small molecule, but because of the shield of
negativity, the entrance of albumin is prevented
 if it were not for the shield of negativity all routine urines would have positive reagent strip
reading for proteins or albumins
 (Kung walang shield of negativity sa Cellular Structure, ang magiging result ng reagent strip test
ay laging positive for proteins)
2. Glomerular Pressure
 The presence of hydrostatic pressure resulting from the smaller size of the efferent arteriole and the glomerular
capillaries and hand says filtration pressure is necessary overcome the opposition of pressure from the fluid within
bowman's capsule and the oncotic pressure of unfiltered plasma proteins in the glomerular capillaries
 Autoregulatory Mechanism
 o (within the juxtaglomerular apparatus) maintains the glomerular blood pressure at a relatively constant
rate regardless of fluctuations in systemic blood pressure by increasing or decreasing the size of the
afferent and efferent arterioles
o NOTE:
 a decrease in blood pressure results in dilation of the afferent arterioles and constriction of the
efferent arterioles this is to prevent decrease in blood flowing through the kidney, thus
preventing an increase in the blood level of toxic waste products
 if there is an increase in blood pressure results in the constriction of the afferent arterioles to
prevent over filtration or damage to the glomerulus

 There are three main pressures of the glomerular filtration:

o The Glomerular Hydrostatic Pressure pushes the blood out
of the glomerulus
o Capsular Hydrostatic Pressure pushes the blood towards
the glomerulus
o These two pressures, the Capsular Hydrostatic Pressure
and the Glomerular Static Pressure have opposing forces
o The opposing forces is for maintaining homeostasis or
osmosis
o Rule of Thumb: the movement of water flows in higher
concentration to lower concentration
o The blood in the kidney has lots of protein in which it
circulate na pero hindi makalabas. Bakit kaya? First reason kung bakit hindi sila makalabas si protein is that,
protein are large molecules. Number Two, semi permeable capsular ang ating membrane and we also have
Colloid osmotic pressure also known as oncotic pressure. Ano nga ba ang ginagawa ng oncotic pressure? It
reverse back proteins. In normal condition, there is a minimal amount of urine. Ito yung normal physiology ng
ating glomerulus.
o (ALWAYS REMEMBER THE 3 PRESSURE) –
a. The Glomerular Hydrostatic pressure na naglalabas ng blood out of glomerulus
b. Capsular Hydrostatic Pressure pushing the blood toward the glomerulus. “The two pressures
opposing forces to maintain homeostasis or osmosis”
c. Colloid Osmotic Pressure or oncotic pressure – it reverse back protein. Eto yung normal physiology
ng glomerulus
o Take note: if abnormal naman yung physiology of glomerulus, kapag decrease ang ating oncotic pressure, wala
ng mag ho hold sa proteins natin kaya nagkakaroon ng leakage of protein outside the capsule and the protein
goes to the extremities of our bodies, nagkakalat na sating katawan.
o Example nito: Kidney patient, nag ca cause ito ng pagmamanas it means nag leak na yung protein sa capsule. Isa
ito sa manifestation sa mga kidney patient ang pagmamanas.
o Another one: kapag mas mataas naman si glomerular hydrostatic pressure natin at mas mababa si oncotic
pressure natin at capsular hydrostatic pressure, dyan nagkakaroon ng GFR or the Glomerular filtration rate.
o The GFR – estimate the function of the nephron to filter the blood in the kidneys.
o Take note:
 If decrease naman ang ating glomerular hydrostatic pressure and normal naman and ating capsular
and oncotic pressure, nag de decrease din ang ating blood filtration causing decrease formation of
urine.
3. Renin-Angiotensin-aldosterone-system (RAAS)
 Controls the regulation of blood flow to and within the glomerulus.
 Juxtaglomerular Apparatus – regulates /monitors change in blood pressure and plasma sodiumcontent.
 Juxtaglomerular cells- (siya and nagpro produce ng renin)
Cells Location Stimulus

Juxtaglomerular cells Afferent arteriole Low blood pressure

Macusa Densa cells Distal convuluted tubule Low plasma sodium

 Take note:
o Low plasma sodium content ka, nag de decrease din ang ating water retention within the circulatory system,
resulting to the decrease of overall blood volume. Kapag decrease ang ating overall blood volume, malamang
mag de decrease din ang ating blood pressure.
o Kapag yun nga na sense na ni macula densa na may changes na ganito, cascade or reaction within the RAAS
occurs.
o (Kung nasaan ang salt nandun din lagi si water)
 o Kapag mababa ang ating plasma sodium content, bababa din ang ating water retention at bababa din ang ating
blood volume. Diba ang ating blood ay composed of (WATER).

 How the RAAS work?

o The renin is an enzyme that converts angiotensinogen which is a blood borne substrate to angiotensin 1(Innate
hormone). The renin converts angiotensinogen which is a blood borne substrate to angiotensin 1. The
angiotensin 1 passes through the alveoli of the lungs and its converted by the angiotensin converting enzyme
to become angiotensin 2 (this is the active form) .
 Ano nga ba ang ginagawa ni angiotensin 2?
o It corrects renal blood flow in the following ways.
o First, causing vasodilation of afferent arterioles and vasoconstriction of the efferent arteriole.
o Second, stimulating reabsorption of sodium and the proximal convoluted tubules.
o Third, it occurs adrenal cortex to release the sodium retaining hormone aldosterone to cause sodium
reabsorption and potassium excretion in the DCT and collecting tubules.
o Water will be reabsorb along with the sodium.
o Fourth, triggers antidiuretic hormone release by the hypothalamus to stimulate water reabsorption in the
collecting ducts.
o TAKE NOTE: DON’T BE CONFUSED
 ALDOSTERONE (FOCUS ON SODIUM REABSORPTION, and POTASSIUM EXCRETION)
 ADH (FOCUS ON STIMULATE WATER)
o The n effect of RAAS, increases systemic blood pressure.
o TAKE NOTE: The a systemic blood pressure and plasma sodium content increase the secretion of the renin
decreases, kasi nga di na kailangan dahil okay naman na ulit yung blood pressure, tumataas na siya, hindi na
kailangan mag secrete ni juxtaglomerular ng renin kasi okay na. Bumabalik na yung normal blood pressure.

3. TUBULAR REABSORPTION
 Substances removed from the filtrate are returned to the blood.
 NOTE: Proximal convoluted tubule (PCT)
o Responsible for most of the reabsorption approximately 65% and secretion that occurs in tubules.
o Major site of reabsorption and also a major site of secretion
o The epithelial cells that line this portion of the tubule have a brush border of microvilli which provides a large
surface for reabsorption and secretion
REABSORPTION MECHANISMS:
1. Active Transport- involves carrier protein in the membranes of the renal tubule
 Occurs when substances to be reabsorb combine with a carrier protein contain in the membrane of renal tubule
 Electrochemical energy produced by this interaction transfers the substance across the cell membrane back into
the bloodstream.
 Kailangan ng carrier protein para maabsorb ulit
2. Passive Transport- movement of molecules across a membrane results in the difference in their concentration gradients or
electrical potential
ACTIVE TRANSPORT
PASSIVE TRANSPORT
SUBSTANCES ABSORBED:
 Glucose, amino acids, salts- PCT
 Chloride- Ascending loop of Henle
 Sodium- PCT and DCT
SUBSTANCES ABSORBED:
● Water- All parts of the nephron except Ascending loop of Henle
● Urea- PCT and Ascending loop of Henle
● Sodium- Ascending loop of Henle
 ● Some analytes there is limitation as to how much solute can be reabsorb so this is defined as RENAL THRESHOLD
● RENAL THRESHOLD - defined as the plasma concentration at which active transport stops
○ the maximal reabsorptive capacity (Tm) of the tubules is exceeded when the substance is in abnormally high
levels and it will appear in the urine. Example: Glucose- have a renal threshold of 160 - 180 mg\dl.
○ NOTE: If a glucose appear in the urine of a person with a normal blood glucose level the result is tubular
damage and hindi na siya nakakapag reabsorb ng glucose and not Diabetes Mellitus
○ Knowledge of renal threshold and the plasma concentration can be used to distinguish between excess solute
filtration and renal tubular damage
■ maximal rate of reabsorption of a solute by the tubular epithelium per minute (milligrams per
minute)
○ The reabsorptive capacity varies with each solute and depends on the GFR
○ Fluid leaving the PCT has the same concentration as the ultrafiltrate because 2\3 of reabsorbed sodium is
accompanied by passive reabsorption of the same amount of water
 Specific gravity of ultrafiltrate: it is 1.010

URINE CONCENTRATION
● Renal concentration begins in the descending and ascending loop of Henle
● The filtrate is exposed to the high osmotic (salt) gradient of the renal medulla
● Maintenance of these osmotic gradients is essential for the final concentration of the filtrate when it reaches the
collecting duct
**Countercurrent Mechanism:
o a selective reabsorption process which serves to maintain the osmotic gradient of the medulla.
o Water is removed via osmosis in the descending loop of Henle.
o OSMOSIS: movement of solvent to a semi-permeable membrane in the solution of higher solute concentration
to lower solute concentration
o Sodium and chloride are reabsorbed in the Ascending loop of Henle
● Filtrate leaving the Ascending loop is diluted or low concentration owing to the reabsorption of salt and not water in
that area of the tubule.
● Final concentration begins in the late distal convoluted tubule and continues in the collecting ducts.
● Reabsorption of water and sodium in the late distal convoluted tubule and collecting ducts is controlled by hormones
(aldosterone, antidiuretic hormone or the arginine vasopressin)
ALDOSTERONE ANTIDIURETIC HORMONE
 Responds to the body’s need for sodium  Responds to the body’s state of hydration
 Produces and released from the adrenal cortex  Produced in the hypothalamus
 Promotes sodium reabsorption in the DCT and potassium  Released by posterior pituitary gland
secretion  Makes the walls of the DCT
NOTE:
● Increase body hydration → decreased ADH → decreased reabsorption → increased urine volume
● Decrease body hydration → increase ADH → increase reabsorption → decreased urine volume
4. TUBULAR SECRETION
 passage of substances from the blood in the peritubular capillaries to the tubular filtrate of excretion
 Two major functions:
o Elimination of waste products not filtered by the glomerulus
o Regulation of the acid base balance thru secretion of hydrogen ions (H+)
 H+ is secreted in exchange for bicarbonate ions in the PCT
 Buffering capacity of the blood depends on bicarbonate. Bicarbonate which are readily
filtered by the glomerulus and should return to the blood to maintain proper pH of the blood
[normal blood pH – 7.4]
 H+ prevents filtered bicarbonate from being excreted in the urine, causing bicarbonate ion to
return to the blood plasma
 H+ pinapalitan njya si bicarbonate wherein si bicarbonate ion talaga ang maeexcrete kasi
bicarbonate ion is needed for buffering of the blood
 Secreted H+ combines with the filtered phosphate ion and is excreted
 Secreted H+ combines with ammonia produced by DCT to form ammonium ion which is then secreted
 NOTE:
o All of these 3 processes (in H+ ions) occur simultaneously at rates determined by the acid-base balance in the
body
o Disruption in the secretory functions can result in metabolic acidosis or renal-tubular acidosis
o Metabolic acidosis/renal-tubular acidosis is the inability to produce acid urine, which then, urine produced is
alkaline urine.
RENAL FUNCTION TESTS
1. Glomerular Filtration Test
● Are used to assess renal waste removal and solute reabsorbing abilities
● Examples:
○ Clearance Test
○ Calculated glomerular filtration estimates
2. Tubular Reabsorption Tests
● Aka Concentration test
● Are used to detect early renal disease
● Examples:
○ Water deprivation test
○ Free water clearance
3. Tubular Secretion & Renal Blood Flow Tests
● Examples:
○ PAH (Para-aminohippurate) test
○ Titratable acidity and ammonia Glomerular Filtration Test
GLOMERULAR FILTRATION TESTS
1.) Clearance Test
● standard test used to measure the filtering capacity of the glomeruli
● measure the rate at which the kidneys are able to remove a filterable substance form the blood
Clinical Significance:
○ monitor the effectiveness of treatment
○ determine the feasibility of administering medications
○ DOES NOT detect early renal disease
○ Determine the extent of nephron damage in known cases of renal disease
Factors to consider:
○ the substance analyzed must be neither reabsorbed nor secreted by the tubules
○ stability of the substance in urine during a possible 24-hour collection period
○ consistency of the plasma level
○ substance’s availability to the body
○ availability of tests for analysis of the substance
NOTE:
● Urea is not normally used in clearance testing because of tubular reabsorption, diet, and urine flow rate. Thus, has been
replaced by other substances like creatinine, inulin, beta 2, cystatin C, or radioisotopes
Tests in Clearance Test:
a) Inulin Clearance
○ originally the reference method for clearance test
○ not currently used for GFR testing
 ○ reference research method
Characteristics of Inulin:
○ polymer of fructose
○ extremely stable substance
○ not reabsorbed nor secreted by the tubules
○ exogenous
ー meaning Inulin is an infused substance/not a normal body constituent at a constant rate
throughout the testing period
B. Creatinine Clearance
 Routinely done for screening GFR
1. Some creatinine is secreted by the tubules, and secretion increases as blood levels rise.
o 1 factor to consider is that it is neither reabsorb nor secreted by the tubules
2. Bacteria will break down urinary creatinine if specimens are kept at room temperature for extended periods.

3. Medications, including gentamicin, cephalosporins, and cimetidine (Tagamet), inhibit tubular secretion of
creatinine, thus causing falsely low serum levels.
4. Chromogens present in human plasma react in the chemical analysis. Their presence, however, may help
counteract the falsely elevated rates caused by tubular secretion.
5. A diet heavy in meat consumed during collection of a 24-hour urine specimen will influence the results if the
plasma specimen is drawn before the collection period because the increased intake of meat can raise the urine
and plasma levels of creatinine during the 24-hour collection period.
o The increase intake of meat can raise the urine and plasma levels of creatinine during 24 hour collection period
o For medications, it causes falsely low serum level if you take gentamicin, cephalosporins, and cimetidin
 Note:
o Measurement of creatinine clearance is not a reliable indicator in patients suffering from muscle-wasting
diseases or persons involved in heavy exercise or athletes supplementing with creatine.
o Creatinine is an endogenous material, it is normally found in the body, it is a waste product of muscle
metabolism
o Accurate results depend on the accurate completeness of a 24-hour collection.
o It must be corrected for body surface area, unless normal is assumed, and must always be corrected for
children.
 Procedure:
o involves collection of blood and urine for creatinine testing

 Urine specimen: 24 hour timed urine

 Greatest source of error: improperly timed urine specimens
o By far the greatest source of error in any clearance procedure using urine is the use of improperly timed urine
specimens.
o The quantity of creatinine excreted does not vary much within the urine volume, it is customary to estimate
whether successive 24 hour urine collections are complete by comparing the creatinine excretion in each
specimen
Formula:

 V= urine volume in mL/min (V),

 U= urine creatinine concentration in mg/dL (U),
 P= plasma creatinine concentration in mg/dL (P)
o Plasma concentration and Clearance are inversely proportional
o As clearance of a substance decreases, its concentration in the circulating plasma increases
Example:
Using urine creatinine of 120 mg/dL (U), plasma creatinine of 1.0 mg/dL (P), and urine volume of 1440 mL obtained from a 24-
hour specimen (V), calculate the GFR.
OTHER TESTS FOR GFR
C. INJECTION OF RADIONUCLEOTIDES SUCH AS 123 I-iothalamate
 Provides method for determining glomerular filtration thru the plasma disappearance of the radioactive material and
enables visualization of the filtration in one or both kidneys
D. CLEARANCE OF B-2 Macroglobulin (MW= 11,800)
 Disassociates form human leukocyte antigens at a constant rate and is rapidly removed from the plasma by glomerular
filtration
 Arise in the plasma level of this substance = more sensitive indicator of a decreased GF than creatinine clearance
 B-2 MACROGLOBULIN clearance = not reliable for patients with immunologic disorder or malignancy
E. CLEARANCE OF CRYSTATIN C (MW=13,359)
 Readily filtered by the glomerulus and reabsorbed and broken down by the renal tubular cells. No crystatin c is secreted
and serum concentration can be directly related to GFR
 Produced at a constant rate by all nucleated cells
 CRYSTATIN C clearance = recom for pediatric, diabetic, elderly, and critically ill patients
1. CALCULATED GLOMERULAR FILTRATION ESTIMATES (eGFR)
 Provides estimates of the GFR based on the serum creatinine w/o the urine creatinine
 Used for monitoring patients already diagnosed with renal disease or at risk for renal disease
A. COCKROFT AND GAULT
 Variables included in original formula:
o Age, sex, and body weight (kg)
 Modifications: ideal body weight and adjusted body weight
B. MODFICATION OF DIET IN RENAL DISEASE (MDRD) SYSTEM
 Newer and utilizes variables such as ethnicity, blood urea nitrogen and serum albumin, but does not
include body weight
C. MDRD-IDMS TRACEABLE FORMULA:
 Isotope dilution mass spectrophotometry reference method
2. TUBULAR REABSORPTION TESTS/ CONCENTRATION TESTS
 Tubular reabsorption test = to test the ability of the tubules to reabsorb the essentials and water that have been non
selectively filtered by the glomerulus
 Used to detect early renal disease
 Ultra-filtrate that enters the tubules has a specific gravity
 Urea has no importance to the evaluation of renal concentration ability
CONCENTRATION TESTS
1. WATER DEPRIVATION TEST
 Useful for screening only and not used nowadays
a. FISHBERG TEST – patients were deprived of fluids for 24 hrs prior to measuring SG
b. MOSENTHAL TEST – compares thee volume and SG of day and night urine samples
 NORMAL VALUES:
o Urine of SG 1.075 when deprived of fluid for 16hrs
o Urine osmolarity of 800mOsm or above the ff overnight water deprivation
2. OSMOMETRY
 Quantitative measurement of renal concentrating ability
o OSMOLALITY – solute dissolved in 1kg of solvent
o OSMOLARITY – solute dissolved in 1L of solvent
 Reported in milliosmole (mOsm)
 Determined by measuring a colligative property and comparing with value obtained from the pure solvent
COLLIGATIVE PROPERTIES
  Solutes dissolved in solvent causes the ff changes in colligative properties:
Ø INCREASE/ ELEVATION – boiling point and osmotic pressure
Ø DECREASE/ DEPRESSION – freezing point and vapor pressure
a. FREEZING POINT OSMOMETERS
o 1st principle incorporated into clinical osmometers
o Determines the freezing point of a solution by supercooling a measured amount of sample to approx 27 celsius
o 1 mol (1000 mOsm) will lower the freezing point by 1.86 celcius
o Used sol of known sodium chloride concentration as their reference standard bc a solution of a partially
ionized substances is more representative of urine and plasma composition
b. VAPOR PRESSURE OSMOMETER
o Uses microsample(<0.01 mL)
o Actual measurement performed is the DEW POINT
o The depression of dew point temperature by solute is proportional to the decrease in vapor pressure
o Technical Factors to consider:
1. Lipemic serum
 the serum water displacement by insoluble lipids produces erroneous results with both
vapor pressure and freezing point osmometers.

2. Lactic acid
 Falsely elevated values owing to lactic acid formation also occurs with both methods if serum
samples are not separated or refrigerated within 20 minutes.
3. Volatile substances
 Vapor pressure osmometers do no detect the presence of volatile substances such as the
alcohol as they become part of the solvent base. However measurements performed on the
similar specimen using freezing point osmometers will be elevated.
Clinical significance:
 Initial evaluation of renal concentration ability
 Monitoring the course of renal disease
 Monitoring fluid and electrolyte therapy
 Establishing differential diagnosis of hypernatremia and hyponatremia
o Hyponatremia
 occurs when total body water is a excess of sodium
o Hypernatremia
o it develops when body water is relatively decrease in relation to sodium (both disorders may be present in
patients with various disease space in which total body sodium is either decrease normal or increase)
 Evaluating secretion of and renal response to ADH
 Note!
o The urine serum osmolarity ranges to 50-1400 milliosmoles
o The normal urine osmolarity values ranges to 275-300 milliosmoles
o It is difficult to establish prefered values because factors such as fluid intake and exercise can greatly influence
the urine concentration
o Urine to serum osmolarity ratio under normal random conditions is 1:1
o Urine to serum osmolarity ratio after controlled fluid intake is 3:1
o If consistent na less than 1.1 meaning or tendency non may distal tubular disease
o If consistent na greater than 1.1 tendency or possible glomerular disease
Nephrogenic Central
Diabetes Insipidus Diabetes Insipidus

 Inability of the renal tubules to respond to ADH  Decreased ADH production

 Failure to achieve 3:1 urine to serum osmolarity  The kidneys are able to concentrate after ADH
ratio following injection of ADH injection.
3. FREE WATER CLEARANCE
 Used to determine the ability of the kidney to respond to the state of body hydration
 Determined by calculating the osmolar clearance and subtracting this value from the urine volume in mL/min
 o Free water clearance can be determined by first calculating the osmolar clearance(Cosm) using the standard
clearance formula then subtracting osmolar clearance value from the urine volume in mL/min
 Osmolar Clearance
o Indicates how much water must be cleared each minute to produce a urine with the same osmolarity as the
plasma
o By comparing the osmolar clearance with the actual urine volume excreted per minute it can be determined
whether the water is being excreted is more or less than the amount needed maintained at osmolarity the
same of the OSHA filtrate.
 Note!
o Negative (-) meaning less water is being excreted possible estate of dehydration
o Zero (0) no veinal concentration or dilation
o Positive (+) excess water is being excreted
TUBULAR SECRETION AND RENAL BLOOD FLOW TESTS
1. P-Aminohippuric Acid (PAH) Test
- Most common test associated to tubular secretion and renal blood flow
- Substance that is a fused into the patient
- Secreted rather than filtered
- Completely removed from the blood by the functional renal tissue
- Exogenous procedure but it meets the criteria needed to measure renal blood flow
- Nontoxic substance which is loosely bound to plasma proteins and is secreted by the PCT
- If renal problem exist the P-Aminohippuric acid will not be removed completely, clearance of this substance
can be used to calculate the effective renal plasma flow
2. Phenolsulfonphthalein (PSP) Test
- Is a dye entirely cleared by the tubules henced used to measure secretory capacity of the tubules
- Not currently performed
- Normal kidneys will excrete 60-75% of the dye in 2 hours following IV injection
- The remaining dye is eliminated by the liver
- Colorless in acid solution, red in alkaline solution
3. Urinary Ammonia and Titratable Acidity
- Determines the defective function in the ability of the kidney to produce an acidic urine
- Test can be run simultaneously on either fresh or tolwin preserve urine specimens collected at two or
intervals from patients who have been primed with an acid load consisting of coral ammonium chloride

Urine Acidity
- A normal person excretes approximately 70 mEq/day of acid in the form of either titratable acid, hydrogen phosphate
ions or ammonium ions.
Diurnal variations in urine acidity:
- Alkaline tides appearing shortly after arising and postprandially at 2pm and 8pm
- Lowest pH is found at night
Clinical Consideration
● Renal Tubular Acidosis
- Inability to produce an acid urine in the presence of metabolic acidosis
- Associated with constantly alkaline urine
- Due to effects associated with:
a. PCT- inpaired tubular secretion of hydrogen iron
b. DCT- defective ammonia secretion