ML S MTA P1

L E S SO N 2 : REN AL PH Y S I OLO GY

SUMMARY • Renal Pelvis – union of major calyces, large

I Kidney collecting funnel which narrows to form ureter
A Important Functions of the Kidney • Hilus – notch in the concave center of the kidney
B Parts of the Kidney through which a ureter leaves the kidney and
II Renal Physiology blood vessels, nerve, lymph vessels enter and exit
A Nephron the kidney
i Two Types of Nephrons
III Parts of Nephron
IV Basic Mechanism of Urine Blood Flow
A Renal Blood Flow
B Glomerular Filtration
i Renin-Angiotensin-Aldosterone System
C Tubular Reabsorption
i Reabsorption Mechanisms
D Tubular Secretion
V Renal Function Tests
VI Glomerular Filtration Tests
A Clearance Tests
i Urea Clearance
ii Inulin Clearance
iii Creatinine Clearance
B Calculation Methods
i Cockgroft-Gault Formula
ii MDRD
iii CKD
C Other Tests
i Cystatin C
ii Beta2 – Microglobulin
iii Radionucleotides
VII Tubular Reabsorption Tests
A Water Deprivation Tests
B Osmolality
C Free Water Clearance Figure 1. Parts of kidney
VIII Tubular Secretion and Renal Blood Flow Tests
A Phenolsulfonpthalein
B p-Aminohippuric Acid Test (PAH)
RENAL PHYSIOLOGY

NOTE: Urine forms in the nephron of the cortex and

medulla. The drained urine will go down the minor
calyx, major calyx, renal pelvis, and ureter and then be
KIDNEY temporarily stored in the urinary bladder.
• Important functions
o Elimination of the end product of metabolism NEPHRON
o Elimination of the excess body water
• Functional unit of the kidney, each kidney has 1-
o Elimination of foreign substances like drugs
1.5M of the nephron
o Maintenance of electrostatic balance
o Secretion of hormone (erythropoietin) • Close at one end (Bowman’s capsule) and open at
the other end (Collecting duct)
• Responsible for nonselective & selective clearing
PARTS OF THE KIDNEY
of the waste product from blood
• Cortex – outer area of kidney • Responsible for the maintenance of essential
• Medulla – inner area of kidney water and electrolyte balance
• Renal Pyramid – striated, triangular structure
within the medulla whose bases face the cortex TWO TYPES OF NEPHRONS
and tips point to the center of kidney (renal
papillae) • Cortical Nephrons
• Renal Column – cortical material that extends o Make up approximately 85% of nephrons
between the pyramids o Situated primarily in the cortex of the kidney
• Minor Calyx – funnel-shaped structures that o Responsible primarily for removal of waste
surround the tip of renal pyramid products and reabsorption of nutrients
• Major Calyx – union of minor calyces

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Figure 2. Nephron
• Juxtamedullary Nephrons • Important in order for the glomerulus to form
o Have longer loops of Henle that extend deep bundles of capillaries
into the medulla of the kidney
o Primary function is concentration of the urine CAPILLARIES

PARTS OF NEPHRON AFFERENT ARTERIOLE

• Refers to small artery

• Small branch of the renal artery through which the
blood flows to the glomerulus of the kidney

EFFERENT ARTERIOLE

• Small branch of the renal artery through which

blood flows away from the kidney

NOTE: Common function of arterioles – the creation of

hydrostatic pressure (necessary for the filtration
process to occur) due to the knotted feature of the
glomerulus.

Figure 3. Parts of nephron RENAL TUBULAR SYSTEM

• Tubes that are located in the nephrons
GLOMERULUS
• Parts:
• Act as non-selective filter of plasma substances o Proximal Convoluted Tubule (PCT)
• Tuft of capillary blood vessels located in o Loop of Henle
bowman’s capsule where filtration process occurs o Descending Loop
• Glomerular filtration is the nonselective process o Ascending Loop
that happens in urine formation o Distal Convoluted Tubule (DCT)
o Collecting Tubules/Ducts
BOWMAN’S CAPSULE
• Containing glomerulus

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Figure 4. Blood flow through the kidney

PROXIMAL CONVOLUTED TUBULE NOTE: The only area of the tubule where glucose can be
reabsorbed is in the proximal convoluted tubule. Once
• Tubules that are found nearest to the glomerulus PCT reaches its threshold, it is automatically secreted.
• Part wherein the reabsorption of essential
substances begins – these are then returned back LOOP OF HENLE
to the system
• Large amounts of water, glucose, protein, amino • U-shaped structure of the renal tubule
acid and electrolytes are reabsorbed • It contains thin descending limb and thick
• 65% of Na+ is reabsorbed ascending limb
• 65% of H2O is reabsorbed o Descending – reabsorption of water, without
• 90% of filtered bicarbonate (HCO3-) reabsorption of salt
• 50% of Cl- and K+ o Ascending – no reabsorption of water, with
• Glucose – threshold substance reabsorption of salt – ONLY PORTION w/o
• Renal threshold – blood concentration of water reabsorption
substance at which reabsorption stops and • Control the retention of water
increase concentration appears in urine • Creates a gradient of increasing sodium ion
o 160-180 mg/dl – renal threshold concentration towards the end of the loop within
o Greater than 180 mg/dl – glucose will start to the interstitial fluid of the renal pyramid
appear in urine o 25% Na+ is reabsorbed in the loop
o 110-120 mg/dl – critical value for glucose level o 15% Water is reabsorbed in the loop
• Clinical diagnosis of glucose o 40% K+ is reabsorbed in the loop
o (-) blood glucose → Kidney problem
(+) urine glucose DISTAL CONVOLUTED TUBULE
o (+) blood glucose → Uncontrolled diabetes
(+) urine glucose • Part of nephron where the final concentration of
o (+) blood glucose → Controlled diabetes the urinary filtrate begins
(-) urine glucose • Under the influence of the hormone aldosterone,
reabsorbs sodium (ReNa) and secretes potassium
(SeK)

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Figure 5. Renin-angiotensin system

• Also regulates pH by secreting hydrogen ion when GLOMERULAR FILTRATION

pH of the plasma is low
• Only 10% of the filtered NaCl and 20% of water • Non-selective process of filtration
remains • Factors that influence the actual filtration process
o Cellular structure of the capillary walls and
Bowman’s capsule
COLLECTING DUCT
o Hydrostatic and oncotic pressure
o Feedback mechanisms of the renin-
• Where the final concentration of urine takes place
angiotensin-aldosterone system
through the reabsorption of water
• Allows for the osmotic reabsorption of water
RENIN-ANGIOTENSIN-ALDOSTERONE SYSTEM
• ADH (antidiuretic hormone) – makes collecting
ducts more permeable to water; produce
• Controls the regulation of the flow of blood to and
concentrated urine
within the glomerulus
• The system responds to changes in blood
BASIC MECHANISM OF URINE BLOOD FLOW
pressure and plasma sodium content that are
1. Renal Blood Flow monitored by the juxtaglomerular apparatus,
2. Glomerular Filtration which consists of the juxtaglomerular cells in the
3. Tubular Reabsorption afferent arteriole and the macula densa of the
4. Tubular Secretion distal convoluted tubule
• Low plasma sodium content decreases water
RENAL BLOOD FLOW retention within the circulatory system, resulting
in a decreased overall blood volume and
• The renal artery supplies blood to the kidney subsequent decrease in blood pressure
• The human kidneys receive approximately 25% of • (1) Renin secreted and reacts with the blood-borne
the blood pumped through the heart at all times substrate (2) angiotensinogen → produces the
• The varying sizes of arterioles help to create the inert hormone (3) angiotensin I → passes through
hydrostatic pressure important for glomerular the lungs → (4) angiotensin-converting enzyme
filtration and to maintain consistency of (ACE) changes it to the active form (5) angiotensin
glomerular capillary pressure and renal blood flow II
within the glomerulus • Angiotensin II corrects renal blood flow in the
• The total renal blood flow is approximately 1200 following ways:
mL/min, and the total renal plasma flow ranges o Causing vasodilation (increase in diameter of
600 to 700 mL/min the blood vessel) of the afferent arterioles
o PLASMA is where the dissolved and (increase blood flow) and constriction of the
undissolved substances are located efferent arterioles
o Stimulating reabsorption of sodium in the
proximal convoluted tubules, and triggering

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the release of the sodium-retaining hormone RENAL FUNCTION TESTS

aldosterone (reabsorption of sodium in the
DCT) by the adrenal cortex and antidiuretic • Tests that determine if a particular part of a nephron is
functioning properly
hormone (controls the retention of water) by
• Tests:
the hypothalamus
1. Glomerular Filtration Tests
2. Tubular Reabsorption Tests
TUBULAR REABSORPTION 3. Water Deprivation Tests
4. Tubular Secretion and Renal Blood Flow Tests
• Selective process filtration
• The body cannot lose 120 mL of water-containing GLOMERULAR FILTRATION TESTS
essential substances every minute; therefore,
when the plasma ultrafiltrate enters the proximal • Tests that will assess the filtration ability of the
convoluted tubule, the nephrons, through cellular glomerulus
transport mechanisms, begin reabsorbing these
essential substances and water CLEARANCE TESTS

REABSORPTION MECHANISMS • Standard tests used to measure the filtering

capacity of the glomeruli
Active Transport • Measures the rate at which the kidneys are able to
• The substance to be reabsorbed must combine “clear” a filterable substance from the blood
with a carrier protein contained in the membranes • Types:
of the renal tubular cells o Urea Clearance - earliest clearance test
• Active transport is responsible for the o Inulin Clearance - original reference method
reabsorption of glucose, amino acids, and salts in o Creatinine Clearance – presently/routinely
the proximal convoluted tubule, chloride in the and most common performed clearance test
ascending loop of Henle, and sodium in the distal
convoluted tubule UREA CLEARANCE TEST (HISTORICAL)

Passive Transport • Urea is a product of protein metabolism

• Movement of molecules across a membrane as a • “Earliest Clearance Test”
result of differences in their concentration or o Urea (major organic constituent of urine) is
electrical potential on opposite sides of the present in all urine samples
membrane o Existence of routinely used methods of
• Passive reabsorption of water takes place in all chemical analysis
parts of the nephron EXCEPT the ascending loop of • Disadvantage:
Henle, the walls of which are impermeable to o Does not provide a full clearance assessment
water. o Because approximately 40% of the filtered
• Urea is passively reabsorbed in the proximal urea is reabsorbed, normal values were
convoluted tubule and the ascending loop of adjusted to reflect the reabsorption, and
Henle patients were hydrated to produce a urine
• Passive reabsorption of sodium accompanies the flow of 2 ml/min to ensure that no more than
active transport of chloride in the ascending loop 40% of the urea was reabsorbed

TUBULAR SECRETION INULIN CLEARANCE TEST (HISTORICAL)

• Part/mechanism wherein there is a creation of • Inulin is a polymer of fructose

acid-base balance • “Original Reference Method”
• Several parts of the kidney will produce hydrogen • Extremely stable substance
ion • Not reabsorbed or secreted by the tubules
• Elimination of waste products not filtered by the • Disadvantages:
glomerulus o It is not a normal body constituent
• Many foreign substances cannot be filtered by the o Must be infused by IV at a constant rate
glomerulus because they are bound to plasma throughout the testing period
proteins
• However, when these protein-bound substances CREATININE CLEARANCE TEST
enter the peritubular capillaries, they develop a
stronger affinity for the tubular cells and • Creatinine is a waste product of muscle
dissociate from their carrier proteins, which
metabolism, produced by CPK from Creatine
results in their transport into the filtrate by the
• “Presently Performed Clearance Test”
tubular cells
o Creatinine is endogenous (normally present
• The major site for removal of these nonfiltered
at our body)
substances is the proximal convoluted tubule
o Relatively at a constant level in blood

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• Disadvantages: 60-69 85
o Some creatinine is secreted by the tubules, 70+ 85
and secretion increases as blood levels rise
o Chromogens (coloring pigments) present in o Older = lower filtering capacity of glomerulus
human plasma react in the chemical analysis ▪ Decreasing the amount of total urine
o Medications, including Gentamicin, produced
Cephalosporins, and Cimetidine (Tagamet),
inhibit tubular secretion of creatinine, thus NOTE: Urea is filtered and reabsorbed. Creatinine is
causing falsely low serum levels filtered and secreted.
o Bacteria will break down urinary creatinine if
specimens are kept at room temperature for CALCULATION METHODS (eGFR)
extended periods
o A diet heavy in meat consumed during • Cockgroft-Gault Formula
collection of a 24-hour urine specimen will • MDRD (Modification of Diet in Renal Disease)
influence the results if the plasma specimen • CKD (Chronic Kidney Disease Epidemiology
is drawn prior to the collection period Collaboration)
o Measurement of creatinine clearance is not a
reliable indicator in patients suffering from COCKGROFT-GAULT FORMULA
muscle-wasting disease
• Older and most commonly used equation for
Creatinine Clearance Procedure estimating creatinine clearance
1. Collect 24-hour urine from patient • Preferred for calculating drug dosages
2. Perform blood extraction for serum/plasma
creatinine (within the time of 24-hour urine Weight (kg)
collection) → determine creatinine GFR (mL/min) = (140 - Age) x ( ) x Serum Crea (mg/mL)
72
3. From the timed urine specimen, determine total
urine volume using graduated cylinder and • For female Px: multiply computed GFR with 0.85
compute for urine volume in mL/min
GFR (mL/min) x 0.85
mL Total Urine Volume (in mL)
Urine Volume ( )=
min 60 mins x 24 hrs (1440 mins) MDRD
4. Determine serum/plasma creatinine in mg/dL • Modification Of Diet in Renal Disease
• Most widely used to estimate GFR in clinical
Jaffe Enzymatic laboratories
Male 0.6 – 1.2 mg/dL 0.9 – 1.3 mg/dL • Unit of measure: mL/min/1.73 m2
Female 0.5 – 1.1 mg/dL 0.5 – 1.1 mg/dL

5. Determine urine creatinine in mg/dL

-1.154
Male 40 – 300 mg/dL GFR = 175 x [(Serum Crea (umol/L)] x Age-0.203
Female 37 – 250 mg/dL
• For female Px: multiply computed GFR with 0.742
6. Compute for creatinine clearance using the
formula GFR x 0.742
• For African American Px: multiply GFR with 1.212
mg mL
Urine Creatinine ( ) x Urine Volume ( )
dL min x 1.73 GFR x 1.212
mg A
Serum Creatinine ( )
dL
CKD
o A = Normalization Factor/Actual body size
o Normal Range (GFR) • Chronic Kidney Disease Epidemiology
▪ below – low filtering capacity of Collaboration
glomerulus • Developed in 2009
Male 107 – 139 mL/min • Perform better with patients of higher GFR
Female 87 – 107 mL/min • Not extensively validated as MDRD
• Unit of measure: ml/min
Table 1. Mean GFR per Age Group • SCR – Serum Creatinine (mg/dL)
Mean GFR
Age • K – Mean Serum Creatinine
(mL/min/1.73 m2)
20-29 116 o 0.7 (female) and 0.9 (male)
30-39 107 • α: -0.349 (female) and -0.411 (male)
40-49 99
50-59 93

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• For female Px: multiply computed GFR with 1.018 • Loss of tubular reabsorption capability is often the
1st function affected by renal disease – earlier than
GFR x 1.018 GFR
• The test measures the ability of the tubules to
• For African American Px: multiply computed GFR reabsorb:
with 1.159 o Water
GFR x 1.159 o Salts

OTHER TESTS
WATER DEPRIVATION TESTS (HISTORICAL)
1. Cystatin C
2. Beta2 Microglobulin • Fishberg Concentration Test
3. Radionucleotides o Px deprived of fluids for 24 hours prior to
measuring the urine specific gravity
• Mosenthal Concentration Test
CYSTATIN C
o Compares the volume and specific gravity of
day and night urine samples
• Cystatin C is a small protein (13,359 D) produced
o Evaluates concentrating ability
at a constant rate by all nucleated cells
• Readily filtered by the glomerulus and reabsorbed
NOTE: Normal person has urine specific gravity (SG) of
and broken down by renal tubular cells
1.025 after 16 hours of water deprivation
• Not secreted by the tubules
• Good procedure for screening & monitoring GFR
o Serum level is determined
o Recommended for pedia, (diabetic) DM,
elderly, critically ill patients
o Independent of muscle mass unlike the usual
creatinine test

BETA2 - MICROGLOBULIN

• Beta2 – Microglobulin is a small protein (11,800 D)

that dissociates from HLA at a constant rate
• Immunology and tumor marker
• Good procedure for screening & monitoring GFR
o Serum level is determined instead of urine
o Sensitive measurement methods are
available
• Disadvantage:
o Not recommended for patients with a history
of immunologic disorders or malignancy

RADIONUCLEOTIDES

• Injection of radionucleotides (I-iothalamate)

• Determination of GFR thru plasma disappearance
of the radioactive material and visualization of
filtration in one or both kidneys (thru radiologic
techniques)
• Disadvantages:
o Exogenous material
o Radioactive
o Labor intensive and costly

TUBULAR REABSORPTION TESTS

• Concentration Tests → test to determine the
ability of tubules to reabsorb essential salts and
water that have been non-selectively filtered by
the glomerulus
Figure 6. Effect of hydration on renal concentration
o Water Deprivation Tests (Historical)
(based on specific gravity): Px given 1 glass of water vs
o Osmometry Px given 4 glasses of water

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OSMOLALITY o Decreased renal blood flow causes:

▪ Impaired tubular secretory ability
• Affected only by the number of particles present ▪ Inadequate presentation of the
unlike specific gravity that is dependent on the substance to the kidney
number of particles and density of these particles
present on a solution PHENOLSULFONPTHALEIN (PSP)
• In evaluating the renal concentrating ability:
o Sodium (23 mw) • Not currently performed
o Chloride (35.5 mw) • Phenolsulfonpthalein dye is administered to Px
• Urea (60 mw) and glucose – NO importance to (exogenous)
Osmolality • Excretion of the dye is used to evaluate renal
• Determined by measuring a property that is functions
mathematically related to the number of particles • Disadvantages:
in the solution (colligative property) and o Standardization and interpretation of results
comparing this value with the value obtained from are difficult
the pure solvent o Interference by medication
• Measured on serum or urine o Elevated waste products in px’s serum
• Measured using osmometers: o Necessity to obtain several very accurately
o Freezing point timed urine specimens
o Vapor pressure o Possibility of producing anaphylactic shock
• Factors affecting osmolality:
o Lipemia – erroneous results P-AMINOHIPPURIC ACID TEST (PAH)
o Lactic acid formation (if samples are not
separated/refrigerated within 20 mins) –
falsely elevated
o Alcohol (volatile substances) – not detected
in vapor pressure but detected on freezing • Similar to Clearance Tests
point • p-Aminohippuric Acid is administered to Px
(exogenous)
FREE WATER CLEARANCE • PAH is radioactive → requires Nuclear Medicine
Section
• Ratio of urine and serum osmolarity
• Determined by first calculating the osmolar
clearance and subtracting the osmolar clearance
value from the urine volume in ml/min
• Osmolar clearance dictates how much water must
be cleared each minute to produce a urine with the
same osmolarity as plasma

• Compute for free water clearance

Interpreting Result:

0 No renal concentration or dilution

+2.0 Excess water would have been excreted
Less than the necessary amount of water
-2.0
is being excreted

REFERENCES
TUBULAR SECRETION AND RENAL BLOOD FLOW
TESTS Urinalysis and Body Fluids ,6th Edition. Susan King
Strasinger and Marjorie Schaub Di Lorenzo
• Tests that measure tubular secretion of non-
filtered substances and renal blood flow are Fundamental of Urine and Body Fluid Analysis, 3rd Edition.
closely related due to: Nancy A. Brunzel
o Total renal blood flow through the nephron
must be measured by a substance that is Notes from synchronous session by Mr. Edison D. Ramos,
secreted rather than filtered to through the RMT, MPH, MSMT
glomerulus

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