2 Renal Physiology

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RENAL

PHYSIOLOGY
Noraine Princess G. Tabangcora, RMT
Faculty, MLS Department
San Pedro College
REVIEW OF RENAL ANATOMY
REVIEW OF RENAL ANATOMY
The Nephrons
REVIEW OF RENAL ANATOMY
REVIEW OF RENAL ANATOMY
The Bowman’s Capsule
RENAL BLOOD CIRCULATION
RENAL BLOOD CIRCULATION
STEPS IN URINE FORMATION
STEP 1. GLOMERULAR FILTRATION
Remember........................... Filtrate?
STEP 1. GLOMERULAR FILTRATION
STEP 1. GLOMERULAR FILTRATION
Factors affecting Glomerular Filtration

A. Cellular Structure of the Capillary Wall


1. Capillary Wall Membrane
2. Basement Membrane (Basal Lamina)
3. Visceral Epithelium of the Bowman’s Capsule
B. Hydrostatic & Oncotic Pressure
1. Hydrostatic Pressure in the arterioles
2. Oncotic Pressures in the Bowman’s Capsule
C. Renin-Angiotensin-Aldosterone System
STEP 1. GLOMERULAR FILTRATION
A. Cellular Structure of the Capillary Wall

Shield of Negativity

The filtration membrane is


held in place by specialized podocytes
STEP 1. GLOMERULAR FILTRATION
B. HYDROSTATIC & ONCOTIC PRESSURE WITHIN NEPHRONS

1. GLOMERULAR BLOOD HYDROSTATIC PRESSURE


2. CAPSULAR HYDROSTATIC PRESSURE
3. GLOMERULAR CAPILLARY ONCOTIC PRESSURE
4. NET FILTRATION PRESSURE
STEP 1. GLOMERULAR FILTRATION
STEP 1. GLOMERULAR FILTRATION
STEP 1. GLOMERULAR FILTRATION

C. RENIN ANGIOTENSIN ALDOSTERONE SYSTEM


1. As BP drops the SNS stimulates
juxtaglomerular cells to produce renin
(enzyme); converting…

2. Angiotensinogen (plasma protein) to


angiotensin I;

3. In the lungs angiotensin-converting


enzyme (ACE) converts angiotensin I
to angiotensin II.

4. Angiotensin II has multiple effects; lets


say they collectively act to raise BP by
reducing water loss, encouraging
water intake, and constricting blood
vessels.
STEP 2. TUBULAR REABSORPTION
STEP 2. TUBULAR REABSORPTION
REABSORPTION – return of most of the filtered water and many solutes to the
bloodstream
– About 99% of filtered water reabsorbed
– Proximal convoluted tubule cells make the largest contribution
– 65% of filtrate is reabsorbed into body
ACTIVE TRANSPORT PASSIVE TRANSPORT
Movement of a substance across a cell  Movement of molecules across a
membrane and against an osmotic gradient membrane as result of differences in the
 Needs a carrier protein to transport electrical potential on opposite sides of
substance; the membrane
 Requires energy  Does not need carrier protein
 Does not require energy

 PCT- Glucose,amino acid,salts  PCT, DLoH, CT- Water


 ALoH- Chloride  PCT, ALoH - urea
 DCT-Sodium  ALoH- sodium
STEP 2. TUBULAR REABSORPTION
STEP 2. TUBULAR REABSORPTION
ACTIVE TRANSPORT
1. Maximal Reabsorptive Capacity (Tm)
* Highest level a substance is reabsorbed before
appearance of substance in the urine
* ex. Glucose is at 350 mg/min.
2. Renal threshold
* Plasma concentration at which active transport
stops
* ex. Glucose is at 160-180mg/dL

Importance: distinguishes excess solute filtration and


extent renal tubular damage
STEP 2. TUBULAR REABSORPTION
RENAL CONCENTRATION (tubular)

Loops Of Henle
 Permeable to salts
 Impermeable to water (ALoH)
 As filtrate moves thru the ascending limb, NaCl
moves out making the filtrate of lesser osmolarity

Significance: Keep the renal medulla


region of the kidney at high osmolarity so
water can move passively out of the
filtrate in the CT
STEP 2. TUBULAR REABSORPTION
Therefore, most of the water delivered
to this segment remains in the tubule,
despite reabsorption of large amounts
of solute.

Thus, the tubular fluid becomes very


dilute and which results diluted urine.
STEP 2. TUBULAR REABSORPTION
STEP 2. TUBULAR REABSORPTION
STEP 2. TUBULAR REABSORPTION
COUNTERCURRENT MECHANISM
 Selective
reabsorption
process

 Prevents excessive
water reabsorption
through the
water-impermeable
walls of the ALoH
STEP 2. TUBULAR REABSORPTION
CONTROL OF WATER LOSS
How concentrated or diluted your urine is, depends upon the
body’s state of hydration:
 Drink a large amount of H2O = hypotonic urine (called water
diuresis)
 CD reabsorb NaCl
 water remains in urine

 Dehydration = hypertonic urine (more concentrated)


 High blood osmolarity in a dehydrated person  stim. Pituitary
gland → release ADH   aquaporin channels,  CD’s water
permeability.
STEP 2. TUBULAR REABSORPTION
STEP 3. TUBULAR SECRETION
 Involves passage of substances from the
blood in the peritubular capillaries to the
tubular filtrate

Function:
a. Elimination of waste products not filtered by
the glomerulus
b. Regulation of acid base balance in the
body through secretion of hydrogen ions
STEP 3. TUBULAR SECRETION
STEP 3. TUBULAR SECRETION
1. Waste removal
 Urea, uric acid, bile acids, ammonia, catecholamines,
prostaglandins and little creatine;

 TS also clears the blood of pollutant, morphine, penicillin, aspirin,


and other drugs;

 one reason prescription drugs are taken 3-4x/day is to keep pace


with the rate of clearance and maintain a therapeutically effective
drug [ ] in the blood.

2. Acid – base balance


 TS of hydrogen and bicarbonate ions regulates pH of body fluids.
Tubular
STEP Secretion
3. TUBULAR SECRETION
Tubular Renal Peritubular
lumen Tubular Cell Plasma

HCO-3 H++HCO3
HCO-3
HCO3 + H+ H2CO3
Carbonic
H2CO3 anhydrase
CO2
H2O + CO2 H2O + CO2
Tubular
STEP Secretion
3. TUBULAR SECRETION

Tubular Renal Peritubular


lumen Tubular Cell Plasma

HPO4- H++HCO3
HCO-3
H2CO3
HPO4- + H+
Carbonic
anhydrase
CO2
H2PO4 H2O + CO2
Tubular
STEP Secretion
3. TUBULAR SECRETION

Tubular Renal Peritubular


lumen Tubular Cell Plasma
NH3
NH3 + H+
H++HCO3
HCO-3

H2CO3
Carbonic
NH4+ anhydrase CO2
H2O + CO2
SUMMARY OF URINE FORMATION
NEXT MEETING:

LONG QUIZ- Renal Physiology


RENAL FUNCTION TESTS
Why test for Renal Function?

1) To asses the functional capacity of kidney


2) Early detection of possible renal impairment
3) severity and progression of the impairment
4) Monitor response to treatment
5) Monitor the safe and effective use of
drugs which are excreted in the urine
RENAL FUNCTION TESTS

GLOMERULAR
FILTRATION TESTS All clearance
(GFT) tests

RFT Urine
TUBULAR
REABSORTION TESTS Concentration
tests

TUBULAR SECRETION PAH


AND RENAL BLOOD Titratable acidity
FLOW TESTS Urinary Ammonia
RENAL FUNCTION TESTS
1. GLOMERULAR FILTRATION TESTS (GFR)

• About 1200 mL of blood (650 mL plasma)


passes through the kidneys, every minute.

• About 120-125 mL is filtered per minute by the


kidneys & this is referred to as glomerular
filtration rate (GFR).
RENAL FUNCTION TESTS

With a normal GFR (120-125 mL/min),


the glomerular filtrate formed in an
adult is about 175-180 litres/day, out of
which only 1.5 litres is excreted as
urine.
RENAL FUNCTION TESTS
CLEARANCE TESTS
 defined as the volume of plasma that would be completely
cleared of a substance per minute.
 Standard test measuring:
a. Filtering capacity of the glomeruli
b. Measures rate at which kidneys are able to remove
filterable substances from the blood
UxV
C = ______
P
• U = Concentration of the substance in urine.
• V = Volume of urine in ml excreted per minute.
• P = Concentration of the substance in plasma.
RENAL FUNCTION TESTS
To test accuracy of the substance being measured:

1) Substance analyzed must be neither


reabsorbed nor secreted by the tubules
2) Stable in a 24-hour collected urine
3) Consistent in the plasma level
4) Availability of the substance in the body
5) availability of the tests for chemical analysis
of the substance
RENAL FUNCTION TESTS
CLEARANCE TESTS SUBSTANCES

1) Urea
Present in all urine specimen but replaced by other
substances
2 ) Inulin
a. Polymer of fructose
b. Extremely stable substance not reabsorbed nor
secreted by the tubules
c. Not a normal body constituent and infused at a
constant rate throughout the testing period
d. Seldom choice if suitable substance is already present
in the body
RENAL FUNCTION TESTS
CLEARANCE TESTS SUBSTANCES

3. Radionucleotides
a. Measures plasma disappearance of infused substances thus
eliminating need for urine collection
b. Injection of radionucleotides to:
*visualize plasma disappearance of radioactive material
* enable visualization of the filtration of one or both
kidneys

4. β2microglobulin
a. Dissociates from human leukocyte antigen and removed
from the plasma by glomerular filtration
b. MW – 11,800 da
c. Increased in patients with inflammatory conditions,
autoimmune disorders, viral infections, multiple myeloma
RENAL FUNCTION TESTS
CLEARANCE TESTS SUBSTANCES

5. Creatinine
a. Waste product of muscle metabolism and found at a
constant rate in the blood

6. Cystatin C
a. Low molecular weight
b. Potential marker for long-term monitoring of renal
function
c. Constant in serum levels
d. Independent of age, gender, and muscle mass
e. Higher analysis cost
RENAL FUNCTION TESTS
Calculations (Creatinine Clearance)
1. Greatest source of error: improper timed specimen
2. GFR reported in mL/min.
3.
U = urine creatinine in mg/dL
V = urine volume in mL/min.
P = plasma creatinine in mg/dL

Ex #1. Calculate the urine volume for a 4-hour specimen measuring 1L:
4 hours X 60 minutes = 240 minutes

1000mL
240 minutes

= 4.17 mL/min (volume)


RENAL FUNCTION TESTS
Standard Formula to calculate millilitres of plasma cleared
per minute (C) is:
C=UV
P
Ex #2. Using urine creatinine of 400 mg/dL (U), plasma creatinine
of 5.0 mg/dL (P), and urine volume of 2500 mL obtained from a
24-hour specimen (V), calculate the glomerular filtration rate.

V= 2500 mL = 1.74 mL/min.


60 minutes X 24 hours = 1440 minutes

C = 400 mg/dL (U) X 1.74 mL/min. (V) = 139.2 mL/min.


5.0 mg/dL (P)
RENAL FUNCTION TESTS
Reference values:
• The normal range of creatinine clearance is around 120-
145 mL/min.
• These values are slightly lower in women.
Men (107 to 139 mL/min.)
Women (87 to 107 mL/min.)

Serum creatinine normal range:


Adult male: 0.7-1.4 mg/dl
Adult female: 0.6-1.3 mg/dl
Children: 0.5-1.2 mg/dl
RENAL FUNCTION TESTS
Clinical Significance in the interpretation of results for
Creatinine Clearance:

1. Determines the number of functioning nephrons


2. Functional capacity of the nephrons

Results may be used to:


1. Measure extent of nephron damage
2. Monitor effectiveness of treatment in the
prevention of further nephron damage
3. Determine feasibility of administering
medications
RENAL FUNCTION TESTS
Renal Threshold Substances
• certain substances in the blood have
excretion rate in urine dependent on their
concentration.
• At a normal concentration in the blood,
they are completely reabsorbed by the
kidneys.
RENAL FUNCTION TESTS
Renal Threshold Of A Substance
is defined as its concentration in blood (or plasma) beyond which it
is excreted into urine.
 Glucose is 180 mg/dL
 Ketone bodies 3 mg/dL
 Calcium 10 mg/dL
 Bicarbonate 30 mEq/L

Tubular maximum (Tm):


The maximum capacity of the kidneys to absorb a particular
substance.
 Glucose: 350 mg/min.
RENAL FUNCTION TESTS
2. TUBULAR REABSORPTION TESTS
 Also known as Concentration tests

Water Deprivation Tests


1. Fishberg Test - patients deprived of fluid for
24 hours prior to measuring the specific
gravity
2. Mosenthal Test – compared the volume of
day and night urine samples to evaluate
concentrating ability
RENAL FUNCTION TESTS
Free Water Clearance
a. How much water must be cleared each
minute to produce a urine with the same
osmolarity as with the plasma

b. Determines the ability of the kidney to


respond to the state of body hydration
RENAL FUNCTION TESTS
3. Tubular Secretion and Renal Blood Flow Tests
 Test to measure tubular secretion of nonfiltered substances
and renal blood flow

1. ρ-amino hippuric acid test (PAH) using the dye


phenolsulfonphthalein

a. test substance easily removed from the blood each


time it comes in contact with a functional renal
tissue
b. does not combine with plasma proteins
c. removed completely from the blood-
d. not anymore performed especially using the dye
PSP because of concern over interference of
medications and elevated waste products in
patient’s serum
e. possible anaphylactic shock
RENAL FUNCTION TESTS
2. Titratable Acidity & Urinary Ammonia
a) Ability of kidney to produce acid urine
depends on tubular excretion of
ammonia by the cells of the DCT
b) Inability to produce acid urine: Renal
Tubular Acidosis
c) Measurement of total hydrogen ion
excretion in urine
NEXT MEETING:

LONG QUIZ- Renal Function Tests

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