Test 1 (Elements of Renal Function Lecture) Flashcards
Physiological Functions of Kidneys
1) Regulate extracellular fluid solute concentration (Osmolarity)
2) Regulate plasma electrolyte concentrations
3) Regulate Acid-Base balance (H+ Concentration)
4) Regulate Extracellular fluid volume, Arterial Blood Pressure
5) Eliminate Metabolic wastes, foreign chemicals
6) Hormone Production: Erythpoietin, Vitamin D, Renin
7) Degrade peptide Hormones
8) Synthesis: Ammonia, Prostaglandins, Kinins, Glucose
The Kidneys are Integrated with Other Body Systems
- Ion Balance: Endocrine, Gastrointestinal
- Water Balance: CNS
- Blood Pressure, Na+, K+ : Autonomic NS
- Acid- Base Balance: Respiratory, CNS
- Blood Pressure: Cardiovascular
- Elimination of Wastes, Toxins: Liver
Types of Nephrons
1) Cortical:
- SHORT Loops of Henle
- Surrounded by Peritubular Capillaries
2) Juxtamedullary
- LONG loops of Henle
- Long EFFERENT Arterioles are divided into specialized Peritubular Capillaries… the VASA RECTA!!!!
- Function ot CENCENTRATE URINE
Renal Microcirculation
1) Afferent Arteriole —->
2) GLOMERULAR Capillaries ——>
3) Efferent Arteriole —–>
4) PERITUBULAR CAPILLARIES
Peritubular and Vasa Recta
1) PERITUBULAR CAPILLARIES:
- Run alongside loops of Henle of CORTICAL NEPHRONS
2) VASA RECTA:
- Run alongside loops of Henle of JUXTAMEDULLARY NEPHRONS
Venous Drainage
1) Interlobular Vein —->
2) Arcuate Vein —->
3) Interlobar Vein —->
4) Renal Vein
Unusual Aspects of Renal Microcirculation
Two sets of Arterioles, 2 sets of Capillary Beds in SERIES:
1) First Capillary Network (GLOMERULAR CAPILLARIES):
- HIGH HYDROSTATIC PRESSURE
- Large Fluid Volume filtered into Bowman’s Capsule
- **FAVOR FILTRATION
- **ONCOTIC PRESURE is LOW!!!
2) Second Capillary Network (PERITUBULAR CAPILLARIES):
- LOW HYDROSTATIC PRESSURE
- Large amounts of Water and Solute are REABSORBED
- ***FAVORS REABSORPTION
- ***ONCOTIC PRESSURE is HIGHER!!!
Renal Blood Flow
- At rest kidneys receive 20% of CARDIAC OUTPUT (Renal Fraction. If CO = 5 L/ min, then Renal Blood Flow at rest oa about 1 L/ min
- Combined, the two kidneys weight about 300 g. Resting Renal Blood Flow is about 3.5 mL/g
- High Pressure in GLOMERULAR CAPILLARIES (About 60 mmHg) causes FILTRATION of BLOOD
- 1100 to 1300 mL filtered/ min which produces 125 to 130 mL of fluid termed the GLOMERULAR FILTRATE
- Lower pressure in the PERTIBURLAR CAPILLARIES (about 13 mmHg) permits fluid reabsorption
- pressure in BOTH Capillary beds can be Regulated by RESISTANCE Changes in Afferent and Efferent Arterioles
Regional Blood Flow
- The Regional Blood Flow is HIGHER in the CORTEX compared to the MEDULLA
Sympathetic Innervation
Sympathetic Neurons Synapse on:
1) SMOOTH MUSCLE
- Causing Arteriolar CONSTRICTION
2) GRANULAR CELLS
- Causing RENIN Secretion in AFFERENT Arterioles
Effects of Sympathetic Stimulation
1) Powerful CONSTRICTION of AFFERENT and EFFERENT Arterioles (Afferent > Efferent)
- Decreases Renal Blood Flow
- Diverts the Renal Fraction to Vital Organs
2) Stimulates RENIN RELEASE from GRANULAR CELLS
3) Stimulates Na+ REABSORPTION in Proximal Tubule, Thick Ascending limb of Henle’s Loop, Distal Convoluted Tubule, Collecting Duct
Basic Processes of Urine Formation
1) GLOMERULAR FILTRATION: Filtration of Plasma from Glomerular Capillaries into Bowman’s Capsule
2) TUBULAR REABSORPTION: Transferral of Substances from TUBULAR LUMEN to PERITUBULAR CAPILLARIES
3) TUBULAR SECRETION: Transferral of Substances from PERITUBULAR CAPILLARIES to TUBULAR LUMEN
4) EXCRETION: Voiding of Substance in the URINE
Quantitative Relationships between the Four Basic Processes
1) URINARY EXCRETION= Amount Filtered - Amount Reabsorbed + Amount Secreted
2) TUBULAR REABSORPTION = Glomerular Filtration - Urinary Excretion
- Is EXCRETION Rate > FILTRATION Rate, Tubular SECRETION must have Occurred
Physiological Importance of Each Process
- Each process is regulated according to the Body’s Needs
- For most substances, the Rate of their Filtration and Reabsorption are LARGE Relative to Rate of EXCRETION
- Therefore, small changes in FILTRATION or REABSORPTION can lead to Large Changes in EXCRETION
- *****Ex: Elevated Plasma Na+ INCREASES Rate at which it is filtered and a Smaller Fraction of the filtered is REABSORBED, leading to an INCREASED EXCRETION
- High Filtration Rate important in removing Waste products and Regulating Volume, composition of Body Fluids
Glomerular Filtration and Filtration Rate (Filtered Load)
Glomerular Filtration Rate (GRF):
- Volume of Plasma filtered into the combined Nephrons of Both Kidneys per unit time
- Normally around 20% of TOTAL RENAL PLASMA FLOW!!!
- FILTRATION RATE (Filtered Load) of any FREELY FILTERED Substance = GFR x Plasma Concentration of Substance
***Ex: If GFR = 125 mL/ min, and Plasma Glucose Concentration = 1 mg/mL, rate of Glucose Filtration = 125 mg/min
Urinary Excration Rate
= Product of Urine Flow Rate x Concentration of Substance in the Urine (Ux x V)
***Ex: If Na+ Concentration in Urine = 20 mEq/L, and Urine Excretion = 2L/ day, Na+ Urinary Excretion Rate = 40 mEq/ day
Reabsorption vs Secretion:
- net rate of Reabsorption or Secretion of a substance = difference between Glomerular Filtration and Urinary Excretion (assuming Substance is NOT PRODUCED or METABOLIZED by the Kidneys)
1) If Excretion Filtration, Net SECRETION occurred
Important Concept: Renal Clearance
- CLEARANCE: The Volume of Plasma from which a SUBSTANCE is COMPLETELY REMOVED (‘Cleared’) by the Kidneys in a given time period
- Units are Volume/ time
ex: mL/min or L/hr - Clearance describes HOW Effectively the Kidneys Remove a substance from the Bloodstream and excrete it in the Urine. Different substances have different Clearance
- Measurement of GFR relies on the Concept of Clearance
Calculation of Clearance
Cx = (Ux x V)/ Px
GFR can be estimated from Clearance of Certain Compounds
REQUIREMENTS: Compound must be Freely Filtered, but CANNOT BE Secreted, Reabsorbed, Produced not Degraded by the Kidneys
(GFR x Px) = (Ux x V)
GFR = (Ux x V)/ Px = Cx
Inulin Clearance = GFR
INULIN: Freely filtered, neither Reabsorbed, Secreted nor Metabolized
- Amount UNILIN Filtered per unit Time = Amount Excreted per unit Time
GFR = (U inulin x V)/ P inulin = C inulin
Inulin Clearance = GFR
- Inulin is freely filtered, but neither Reabsorbed, Secreted, Produced nor Metabolized by the Nephrons
- Amount of Inulin filtered = Amount Excreted, so Cin = GFR
Creatinine Clearance approximates GFR
- Use of INULIN is Cumbersome; Creatine is produced ENDOGENOUSLY from Metabolism or Creatine by Skeletal Muscle
- NOT PERFECT: Creatinine Secretion in Proximal Tubule OVERESTIMATES U creatinine; Substances in Blood causes OVERESTIMATION of P creatinine
C creatinine = (U creatinine x V)/ P creatinine = GFR
P creatinine: Long term monitoring of Glomerular Filtration
- Normally, Creatinine Excretion = Creatinine production
- P creatinine INVERSELT proportional to GFR
- Theroetically, if GFR falls to 25% of Normal, P creatinine should INCREASE 4x over a few days!
In reality, INVERSE relationship isn’t perfect:
- Differences in Lean Muscle Mass Among Patients
- Compensatory INCREASED Proximal Tubule Secretion
Useful: LONG TERM MONITORING of Renal Function!!!!**
**Theroretically, as Renal Function (GFR) Rises, so should CREATININE Clearance and conversely, as GFR falls SERUM CREATININE RISES!!!!!!!!
BUN/ Cr > 20/1
***PRERENAL
- BUN Reabsorption is INCREASED
- BUN is disproportionately elevated relative to Creatinine in Serum
- Reduced Renal Perfusion due to HYPOVOLEMIA
The principle behind this ratio is the fact that BOTH UREA (BUN) and Creatinine are freely filtered by the Glomerulus, however Urea absorbed by the Tubules can b regulated (Increased or Decreased) whereas Creatinine Reabsorption remains the same (Minimal Reabsorption)*
BUN/ Cr (10 - 20/1)
***NORMAL RANGE or POSTRENAL
- Can also be POSTRENAL DISEASE (obstruction)
- BUN Reabsorption is within NORMAL LIMITS
The principle behind this ratio is the fact that BOTH UREA (BUN) and Creatinine are freely filtered by the Glomerulus, however Urea absorbed by the Tubules can b regulated (Increased or Decreased) whereas Creatinine Reabsorption remains the same (Minimal Reabsorption)*
BUN/ Cr (
***INTRARENAL
- Renal Damage causes REDUCED Reabsorption of BUN and a Lower BUN:Cr Ratio
The principle behind this ratio is the fact that BOTH UREA (BUN) and Creatinine are freely filtered by the Glomerulus, however Urea absorbed by the Tubules can b regulated (Increased or Decreased) whereas Creatinine Reabsorption remains the same (Minimal Reabsorption)*
Another Marker of GFR…. Cystatin C
- Serum Creatinin has a drawback in the measurement of the Glomerular Filtration Rate (GFR) in that it may vary according to MUSCLE MAS
- Cystatin C is a 13 kilodalton Protein that is CONTINUOUSLY produced by ALL NUCLEATED CELLS in the Body
- Freely Filtered by the Glomerulus
- Similar to CREATININE, Serum levels rise if Filtration is compromised however NOT DEPENDENT on MUSCLE MASS
- Similar to Creatinine, Serum levels become ELEVATED when GFR DECLINES!!!!
- ADVANTAGE of Nystatin C: Levels not affected by Muscle Mass, Age, or Gender
- Also similar to Creatinine, has been proposed as an alternate marker which can be used in calculation of eGFR (Estimated GFR)
Estimated GFR (eGFR)
- Formular which try to “correct” Creatinine clearance measurements for Age, Race, Sex, Muscle Mass (Weight and Height) to Improve Accuracy
At low Plasma Concentration (Below Tm), PAH Clearance Estimates RENAL PLASMA FLOW
PARA- AMINOHIPPURIC ACID (PAH):
- Freely Filtered
- Avidly SECRETED in PROXIMAL TUBULE
- PAH: Completely cleared from Plasma of PERITUBULAR CAPILLARIES when plasm PAH Concentration is LOW by SECRETION via OAT!!!!!!
FICK PRINCIPLE:
- Amount of PAH which enters Kidney equals the amount leaving
[PAH] RA x RPF = Entering
[PAH] RV x RPF + [PAH]U x V = Leaving
At low Plasma Concentration (Below Tm), PAH Clearance Estimates RENAL PLASMA FLOW Cont……
RPF = (Upah x V)/ Ppah
RPF = Cpas
- At HIGHER Concentration of PAH, Tm for OAT Transporters is reached due to SATURATION, Clearance (Secretion) is DECREASED and RPF cannot be estimated accurately
Filtration Fraction
- The Filtration Fraction (FF) is the part of the Renal Plasma Flow (RPF) that is Filtered/ Diverted into the Tubule:
FF = GFR/ RPF
- FF changes with ULTRAFILTRATION PRESSURE
- With an INCREASED FF, the ONCOTIC Pressure of the EFFERENT Arteriole INCREASES, facilitating REABSORPTION of Tubular Fluid
* FF = 20%!!!!!!!!!***
What would change the FF?
FF = GFR/ RPF
Clinical Application:
- In RENAL ARTERY STENOSIS or Severe Hemorrhage, Blood Flow (RPF) to Kidney is REDUCED
- A HIGHER proportion of that flow reaching the Kidneys must be passed into the Renal Tubules in order to MAINTAIN HOMEOSTASIS
- Reflected in HIGHER FILTRATION FRACTION!!!!!!!!!!
Summary
- Nephron Segments
- Renal Microcirculation: 2 sets of Arterioles and 2 Capillary beds in Series
- Sympathetic Innervation
- Basic Processes: Glomerular Filtration, Tubular Reabsorption and Secretion, Urinary Excretion
- Clearance and GFR: (U x V)/ P
