Test 2 (Renal Control of Acid-Base Balance) Flashcards
(35 cards)
Importance of Maintaining pH
- H+: Reactant or product of many Enzymatic Reactions; Affects Reaction Rate
- Effects of H+ on net Electrostatic Charge of Proteins (Amphoteric): Affects Protein Function
- Effects of H+ on Free Plasma Concentrations of other cations (EX: Ca2+)
- Effects of H+ on Intracellular Cation Concentration (Na+/ H+, K+/ H+ Exchanger)
Chemical Buffer Systems
- Mixture of WEAK ACID and its CONJUGATE BASE in aqueous Solution
- Chemical buffers minimize but don’t completely prevent pH changes caused by STRONG ACID or BASE
- Ability (“Strength”) of buffer to minimize pH Changes depends on:
a) Concentrations of Buffer System Components
b) Nearness of Buffer’s pKa to pH of Solution
Example: Phosphate Buffer System
- Buffer fixed acids within you body
pKa= 6.8
Two Kinds of Acid in Body: “Volatile” and “Fixed”
1) VOLATILE ACID: Carbonic Acid —> H2CO3
- In Chemical Equilibrium with CO2, a Volatile Gase:
H2CO3 CO2 + H2O
- Pulmonary Ventilation controls H2CO3 Concentration in Body Fluids
2) FIXED ACIDS: Non Carbonic Acids generated Metabolically (Ex: Sulfuric, Phosphoric Acids)
- Initially Neutralized by Buffers in Body Fluids
- Ultimately Excreted in Urine
Metabolic Sources of H+
1) OXIDATIVE METABOLISM: Co2 (15,000 mEq/ Day)
CO2 + H2O H2CO3 H+ + HCO3-
2) NONVOLATIEL (Fixed) ACIDS: 40 - 80 mEq/ day
- Glycolysis: Lactic Acid (pKa 3.9)
- Incomplete Oxidation of Fatty Acids: Ketone Acid (pKa 4.5)
- Protein, Nucleic Acid, Phospholipid Metabolism: Sulfuric, Phosphoric, Hydrochloric Acids
- CANNTO BE REMOVED FROM BODY BY VENTILATION!!!!!!!!!
3 Lines of Defense against pH Changes
1) Chemical Buffers
2) Respiration
3) Kidneys
First Line of Defense: Chemical Buffers
- Bicarbonate
- Intracellular Fluid
- Bone
Bicarbonate System is the Major EC BUFFER
- Equilibrium between H2CO3 and HCO3 (pKa = 3.8)
pH = 3.8 log [HCO3-]/ [H2CO3]
- H2CO3 is also in Equilibrium with CO2 and H2); CO2 Concentration is 400x [H2CO3]
- CO2 Concentration is related to PCO2. For each mmHg PCO2, 0.3 millimolar CO2 is in Solution at 37 Degrees Celsius. Thus
pH = 6.1 + log [HCO3-]/ (0.03 x PCO2)
**Advantage: [HCO3-] and PCO2 are EASILY MEASURED!!!
Why is a Bicarbonate Buffer System so Powerful?
- Components (HCO3-, CO2) are ABUNDANT
- Bicarbonate Buffer System is “OPEN”; Concentration of HCO3- and CO2 are readily adjusted by Respiration and Renal Function
**RESPIRATORY adjustment HAPPENS FIRST!!!!!
**Kidneys CAN compensate for Lungs but Lungs CANT compensate for Kidneys!!!
Response of Bicarbonate System to Strong Acid
CLOSED SYSTEM:
- The [CO2] will build up and the pH will start to drop to around 6.2
OPEN SYSTEM:
- The [CO2] will be low and the pH will rise back to Normal
Renal Regulation of pH
Urine pH Range: 4.5 - 8.0!!!!!!!**
1) Renal Response to Excess ACID:
- All of filtered HCO3- is REABSORBED
- Additional H+ is Secreted into Lumen, Excreted PRIMARILY as AMMONIUM (NH4+)!!!!!!!!!!!!!!
2) Renal Response to Excess BASE:
- Incomplete Reabsorption of filtered HCO3- (Secreted)
- Decreased H+ Secretion
- Secretion of HCO3- in COLLECTING DUCT
Renal Regulation of pH Stats
- Each day, 40-80 mEq H+ are EXCRETED in URINE
- Free Urinary [H+} is only 40 microbial/L at a pH of 4.5, thus daily Urine Volume of 2500L would be required to Excrete 100 mEq of H+ …. this is NOT PHYSIOLOGICALLY POSSIBLE
- Most H+ is EXCRETED in combination with Urinary Biuffers. Two types:
1) TITRATABLE ACID: Conjugate bases of Metabolic Acids (Phosphate, Creatinine, Urate) accept H+ in LUMEN
2) AMMONIA: Generated by Tubular Epithelium
Total Renal H+ Excretion
- H+ Excretion = Urinaruy Excretion of Titratable Acid + Ammonium - HCO3
- Typical Rates (mEq/day):
24 + 48 - 2 = 70 mEq/ day
Note: HCO3 EXCRETION is Equivalent to ADDING Acid to Body Fluids (for each mEq of HCO3 lost, a free H+ is left behind)
Luminal pH along Nephron
- Acidification of Luminal Fluid is rather modest (pH 6.7) before COLLECTING DUCT.
- In Collecting Duct, Fluid can be Acidified to a pH as low as 4.5!!!!!!!!
**AMMONIA is FORMED in the PROXIMAL TUBULE
Collecting Ducts can Secrete H+ or HCO3-
1) ALPHA Intercalated Cells:
- ACTIVELY SECRETE H+
- H+-ATPase
- Up to 900 fold [H+] Gradient
2) Beta- Intercalated Cells
- Secrete HCO3 to Eliminate Excess base
Acid-Secreting Type A Intercalated Cells
- Aldosterone INCREASES the activity of the ATPase and causes the ALPHA intercalated cells to EXCRETE H+ ions
Acidification of Urine begins in Proximal Tubule
- Most of the H+ Secreted by the PROXIMAL TUBULE is used to REABSORB Filtered HCO3-, so LUMINAL pH FALLS only SLIGHTLY (6.7) in this Segment
Tubular Reabsorption of Filtered HCO3-
- At 25 mEq/L Plasma concentration, 4500 mEq of HCO3- are filtered into Nephrons Per Day
- EXCRETION of HCO3- has same effects as Gaining H+; EXCRETION of even Small Fraction of filtered HCO3- must be RECAPTURED
- If Arterial pH is TOO HIGH, Kidneys respond by INCOMPLETELY REABSORBING HCO3-
Mechanism to reabsorb Filtered HCO3-
- CO2 is brought back into the Cell
- CO2 combines to H2O in the cell to form H2CO3
- H2CO3 dissociates into H+ and HCO3-
- The HCO3- is REABSORBED back into the Blood
Important Features of HCO3- Reabsorption
- HCO3- is temporarily converted to CO2
- Ultimately dependent on Na+, K+, ATPase
- Process DOES NOT result in Secretion of H+***
- By this Mechanism, about 80% of filtered HCO3- is Reabsorbed is PROXIMAL TUBULE, most of remainder in THICK ASCENDING LIMB
- A SATURABLE Process: at [HCO3-] > 26 mEq/L, some is EXCRETED in URINE!!!
Saturation of HCO3- Reabsorption
- Once the HCO3- Transporters are Saturated, the Reabsorbed HCO3- starts to Plateau and the Excreted starts to Increase!!!
Excretion of H+ as Titratable Acid
- Filtered HPO4 2- is the MOST IMPORTANT BUFFER converted to TITRATABLE ACID
- These buffers can bind to the H+ and Excrete them out!!!!!!!! (Titratable Acid)
Excretion of H+ and AMMONIUM
- Two NH4+ are generated by GLUTAMINE OXIDATION within the Tubular Epithelial Cells
- Two HCO3- are produced by GLUTAMINE OXIDATION
We get an ACIDIFICATION of the Urine!!!!!***
Chronic Acidemia (Elevated H+ Concentration) up-regulates Renal NH4+ Production, Excretion
- Chronic Acidemia causes the URINARY AMMONIUM EXCRETION to Increase at a HIGHER RATE than it would under normal conditions
