Test 2 (Renal Control of Acid-Base Balance) Flashcards Preview

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Flashcards in Test 2 (Renal Control of Acid-Base Balance) Deck (35):
1

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)

2

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

3

Example: Phosphate Buffer System

- Buffer fixed acids within you body

pKa= 6.8

4

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

5

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!!!!!!!!!

6

3 Lines of Defense against pH Changes

1) Chemical Buffers

2) Respiration

3) Kidneys

7

First Line of Defense: Chemical Buffers

- Bicarbonate

- Intracellular Fluid

- Bone

8

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!!!

9

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!!!

10

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

11

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

12

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

13

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)

14

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

15

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

16

Acid-Secreting Type A Intercalated Cells

- Aldosterone INCREASES the activity of the ATPase and causes the ALPHA intercalated cells to EXCRETE H+ ions

17

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

18

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-

19

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

20

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!!!

21

Saturation of HCO3- Reabsorption

- Once the HCO3- Transporters are Saturated, the Reabsorbed HCO3- starts to Plateau and the Excreted starts to Increase!!!

22

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)

23

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!!!!!******

24

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

25

Alkalemia (Reduction in H+ Concentration, Collecting Ducts Secrete HCO3-

- Beta Intercalated Cells can Secrete HCO3- in the Collecting Duct!!!!!!!

26

Factors Controlling Renal H+ Secretion

1) Intracellular pH:
- Ex: Decreased Intracellular pH causes H+ to be SECRETED

2) Plasma PCO2:
- Increased PCO2 caused H+ to be SECRETED

3) Carbonic Anhydrase Activity (Affecting H+ and HCO3-):
- We

4) Na+ Reabsorption (ECF Volume Changes due to Angiotensin/ Aldosterone):
- Ex: Increased Sodium Reabsorption causes for the H+ to be Secreted!!!

- Look at the Body Volume Status

5) Extracellular [K+]:
- Ex: Decreased [K+] causes for the K= to be Reabsorbed and for the H+ to go into the cell which causes the H+ to be SECRETED leading to an ALKALOSIS

6) Aldosterone:
- Na Reabsorbed
- K Secreted
- H Secreted

27

Diuretic Abuse can cause Alkalemia

Volume Contracts (Dehydration) = HYPOKALEMIA
- The INCREASE in Distal Delivery of Na causes K= to be dumped out into the Lumen and be SECRETED!!!

***Generated METABOLIC ALKALOSIS!!!!!!*******

28

Simple Acid-Base Disorders

- Normal Arterial Plasma pH Range: 7.35 - 7.45

- ACIDEMIA: A reduction in Arterial pH below 7.35

- ACIDOSIS: Any abnormal condition that PRODUCES ACADEMIA

- ALKALEMIA: An Increase in Arterial pH above 7.45

- ALKALOSIS: Any Abnormal condition that PRODUCES ALKALEMIA

29

Respiratory Acid-Base Distrurbances

1) RESPIRATORUY ACIDOSIS: Increased Arterial PCO2:

- Renal Response: INCREASED H+ Secretion RESTORES Extracellular pH, INCREASES HCO3- further


2) RESPIRATORY ALKALOSIS: Decreased Arterial PCO2:

- Renal Response: LESS H+ SECRETION, more HCO3- EXCRETION in Urine

30

Metabolic Acidosis

Low Plasma pH (Lowered Ratio of HCO3- to PCO2) due to:
a) Gain of Fixed Acid in Body Fluids (Ketone Bodies, Lactic Acid) or

b) Loss fo HCO3- (Diarrhea)

- In either case, [HCO3-] FALLS!!!!!!!!


RESPIRATORY COMPENSATION: Increased VENTILATION (Peripheral Chemoreceptors)

RENAL COMPENSATION: Increased H+ Secretion; Production of new HCO3-
****HCO3- formed in the Proximal Tubule****

31

Metabolic Alkalosis

Abnormally HIGH Plasma pH (Increased Ratio of HCO3- to PCO2) due to:
a) Excessive Gain of STRONG BASE or HCO3- (Alkali Ingestion)

b) Excessive Loss of Fixed Acid (Loss of GASTRIC ACID through Vomiting)


- HCO3- Concentration rises due to Shift in Carbonic Anhydrase Equilibrium toward HCO3-

RESPIRATORY COMPENSATION: Decreased VENTILATION

RENAL COMPENSATION:
- Incomplete Reabsorption of filtered HCO3-

- Beta Intercalated Cells SECRETE HCO3-

32

Primary Acid-Base Disturbances

1) Respiratory Alkalosis:
- pH INCREASES (Decr CO2) so HCO3- DECREASES

2) Respiratory Acidosis:
- pH DECREASES (Incr CO2) so HCO3- INCREASES

3) Metabolic Alkalosis:
- pH INCREASES (Incr HCO3) so CO2 INCREASES

4) Metabolic Acidosis:
- pH DECREASES (Decr HCO3) so CO2 DECREASES

***Compensation is NEVER COMPLETE

33

Know Davenport Diagrams

- Move Horizontally on the line for any type of RESPIRATORY CHANGE

- Move Vertically on the line for any type of METABOLIC CHANGE

34

Anion Gap

- Used in Differential Diagnosis of Metabolic Acidosis

*******AG= Measured Cation (Na+) - Measured Anions (CL-, HCO3-)
- Gap is comprised of UNMEASURED Anions including Plasma Albumin, Phosphate, Sulfate, Citrate, Lactate, Ketoacids


- Normal Range: 8 - 16 mEq/L (Method Dependent)

- Anion Gap is either NORMAL or INCREASED, depending on cause of Metabolic Acidosis

1) HYPERCHLORIC ACIDOSIS: AG is UNCHANGED
- Loss of HCO3- is matched by GAIN of CL-

2) HIGH ANION GAP ACIDOSIS (Normochloremic):
- HCO3- is replaced by UNMEASURED ANION (Lactate, Ketoacidosis, Poisoning)
---------> In this case the Anion Gap INCREASES!!!!

35

Causes of High Anion Gap Acidosis

M- Methanol
U- Urea
D- Diabetic Ketoacidosis

P- Paraldehyde
I- Isonazide
L- Lactic Acid
E- Ethylene Glycol, Ethanol
S- Salicylic Acid (Aspirin)