describe how the lungs and kidneys regulate volatile and fixed acids. describe how an acid’s...

Describe how the lungs and kidneys regulate volatile and fixed acids.

Describe how an acid’s equilibrium constant is related to its ionization and strength.

State what constitutes open and closed buffer systems.

Explain why open and closed buffer systems differ in their ability to buffer fixed and volatile acids.

Explain how to use the Henderson-Hasselbalch equation in hypothetical clinical situations.

2

Describe how the kidneys and lungs compensate for each other when the function of one is abnormal.

Explain how renal absorption and excretion of electrolytes affect acid-base balance.

Classify and interpret arterial blood acid-base results.

Explain how to use arterial acid-base information to decide on a clinical course of action.

3

Explain why acute changes in the blood’s carbon dioxide level affect the blood’s bicarbonate ion concentration.

Calculate the anion gap and use it to determine the cause of metabolic acidosis.

Describe how standard bicarbonate and base excess measurements are used to identify the nonrespiratory component of acid-base imbalances.

State how Stewart’s strong ion difference approach to acid-base regulation differs from the Henderson-Hasselbalch approach.

4

First, a Review:A. To be in balance, the quantities of

fluids and electrolytes (molecules that release ions in water) leaving the body should be equal to the amounts taken in.

B. Anything that alters the concentrations of electrolytes will also alter the concentration of water, and vice versa.

5

A. Electrolytes that ionize in water and release hydrogen ions are acids; those that combine with hydrogen ions are bases.

B. Maintenance of homeostasis depends on the control of acids and bases in body fluids.

6

C. Sources of Hydrogen Ions1.Most hydrogen ions originate as byproducts of metabolic processes,

including the: a. aerobic and anaerobic respiration

of glucose,b. incomplete oxidation of fatty

acids,c. oxidation of amino acids

containing sulfur, and thed. breakdown of phosphoproteins

and nucleic acids. 7

8

Fig18.06

H+

Internal environment

Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

Aerobicrespirationof glucose

Anaerobicrespirationof glucose

Incompleteoxidation offatty acids

Oxidation ofsulfur-containingamino acids

Hydrolysis ofphosphoproteinsand nucleic acids

Phosphoricacid

Sulfuricacid

Acidic ketonebodies

Lacticacid

Carbonicacid

Even small hydrogen ion [H+] concentration changes can cause vital metabolic processes to fail;

Normal metabolism continuously generates [H+];

[H+] regulation is of utmost biologic importance.

Various physiologic mechanisms work together to keep the [H+] of body fluids in a range compatible with life.

9

Acid-base balance is what keeps [H+] in normal range◦ For best results, keeps pH 7.35–7.45

Tissue metabolism produces massive amounts of CO2, which is hydrolyzed into volatile acid H2CO3

Reaction is catalyzed in RBCs by carbonic anhydrase

Aerobic Metabolism CO2 + H2O H2CO3 H+ + HCO3

– (within RBC: H+ + Hb HHb)

The hemoglobin in the erythrocyte (RBC) immediately buffers the H+, causing no change in the pH: Isohydric buffering

10

◦Lungs eliminate CO2; falling CO2 reverses Reaction:

Ventilation ↑ CO2 + H2O H2CO3 H+ + HCO3

–

↑ HHb → H+ +

HCO3–

11

12

Fig16.22

Tissue cell

TissuePCO2

= 40 mm HgCellular CO2

CO2 dissolvedin plasma

PCO2 = 40 mm Hg

CO2 combined withhemoglobin to form

carbaminohemoglobinBloodflow fromsystemicarteriole

Plasma

CO2 + H2OH2CO3

HCO3− + H+

HCO3−

H+ combineswith hemoglobin

Red blood cell Capillary wall

Bloodflow tosystemicvenule

PCO2 = 45 mm Hg


13

Buffer solution characteristics◦ A solution that resists changes in pH when an

acid or a base is added

◦ Composed of a weak acid and its conjugate base (i.e., carbonic acid/bicarbonate: in blood exists in

reversible combination as NaHCO3 and H2CO3

Add strong acid HCl + NaHCO3 → NaCl + H2CO3; buffered with only small acidic pH change

Add base NaOH + H2CO3 → NaHCO3 + H2O; buffered with only slight alkaline pH change

14

Bicarbonate & NonBicarbonate buffer systems◦ Bicarbonate: composed of HCO3

– and H2CO3

Open system as H2CO3 is hydrolyzed to CO2

Ventilation continuously removes CO2 preventing equilibration, driving reaction to the right:

HCO3– + H+ → H2CO3 → H2O + CO2

Removes vast amounts of acid from body per day

15

Fig18.07

Rate and depth of breathing increase

Respiratory center is stimulated


Cells increase production of CO2

CO2 reacts with H2O to produce H2CO3

H2CO3 releases H+

More CO2 is eliminated through lungs

16

Bicarbonate & Nonbicarbonate buffer systems (cont.)

◦ NonBicarbonate: composed of phosphate & proteins Closed system: All the components remain in the

system; no gas to remove acid by ventilation

Hbuffer/buffer– represents acid & conjugate base H+ + buffer– ↔ Hbuf reach equilibrium, buffering stops

Both systems are important to buffering fixed & volatile acids

(a volatile acid is one that is in equilibrium with a dissolved gas.)

Describes [H+] as ratio of [H2CO3]/ [HCO3

–]

◦ pH is logarithmic expression of [H+].

◦ 6.1 is the log of the H2CO3 equilibrium constant

◦ (PaCO2 × 0.03) is in equilibrium with, & directly proportional to blood [H2CO3]

Blood gas analyzers measure pH & PaCO2; then use H-H equation to calculate HCO3

–

18

The ratio between the plasma [HCO3-] and

dissolved CO2 determines the blood pH, according to the H-H equation.

A 20:1 [HCO3-]/dissolved CO2 ratio always

yields a normal arterial pH of 7.40

19

20

What is the role of proteins in the acid-base regulation process?

a.a. produces fixed (nonvolatile) acidsproduces fixed (nonvolatile) acids

b.b. produces volatile acidsproduces volatile acids

c.c. isohydric bufferingisohydric buffering

d.d. produces carbonic acidproduces carbonic acid

.

21

a.a. Catabolism of proteins produces Catabolism of proteins produces fixed (nonvolatile) acidsfixed (nonvolatile) acids

22

Bicarbonate buffer system ◦ HCO3

– can continue to buffer H+ as long as ventilation is adequate to exhale CO2:

Ventilation H+ + HCO3

– → H2CO3 → H2O + CO2

In hypoventilation, H2CO3 accumulates; only the NonBicarbonate system can serve as buffer

23

NonBicarbonate buffer system:◦ Hemoglobin is the most important buffer in

this system, because it’s the most abundant;

◦ Can buffer any fixed or volatile acid;◦ As closed system, products of buffering

accumulate & buffering may slow or or reach equilibrium:(H+ + Buf- ↔ HBuf).

◦ HCO3– and buf– exist in same blood system

Ventilation

Open: H+ + HCO3

– → H2CO3 → H2O + CO2

Closed: Fixed acid → H+ + Buf- ↔ HBuf

Classification of Whole Blood Buffers

Open System Bicarbonate:oPlasmaoErythrocyte

Closed System NonBicarbonate:oHemoglobinoOrganic PhosphatesoNonorganic PhosphatesoPlasma Proteins

24

25

Which one of the following blood buffers systems is classified as a bicarbonate buffer (open buffer system)?

a.a.HemoglobinHemoglobin

b.b.Erythrocyte (RBC)Erythrocyte (RBC)

c.c.Organic phosphatesOrganic phosphates

d.d.Plasma proteinsPlasma proteins

b. b. Erythrocyte (RBC)Erythrocyte (RBC)

26

Definitions:1.Excretion: Elimination of substances from the body;

2.Secretion: The process by which substances are actively transported;

3.Reabsorption: Active or passive transport of substances back into the circulation.

27

28

Buffers are temporary measure; if acids were not excreted, life-threatening acidosis would follow.

Lungs:

◦Excrete CO2, which is in equilibrium with

H2CO3

◦Crucial: body produces huge amounts of CO2

during aerobic metabolism (CO2 + H2O →

H2CO3)

◦In addition, through HCO3– , fixed acids are

eliminated indirectly as byproducts CO2 & H2O

(Remove ~24,000 mmol/L CO2 removed daily)

29

Kidneys◦Physically remove H+ from body◦Excrete <100 mEq fixed acid per day◦Also control excretion or retention of HCO3

–

◦If blood is acidic, then more H+ are excreted & all HCO3

– is retained. ◦If blood is alkaline, then more HCO3

– are excreted & all H+ is retained.

◦While lungs can alter [CO2] in seconds, kidneys require hours/days to change HCO3

– & affect pH

30

Basic kidney function◦ Renal glomerulus filters the blood by passing

water, electrolytes, and nonproteins through semipermeable membrane. Filtrate is modified as it flows through renal

tubules◦ HCO3

– is filtered through membrane, while CO2 diffuses into tubule cell, where it’s hydrolyzed into H+, which is then secreted into renal tubule H+ secretion increases in the face of acidosis

therefore, hypoventilation or Ketoacidosis increases secretion

31

Basic kidney function (cont.)◦ Reabsorption of HCO3

–

For every H+ secreted, an HCO3– is reabsorbed

Reacts in filtrate, forming H2CO3 which dissociates into H2O & CO2

CO2 immediately diffuses into cell, is hydrolyzed, & H+ is secreted into filtrate, HCO3

– diffuses into blood Thus, HCO3

– has effectively been moved from filtrate to blood in exchange for H+

If there is excess HCO3– that does not react with H+, it

will be excreted in urine

34

Basic kidney function (cont.)◦ Role of urinary buffers in excretion of excess H+

Once H+ has reacted with all available HCO3–,

excess reacts with phosphate & ammonia If all urinary buffers are consumed, further H+

filtration ends when pH falls to 4.5 Activation of ammonia buffer system

enhances Cl– loss & HCO3– gain

The lungs regulate the volatile acid content (CO2) of the blood, while the kidneys regulate the fixed acid concentration of the blood

In the OPEN bicarbonate buffer system, H+ is buffered to form the volatile acid H2CO3, which is exhaled as CO2 into the atmosphere.

In the CLOSED nonbicarbonate buffer system, H+ is buffered to formed fixed acids which accumulate in the body.

35

Normal acid-base balance◦Kidneys maintain HCO3

– of 22-26 mEq/L

◦Lungs maintain CO2 of 35-45 mm Hg◦These produce pH of 35-45 (H-H equation)

pH = 6.1 + log (24/(40 × 0.03) → pH = 7.40◦Note pH determined by ratio of HCO3

– to dissolved CO2

Ratio of 20:1 will provide normal pH (7.40) Increased ratio results in alkalemia Decreased ratio results in acidemia

36

37

Primary respiratory disturbances◦PaCO2 is controlled by the lung,

changes in pH caused by PaCO2 are considered respiratory disturbances Hyperventilation lowers PaCO2, which

raises pH; referred to as respiratory alkalosis

Hypoventilation (PaCO2) decreases the pH; called respiratory acidosis

40

Primary metabolic disturbances◦ Involve gain or loss of fixed acids or HCO3

–

◦ Both appear as changes in HCO3– as changes in

fixed acids will alter amount of HCO3– used in

buffering

41

Fig18.12

Accumulation of nonrespiratory acids

Metabolic acidosis

Excessive loss of bases


Kidney failureto excrete acids

Excessive production of acidicketones as in diabetes mellitus

Prolonged diarrheawith loss of alkalineintestinal secretions

Prolonged vomitingwith loss of intestinalsecretions

Primary metabolic disturbances (cont.)◦ Decrease in HCO3

– results in metabolic acidosis◦ Increase in HCO3

– results in metabolic alkalosis

Compensation: Restoring pH to normal◦Any primary disturbance immediately

triggers compensatory response Any respiratory disorder will be compensated for

by kidneys (process takes hours to days) Any metabolic disorder will be compensated for

by lungs (rapid process, occurs within minutes)

42

Compensation: Restoring pH to normal (cont.)◦Respiratory acidosis (hypoventilation) Renal retention HCO3

– raises pH toward normal

◦Respiratory alkalosis Renal elimination HCO3

– lowers pH toward

normal

◦Metabolic acidosis Hyperventilation ↓CO2, raising pH toward

normal◦Metabolic alkalosis Hypoventilation ↑CO2, lowering pH toward

normal

43

45

The CO2 hydration reaction’s effect on [HCO3

–]

◦Large portion of CO2 is transported as HCO3

–

◦As CO2 increases, it also increases HCO3–

◦In general, effect is increase of ~1 mEq/L HCO3

– for every 10 mm Hg increase in PaCO2

An increase in CO2 of 30 would increase HCO3

– by ~3 mEq/L

46

To maintain a normal pH range of 7.35–7.45, the ratio of HCO3

– to dissolved CO2 should be:

a.a. 10:110:1

b.b. 15:115:1

c.c. 20:120:1

d.d. 30:130:1

c. c. 20:120:1

47

50

Respiratory acidosis (alveolar hypoventilation):◦ Any process that raises PaCO2 > 45 mm

Hg & lowers pH below 7.35 Increased PaCO2 produces more carbonic

acid◦ Causes:

Anything that results in VA that fails to eliminate CO2 equal to VCO2

. .

. .

Respiratory acidosis (cont.)

◦ Compensation is by renal Reabsorption of HCO3–

Partial compensation: pH improved but not normal Full compensation: pH restored to normal

◦ Correction (goal is to improve VA) May include:

Improved bronchial hygiene & lung expansion Non-invasive positive pressure ventilation, endotracheal

intubation & mechanical ventilation If chronic condition with renal compensation, lowering

PaCO2 may be detrimental for patient

52

. .

Respiratory alkalosis (alveolar hyperventilation):

◦ Lowers arterial PaCO2 decreases carbonic acid, thus increasing pH

◦ Causes (see Box 13-4 in Egan) Any process that increases VA so that CO2 is eliminated

at rate higher than VCO2. Most common cause is hypoxemia Anxiety, fever, pain

◦ Clinical signs: early Paresthesia; if severe, may have hyperactive reflexes, tetanic convulsions, dizziness

53

. . . .

54

Fig18.13

Hyperventilation

Respiratory alkalosis


• Anxiety• Fever

• Poisoning

• High altitude

Excessive loss of CO2

Decrease in concentration of H2CO3

Decrease in concentration of H+

55

Respiratory alkalosis (cont.)◦ Compensation is by renal excretion of HCO3

–

Partial compensation returns pH toward normal

Full compensation returns pH to high normal range

◦ Correction Involves removing stimulus for

hyperventilation i.e., hypoxemia: give oxygen therapy

Alveolar hyperventilation superimposed on compensated respiratory acidosis (chronic ventilatory failure):◦ Typical ABG for chronic ventilatory failure:

pH 7.38, PaCO2 58 mm Hg, HCO3– 33 mEq/L

Severe hypoxia stimulates increased VA, lowers PaCO2, potentially raising pH on alkalotic side i.e. pH 7.44, PaCO2 50 mm Hg, HCO3

– 33 mEq/L

Appears to be compensated metabolic acidosis Only medical history & knowledge of situation

allow correct interpretation of this ABG

57

. .

describe how the lungs and kidneys regulate volatile and fixed acids. describe how an acid’s...

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