Patholphysiology of Acid base Balance Altered by respiratory compensation for metabolic disorders...

31
Patholphysiology of Acid base Balance Altered by respiratory compensation for metabolic disorders Primarily altered in metabolic disorders Altered by bufferi ng Altered by renal compensation for respiratory disorders pH = pK a + + log [ HCO 3 - ] α pCO 2 Metaboli c componen t Respirator y component Primarily altered in respiratory disorders The result of the interplay between metabolic and respiratory components 1H + 3 000 000 Na + EC:

Transcript of Patholphysiology of Acid base Balance Altered by respiratory compensation for metabolic disorders...

Page 1: Patholphysiology of Acid base Balance Altered by respiratory compensation for metabolic disorders Primarily altered in metabolic disorders Altered by buffering.

Patholphysiology of Acid base Balance

Altered by respiratory compensation for metabolic disorders

Primarily altered in metabolic disorders

Altered by buffering

Altered by renal compensation for respiratory disorders

pH = pKa+ + log

[ HCO3- ]

α pCO2

Metabolic component

Respiratory component

Primarily altered in respiratory disorders

The result of the interplay between metabolic and respiratory components

1H+

3 000 000 Na+EC:

Page 2: Patholphysiology of Acid base Balance Altered by respiratory compensation for metabolic disorders Primarily altered in metabolic disorders Altered by buffering.

Buffering of Strong Acid added to Extracellular Fluid

Compartment Contribution Time course

Physochemical buffering

Extracellular fluid

Cells

Bone and connective tissue

Physiological regulation

40%

50%

10%

PCO2

HCO-

3

Instantaneous

Rapid

Slow

Min

Hrs/days

Extracellular pH

40

80

120

160

200

240

Cel

lula

r (H

+)

nmol

/l

7.77.4

7.1

6.9

6.7

Cel

lula

r pH

0 40 120 200

(H+) nmol/l

7.4 7.1 6.9 6.7

80

Respiratory

Renal

Page 3: Patholphysiology of Acid base Balance Altered by respiratory compensation for metabolic disorders Primarily altered in metabolic disorders Altered by buffering.

Cell functions depending on regional pH

Plasma membrane function

- Passive permeability to cations and anions

- Active transport processes

- Hormon receptor functions

- Cell shape, motility and excitability

- Endo- and exocytosis

Mitocondrial function

- Energy storage

- ATP generation

- Ammoniagenesis

- Other enzyme activities

Cytoplasmic function

- Glycolysis

- Glyconeogenesis

- Cyclic nucleotid function

- Function of actin and myosin

- Cytoskeleton function

- O2 affinity of hemoglobin

Function of other organelles

Page 4: Patholphysiology of Acid base Balance Altered by respiratory compensation for metabolic disorders Primarily altered in metabolic disorders Altered by buffering.

Metabolic Acidosis

Acid excess Base loss

Exogen acids: -HCl (fe. arginin chlorid, NH4Cl )

-H2SO4 ( fe. Methionin)

Incomplete fat oxidation:

-diabetes mellitus (ketoacid) -starvation -alcoholic ketoacidosis

Incomplete carbohydrate oxidation: (lactic acidosis)

-shock, diabetes -cirrhosis -leukemia

Failure of acid excretion: ARF, CRF

Ingestion of toxic substances: - salicylate overdose, - methanol, ethylene glycol

Gastrointestinal loss of HCO-

3

- diarrhea

- small- bowel or pancreatic fistula, drainage

- ureterosigmoidostomy

- anion exchange resins

Renal loss of HCO-

3

- carbonic anhydrase

inhibitors

- renal tubular acidosis (RTA)

- hyperparathyroidism

- hypoaldosteronism

Page 5: Patholphysiology of Acid base Balance Altered by respiratory compensation for metabolic disorders Primarily altered in metabolic disorders Altered by buffering.

Metabolic acidosis

Buffering

EC IC Bone

Compensation

Lung: hyperventillation

pCO2 = 1,0 1,5* (HCO-

3)

(CO2 =34-31 mmHg 18mmol HCO-

3)

Kidney: total acid excretion =

UNH4 *V+ UTA *V U HCO-3*V

1mmol/kg/day max. ca. 600 mmol/kg/day

Page 6: Patholphysiology of Acid base Balance Altered by respiratory compensation for metabolic disorders Primarily altered in metabolic disorders Altered by buffering.

Laboratory of Metabolic Acidosis

pH , HCO-3 , pCO2 Se-K (ICK ECK: total – K )

Anion gap = Na+ + K+- Cl- - HCO-3 norm: 12-20 mmol/l

Na++ K++ Ca++ + Mg++ = Cl-+ HCO-3+ PO=/-

4 + organic anions +

protein + SO- -4

Non measured anions

(~ // mmol/l – albumin)

AG : (strong acids buffering HCO3 other anions ) Increased acid formation

-diabetic ketoacidosis-alcoholic lactic acidosis

Toxic materials -salycilate -methanol -ethylen glycol

AG : (HCO-3 Cl- - reabsorption hypercloremia):

Gastrointertinal loss: Renal loss -diarrhea etc. - Carbonic anhydrase inhibitors - pancreatic fistula - Renal tubular acidosis (RTA)

- Hyperparathyroidism - Hyperaldosteronism

Acid excretion

-ARF, CRF

~ Ø

Page 7: Patholphysiology of Acid base Balance Altered by respiratory compensation for metabolic disorders Primarily altered in metabolic disorders Altered by buffering.

Failure of Acid Excretion in Renal Disease

Bone buffering

Daily acid load

Buffering by ECF and

intracellular buffers

Diseased kidney

Nephron population

Solute and water load per

nephron

Filtered phosphate

Proximal HCO3

- reabsorption per nephron

Ability to maintain or

increase NH3 secretion

Urinary buffer

(phosphate)

Distal HCO3-

delivery

Plasma HCO3

- concentration

Urinary HCO3

- leak

Complete HCO3

- reabsorption

Acid urine

NH4 excretion

Titratable acid

excretion relative to degree of acidosis

Net acid excretion

Page 8: Patholphysiology of Acid base Balance Altered by respiratory compensation for metabolic disorders Primarily altered in metabolic disorders Altered by buffering.

Respiratory response to metabolic acidosis. The increase in (H+) produced by metabolic acidosis is sensed by chemoreceptors in the brainstem and ventilation is stimulated, reducing PCO2. Altough no units are shown on the time axis, this response is fully manifest in 1 to 3 hours, and the reduction in PCO2 induced is sustained until the bicarbonate deficit is repaired. During the recovery process, a similar delay occurs between correction of the acidosis and restoration of normal ventilation, resulting in a transient period of alkalemia.

Page 9: Patholphysiology of Acid base Balance Altered by respiratory compensation for metabolic disorders Primarily altered in metabolic disorders Altered by buffering.

Causes of Lactic Acidosis

Clinically characterised by decrease in tissue oxigenation

Cardiogenic shock

Hypovolemic shock

Septic shock

Hypoxemia (O2 < 35mmHg)

Anemia

No clinical sign of decreased tissue oxigenation

Systemic disorders or conditions

-diabetes mellitus

-liver failure

-sepsis

-malignancy

-pregnancy

Intoxication

-Ethanol

-Etlylenglycol

-Strychnine

Muscular hyperactivity

-seizures

-marathon running

ATP NADH

lactate

mortality

If > 4 mmol /l

Venous constriction

Arteriolar dilatation

Myocordial

contraction

Congrestive

Heart failure

(pH7.10-7.20)

Page 10: Patholphysiology of Acid base Balance Altered by respiratory compensation for metabolic disorders Primarily altered in metabolic disorders Altered by buffering.

Increased lactic acid production

Generation of HCO3

-

Lactic Acidosis

Decreased lactate metabolism

anion gap H+ + lactate

HCO3-

Renal NH3 production

Distal nephron anion (lactate)

delivery ECF volume

Difference in lumen negative potential

Buffering (ECF + ICF)

pH

Ventilation

Distal nephron delivery of lactate(if plasma lactate > 7 to 8 mmol/l)

Na+ lacate- excretion

Distal nephron Na+ avidity

Renal H+ secretion

Renal TA excretion

Renal NH4+

excretion

Generation of HCO3

-

pCO2

Rise in pH toward normal

Page 11: Patholphysiology of Acid base Balance Altered by respiratory compensation for metabolic disorders Primarily altered in metabolic disorders Altered by buffering.

Distal Proximal

Hypokalemic or normokalemic- Primary- Hypercalcemia- Nephrocalcinosis- Multiple myeloma- Hepatic cirrhosis- Lupus erythematosus- Amphotericin B- Lithium- Toluene- Renal transplant rejection- Medullary sponge kidney

Hyperkalemic- Hypoaldosteronism- Obstructive nephropathy- Sickle cell nephropathy- Lupus erythematosus

PrimaryCystinosisWilson’s diseaseLead toxicityCadmium toxicityMercury toxicityAmyloidosisMultiple myelomaNephrotic syndromeEarly renal transplant injuryMedullary cystic diseaseOutdated tetracycline

Causes of Renal Tubular Acidosis

Page 12: Patholphysiology of Acid base Balance Altered by respiratory compensation for metabolic disorders Primarily altered in metabolic disorders Altered by buffering.

Proximal Tubular Acidosis

Proximal tubules: HCO-3 reabsorption distal HCO-

3 load

(norm: 85%)

urine HCO-3 hypercloremic metabolic alkalosis

urine : Na+ , K+ , H2O

Hyponatremia, hypokalemia, hypovolemia

Page 13: Patholphysiology of Acid base Balance Altered by respiratory compensation for metabolic disorders Primarily altered in metabolic disorders Altered by buffering.

HC

O- 3 R

eabs

orpt

ion

(meq

/L

GF

R)

15

20

25

COMPLETE REABSORPTION

NORMAL

PROXIMAL ( Type II) RTA

15 20 25

TR

ESH

OL

D

Plasma

(HCO-3) (meq/L)

Filtered load

Proximal reabsorption

Distal delivery

Distal reabsorption

Urinary excretion

pH 5.5 pH 6.5 pH 7.8

60%

15%

Norm:

„6” „8” „10”

~ 80%: ~ 20

15%: ~ 4-6

„4 ~ 6”

Bicarbonate titration curve and segmental nephron deliver and absorption in proximal (type II) RTA

Page 14: Patholphysiology of Acid base Balance Altered by respiratory compensation for metabolic disorders Primarily altered in metabolic disorders Altered by buffering.

Proximal RTA (type II): hypokalemic, hyperchloremic metabolic acidosis (in acidosis: net acid excretion = acid generated)

2

8

6

K+

Na+

HCO3- H2CO3 CO2

HCO3-

H2O

CAIV

H+

CO2

OH-

CAIII

3

41

5

ADP

7 Pi

ATPADPPi

Pathophysiology of proximal (type II) RTA. The possible causes of abnormal proximal acidification include defects in the luminal Na+-H+ antiporter (1); the basolateral Na+-HCO3

- symporter (2); the intracellular (3) or luminal (4) carbonic anhydrases (CA); sodium permeability (5); the Na-K ATPase (6); the intracellular generation of ATP (7); or membrane recycling, metabolism, or trafficking (8).

LUMEN

PROXIMAL TUBULE CELL

BLOOD

Page 15: Patholphysiology of Acid base Balance Altered by respiratory compensation for metabolic disorders Primarily altered in metabolic disorders Altered by buffering.

Defect Mechanism Example

Gradient or backleak

Secretory

Voltage-dependent

Rate-dependent

Hypoaldosteronism

Amphotericin B

Classic distal RTA

Amiloride, obstructive nephropathy, sickle cell disease

Interstitial nephropathy

Hyporeninemic hypoaldosteronism

Pathophysiologic Mechanisms of Distal Renal Tubular Acidosis

Inability to achieve or maintain a low urine pH due to backleak of H+ or H2CO3

Decrease in both force and rate (conductance) of the H+ pump system; acidification impaired under all conditions

Failure to maintain a negative potential difference in the collecting duct lumen due to decreased sodium reabsorption

Decreased rate of H+ secretion, but intact ability to achieve a low pH with an acid load (force intact)

Probably a combination of voltage-dependent and rate-dependent defects and decreased ammonia production

Page 16: Patholphysiology of Acid base Balance Altered by respiratory compensation for metabolic disorders Primarily altered in metabolic disorders Altered by buffering.

Classical Distal RTA (type I): hypokalemic, hyperchloremic metabolic acidosis (in urine: inappropriate acidification)

Pathophysiology of classical distal (type I) RTA. The possible causes of abnormal intercalated cell acidification in the distal nephron include defects in the luminal proton-translocating ATPase (1), the basolateral HCO3

-Cl- antiporter (2), or luminal hydrogen ion permeability (3). TA, titratable acid; CA, carbonic anhydrase.

H2PO4- (TA)

LUMEN

H+

1

HPO4

NH3 NH4+

3

ATP Pi

ADP

H2ODISTAL TUBULE

BLOOD

OH-

CO2CA

HCO

3-

2

Cl-

Page 17: Patholphysiology of Acid base Balance Altered by respiratory compensation for metabolic disorders Primarily altered in metabolic disorders Altered by buffering.

Metabolic alkalosis

Netto H+ loss

(vomiting hyperaldosteronism)

Netto HCO-3

increase

(milk-alkali syndrome, baking powder)

Cl- loss>HCO-3 loss

(diureticum)

Buffering ( IC+EC)

HCO3+ + H+ CO2+H2O

Compensation

Pulmonary : hypoventillation

Max. pCO2 ~ 60 mmHg

ΔpCO2=0.25-1.0 * Δ HCO-3

(Fe: pCO2 43-50 mmHg 34mmol/l (HCO-3)

Kidney: HCO3- secretion

Maintaining factors:

1. Hypocloremia prox. tub. HCO-

3 – reabs.

2. Hypokalemia „paradox aciduria”

3. Hypovolemia

4. Hyperaldosteronism

Page 18: Patholphysiology of Acid base Balance Altered by respiratory compensation for metabolic disorders Primarily altered in metabolic disorders Altered by buffering.

WATER POTASSIUM

NASOGASTRIC SUCTION

REMOVAL OF

HYDROGEN ION

PLASMA HCO3- pH

SODIUM CHLORIDE

ECF VOLUME

PLASMA AND FILTERED Cl-

H+ SHIFTSINTO ECFK+ SHIFTSINTO CELLS

HYPOKALEMIA

FILTERED HCO3- HYPOVENTILATION

PaCO2

ALDOSTERONE

K+ EXCRETION

HCO3- ” REABSORPTION”

MAINTENANCE OF METABOLIC ALKALOSIS

Metabolic alkalosis

Page 19: Patholphysiology of Acid base Balance Altered by respiratory compensation for metabolic disorders Primarily altered in metabolic disorders Altered by buffering.

NaCl-sensitive metabolic alkalosis(f.e.: vomiting)

ECV

HCO3- reabsorption

Low [Cl-]

NaCl Na+ reabsorption

Urine Cl-

< 10 mmol/l

Alkalosis

+

(priority of volumen regulation over the pH)

Page 20: Patholphysiology of Acid base Balance Altered by respiratory compensation for metabolic disorders Primarily altered in metabolic disorders Altered by buffering.

NaCl resistant metabolic alkalosis(f.e.: glycocorticoid therapy)

ECV

H+, K+ excretion HCO3

- reabsorption

Diastalis Na+ reabsorption

NaCl Proximalis NaCl reabsorption

Alkalosis

Page 21: Patholphysiology of Acid base Balance Altered by respiratory compensation for metabolic disorders Primarily altered in metabolic disorders Altered by buffering.

Differential Diagnosis of Metabolic Alkalosis

Sodium chloride-responsive (UCl- <10 mmoles/L)

Gastrointestinal disordersVomitingGastric drainageVillous adenoma of the colonChloride diarrhea

Diuretic therapy Correction of chronic hypercapnia Cystic fibrosisSodium chloride-resistant (UCl

- < 20 mmoles/L) Excess mineralocorticoid activity

HyperaldosteronismCushing’s syndromeBartter’s syndromeExcessive licorice intake

Profound potassium depletionUnclassified Alkali administration Recovery from organic acidosis Antacids and exchange resins in renal failure Milk-alkali syndrome Massive blood or Plasmanate transfusion Nonparathyroid hypercalcemia Glucose ingestion after starvation Large doses of carbenicillin or penicillin

Page 22: Patholphysiology of Acid base Balance Altered by respiratory compensation for metabolic disorders Primarily altered in metabolic disorders Altered by buffering.

Causes of Acute Respiratory Acidosis

Neuromuscular abnormalitiesBrain stem injuryHigh cord injuryGuillain-Barré syndromeMyasthenia gravisBotulismNarcotic, sedative, or tranquilizer overdose

Airway obstructionForeign bodyAspiration of vomitusLaryngeal edemaSevere bronchospasm

Thoracic-pulmonary disordersFlail chestPneumothoraxSevere pneumoniaSmoke inhalationSevere pulmonary edema

Vascular diseaseMassive pulmonary embolism

Respirator-controlled ventilationInadequate frequency, tidal volume settingsLarge dead spaceTotal parenteral nutrition (increased CO2 production)

Page 23: Patholphysiology of Acid base Balance Altered by respiratory compensation for metabolic disorders Primarily altered in metabolic disorders Altered by buffering.

pCO2 ; pH ; pO2 ; act. HCO3 ; st. HCO3

[HCO3-] = (pCO2/10)3

(f.e.: [HCO3-] 24-30 mmol/l pCO2 70 mmHg (12-24 ))

Acute Respiratory Acidosis

Page 24: Patholphysiology of Acid base Balance Altered by respiratory compensation for metabolic disorders Primarily altered in metabolic disorders Altered by buffering.

Causes of Chronic Respiratory Acidosis

Neuromuscular abnormalitiesChronic narcotic or sedative ingestion Primary hypoventilationPickwickian syndromePoliomyelitisDiaphragmatic paralysis

Thoracic-pulmonary disordersChronic obstructive airway diseaseKyphoscoliosisEnd-stage interstitial pulmonary disease

pCO2 ; pH ; pO2 ; act. HCO3 ; st. HCO3-

[HCO3] = 4x pCO2/10 4

(f.e.: [HCO3] 32-40 mmol/l pCO2 70 mmHg)

Laboratory

Page 25: Patholphysiology of Acid base Balance Altered by respiratory compensation for metabolic disorders Primarily altered in metabolic disorders Altered by buffering.

H2CO3 AND pH

Respiratory acidosis

EFFECTIVE ALVEOLAR VENTILATION

CO2 EXCRETION

PaCO2

RENAL H+ SECRETION

NH4 EXCRETION BALANCED BYCl- EXCRETION

INTRACELLULAR BUFFERS CONSUME H+

NET ACID EXCRETION

HCO3 –

RECLAMATION AND GENERATION

PLASMA HCO

CONCENTRATION

APPROPRIATELY DEFENDED CHRONIC

RESPIRATORY ACIDOSIS

Page 26: Patholphysiology of Acid base Balance Altered by respiratory compensation for metabolic disorders Primarily altered in metabolic disorders Altered by buffering.

Figure: Schematic time course of the changes in plasma acid-base equilibrium during the development of respiratory acidosis.

Page 27: Patholphysiology of Acid base Balance Altered by respiratory compensation for metabolic disorders Primarily altered in metabolic disorders Altered by buffering.

Causes of Respiratory Alkalosis

Central stimulation of respirationAnxietyHead traumaBrain tumors or vascular accidentsSalicylatesFeverPainPregnancy

Peripheral stimulation of respirationPulmonary emboliCongestive heart failureInterstitial lung diseasesPneumonia„Stiff lungs” without hypoxemiaAltitude

UncertainHepatic insufficiencyGram-negative septicemia

Mechanical or voluntary hyperventilation

Page 28: Patholphysiology of Acid base Balance Altered by respiratory compensation for metabolic disorders Primarily altered in metabolic disorders Altered by buffering.

(f.e.: [HCO3 -] 23-21 mmHg pCO2 30 mmHg)

Acute:

[HCO3 -] = 1-3x (pCO2/10)

Chronic:

[HCO3 -] = 2-5x (pCO2/10)

(f.e.: [HCO3 -] 22-19 mmHg pCO2 30 mmHg)

Respiratory Alkalosis

Page 29: Patholphysiology of Acid base Balance Altered by respiratory compensation for metabolic disorders Primarily altered in metabolic disorders Altered by buffering.

ECF pH

HCO3 RECLAMATION

Acute respiratory alkalosis

[HCO3-]= 1-3x (pCO2/10)

(f.e.: pCO2: 30 mmHg [HCO3-]: 23-21 mmol/l)

Respiratory alkalosis

ALVEOLAR VENTILATION

CO2 EXCRETION

PaCO2

RENAL H+ SECRETION

NH4 EXCRETION TA EXCRETION

INTRACELLULAR BUFFERS ADD H+ TO ECF

BICARBONATURIA

NET ACID EXCRETION

Na+ K+ EXCRETION

PLASMA HCO3 -

CONCENTRATION Chronic respiratory alkalosis

[HCO3-]= 2-5x (pCO2/10)

(f.e.: pCO2: 30 mmHg [HCO3-]: 22-19 mmol/l)

Page 30: Patholphysiology of Acid base Balance Altered by respiratory compensation for metabolic disorders Primarily altered in metabolic disorders Altered by buffering.

Mixed Acid-Base Disorders

Disorders Compensation pH

Type 1: Failure of compensation

PaCO2 too high and [HCO3

-] too low for simple disorders

Metabolic acidosis and respiratory alkalosis

Metabolic alkalosis and respiratory alkalosis

PaCO2 too low and [HCO3

-] too high for simple disorders

Type 2: Excessive compensation

Metabolic acidosis and respiratory alkalosis

PaCO2 too low and [HCO3

-] too low for simple disorders

Normal or slightly or

PaCO2 too high and [HCO3

-] too high for simple disorders

Metabolic alkalosis and respiratory alkalosis

Normal or slightly or

Page 31: Patholphysiology of Acid base Balance Altered by respiratory compensation for metabolic disorders Primarily altered in metabolic disorders Altered by buffering.

Clinical event

Acid-base disorder

pH

PaCO2 (mm Hg)

[HCO3-] (mmoles/l)

Anion gap (mEq/L)

Vomiting

Metabolicalkalosis

7.53

44

36

14

Example of a Triple Acid-Base Disorder

Hypovolemicshock

Metabolicacidosis

7.35

30

16

32

Hyperventilation

Respiratoryalkalosis

7.46

20

14

34