Acid and Base Balance and

Imbalance

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 pH Review
• “pH” = latin p (potentia) and H (hydrogen)

• pH = - log [H+]
• H+ is a proton

• Range is from 0 – 14

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• If [H+] is high, the solution is acidic (pH<7)
• If [H+] is low, the solution is alkaline (pH>7) 3
• Acids are H+ donors.
• Bases are H+ acceptors (give up OH- in
solution).
• Acids and bases can be:
– Strong – dissociate completely in
solution
• HCl, NaOH
– Weak – dissociate only partially in
solution
• Lactic acid, Carbonic acid
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 The Body and pH
• Homeostasis of pH is tightly controlled
• Extracellular fluid = 7.4

• Blood = 7.35 – 7.45

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• Acidosis (acidemia) below 7.35
• Alkalosis (alkalemia) above 7.45 6
 Small changes in pH can produce
major disturbances
• Most enzymes function only with narrow
pH ranges
• Acid-base balance can also affect
electrolytes (Na+, K+, Cl-)
• Can also affect hormones

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 The body produces more acids
than bases

• Both acids and alkali are produced from

the diet
• Animal foods are high in protein → acid
load
• Plant foods are high in organic anions →
alkaline load
• Cellular metabolism produces CO2.
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 Mechanism to maintain pH

• Buffer systems

• Respiratory mechanisms

• Renal mechanisms

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10
 1. Buffer systems
1. HCO3- buffer system – the primary
ECF buffer
2. Protein buffer system – the primary
ICF buffer (also buffers ECF)
3. Phosphate buffer system

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 Bicarbonate buffer
• Sodium Bicarbonate (NaHCO3) and
carbonic acid (H2CO3)
• Maintain a 20:1 ratio : HCO3- : H2CO3

HCl + NaHCO3 ↔ H2CO3 + NaCl

NaOH + H2CO3 ↔ NaHCO3 + H2O

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 Protein Buffers
• Includes hemoglobin
• Carboxyl group gives up H+
• Amino Group accepts H+
• Side chains that can buffer H+ are present on
27 amino acids.

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 Phosphate buffer
• Intracellular buffer
• HCl + Na2HPO4 ↔ NaH2PO4 +NaCl

• NaOH + NaH2PO4 ↔ Na2HPO4 + H2O

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 2. Respiratory mechanisms
• Exhalation of carbon dioxide
• Powerful, but only works with volatile
acids
• Doesn’t affect fixed acids like lactic acid
• Body pH can be adjusted by changing rate
and depth of breathing

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 3. Kidney excretion
• Can eliminate large amounts of acid

• Can also excrete base

• Can conserve and produce bicarbonate

• Most effective regulator of pH – If kidneys

fail, pH balance fails
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 Acid–base handling along the
nephron
1. the reabsorption of filtered bicarbonate

2. regeneration of bicarbonate → H+
secretion (which will be buffered by NH3)

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Reabsorption of filtered
bicarbonate

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Mechanism of proximal
acidification

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Mechanism of proximal
acidification

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Mechanism of proximal
acidification

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Mechanism of proximal
acidification

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Mechanism of distal acidification
• compared with the proximal tubule, it has a
limited capacity to secrete H+ and thereby,
reabsorb HCO3-
• however, is able to generate a large
transepithelial pH gradient (urine pH<5
with blood pH approximately 7.4)
• several distinct morphologic and functional
segments (the DCT, the connecting segment, and
several distinct collecting duct segments, each with
several cell types).
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 Mechanism of distal acidification
• The intercalated cells are chiefly responsible
for acid-base transport.

• There are at least three types of ICs:

• type A IC – secrete H+;
• type B IC – secrete HCO3-;
• non–A, non–B IC, with a range of function that
remains under investigation.

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Mechanism of distal acidification
LUMEN BLOOD

H20+CO2

H++HCO3
-

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 Role of buffer in distal nephron
acidification

• NH3/NH4+ system prevents extreme luminal

acidity;
• Of the net acid excreted by the kidneys, ½
to ⅔ (≈40–50 mmol/d) is because of NH4+
excretion in the urine.
• Stimulated by metabolic acidosis,
hypokalemia, glucocorticoid hormones,
protein intake
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 Role of buffer in distal nephron
acidification

• NH3/NH4+ system prevents extreme luminal

acidity;
• Of the net acid excreted by the kidneys, ½
to ⅔ (≈40–50 mmol/d) is because of NH4+
excretion in the urine.
• Stimulated by metabolic acidosis,
hypokalemia, glucocorticoid hormones,
protein intake
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Distal nephron alkali secretion
LUMEN BLOOD

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 Rates of correction
• Buffers function almost instantaneously

• Respiratory mechanisms take several

minutes to hours

• Renal mechanisms may take several

hours to days

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 Acid-Base Imbalances
• pH < 7.35 acidosis
• pH > 7.45 alkalosis

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 Acid-Base Imbalances
• pH < 7.35 acidosis
• pH > 7.45 alkalosis

• PCO2 > 45 mmHg (respiratory acidosis)

• PCO2 < 35 mmHg (respiratory alkalosis)

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 Acid-Base Imbalances
• pH < 7.35 acidosis
• pH > 7.45 alkalosis

• PCO2 > 45 mmHg (respiratory acidosis)

• PCO2 < 35 mmHg (respiratory alkalosis)

• HCO3- < 22 mmol/L (metabolic acidosis)

• HCO3- > 26 mmol/L (metabolic alkalosis)
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 Acid-Base Imbalances
• The body response to acid-base
imbalance is called compensation

• May be complete if brought back within

normal limits

• Partial compensation if range is still

outside norms.
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 Acid-Base Imbalances
• The body response to acid-base
imbalance is called compensation

• May be complete if brought back within

normal limits

• Partial compensation if range is still

outside norms.
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 Compensation
• If underlying problem is metabolic,
hyperventilation or hypoventilation can
help : respiratory compensation.

• If underlying problem is respiratory, renal

mechanisms can bring about metabolic
compensation.

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Compensation

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 Acidosis
• Principal effect of acidosis is depression of
the CNS through ↓ in synaptic transmission.
• Generalized weakness
• Deranged CNS function the greatest threat
• Severe acidosis causes
– Disorientation
– Coma
– Death

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 Alkalosis
• Alkalosis causes over excitability of the
central and peripheral nervous systems.
• Numbness
• Lightheadedness
• It can cause :
– Nervousness
– Muscle spasms or tetany
– Convulsions
– Loss of consciousness
– Death

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 Respiratory Acidosis
• Carbonic acid excess caused by blood
levels of pCO2 above 45 mm Hg.
• Hypercapnia – high levels of CO2 in blood
• Chronic conditions:
– Depression of respiratory center in brain that
controls breathing rate – drugs or head
trauma
– Paralysis of respiratory or chest muscles
– Emphysema/COPD

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 Respiratory Acidosis
• Acute conditons:
– Adult Respiratory Distress Syndrome
– Pulmonary edema
– Pneumothorax

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 Compensation for Respiratory
Acidosis
• Kidneys eliminate hydrogen ion and retain
bicarbonate ion

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 Treatment of Respiratory Acidosis
• Restore ventilation
• Treat underlying dysfunction or disease

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 Respiratory Alkalosis
• Carbonic acid deficit
• pCO2 less than 35 mm Hg (hypocapnea)
• Most common acid-base imbalance
• Primary cause is hyperventilation

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 Respiratory Alkalosis
• Conditions that stimulate respiratory
center:
– Oxygen deficiency at high altitudes
– Acute anxiety
– Fever, anemia
– Early salicylate intoxication
– Cirrhosis
– Gram-negative sepsis

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 Compensation of Respiratory
Alkalosis
• Kidneys conserve hydrogen ion
• Excrete bicarbonate ion

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Treatment of Respiratory Alkalosis
• Treat underlying cause
• Breathe into a paper bag
• IV Chloride containing solution – Cl- ions
replace bicarbonate ions

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 Metabolic Acidosis
• Bicarbonate deficit - blood concentrations of
bicarbonate drop below 22 mEq/L
• Causes:
– Loss of bicarbonate through diarrhea or renal
dysfunction
– Accumulation of acids (lactic acid or ketones)
– Failure of kidneys to excrete H+

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Breathing abnormalities

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 Metabolic Acidosis
• Anion Gap
AG = Na+ - (Cl- + HCO3-) = 10 ± 2 mEq/L

• represents the unmeasured anions normally

present in serum: albumin, PO43-, SO42-, and
organic anions

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 Metabolic Acidosis
• Anion Gap
AG = Na+ - (Cl- + HCO3-) = 10 ± 2 mEq/L

• represents the unmeasured anions normally

present in serum: albumin, PO43-, SO42-, and
organic anions

• ↓ 1g/dL in the albumin → ↓ 2.5 mEq/L in the AG

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Metabolic Acidosis

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Metabolic Acidosis

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 Hyperchloremic Metabolic
Acidosis
• Urinary Anion Gap
UAG = (UNa + UK) – Ucl
• indirectly estimate the urinary NH4+ excretion

• Nonrenal origin: the kidneys ↑ NH4+ → ↑ Cl- →

negative UAG

• Renal origin: ↓ NH4+ → ↓ Cl- → positive UAG

(renal tubular acidosis) 54
 Proximal RTA (Type II)
• reduced ability of the proximal tubule to
reclaim filtered HCO3-
• Self-limited disorder (certain “threshold“ - HCO3-
wasting ceases → urine pH<5.5)
• Serum HCO3- – 14 to 20 mEq/L
• Serum K – low (activation of the RAAS)

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 Proximal RTA (Type II)
• Fanconi Syndrome (impaired reabsorbtion of
glucose, phosphate, uric acid) → MM!!!

• Treatment – difficult
• NO HCO3-
• Potassium-sparing diuretics

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 Proximal RTA (Type II)
• Fanconi Syndrome (impaired reabsorbtion of
glucose, phosphate, uric acid) → MM!!!

• Treatment – difficult
• NO HCO3-
• Potassium-sparing diuretics

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 Hypokalemic distal RTA (Type I)
• reduced ability of the distal tubule to secrete
H+
• Inability to lower urine pH maximally (>5.5)
• Serum HCO3- < 15 mEq/L
• Serum K – low (activation of the RAAS)

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 Hypokalemic distal RTA (Type I)
• Idiopathic/Secondary (autoimmune disorders:
Sjogren, SLE; renal transplantation)
• Frequently associated with nephrolithiasis or
nephrocalcinosis (reduce Ca2+ reabsorbtion in
the presence of alkaline pH)

• Treatment
• Potassium citrate
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 Hypokalemic distal RTA (Type I)
• Idiopathic/Secondary (autoimmune disorders:
Sjogren, SLE; renal transplantation)
• Frequently associated with nephrolithiasis or
nephrocalcinosis (reduce Ca2+ reabsorbtion in
the presence of alkaline pH)

• Treatment
• Potassium citrate
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 Hyperkalemic distal RTA (Type IV)
• reduced ability of the distal tubule to secrete
both H+ and K+
• Urine pH (<5.5 or >5.5)
• Serum HCO3- = 18-22 mEq/L
• Serum K – 5.5-6.5 mEq/L

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 Hyperkalemic distal RTA (Type IV)
1. Deficiency in circulating aldosterone (Diabetes,
Adrenal destruction, NSAID, Cyclosporine, ACEI and
ARAII).
2. Disease of the cortical collecting duct
(Absent/Defective mineralocorticoid receptor,
Spironolactone, trimethoprim, chronic
tubulointerstitial disease)

• Treatment
• Usually not necessary
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• Sodium bicarbonate
 Hyperkalemic distal RTA (Type IV)
1. Deficiency in circulating aldosterone (Diabetes,
Adrenal destruction, NSAID, Cyclosporine, ACEI and
ARAII).
2. Disease of the cortical collecting duct
(Absent/Defective mineralocorticoid receptor,
Spironolactone, trimethoprim, chronic
tubulointerstitial disease)

• Treatment
• Usually not necessary
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• Sodium bicarbonate
 Metabolic Alkalosis
• Bicarbonate excess - concentration in
blood is greater than 26 mEq/L
• Causes:
• either retention or exogenous
administration of HCO3-, or
• net acid loss from the kidney or GI
tract must occur.

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 Metabolic Alkalosis
Chloride Responsive
Urine Cl- < 20 mEq/L
Causes
• Volume Contraction:
– Nasogastric suctioning, Gastric fistula
– Vomiting , pyloric stenosis
• Post Hypercapnia
• Low chloride intake
• Hypomagnesemia
• Penicillin
• Cystic fibrosis (sweat)
• Alkali therapy (NaHCO3, Antacid abuse)
• Chloride depletion (Diarrhoea & Diuretics)
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 Metabolic Alkalosis
Chloride Unresponsive
Urine Cl- > 20 mEq/L
Causes
• Mineralcorticoid excess (Hyperaldosteronism)
• Exogenous steroids, Cushing’s disease
• Tobacco chewers
• Bartter’s Syndrome

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 Treatment of Metabolic Alkalosis
• Electrolytes to replace those lost
• Treat underlying disorder
• IV chloride containing solution e.g saline
(Chloride Responsive)
• Aldosterone antagonist (Chloride resistant)

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Clinical approach

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 Clinical approach
1. Blood pH – determine the primary
disorder
2. HCO3-, pCO2 – primary mechanism

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Acid Base Disorder Initial Chemical Change Compensatory
Response

Respiratory Acidosis
↑ PCO2 ↑HCO3-
Respiratory Alkalosis
↓ PCO2 ↓ HCO3-
Metabolic Acidosis
↓ HCO3- ↓ PCO2
Metabolic Alkalosis
↑ HCO3- ↑ PCO2
 Clinical approach
1. Blood pH – determine the primary
disorder
2. HCO3-, pCO2 – primary mechanism
3. Determine the compensatory response

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Compensation

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 Clinical approach
1. Blood pH – determine the primary
disorder
2. HCO3-, pCO2 – primary mechanism
3. Determine the compensatory response
4. Determine the anion gap (metabolic
acidosis)

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 Case 1
A 30-year-old female presents to the
emergency room with mental status
changes and with smell of alcohol in her
breath.

Na+=138 pH=7.34
K+=3.8 pCO2=28
Cl-=104 pO2=99
HCO3-=13
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 Case 1
1. pH = 7.34 → acidosis

2. HCO3-=13, pCO2=28 → metabolic

3. Estimated pCO2 = 26-30 → compensated

4. AG = 138-(104+13) = 21 → high

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 Case 1
1. pH = 7.34 → acidosis

2. HCO3-=13, pCO2=28 → metabolic

Compensated high anion gap
3. Estimatedmetabolic → compensated
acidosis
pCO2 = 26-30

4. AG = 138-(104+13) = 21 → high

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 Case 2
A 25-year-old female presents with peri-oral
paresthesias and dental erosions

Na+=140 pH=7.50
K+=5 pCO2=51
Cl-=91
HCO3-=40 urinary Cl-=8 mEq/L

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 Case 2
1. pH = 7.50 → alkalosis

2. HCO3-=40, pCO2=51 → metabolic

3. Estimated pCO2 = 0.7 ↑ in pCO2 for

every 1 mEq ↑ in HCO3-

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 Case 2
1. pH = 7.50 → alkalosis

2. HCO3-=40, pCO2=51 → metabolic

3. Estimated pCO2 = 0.7 x 16 = 11 (40+11)

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 Case 2
1. pH = 7.50 → alkalosis

2. HCO3-=40, pCO2=51 → metabolic

3. Estimated pCO2 = 51 → compensated

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 Case 2
1. pH = 7.50 → alkalosis

2. HCO3-=40, pCO2=51 → metabolic

3. Estimated pCO2 = 51 → compensated

4. Cl- responsive vs. Cl- resistant metabolic

alkalosis?
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 Case 2
1. pH = 7.50 → alkalosis

2. HCO3-=40, pCO2=51 → metabolic

3. Estimated pCO2 = 51 → compensated

4. urinary Cl-=8 mEq/L

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 Case 2
1. pH = 7.50 → alkalosis

2. HCO3-=40, pCO2=51 → metabolic

3. Estimated pCO2 = 51 → compensated

4. urinary Cl-=8 mEq/L → Cl- responsive

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 Case 2
1. pH = 7.50 → alkalosis

2. HCO3-=40, pCO2=51 → metabolic

Compensated chloride responsive
metabolic
3. Estimated pCO2 → compensated
= 51alkalosis

4. urinary Cl-=8 mEq/L → Cl- responsive

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 Case 3
60-year-old male with hypertension,
diabetes and coronary artery disease,
develops dyspnea and profound weakness
with cyanosis.

Na+=134 pH=7.20
K+=4.4 pCO2=52
Cl-=80 pO2=40
HCO3-=20
Glucose=245 urine ketones 3+ 85
 Case 3
1. pH = 7.20 → acidosis

2. HCO3-=20, pCO2=52 → both!!!

3. AG = 138-(80+20) = 34 → high

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 Case 3
1. pH = 7.20 → acidosis

2. HCO3-=20,Respiratory
pCO2=52 → acidosis
both!!! and
high anion gap
metabolic acidosis
3. AG = 138-(80+20) = 34 → high

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