Acid and Base Balance and
Imbalance
1
pH Review
• “pH” = latin p (potentia) and H (hydrogen)
• pH = - log [H+]
• H+ is a proton
• Range is from 0 – 14
2
• 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
4
The Body and pH
• Homeostasis of pH is tightly controlled
• Extracellular fluid = 7.4
• Blood = 7.35 – 7.45
5
• 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
7
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.
8
Mechanism to maintain pH
• Buffer systems
• Respiratory mechanisms
• Renal mechanisms
9
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
11
Bicarbonate buffer
• Sodium Bicarbonate (NaHCO3) and
carbonic acid (H2CO3)
• Maintain a 20:1 ratio : HCO3- : H2CO3
HCl + NaHCO3 ↔ H2CO3 + NaCl
NaOH + H2CO3 ↔ NaHCO3 + H2O
12
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.
13
Phosphate buffer
• Intracellular buffer
• HCl + Na2HPO4 ↔ NaH2PO4 +NaCl
• NaOH + NaH2PO4 ↔ Na2HPO4 + H2O
14
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
15
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
16
Acid–base handling along the
nephron
1. the reabsorption of filtered bicarbonate
2. regeneration of bicarbonate → H+
secretion (which will be buffered by NH3)
17
Reabsorption of filtered
bicarbonate
18
Mechanism of proximal
acidification
19
Mechanism of proximal
acidification
20
Mechanism of proximal
acidification
21
Mechanism of proximal
acidification
22
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).
23
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.
24
Mechanism of distal acidification
LUMEN BLOOD
H20+CO2
H++HCO3
-
25
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
26
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
27
Distal nephron alkali secretion
LUMEN BLOOD
28
Rates of correction
• Buffers function almost instantaneously
• Respiratory mechanisms take several
minutes to hours
• Renal mechanisms may take several
hours to days
29
Acid-Base Imbalances
• pH < 7.35 acidosis
• pH > 7.45 alkalosis
31
Acid-Base Imbalances
• pH < 7.35 acidosis
• pH > 7.45 alkalosis
• PCO2 > 45 mmHg (respiratory acidosis)
• PCO2 < 35 mmHg (respiratory alkalosis)
32
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)
33
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.
34
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.
35
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.
36
Compensation
37
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
38
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
39
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
40
Respiratory Acidosis
• Acute conditons:
– Adult Respiratory Distress Syndrome
– Pulmonary edema
– Pneumothorax
41
Compensation for Respiratory
Acidosis
• Kidneys eliminate hydrogen ion and retain
bicarbonate ion
42
Treatment of Respiratory Acidosis
• Restore ventilation
• Treat underlying dysfunction or disease
43
Respiratory Alkalosis
• Carbonic acid deficit
• pCO2 less than 35 mm Hg (hypocapnea)
• Most common acid-base imbalance
• Primary cause is hyperventilation
44
Respiratory Alkalosis
• Conditions that stimulate respiratory
center:
– Oxygen deficiency at high altitudes
– Acute anxiety
– Fever, anemia
– Early salicylate intoxication
– Cirrhosis
– Gram-negative sepsis
45
Compensation of Respiratory
Alkalosis
• Kidneys conserve hydrogen ion
• Excrete bicarbonate ion
46
Treatment of Respiratory Alkalosis
• Treat underlying cause
• Breathe into a paper bag
• IV Chloride containing solution – Cl- ions
replace bicarbonate ions
47
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+
48
Breathing abnormalities
49
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
50
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
51
Metabolic Acidosis
52
Metabolic Acidosis
53
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)
55
Proximal RTA (Type II)
• Fanconi Syndrome (impaired reabsorbtion of
glucose, phosphate, uric acid) → MM!!!
• Treatment – difficult
• NO HCO3-
• Potassium-sparing diuretics
56
Proximal RTA (Type II)
• Fanconi Syndrome (impaired reabsorbtion of
glucose, phosphate, uric acid) → MM!!!
• Treatment – difficult
• NO HCO3-
• Potassium-sparing diuretics
57
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)
58
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
59
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
60
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
61
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
62
• 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
63
• 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.
64
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)
65
Metabolic Alkalosis
Chloride Unresponsive
Urine Cl- > 20 mEq/L
Causes
• Mineralcorticoid excess (Hyperaldosteronism)
• Exogenous steroids, Cushing’s disease
• Tobacco chewers
• Bartter’s Syndrome
66
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)
67
Clinical approach
68
Clinical approach
1. Blood pH – determine the primary
disorder
2. HCO3-, pCO2 – primary mechanism
69
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
71
Compensation
72
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)
73
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
74
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
75
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
76
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
77
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-
78
Case 2
1. pH = 7.50 → alkalosis
2. HCO3-=40, pCO2=51 → metabolic
3. Estimated pCO2 = 0.7 x 16 = 11 (40+11)
79
Case 2
1. pH = 7.50 → alkalosis
2. HCO3-=40, pCO2=51 → metabolic
3. Estimated pCO2 = 51 → compensated
80
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?
81
Case 2
1. pH = 7.50 → alkalosis
2. HCO3-=40, pCO2=51 → metabolic
3. Estimated pCO2 = 51 → compensated
4. urinary Cl-=8 mEq/L
82
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
83
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
84
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
86
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
87
