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DISORDERS OF
ACID-BASE
BALANCE
ACID-BASE BALANCE
ISOHYDRIA – stability of H+ concentration
[H+] = 40 nmol/L = 0,00000004 mol/L
pH = - log [H+]
ACID-BASE BALANCE
ISOHYDRIA – stability of H+ concentration
[H+] = 40 nmol/L = 0,00000004 mol/L
pH = - log [H+]
pH → main determinant of physiological & biochemical processesactivity of enzymes varies due to charge and conformation of proteins
effecting activity of transport proteinseffecting molecule distributions across cell membranesalterations in drug dissociation
pH
Physiological value of pH?
pH
pH 7,4 ± 0,05
pH 7,4 pH 7,35
sources of H + :
1. the metabolism of proteins and phospholipids + incomplete metabolism of fatty acids and carbohydrates
→ non-volatile acids (40 mmol/d)
sulfuric acid phosphoric acid
lactic acid ketone bodiesuric acid
• no further dissociation• elimination by kidneys
2. complete metabolism of fatty acids & carbohydrates
→ CO2 (20 000 mmol/d)
ACID-BASE BALANCE
H+ source
fixed acids CO2
CO2 + H2O H 2CO3 H+ + HCO3
–
MECHANISMS FOR MAINTAINING AB BALANCE
1. bicarbonate – carbonic buffer
2. hemoglobin buffer
3. protein buffer
4. phosphate buffer
BUFFERING SYSTEMS:
buffer systems
ECF
bicarbonate
protein
ICF
hemoglobin
phosphate
BICARBONATE –CARBONIC BUFFER
efficient:• biggest in extracellular fluid • open system
BUFFERING SYSTEM:
CO2 + H2O H 2CO3 H+ + HCO3
–
weak acid strong base
MECHANISMS FOR MAINTAINING AB BALANCE
CO2 + H2O H 2CO3 H+ + HCO3
–
pH = [HCO3
–][H2CO3]pCO2
Henderson-Hesselbach‘sequation
pH = pK + log [HCO3
–][H2CO3]
pH = pK + log [HCO3
–][H2CO3]
24 mmol/L
1,2 mmol/L6,37,4
MECHANISMS FOR MAINTAINING AB BALANCE
CO2 transport
• CO2 diffuse into plasma- 90% in RBC• carbon anhydrase – H2C03 production
(H+, HCO3-)• H+ ion binds to HGB (HGB buffering)
• HCO3- diffuse into plasma• in lung capillaries - ox. HGB
H+ release• H2CO3 synthesis (H2O + CO2)
MECHANISMS FOR MAINTAINING AB BALANCE
elimination of H + elimination of non-volatilereabsorption of HCO3
– acidsHPO42- + H + → H2PO4NH3 + H + → NH4+
MECHANISMS FOR MAINTAINING AB BALANCE
BICARBONATE –CARBONIC BUFFER: open system
pCO2 HCO3–
↓↑ reabsorption of HCO3–
prox. & distal. tubule– dissociation of H2CO3
H+ elimination into tubular fluidHCO3
– reabsorbed
elimination of CO2
ventilation regulated by respiratory center (med. oblongata)responding via alteration in
frequency & depth
respiratory component onset – minutes
metabolic componentonset – days
H+ + HCO3– H2CO3 CO2 + H2O
MECHANISMS FOR MAINTAINING AB BALANCE
MECHANISMS FOR MAINTAINING AB BALANCE
ACIDAEMIA ACIDOSIS
ALKALAEMIA ALKALOSIS
pH of arterial blood < 7,35
pH of arterial blood > 7,45
processes resulting in pH decrease
• ↓ serum HCO3–
• ↑ pCO2
processes resulting in pH increase
• ↑ serum HCO3–
• ↓ pCO2
pH = [HCO3
–]
pCO2
pH HCO3– pCO2 compensation
physiological values 7,4 ± 0,05 24± 2 mmol/L5,3 ± 0,5 kPa(40 mmHg)
Metabolic acidosis
Metabolic alkalosis
Respiratory acidosis
Respiratory alkalosis
primary change
compensatory change
hyperventilation
ACID-BASE BALANCE
respiratory compensation of metabolic acidosis:KUSSMAUL BREATHING pattern
ACID-BASE BALANCE
pH = [HCO3
–]
pCO2
pH HCO3– pCO2 compensation
physiological values 7,4 ± 0,05 24± 2 mmol/L5,3 ± 0,5 kPa(40 mmHg)
Metabolic acidosis
Metabolic alkalosis
Respiratory acidosis
Respiratory alkalosis
primary change
compensatory change
hyperventilation
hypoventilation ?
ACID-BASE BALANCE
ACID-BASE BALANCE
anion deficiency, AG
AG = [Na+] – ([Cl –] + [ HCO3–])
AG = 140 – (104 + 24) = 12 mmol/L (norm 8-12 mmol/L)
albumin, phospate, sulphate, lactate
ANION GAP
accumulation of anions
reaction with HCO3–
AG
METABOLIC ACIDOSIS
pH < 7,35 primary decrease of HCO3–
pH = [HCO3
–]
pCO2
pH HCO3– pCO2 compensation
physiological value 7,4 ± 0,05 24± 2 mmol/L 5,3 ± 0,5 kPa(40 mmHg)
Metabolic acidosis
concentration of plasma HCO3
– < 22 mmol/L
DISORDERS OF ACID-BASE BALANCE
pH < 7,35 primary decrease of HCO3–
1. reaction with H + (non-volatile acids) • ↑ intake of substances producing H +
• metabolic production of non-volatile acids
• ↓ excretion of H +
2. ↑ losses of HCO3–
concentration of plasma HCO3
–< 22 mmol/L
METABOLIC ACIDOSIS
DISORDERS OF ACID-BASE BALANCE
intoxication by salicylates – metabolic block
intoxication by inorganic acids
ketoacidosis: insufficient glucose utilization
1. reaction with H + (acids)
METABOLIC ACIDOSIS
DISORDERS OF ACID-BASE BALANCE
intoxication by salicylates – metabolic block
intoxication by inorganic acids
ketoacidosis: insufficient glucose utilization
diabetic: fatty acids oxidation – source H +
hyperkalemiastarvation: (fever with anorexia - mild ketoacidosis)
reduced carbohydrates intake →↓ insulin secretion ↑ glucagon secretion
alcoholic
H+
K+
H+ H+
H+
1. reaction with H + (acids)
METABOLIC ACIDOSIS
DISORDERS OF ACID-BASE BALANCE
lactic acidosis: lactate overproduction
type A: circulatory shock, heart failure, anemia, CO poisoningtype B: organ failure (kidney, liver), malignant tumors
intoxication by methanol, etylene glycol, paraldehyd
METABOLIC ACIDOSIS
DISORDERS OF ACID-BASE BALANCE
2. ↑ losses of HCO3–
hyperchloremic acidosis
severe diarrhea – loss of HCO3–, Na+, K+, H2O
chronic vomiting –loss of duodenal content (pH 7-8,5),loss of HCO3– > gastric acidsaccumulation of Cl-
renal tubular acidosis –↓ H+ excretion & HCO3
– loss
chronic renal insufficiency: ↓ H + excretionloss of functional parts of kidney parenchyma↓ nb of nephrons - SO4
2- , PO43- , organic aids accumulation
normal Anion GAP
METABOLIC ACIDOSIS
DISORDERS OF ACID-BASE BALANCE
METABOLIC ACIDOSIS
DISORDERS OF ACID-BASE BALANCE
K+
H+ H+
H+
compensatory hyperventilation KUSSMAUL BREATHING
↓ pH – stimulation of peripheralreceptors
H+ crossing blood-brain barrier↓ pH - in respiratory center in
medulla oblongata
METABOLIC ACIDOSIS
DISORDERS OF ACID-BASE BALANCE
pH = [HCO3
–]
pCO2
pH HCO3– pCO2 compensation
Physiological values 7,4 ± 0,05 24± 2 mmol/L 5,3 ± 0,5 kPa(40 mmHg)
metabolic alkalosis
pH > 7,45 primary increase of HCO3–
concertation of plasma HCO3
– > 26 mmol/L
DISORDERS OF ACID-BASE BALANCE
METABOLIC ALKALOSIS
pH > 7,45 primary increase of HCO3–
concentration ofplasma HCO3
– > 26 mmol/L
1. ↑ concentration of HCO3–
• ↑ intake (IV infusion, oral intake)
• ↓ excretion
2. ↑ loss of acids (hydrochloric acid)
DISORDERS OF ACID-BASE BALANCE
METABOLIC ALKALOSIS
↑ intake:
intravenous infusion
oral intake – huge capacity for elimination in healthy kidneys
blood transfusion – sodium citrate (anticoagulant)
↓ excretion:primary hyperaldosteronismadministration of mineralocorticoids↑ aldosterone –Na + reabsorption, HCO3
– reabsorptionK + & H+ elimination
1. ↑ concentrations of HCO3–
DISORDERS OF ACID-BASE BALANCE
METABOLIC ALKALOSIS
hypochloremic alkalosis:
vomitingremoval of gastric content
loss of gastric acid = loss of HCl
dehydration↓ ECF - RAAS activation –↑ release of aldosterone
→ retention of Na+ a H2O→ loss of H +
2. ↑ losses of acids
normal Anion Gap
DISORDERS OF ACID-BASE BALANCE
METABOLIC ALKALOSIS
DISORDERS OF ACID-BASE BALANCE
METABOLIC ALKALOSIS
K+K+
K+
pH = [HCO3
–]
pCO2
pH HCO3– pCO2 compensation
physiological values 7,4 ± 0,05 24± 2 mmol/L 5,3 ± 0,5 kPa(40 mmHg)
Respiratory acidosis
pH < 7,36 primary increase in pCO2
pCO2 > 5,8 kPa
DISORDERS OF ACID-BASE BALANCE
RESPIRATORY ACIDOSIS
pH < 7,36 primary increase in pCO2pCO2 > 5,8 kPa
exhaled CO2 < metabolic production
HYPERCAPNIA
DISORDERS OF ACID-BASE BALANCE
RESPIRATORY ACIDOSIS
ACUTE: failure of ventilation & depression of resp. center
cardiopulmonal failure – sudden failure in ventilation & perfusionpulmonary embolization, heart failure
drugs intoxication (hypnotics, sedatives, morphium) depression of respiratory center
trauma, infection, ischemia of CNS – local damage
CHRONIC: ↓ alveolar ventilation
chronic obstructive pulmonary disease (emphysema, bronchitis)
↓ effective alveolar ventilationsufficient renal compensation: ↑ HCO3
– reabsorptionadaptation to hypoxemia →↑ nb of RBC (erythrocythemia)
DISORDERS OF ACID-BASE BALANCE
RESPIRATORY ACIDOSIS
DISORDERS OF ACID-BASE BALANCE
RESPIRATORY ACIDOSIS
pH > 7,44 primary decrease in pCO2
pCO2 < 4,8 kPa
pH = [HCO3
–]
pCO2
pH HCO3– pCO2 compensation
physiological values 7,4 ± 0,05 24± 2 mmol/L 5,3 ± 0,5 kPa(40 mmHg)
respiratory alkalosis
DISORDERS OF ACID-BASE BALANCE
RESPIRATORY ALKALOSIS
pH > 7,44 primary decrease in pCO2pCO2 < 4,8 kPa
HYPOCAPNIA
exhaled CO2 > metabolicproduction
DISORDERS OF ACID-BASE BALANCE
RESPIRATORY ALKALOSIS
CNS DISORDERS
cerebrovascular incidents – hypoxia in area of resp. center
trauma, inflammation, tumors – stimulation of CNS
drugs (salicylates, progesterone) – stimulation of resp. center
fear, anxiety, hysterical fit – hyperventilation due to subjective feeling of air shortage
LUNG DISEASE
gas exchange disorders – ventilation/perfusion imbalance
pulmonary fibrosis, edema, pneumonia, asthma
mountain sickness↓ pO2 stimulation of hyperventilation
DISORDERS OF ACID-BASE BALANCE
RESPIRATORY ALKALOSIS
DISORDERS OF ACID-BASE BALANCE
RESPIRATORY ALKALOSIS
MIXED ACID-BASE DISORDERS
acute disorder
chronic disorderCOMPENSATION
metabolic acidosis + metabolic alkalosis
metabolic acidosis + respiratory acidosis
diarrhea + vomiting
circulatory failure: lactic acidosis + respiratory failure
↓HCO3– /↑ HCO3
–
↓HCO3– /↑ pCO2
DISORDERS OF ACID-BASE BALANCE
COMPENSATION OF AB DISORDERS
Uncompensated disorder:• pH – abnormal• HCO3 – conc. or pCO2 - abnormal
Partially compensated disorder:• pH – abnormal• HCO3 – conc. - abnormal• pCO2 – abnormal
Compensated disorder:• pH – normal• HCO3 – conc. – abnormal but neutralized• pCO2 – abnormal but neutralized
Corrected disorder:• pH – normal• HCO3 – conc. – normal (returned to physiological value)• pCO2 – normal (returned to physiological value)
DISORDERS OF ACID-BASE BALANCE
DISORDERS OF ACID-BASE BALANCE
VIDEOs explaining AB disorders
Introduction to Acid-Base Disorders:https://www.youtube.com/watch?v=jWpKJVop6G8
Metabolic acidosis - The Acid-Base Serieshttps://www.youtube.com/watch?v=IF6oF5H43Ac
Metabolic alkalosis - The Acid-Base Serieshttps://www.youtube.com/watch?v=Wf0ruPTmP1o&list=PLN4mLNb7L4VeCRfA7kB2Sj0sYvaxW4KB5&index=4
Respiratory acidosis - The Acid-Base Serieshttps://www.youtube.com/watch?v=wZICSJZOTH4&list=PLN4mLNb7L4VeCRfA7kB2Sj0sYvaxW4KB5&index=3
Respiratory alkalosis - The Acid-Base Serieshttps://www.youtube.com/watch?v=7aPzaVkCjss&list=PLN4mLNb7L4VeCRfA7kB2Sj0sYvaxW4KB5&index=2
https://www.youtube.com/watch?v=jWpKJVop6G8https://www.youtube.com/watch?v=IF6oF5H43Achttps://www.youtube.com/watch?v=Wf0ruPTmP1o&list=PLN4mLNb7L4VeCRfA7kB2Sj0sYvaxW4KB5&index=4https://www.youtube.com/watch?v=wZICSJZOTH4&list=PLN4mLNb7L4VeCRfA7kB2Sj0sYvaxW4KB5&index=3https://www.youtube.com/watch?v=7aPzaVkCjss&list=PLN4mLNb7L4VeCRfA7kB2Sj0sYvaxW4KB5&index=2