Lecture 7: Acid-Base Imbalance on Control (I) Flashcards
Why regulate acidity?
Protein structure and enzymatic activities are dependent on pH
Inability to maintain pH within acceptable levels will stop enzyme reactions and lead to death
Body has developed various mechanisms (buffers) to maintain pH within a narrow range of 7.37-7.44 (Limits of pathological range – 6.8-7.8)
How does the body maintain the pH balance?
Acid-Base balance is maintained with the aid of buffers.
3 main buffer systems
What are the three main buffer systems of the body?
Bicarbonate – extracellular buffer
Phosphate – intracellular
Proteins - intracellular (acidic and basic side chains)
Volatile acids
CO2
Produced by cellular oxidation, TCA cycle
Non volatile acids
Catabolism of proteins and S-containing amino acids
Partial oxidation of fatty acids and glucose ( -OH butyrate, acetoacetate, lactate)
Ingestion of nonvolatile acid precursors (Phospholipids, Phosphoproteins, nutrients with more inorganic anions than inorganic cations)
How is CO2 used as a buffer system?
used as a buffer system to prevent rapid changes in extracellular pH
CO2 reacts with water to form carbonic acid: CO2 + H2O H 2CO3 H+ + HCO3-
Production of CO2 by body
Body produces 13000-15000 mmol of CO2 per day
If not removed, would be hazardous to health
What organs are involved in maintenance of acid-base balance?
Lungs
RBC
Kidneys
Henderson Hasselbach equation
pH = 6.1 + log(bicarbonate)/pCO2
How is normal pH range maintained?
by regulating the levels of bicarbonate ion concentration and pCO2 (concentration of carbon dioxide) in the blood.
What does binding of H+ to Hb do to Hb?
Reduces affinity for H+
Carbonic anhydrase
Converts CO2 and H2O into H2CO3 and reverse
CO2 transport in tissues and in lungs
See figure
Where does reabsorption of bicarbonate ions occur primarily?
Proximal tubule
See figure
Regulation of HCO3 concentration
Regulated by kidneys, depending on acid-base imbalance
Can only REDUCE the amount it reabsorbs
Where is H+ secreted predominantly?
Distal tubule
Which compensatory mechanisms are the fastest?
Lungs are faster than kidneys
When is ammonia buffer system used?
During extreme starvation and acidic conditions, amino acids are broken down to produce ammonia.
Ammonia can be used to buffer the H+
What is acidemia
acidic blood
What is alkalemia?
alkaline blood
What is acidosis?
Process which creates excess H+
What is alkalosis?
Process which creates a deficit in H+
Compensation
Describes the change that occur to avoid pH changes
Respiratory
Changes in pCO2
Metabolic
Changes in HCO3-
Metabolic acid-base disorders
directly cause changes in the bicarbonate ion (or H+) concentration.
The changes are corrected by respiratory effects (via lungs).
Respiratory acid-base disorders
Directly change the pCO2.
Corrected by metabolic effects (kidneys)
Metabolic acidosis
decreased [HCO3-] concentration in blood.
Increased H+ causes low HCO3- (used to neutralize)
Metabolic alkalosis
increased [HCO3-] in blood.
Respiratory acidosis
increased CO2 concentration in blood
Respiratory alkalosis
decreased CO2 concentration
Reasons for reduced bicarbonate ion leading to metabolic acidosis
Increased production of hydrogen ions
Diabetic ketoacidosis, consequences of lack of insulin
Lactic acidosis due to tissue hypoxia, liver disease, cardiac arrest , hemolytic anemia
Methanol poisoning- metabolized to formic acid which builds up;
Ethylene glycol poisoning – metabolized to glycolic acid
Acid ingestion – (acid poisoning)
Salicylate (Aspirin) poisoning –uncouples oxidative phosphorylation, inhibits Krebs cycle, leading to acidosis from production of multiple organic acids
Diarrhea
Pancreatic/intestinal or biliary fistulae or drainage
Decreased H+ excretion
Compensatory response to metabolic acidosis
Hyperventilation (respiratory alkalosis)
H+ combines with HCO3- which is converted to carbonic acid
Carbonic acid dissociates into CO2 and H20 which are exhaled
(low pCO2)
Clinical effects of metabolic acidosis
can lead to hyperkalaemia and potentially cardiac arrest.
Increased [H+] can also act as a stimulant of the respiratory center in the brain, further stimulating rapid breathing.
What is the anion gap?
biochemical measurement that is usually used for assessing acid-base imbalance relating to metabolic acidosis.
What ions are measured in the calculation of ion gap?
Na+, K+, Cl- and HCO3-
What does a large anion gap indicate?
Presence of a strong acid
What is the anion gap in a healthy human?
6-18 mM
What happens to anion gap when lactate, acetoacetate, or hydroxybutyrate are produced?
Anion gap increases
Anion gap in metabolic acidosis
Reduced bicarbonate is balanced by increased chloride anions
Gap is normal
Conditions resulting in metabolic alkalosis
Loss of hydrogen ions in the gastric/stomach fluid during vomiting.
As seen in infant pyloric stenosis (closing of the pylorus)
Incorrect administration of bicarbonate ion solution to correct for acidosis
Ingestion of absorbable alkali/sodium bicarbonate in large amounts
Potassium deficiency.
Usually, in the kidneys, sodium ion is absorbed, whereas potassium and hydrogen ions are excreted to maintain electrical neutrality in kidney tubular cells. However, in the absence of normal levels of potassium, more hydrogen ions are lost (i.e. more acid being lost making the blood more more alkaline/basic) than usual (to compensate for the less amount of potassium being excreted).
Compensatory response to metabolic alkalosis
Hypoventilation
Respiratory acidosis
(increased CO2)
What are respiratory acid-base disorders caused by?
Change in pCO2 in plasma
Can be acute or chronic
Compensation in respiratory imbalances
No compensation in acute conditions relative to chronic because the metabolic compensatory effect by the kidneys takes days
Acute respiratory acidosis - cause? concentrations?
Cause: air is blocked (hypoventilation)
pCO2 increases (hypercapnia)
pH decreases
Examples of conditions that result in acute respiratory acidosis
Choking
Bronchopneumonia
Acute exacerbation of asthma
Anesthetics, sedatives (depression of respiratory centre)
Acute respiratory acidosis can cause coma and death if not resolved quickly
Chronic respiratory acidosis - cause, compensation.
Chronic airway diseases
Maximum renal/kidney compensation: secretion of H+ and reabsorption of HCO3-
HCO3- will be high, pH will be normal
Respiratory alkalosis
Low pCO2
Low H+ (high pH)
Causes of decreased pCO2
Respiratory centre stimulants e.g. salicylates
Voluntary hyperventilation
Anxiety (acute condition)
Mechanical over ventilation in an intensive care patient
Cerebral disturbances e.g. trauma, raised intra cranial pressure, or hypoxia, both of which can stimulate the respiratory centre to increase gas exchange
Pulmonary disease – pulmonary edema, pulmonary embolism
Compensatory response to respiratory alkalosis
Kidneys reduce reabsorption of HCO3-, resulting in metabolic acidosis
Metabolic and respiratory acidosis
such as in:
Bronchitis and kidney failure/renal impairment, with a raised carbon dioxide concentration, low pH, and very low bicarbonate ion concentration because of the reduce excretion of the hydrogen ions, when compared to bronchitis alone.
Salicylate poisoning
stimulates respiratory centre directly to induce hyperventilation which leads to respiratory alkalosis.
The effects of the compound on metabolic pathways leads to metabolic acidosis.
Hyperventilation
causing respiratory alkalosis, followed by prolonged nasogastric suction (removing hydrogen ions) that causes metabolic alkalosis.
What do extremely high O2 levels indicate?
Mechanic ventilation
