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FRCA Primary - Physiology > Acid-base physiology > Flashcards

Acid-base physiology Flashcards

1
Q

Acid (pH)

A

Acid (pH) - proton donor i.e. H+ donor.

Strong acid - this is an acid that fully dissociates in solution. An example is hydrochloric acid (HCl).

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2
Q

Base

A

Base - proton acceptor.

In the same way that an acid’s strength is determined by its degree of dissociation, so is that of a base. A strong base will be fully dissociated.

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3
Q

Weak acid

Weak base

A

Weak acid - acid that is not fully dissociated in solution e.g. carbonic acid (H2CO3).

Weak base- -a weak base is one that is not fully dissociated in solution.

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4
Q

Acid-base buffer

Congugate base for:

  1. Carbonic acid H2CO3
  2. Lactic acid C3H6O3
  3. Ammonium ion NH4+
  4. Dihydrogen phosphate H2PO4
  5. Acetoacetic acid CH3COCH2CO2H
A

Acid-base buffer - weak acid and its conjugate base. A conjugate base is the dissociated anionic product of an acid.

A buffer will limit the effect of a proton load in any physiological solution i.e. converting strong acid to weak acid.

  1. Bicarbonate ion HCO3-
  2. Lactate ion C3H5O3-
  3. Ammonia NH3
  4. Monohydrogen phosphate HPO42-
  5. Acetoacetate CH3COCH2CO2-
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5
Q

pH

A

pH - negative logarithm to the base 10 of the hydrogen ion concentration in nanomoles per litre (nmol/L).

The concept of pH was first introduced by Danish chemist Sørensen at the Carlsberg Laboratory in 1909.

The name pH has been claimed to have come from any of several sources including:

Pondus hydrogenii

Potentia hydrogenii

Potentiel hydrogène

Potential of hydrogen

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6
Q

Normal hydrogen ion concentration

A

Normal hydrogen ion concentration = 40 nmol/L.

Normal physiological pH = 7.4.

A change of one pH unit corresponds to a ten-fold change in hydrogen ion concentration.

A chemical solution is said to be neutral when pH = 7.0 and the hydrogen and hydroxyl (OH) concentrations are equal. This is true for a temperature of 25oC; at 37oC a neutral solution will have a pH of 6.8.

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7
Q

Acidosis

Acidaemia

A

Acidosis is the excess of acid moieties within a physiological system

Acidaemia is a reduction in pH to less than 7.4.

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8
Q

Volatile acid production

A

KREBS CYCLE produces ATP and CO2

Each day 13 000-15 000 mmol of volatile acid in the form of carbon dioxide (CO2) is produced from the metabolism of glucose

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9
Q

Non-volatile acid formation

A

AMINO ACIDS produces glutamine, alanine, keto-acids and NH3

The metabolism of amino acids results in the production of non-volatile or fixed acids. The degree of production varies between 50-80 mmol/day

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10
Q

The maintenance of a normal hydrogen ion concentration is important for:

A
  • Homeostasis: The maintenance of a constant physiological environment
  • Homeostasis: The maintenance of a constant physiological environment
  • Ionic flux: H+ has high charge density and can influence ionic flux
  • Other functions: Hydrogen bonds are an integral part of molecular structure hence hydrogen ion concentration influences the function of:
  1. Enzymes (Fig 1)
  2. Proteins
  3. Ions
  4. Organ function
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11
Q

pKa

A
  • The negative logarithm of the dissociation constant.
  • pH at which the system exisits in ionic equilibirum ie 50% ionized, 50% un-ionized.
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12
Q

Key buffers in the body

A

Blood:

  • Bicrabonate pKa 6.1
  • Haemoglobin (histidine) pKa 7.8
  • Plasma proteins (amino and carboxyl) pKa 7.4

Interstitium:

  • Bicarbonate pKa 6.1

Intracellular:

  • Proteins pKa 7.4
  • Phosphate pKa 6.8
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13
Q
  • Henderson-Hasselbach equation
  • Derive equation
A

pH = pK + Log10 [A-]/[HA]

H+ + A- ⇔ HA

At equilibrium: k1[H+] [A-] = k2 [HA] k1 and k2 rate constants for reacrtion in each direction

Rearrange: [H+] = k[HA]/[A-] (k=k1/k2) k=dissociation constant

Then take logs: Log10[H+] = Log10k + Log10[HA]/[A-]

Negative logs: -Log10[H+] = -Log10k - Log10[HA]/[A-]

Substitute pH for -Log10[H+] anf pK for -Log10k :

pH + pK = Log10 [A-]/[HA]

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14
Q

The isohydric principle

A

When a solution (or compartment) contains more than one buffer, all buffer pairs (HA and A-) in the system are in equilibrium with the same proton concentration [H+]: Only those buffers with a pK within 1 pH unit of that in the solution participate effectively in the buffering of the solution pH.

therefore assessment of any one of the buffering systems provides and reflection og the overall acid-base status. We measure carbonic acid- bicarbonate buffer system

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15
Q

What is the respiratory response to an excess of hydrogen ions?

A

The concentration of carbon dioxide in alveolar gas is governed by the amount produced and the amount eliminated by the lungs.

A rise in carbon dioxide is detected by the chemoreceptors of the medulla and carotid bodies, resulting in an increase in alveolar ventilation

H+ acts directly on the respiratory centre in the medulla oblongata:

2 x ventilation - pH 7.4 => 7.63
1/4 ventilation - pH 7.4 => 6.95

The respiratory system is a typical feedback controller of hydrogen ion concentration. It has a control effectiveness of 50-75%.

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16
Q

Renal control of acid base balance

A
  • H+ secreted
  • HCO3- filtered
  • Generation of HCO3-

Within the collecting system of the kidneys, epithelial cells secrete H+ by:

  • Secondary active transport: proximally in the collecting ducts. Hydrogen ions are transported out of the luminal cell as sodium is transported by primary active transport into the cell. This is countercurrent transport
  • Primary active transport: distally in the collecting duct in intercalated cells. There is a specific hydrogen transporting ATPase enzyme and transport protein (hydrogen transporting adenosine triphosphate (ATP))
  • Hydrogen ion and bicarbonate interacting within the collecting system:

Bicarbonate (HCO3-) is filtered by the glomerulus and combines with the secreted hydrogen ion (H+) to form carbonic acid (H2CO3) which then dissociates to carbon dioxide (CO2) and water (H2O). The carbon dioxide diffuses back into the luminal cell, where it either diffuses back into the extracellular space or is involved in the regeneration of bicarbonate.

17
Q

Role of liver in acid-base balance

A
  1. Carbon dioxide production (oxidation)
  2. Metabolism of organic acid anions
  3. Production of plasma proteins
  4. Metabolism of ammonium
  5. Ureagenesis

There is no net acid or base production if CO2 is removed by the lungs. The liver regulates the degree to which ureagenesis occurs, in the face of the need either to conserve or consume bicarbonate.

Amino acid metabolism → HCO3- and NH4+

2NH4+ + 2HCO3- → NH2.CO.NH2 + CO2 + 3H2O

18
Q

Hyperlactataemia

Anaerobic metabolism produces

Causes of hyperlactataemia

A

Definition: >2 mmol/L (lactic acidosis >5 mmol/L) and pH <7.35

Type A hyperlactataemia impairs oxygen delivery

Type B hyperlactataemia does not impair normal oxygen delivery

Anaerobic metabolism produces:

  • Adenosine triphosphate (ATP)
  • Lactate (Fig 1)
  • Water

H+ is generated from the breakdown of ATP.

Aerobic metabolism produces 36 molecules of ATP; anaerobic metabolism produces two molecules of ATP.

Causes:

  • Increased cellular production
  • Reduced uptake/utilization of oxygen
  • Reduced lactate clearance
19
Q

Lactate: pyruvate ratio

A
  • Will tell you if tissue hypoxis is present
  • Normal = 10:1
  • Abnormal = >10:1 (indicates tissue hypoxia)
20
Q

The Anion Gap

High anion gap causes

Normal anion gap causes

Low anion gap causes

A
  • Difference bewteen measured cations and ions:
  • (NA++K+) - (Cl-+HCO3-)
  • Normal 8-16

Causes high anion gap:

  • Lactic acidosis
  • Ketoacidosis
  • DKA
  • Toxins:
    • Ethanol
    • Ethylene glycol
    • Lactate
    • Paraldehyde
    • Phenformin
    • Aspirin
    • Cyanide, coupled with elevated venous oxygenation
    • Iron
    • Isoniazid

HCO3 conc decrease due to buffering increased acids. bicarb replaced by unmeasured anions (lactate, beta-hydroxybutyrate and acetoacetate, PO4-, and SO4-) causing anion gap increase.

Normal anion gap causes:

  • Gastrointestinal loss of HCO3- (Diarrhoea)
  • Renal loss of HCO3- (Proximal renal tubular acidosis)
  • Renal dysfunction (Renal failure, Hypoaldosteronism, Distal renal tubular acidosis)
  • Ingestions (Ammonium chloride, Acetazolamide, Hyperalimentation fluids (i.e. total parenteral nutrition)
  • Some cases of ketoacidosis (Particularly during rehydration with Na+ containing IV solutions)

hyperchloraemic acidosis (drop in bicarb compensated by rise in chloride ions)

Low anion gap:

  • hypoalbuminaemia
  • increase cations
    • organic (paraproteins in multiple myeloma)
    • inorganic (bromide, lithium, iodine or polymyxin B)
21
Q

Hypoalbuminaemia causes

A

albumin constitutes ~80% of the unmeasured anions

Causes:

  • Decreased synthesis (liver disease)
  • Increased catabolism (very slow)
  • Increased loss:
    • Nephrotic syndrome
    • Exudative loss in burns
    • Haemorrhage
    • Gut loss
  • Redistribution:
    • Haemodilution
    • Increased capillary permeability (leakage into the interstitium)
    • Decreased lymph clearance
  • Capillary leak syndrome: albumin leaks into extravascular space. SIRS/sepsis

Low albumin levels may also be seen in pre-eclamptic toxaemia + the stress response to surgery

22
Q

Base excess

A

Base excess (BE) is the amount of acid or base that must be added to a sample of whole blood in vitro to restore the sample to pH 7.4, while the PaCO2 is held at 5.33 kPa (pH 7.4, Hb 15 + PaCO2 of 5.33 kPa = BE of 0).

23
Q

Stewart’s theory

A
  • dependent variables produce ‘effects’ eg. H+, pH, HCO3
  • independent variables act as ‘controllers’ eg. pCO2, net strong ion charge, total weak acid
  • Strong ion differnece
    • positive-negative
    • (Na+ + K+ + CA+ + Mg+) - (Cl- + lactate)
    • normal value 40-42
    • increase SID = increase pH
    • NA+ controlled -> Cl- change important

FRCA Primary - Physiology (12 decks)

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