General pathophysiology - acid-base balance Flashcards
What 3 main parameters in blood will determine the body acid-base homeostasis:
– pH
(arterial = 7.35 to 7.45, venous 7.3)
– Pa CO2 – partial pressure of CO2
– HCO3 (bicarbonate or hydrogen carbonate) concentration
If there is at least one of them out of the normal range, it is a interpreted as disorder of acid-base balance.
Acid does what in solution
gives away H+ ions in solution
e.g. H2CO3 carbonic acid
What is a buffer
is a mixture of compounds which have the ability to absorb large amounts of H+ or OH- (hydroxide) with very little change of pH.
Proteins act as buffers due to
their amino and carboxyl parts which binds or release H+ ions.
Since small fluctuations in pH are dangerous, there are what 3 mechanisms how the body maintains acid-base balance (3)
– Buffers
– Respiratory and
– renal regulatory systems
Blood buffer systems (5)
- Plasma bicarbonate buffer
- Erythrocyte bicarbonate buffer
- Hgb and oxy-Hgb
- Plasma proteins
- Phosphate buffer
Plasma bicarbonate buffer is the most important since H+ ions can be removed or retained by regulation of blood CO2 levels (changing in breathing) or HCO3- (excretion and/or retention in the kidneys).
Henderson Hasselbalch equation
One way to determine the pH of a buffer is by using the Henderson–Hasselbalch equation, which is pH = pKₐ + log([A⁻]/[HA]).
In this equation, [HA] and [A⁻] refer to the equilibrium constant concentrations of the conjugate acid–base pair used to create the buffer solution.
Renal compensation is slow. Starts within hours, and the full development takes 2-5 days.
Renal compensation involves what
elimination or retention of H+ and increase or decrease of HCO3- reabsorption.
a change in the partial pressure of carbon dioxide of arterial blood is a
respiratory acid-base disorder
either resp. acidosis or alkalosis
a change in the bicarbonate concentration in blood is
a metabolic acid-base disorder.
either metabolic alkalosis or acidosis
ddescribe acid-base parameters in respiratory acidosis
↑ PaCO2 → ↓ pH
describe acid-base parameters in
metabolic acidosis
↓ HCO3- → ↓ pH
describe acid-base parameters in respiratory alkalosis
↓ PaCO2 → ↑ pH
describe acid-base parameters in metabolic alkalosis
↑ HCO3- → ↑ pH
What is base excess and base deficit?
The value is usually reported as a concentration in units of mEq/L, with positive numbers indicating an excess of base and negative a deficit, present in blood.
Base excess (BE) is the titratable acidity (or base) of the blood sample. It is defined as the amount of acid or base that must be added to a sample of oxygenated whole blood to restore the pH to 7.4 at 37° C and at a PCO2 of 40 mm Hg.
What is a decompensated acid-base disorder
the pH is outside the normal range and a compensatory shift does not exist or is not sufficient
What is a compensated acid-base disorder
the pH is in the normal range,
and there is compensatory shift in respiratory or metabolic
component
what do the following parameters describe?
pH < 7.40; PaCO2 > 45 mmHg; normal HCO3-
respiratory acidosis
what do the following parameters describe?
pH > 7.40; PaCO2 < 35 mmHg; normal HCO3-
respiratory alkalosis
Causes of respiratory acidosis (5)
– Decline in alveolar ventilation – hypoventilation
– Impaired ventilation/perfusion ratio (V/Q ratio) in lung
– Pulmonary diseases, obstruction of the upper airways
– CNS pathology, neuromuscular diseases
– Iatrogenic
what do the following parameters describe?
pH 7.35 – 7.40;
PCO2 >45 mmHg;
HCO3- >24 mmol/l
Respiratory acidosis, compensated disorder
What IVFT is used for correction of respiratory acidosis?
lactated ringers solution
Lactate is converted to bicarbonate ions in the liver.
Ringer’s Lactate provides appropriate amounts of sodium and calcium.
Used as an alkalinizing agent, which increases the pH level of the body.
Causes of respiratory alkalosis (2)
– Increase of alveolar ventilation
– hyperventilation,
which may be due to the active hyperventilation
(CSF acidosis, hypoxemia, pain, anxiety)
or passive hyperventilation (controlled breathing)
What state is the following
pH > 7.40;
PaCO2 < 35 mmHg;
normal HCO3-
respiratory alkalosis
What state is the following
pH 7.40 – 7.45;
PaCO2 <35 mmHg;
HCO3- <20 mmol/l
respiratory alkalosis,
compensated disorder
What IVFT is used for correction of respiratory alkalosis?
chloride-containing solution
HCO3- ions are replaced by Cl- ions.
Causes of metabolic acidosis (3)
– Accumulation of acidic substances (lactate) because of diffuse hypoxia such as
(anemia, heart failure, shock, sepsis, hypoxemia, hypovolemia)
– Decreased elimination of acids (renal failure)
– Renal or intestinal loss of bicarbonate (renal tubular acidosis, diarrhea)
What is described:
pH 7.35 – 7.40;
HCO3- < 20 mmol/l;
PaCO2 < 35 mmHg
Metabolic acidosis,
compensated disorder
Secondary compensation
– Respiratory compensation – decrease of PCO2 through
hyperventilation
– Renal compensation – increase of H+ excretion and HCO3-
reabsorption
Causes of metabolic alkalosis (3)
– Loss of acidic gastric juices (excessive gastric aspiration, vomiting)
– Acid-base regulation disorder of the kidneys (treatment with
corticosteroids, diuretics)
– Iatrogenic causes (large quantity of bicarbonate administration)
What do the following parameters describe:
pH 7.40 – 7.45;
HCO3- > 24 mmol/l;
PCO2 > 45 mmHg
Metabolic alkalosis,
compensated disorder
Secondary compensation
– Respiratory compensation may be inadequate as hypoxemia
develops because hypoventilation
– Renal compensation – decrease of H+ excretion and HCO3- reabsorption
– Renal compensation is impaired if hypovolemia, hypokalemia and
hyponatremia occur
abomasal torsion and acid base balance status?
what about compensation?
H+ accumulates in distended abomasum
bicarbonate increases because there is less H+ to buffer
base excess results
and consequently an increase in pH toward alkalinity
compensation: renal excretion of HCO3- and decreased resp. ventilation to gain more CO2
neonatal diarrhea and acid base balance status?
what about compensation?
fluid, electrolyte/HCO3- loss in feces
-> decreased bicarbonate levels
base deficit results and consequently a decrease in pH toward acidity
compensation: increased renal H+ excretion, complete HCO3- reabsorption &
increased resp. ventilation to blow off excess CO2
3 main causes of respiratory acidosis
hypoventilation (apnea, pneumothorax etc.)
V/Q mismatching (Ventilation/perfusion ratio) (aspiration, pulmonary edema etc.)
cardiac disease
what is V/Q
ventilation - perfusion ratio on alveolar level
2 main causes of respiratory alkalosis
hyperventilation (iatrogenic, mechanical)
CNS response (to hypoxia)
2 main causes of METABOLICc alkalosis
gain of base (bicarb or acetate administration)
loss of acids (vomiting, hypokalemia, hypochloremia etc.)
2 main causes of metabolic acidosis
increased acid formation (hypoxia-lactic acidosis)
loss of base (diarrhea, renal tubular acidosis)
What are mixed acid-base disorders?
A mixed acid-base disorder is the simultaneous coexistence of two or more primary acid-base disorders in the same patient.
Evaluation of anion gap aids diagnosis.
All three measures (pH, PaCO2, HCO3-) shift to the same direction, either in the direction of acidosis or alkalosis.
4 main points for acid-base interpretation (+2)
- Evaluation of arterial blood pH (pH value)
- Evaluation of the respiratory component (PCO2 levels)
- Evaluation of the metabolic component (HCO3- levels)
- Evaluation of compensation
(5. Provisional assessment of the severity of an acid-base
disturbance based on the pH value.
- Capillary pH is lower and capillary PCO2 higher than respective
arterial values)
- Explain evaluation of compensation when interpreting acid-base balance
- Normal pH and abnormal respiratory and metabolic components (going in
the opposite direction to each other) indicate compensated acid-base
disorder - In case of a compensated acid-base disorder, it is usually difficult to determine which one of the shifts in the components is primary (the cause of the disorder), and which one is secondary (compensatory).
Abnormal pH occurring with missing or insufficient compensation
indicates
uncompensated acid-base disturbance.
If all three acid-base variables are abnormal in the same direction pH-wise, a what occurs?
a complex mixed-type acid-base disturbance occurs.
A disturbance of this kind is always uncompensated.
Severe acidosis pH and symptoms
pH ˂ 7.25
decrease in myocardial contractility;
vasodilation, arterial hypertension.
Severe alkalosis pH and symptoms
pH > 7.55
tissue hypoxia; disturbance of
consciousness;
muscle hypotonia; heart rhythm disorders.
What is anion gap?
The anion gap is the quantity difference between cations and anions in serum, plasma, or urine.
The anion gap is a value calculated from the results of multiple individual medical lab tests. It may be reported with the results of an electrolyte panel, which is often performed as part of a comprehensive metabolic panel.
The evaluation of the anion gap can be can be useful for
distinguishing between different types of metabolic acidosis
so the existance, size and nature of an anion gap can help you determine cause of metabolic acidosis
e.g. a normal gap with metabolic acidosis and hyperchloremia indicate bicarbonate loss as cause of acidosis (ie. diarrhea)
an increased gap with metabolic acidosis indicates increased organic acids (causing the gap)
Respiratory disorders are compensated by
renal changes.
Metabolic disorders are compensated by
both renal changes and by respiratory changes.
When the body’s
buffer systems do not ensure optimal pH in blood, what happens?
compensatory mechanisms are activated
normal blood HCO3- is?
24 mmol/liter
With a PaCO2 of 40mmHg, a HCO3- of 29 mmol/L and a pH of 7.5 what do we have?
metabolic alkalosis
With a PaCO2 of 40mmHg, a HCO3- of 15 mmol/L and a pH of 7.22 what do we have?
metabolic acidosis
Renal compensation of respiratory acidosis
increase of H+ excretion and increase HCO3- reabsorption in
kidneys
Renal compensation of respiratory alkalosis
decrease of H+ excretion
and decrease HCO3- reabsorption in kidneys
What IVFT is used for correction of metabolic alkalosis?
chloride-containing solution
HCO3- ions are replaced by Cl- ions.
What IVFT is used for correction of metabolic acidosis?
Lactated ringers solution
Lactate is converted to bicarbonate ions in the liver.
Respiratory compensation of metabolic alkalosis
hypoventilation and an elevation in arterial PCO2. This lowers the arterial pH toward normal.
Respiratory compensation of metabolic acidosis
hyperventilation and “blowing off” excess CO2 thus lowering arterial PCO2 and increasing pH toward normal.
What does the anion gap tell you?
whether the electrolytes are out of balance or if the blood is too acidic or not acidic enough.
Normally the
concentrations of cations and anions in the plasma are
equivalent.
the normal anion gap represents the difference between the sum of ? and the sum of ?
the difference between Na+ and K+
and
HCO3- and Cl-
or about 1O to 12 mEq
What does a high anion gap mean?
possible acidosis
What does a low anion gap mean?
possible alkalosis
In metabolic acidosis a normal anion gap is characteristic of
conditions related to
bicarbonate loss with retention of chloride
to maintain an ionic balance.
This is called hyperchloremic
metabolic acidosis.
An elevated anion gap is characteristic of
acidosis associated with accumulation of anions other than chloride
(e.g., lactate, ketoacids [i.e., acetoacetate and beta butyrate])
Base excess is defined as
the amount of strong acid that must be added to each liter of fully oxygenated blood to return the pH to 7.40 at a temperature of 37°C and a pCO2 of 40 mmHg (5.3 kPa).
A base deficit (i.e., a negative base excess) can be correspondingly defined in terms of the amount of strong base that must be added.
How much is PaO2 typically?
arterial ~ 100 mm Hg
if increased, or decreased The HC03- indicates
if increased,
metabolic alkalosis
if decreased,
metabolic acidosis
To decide whether the pCO2 or HCO3 change represents the disease process and not the
compensatory attempt, use
the deviation of the pH from its normal mean to
indicate the net disease affect.
What is Kussmaul breathing?
is a deep and labored breathing pattern often associated with severe metabolic acidosis, particularly diabetic ketoacidosis but also kidney failure. It is a form of hyperventilation, which is any breathing pattern that reduces carbon dioxide in the blood due to increased rate or depth of respiration.
In metabolic acidosis, breathing is first rapid and shallow[1] but as acidosis worsens, breathing gradually becomes deep, labored and gasping. It is this latter type of breathing pattern that is referred to as Kussmaul breathing.
Why does shock lead to metabolic acidosis?
This acidosis results from the production of acid metabolites by cells forced into anaerobic metabolism by hypoxia brought on by the shock.
Body may compensate by inducing hyperventilation to bring PCO2 down.
Are mixed acid-base disorder compensated or
decompensated?
Mixed acid-base disorder is always decompensated.
Acute resp. acidosis 1st compensatory step
Initial response is cellular buffering (plasma protein buffers). This elevates plasma bicarbonate only slightly.
Acute resp. acidosis 2nd compensatory step
Second step is renal compensation, is slow.
Renal excretion of carbonic acid increases and bicarbonate reabsorption increases.
Bicarbonate does not act as a buffer in
acute respiratory acidosis
because a buffer system cannot buffer itself so to speak.
what happens to bicarbonate in metabolic acidosis
results in an abnormally low serum bicarbonate level.
what happens to bicarbonate in metabolic alkalosis
there is excess of bicarbonate in the body fluids
hyperkalemia/hypokalemia in acid-base balance
Acid-base disorders alter potassium transport.
In general, acidosis causes decreased K+ secretion and increased reabsorption in the collecting duct leading to hyperkalemia.
Alkalosis has the opposite effects, often leading to hypokalemia.
e.g. metabolic acidosis -> hyperkalemia, metabolic alkalosis -> hypokalemia
Hyperkalemia is exacerbated in calves with marked dehydration, because hypovolemia decreases renal blood flow and consequently the glomerular filtration rate, thereby minimizing the ability of the animal to excrete potassium.
hypernatremia/hyponatremia in acid-base balance
Na+ plays a role in maintaining acid-base balance.
Severe vomiting causes loss of hypokalemia and hyponatremia.
The kidneys compensate for these losses by retaining sodium in the collecting ducts at the expense of hydrogen ions, leading to metabolic alkalosis.
So the eventual hypernatremia from compensatory mechanism is accompanied by metabolic alkalosis because all the H+ is gone.
hypernatremia with e.g. salt toxicosis
hyperchloremia/hypochloremia in acid-base balance
Chloride and bicarbonate concentrations share an inverse reciprocal relationship during either acidosis or alkalosis. They together maintain an ionic balance of the cellular space.
Hyperchloremia forces bicarbonate to move intracellularly to maintain ionic equilibrium, thus reducing the available bicarbonate for the pH buffering system leading to net acidosis.
Hypochloremia can contribute to the maintenance of metabolic alkalosis by increasing the reabsorption of and reducing the secretion of bicarbonate in the distal tubule.
e.g. hyperchloremia in Renal Tubular Acidosis
Hypochloremia in abomasal impaction because chloride ions are continually secreted into the abomasum.
hypercalcemia/hypocalcemia in acid-base balance
Ca++ binding is pH dependent and alters the level of ionized calcium in the blood. Alkalosis promotes increased protein binding, which decreases free calcium levels (hypocalcemia).
Acidosis, on the other hand, decreases protein binding, resulting in increased free calcium levels (hypercalcemia).
e.g. hypocalcemia in milk fever, called puerperal tetany/eclampsia in dogs
hypercalcemia can be caused by primary hyperparathyroidism and renal failure (to excrete Ca++)
hyperphosphatemia/hypophosphatemia in acid-base balance
Phosphorus also helps maintain normal acid-base balance (pH) by acting as one of the body’s most important buffers.
Acute respiratory alkalosis induces hypophosphatemia via changes in cellular pH. Increased pH stimulates phosphofructokinase, thus stimulating glycolysis to produce ATP, thus consuming phosphate from the cellular space. Serum phosphate is shifted intracellularly to meet this demand.
Hyperphosphatemia can cause high anion gap (AG) metabolic acidosis mainly through generation of acidic compounds that neutralize bicarbonate.
e.g. Hyperphosphatemia can be a result of rhabdomyolysis
hypophosphatemia is commonly seen during the periparturient period in cattle due to the onset of lactation
hypermagnesemia/hypomagnesemia in acid-base balance
hypomagnesemia and metabolic alkalosis are associated.
Normally, the parathyroid glands release a hormone that increases blood calcium levels when they are low. Magnesium is required for the production and release of parathyroid hormone, so when magnesium is too low, insufficient parathyroid hormone is produced and blood calcium levels are also reduced.
Hypocalcemia is associated with alkalosis.
“Both ionized calcium and ionized magnesium concentrations decreased as the pH in the specimen increased, indicating the stronger binding of these ions with proteins in the more alkaline environment.”
e.g. hypomagnesemia in grass tetany
hypermagnesemia is most commonly iatrogenic as its otherwise rare
Metabolic acidosis with normal anion gap is described as?
hyperchloremic
In patients with a normal anion gap the drop in HCO3- is the primary pathology.
Since there is only one other major buffering anion, it must be compensated for almost completely by an increase in Cl−. This is therefore also known as hyperchloremic acidosis.
A high anion gap is indicative of
If the gap is greater than normal, then high anion gap metabolic acidosis is diagnosed.
In these conditions, bicarbonate concentrations decrease by acting as a buffer against the increased presence of acids (as a result of the underlying condition).
The bicarbonate is consumed by the unmeasured cation (H+) (via its action as a buffer) resulting in a high anion gap.
A low anion gap is
rare - caused by hypoalbuminemia
Albumin is an anionic protein and its loss results in the retention of other negatively charged ions such as chloride and bicarbonate. As bicarbonate and chloride anions are used to calculate the anion gap, there is a subsequent decrease.
What is osmolal gap
the difference between measured serum osmolality and calculated serum osmolality
A normal osmol gap is < 10 mOsm/kg.
Osmol gaps are used as a screening tool to identify toxins.
What does an osmolal gap tell you?
An osmolal gap greater than 10 mOsm/kg indicates the presence of abnormal, unmeasured osmotically active molecules.
salicylate poisoning
also known as aspirin poisoning
can cause metabolic acidosis
Diagnosis is clinical, supplemented by measurement of the anion gap, arterial blood gases.
Contraction alkalosis
This results from a loss of water in the ECF such as from dehydration. Decreased extracellular volume triggers RAAS, and aldosterone subsequently stimulates reabsorption of sodium (and thus water) within the nephron of the kidney.
However, a second action of aldosterone is to stimulate renal excretion of hydrogen ions (while retaining bicarbonate), and it is this loss of hydrogen ions that raises the pH of the blood.
