Clinical BioChemistry Flashcards
Acid Base Balance
Why is Acid-Base Balance important?
*LOB: Outline importance of tight regulation of pH control due to influence on protein folding and enzyme function
H+ ions are by product of ATP production
Maintenance of extracellular H+ is the same as pH maintenance
Essential to maintain protein / enzyme function
Acid Base Balance
What does extracellular H+/ pH rely on?
*LOB: Outline importance of tight regulation of pH control due to influence on protein folding and enzyme function
Depends on the relative balance between acid production and excretion
Respiration: Carbon Dioxide production and excretion
Renal: Hydrogen ion production and excretion
Acid Base Balance
Why is acid-base balance important?
*LOB: Outline importance of tight regulation of pH control due to influence on protein folding and enzyme function
We often view it as a measure of the physiological events such as ions being removed by vomitting and therefore can find the source of imbalance
For example, Hypercholoraemia is common in sepsis.
Acidosis can cause Hyperkalaemia- a risk on heart arrythmia
Acid Base Balance
What are the three compensatory mechanisms
*LOB: Describe buffering and compensation techniques in pH alterations
Buffering
Compensation
Treatment
Acid Base Balance
What is buffering?
*LOB: Describe buffering and compensation techniques in pH alterations
Bicarbonate buffer in serum
Phsophate in urine excreted
Skeleton (low pH = calcium release)
Intracelllular accumulation/ loss of H+
Excess hydrogen ions (H⁺) are neutralized by bicarbonate (HCO₃⁻) to form carbonic acid (H₂CO₃), which then dissociates into carbon dioxide (CO₂) and water (H₂O).
Acid Base Balance
What is compensation?
*LOB: Describe buffering and compensation techniques in pH alterations
Diametric opposite of original abnormlaity
Never overcompensates
Delayed and limited.
Acid Base Balance
What are the two types of compensation?
*LOB: Describe buffering and compensation techniques in pH alterations
Respiratory compensation for primary metabolic disturbance is quick
*Kussmal Breathing in response to DKA
Metabolic compensation for primary respiratory abnormalities takes 36-72 hours to occur.
*enzyme induction, more chronic scenario
Acid Base Balance
How is renal bicarbonate regenerated?
*LOB: Describe buffering and compensation techniques in pH alterations
The kidneys regulate the [HC03-] by
1) conserving or excreting the HC03- present in the glomerular ultrafiltrate;
2) producing new HCO3- which enters the body fluids as the kidneys excrete ammonium salts and titratable acids (this sum is called net acid) in the urine
3) Reabsorbtion ** H+ secretion from cells across the luminal membrane is mostly in exchange for Na+ ions, and to a small extent ,through a proton ATPase.**
4) Regulation **Proximal reabsorption HCO3- is stimulated by decreases in cell pH acutely activates Na-H exchange and chronically induces expression of NHE3 and Na-3HCO3 cotransporters and high levels of Angiotensin II stimulate Na-H exchange (e.g., contraction of the extracellular fluid ).
http://www.hsc.edu.kw/student/materials/course_notes/renal/OutBicarb.htm
Acid Base Balance
How does renal regulation affect ions?
*LOB: Describe buffering and compensation techniques in pH alterations
Aldosterone at the distal tubule encourages the cellular reabsorbtion of Na+ and the excretion of K+ and H+.
As this is beneficial in Alkalosis, the body needs to excrete H+ ions, but this causes hypokalaemia
And thus the inverse is true that in Acidosis this causes Hyperkalaemia
http://www.hsc.edu.kw/student/materials/course_notes/renal/OutBicarb.htm
Acid Base Balance
How does the respiratory system effect acid-base?
*LOB: Describe buffering and compensation techniques in pH alterations
Hyperventiliation removed CO2 reducing acidity and H+ ions
Hypoventilation retains CO2 which increases acidity
Remember H⁺+HCO₃⁻↔H₂CO₃↔CO₂+H₂O
Acid Base Balance
What is ABG?
*LOB: Develop a system of arterial blood gas analysis to show first the primary alteration, then identify any compensation that may have developed
Arterial Blood Gas- measures key set parameters
pH (H+ electrode)
pCO2
pO2
And can calculate other parameters
Acid Base Balance
What are ABG errors?
*LOB: Develop a system of arterial blood gas analysis to show first the primary alteration, then identify any compensation that may have developed
Need to collect blood anaerobically into a heparinsed blood gas syringe or capillary – NO air bubles (to prevent loss of CO2 from blood into air)
K+ result may not be valid if haemolysed sample – but YOU WILL
NOT KNOW!
Acid Base Balance
How to interpret respiratory ABG?
*LOB: Develop a system of arterial blood gas analysis to show first the primary alteration, then identify any compensation that may have developed
Remember always respiratory as we can see the pO2, pCO2 in blood
Acidosis Low pH high CO2
Alkalosis High pH, Low CO2
Acid Base Balance
How to interpret respiratory ABG and if there is compensation?
*LOB: Develop a system of arterial blood gas analysis to show first the primary alteration, then identify any compensation that may have developed
Take the basic understanding that pH and CO2 shows respiratory acidosis or alkalosis
The HCO3- shows compensation
HOWEVER Metabolic compensation is NOT if HCO3- is high
Respiratory Acidosis with metabolic compensation has a HIGH HCO3-
Respiratory Alkalosis with metabolic compensation has a LOW HCO3-
Acid Base Balance
What if its a metabolic error?
*LOB: Develop a system of arterial blood gas analysis to show first the primary alteration, then identify any compensation that may have developed
If the CO2 is normal and HCO3- is derranged it is Metabolic Error
Metabolic Acidosis Low pH, Low HCO3-, normal CO2
Metabolic Alkalosis High pH, High HCO3-, normal CO2
Acid Base Balance
What about a metabolic error with respiratory compensation?
*LOB: Develop a system of arterial blood gas analysis to show first the primary alteration, then identify any compensation that may have developed
Metabolic acidosis with respiratory compensation
low pH, low HCO3-, low CO2
Metabolic alkalosis with respiratory compensation
high pH, high HCO3, high CO2
Acid Base Balance
How to interpret ABG overall?
*LOB: Develop a system of arterial blood gas analysis to show first the primary alteration, then identify any compensation that may have developed
1) Is it acidosis? (low pH) or alkalosis (high pH)
2) Is it respiratory (CO2 inverse) or metabolic (CO2 match) ?
3) Is there compensation?
Remember ROME
Respiratory Opposite, Metabolic Equal
Respiratory look at CO2
Metabolic look at HCO3-
Acid Base Balance
Causes of disturbed Acid-Base
*LOB: Describe clinical case correlation with each conditition (acidosis and alkalosis)
Respiratory Acidosis
* CO2 retention
* Compensation is metabolic acidosis
Respiratory Alkalosis
* Increased CO2 loss
* Compensation is metabolic acidosis
Metabolic Acidosis
* Acid ingestion
* Increased acid production, reduced excretion
* Compensatory respiratory alkalosis
Metabolic Alkalosis
* Difficult primary disturbance to produce
* Compensatory respiratory acidosis
Acid Base Balance
Causes of Respiratory Acidosis
*LOB: Describe clinical case correlation with each conditition (acidosis and alkalosis)
Airway Obstruction
* Bronchospasms
* COPD
* Aspiration
* Strangulation
Respiratory Center Depression
* Anaesthetics
* Sedatives
* Cerebral Trauma
* Tumour
Neuromuscular Disease
* Guillian Barre Syndrome
* Motor Neurone Disease
Pulmonary Disease
* Pulmonary Fibrosis
* Respiratory Distress Syndrome
* Pneumonia
Extrapulmonary Thoracic Disease
Acid Base Balance
Causes of Metabolic Acidosis
*LOB: Describe clinical case correlation with each conditition (acidosis and alkalosis)
Increased H+ Formation
* Ketoacidosis
* Lactic Acidosis
* Poisoning- methanol, ehtanol, ethylene glycol, salicylate
* Inhertied organic acidosis
Acid Ingestion
* Acid poisoning
* XS paranteral administration of amino acids
H+ Excretion
* Renal Tubular Acidosis
* Renal Failure
* Carbonic dehydrase inhibitors (renal conversion enzyme)
Loss of Bicarbonate
* Diarrhoea
* Pancreatic, intestinal, or biliary fistula/ drainage
*Think Kussmaul
Ketones DKA
Uraemoa
Sepsis
Salicylate
Methanol
Aldehyde
Lactic Acid
Acid Base Balance
Causes of Respiratory Alkalosis
*LOB: Describe clinical case correlation with each conditition (acidosis and alkalosis)
Hypoxia
* High altitude
* Severe Anaemia
* Pulmonary Disease
Pulmonary Disease
* Pulmonary Oedema
* Pulmonary Embolism
Increased Respiratory Drive
* Respiratory stimulants incl salicylate
* Cerebral disturbance
* Hepatic failure
* G-ve septicaemia
* Primary Hyperventilation syndrome
* Voluntary Hyperventilation
Acid Base Balance
Comment on the following?
*LOB: Describe clinical case correlation with each conditition (acidosis and alkalosis)
Think ROME:
First Results
Low pH, High CO2 = Respiratory Acidosis due to COPD
Bicarbonate high = Metabolic compensation
Second Results Low PH, Normal CO2, Bicarbonate High. The normal CO2 is a false friend.
Those with COPD run on hypoxic drive and so if remove hypoxic drive with high O2 then respiratory depression.
Acid Base Balance
Comment on the following?
*LOB: Describe clinical case correlation with each conditition (acidosis and alkalosis)
Think ROME:
Low pH, low CO2 = Respiratory Acidosis
Low pH, low bicarbonate = metabolic acidosis
So which is it?
This is a metabolic acidosis with respiratory compensation Removal of CO2 via Kussmal Breathing. She has DKA.
Acid Base Balance
Comment on the following?
*LOB: Describe clinical case correlation with each conditition (acidosis and alkalosis)
Think ROME
high pH, low CO2, Respiratory Alkalosis
Low Bicarbonate = compensation
Salicylate O/D associated with tinitus
Acid Base Balance
Comment on the following?
*LOB: Describe clinical case correlation with each conditition (acidosis and alkalosis)
Think ROME
High pH, High CO2, High Bicarbonate
Metabolic Alkalosis with respiratory compensation
Low Potassium, Low Chloride, High Urea, High Creatinine
Hypovolaemic.
So ions are being lost due to vomitting and loss of fluid activates aldosterone to maintain blood pressure.
Tx correct plasma volume / switch off aldosterone, IV fluids and Potassium supplement
Acid Base Balance
Comment on the following?
*LOB: Describe clinical case correlation with each conditition (acidosis and alkalosis)
Think ROME
Low pH, low bicard = Metabolic Acidosis
CO2 low= respiratory compensation
Sodium High, Potassium Low, Bicarb Low, Urea High
Injestion of ethylene glycol has lead to dehydration so high Na, K+ moves out of cells and is excreted to absorb excess H+
High Urea is caused by dehydration or volume depletion
Ethylene glycol causes diuresis, increasing urine output
It can also cause oxalate crystal formation and injure kidneys.
Acid Base Balance
Comment on the following?
*LOB: Describe clinical case correlation with each conditition (acidosis and alkalosis)
Low Bicarb and rapidly breathing (low CO2)= Metabolic acidosis.
Osmolar Gap: 2(Na) + Urea + Glucose = 297.6
Osmolality = 315 (High)
Osmolar gap of 17
Is there an ion gap?
((Na) +(K)) -((HCO3) + Cl-)) = 24.2
Causes of Gap include (CAT MUDPILES below)
But, we know theres vision loss so we are thinking methanol
Tx use ethanol to override the enzymes so that formic acid is not formed (ethanol infusion) or if Methanol >200mg/dL Haemodyalisys or Fomepizole inhiits alcohol dehydrogenase.
Fluid and Electrolytes.
Physiological Response to Water loss
*LOB: Outline regulation of water balance: hormone involved, stimulus to secretion, function of hormone
Increase in ECF osmolality (less water same ions, ratio of solutes to water increases)
Stimulates 3 mechanisms
- vasopressin / ADH release (renal water retention)
- stimulation of hypothalamic thirst
- redistribution of water from ICF
Fluid and Electrolytes.
Comment on the following?
*LOB: Outline regulation of sodium and water balance: hormone involved, stimulus to secretion, function of hormone
Hypovolaemic Water loss via fever and shown by hypotension, dry tongue
Hypernatraemia Sodium is 163mmol/L
Why? Water loss so sodium more concentrated, RAAS in response to dehydration so sodium reabsorbtion. And ADH water reabsorbtion activated but. not adequate to compensate.
Next Identify cause of pyrexia, evaluate renal function before rehydration
Tx rehydrate.
Fluid and Electrolytes.
Comment on the following?
*LOB: Outline regulation of sodium and water balance: hormone involved, stimulus to secretion, function of hormone
Euvolaemic “she drank water” & normal potassium level, low urine sodium (< 20 mmol/L), suggests that the kidneys are not actively excreting sodium, low urine osmolality (172 mosm/Kg) also indicates that the kidneys are diluting the urine
Hyponatraemia due to excessive water intake.
High Creatinine may be due to dilution Effect: Low urine output may also result in a higher serum creatinine level due to decreased clearance. AKI not likely as normal urea and potassium.
water intoxication or psychogenic polydipsia
Fluid and Electrolytes.
Comment on the following?
*LOB: Outline regulation of sodium and water balance: hormone involved, stimulus to secretion, function of hormone
Hypovolaemia drop in lying/ standing BP
Salt and water being lost via GI D & V
Urine Na is low, as retaining as much sodium as possible. due to RAAS when volume depleted.
Urine Osmol is showing a concentrated urine as trying to retain water.
Fluid and Electrolyte
Causes of Hyponatraemia and how to idenitfy DDx
*LOB: Review causes of hyponatraemia
1) Hypovolaemic, Euvolaemic or Hypervolaemic?
2) If Hypo/Hyper check Urine Na
3) If Euvo check Urine Osmo
Fluid and Electrolyte
Hypokalaemia lab investigations
*LOB; Describe regulation of potassium in body
Fluid and Electrolytes
Sodium in IV fluids
*LOB: Describe the management of fluid balance and electrolyte disturbance
Remember distribution changes too
* colloid - plasma volume
* Saline/ balanced crystalloids - interstitial and lymphatic
* Glucose 5% - major ICF
Fluid and Electrolytes
Errors with managing fluid/ electrolyte balance
*LOB: Describe the management of fluid balance and electrolyte disturbance
Correct sodium at the same speed.
No more than 10mmol/L / 24hours sodium change
Fluid and Electrolytes
How is magnesium implicated?
*LOB: Review causes of hypokalaemia and hyperkalaemia and role of hypomagnesaemia in hypokalaemia
Severely hypomagnesaemic patients often have co-existent hypokalaemia and a cellular potassium deficit
reduced activity of the magnesium dependent sodium dependent ATPase system of cell membrane
Potassium is thus lost to the ECF
magnesium deficiency also impairs the renal conservation of potassium by inhibiting ROMK in apical tubular membrane
Potassium is thus lost in the urine
Fluid and Electrolytes
Causes of hypomagnesaemia
*LOB: Describe the management of fluid balance and electrolyte disturbance
Acid Base/ Fluid and Electrolytes.
Putting acid base and fluid and electrolytes together
