Acid-Base Balance Lecture Neal Padmahan Flashcards
Give 4 threats to acid/base homeostasis in the body
• generation of CO2 from aerobic respiration generates carbonic acid
• metabolism of acidic/alkaline foods - metabolism of amino acids great acid
load (eg lysine, arginine, cysteine) or an alkali load (eg glutamate or
aspartate)
protein rich Western diet is acid load
• incomplete (anaerobic) respiration - makes keto-acids, lactic acid
• loss of alkali in stool or loss of acid in vomiting
List the 3 major components of acid-base regulation in the body
• buffering
• ventilation - control of CO2 level
• RENAL regulation of bicarbonate
and H+ secretion and reabsorption
It’s rare that H+ concentration is abnormal for long. Maintenance of H+ conc may be at the expense of what other molecules of blood chemistry?
Bicarbonate ion conc
And partial pressure of CO2
Formula for pH?
pH = -log10 H+
Define buffers?
Weak acids, partially dissociated in solution
Acid base + H+
What is the principle physiological buffer?
The carbon dioxide - bicarbonate system
What is the formula for hydrogen ion concentration of a weak acid?
Acid base + H+
[H+] = K [acid] / [base]
What’s the equation for the CO2-bicarbonate buffer system?
CO2 + H2O H2CO3 HCO3- + H+
Carbonic anhydrase catalyses INTERconversion of CO2 & H2O to bicarbonate and hydrogen ion ^^
What enzyme catalyses INTERconversion of CO2 and H2O to bicarbonate and hydrogen ions?
Carbonic anhydrase
What is the equation for pH the physiological buffer system? (Hasselbach equation)
pH = 6.1 + log ([HCO3-] / [CO2])
What is the purpose of buffers?
To prevent large changes in pH
Why is the CO2 concentration kept constant?
Because CO2 is highly diffusible and the CO2 concentration is regulated by respiration
?
Addition of H+ consumes HCO3 which generates CO2 + H2O
The CO2 is then exhaled and there is little H+
What happens to bicarbonate ions as H+ ions are lost? And why?
Loss of H+ lead to the opposite, generation of HCO3-
This is because there is no H+ to bind with the bicarbonate ion to make H2CO3 so the HCO3- level rises
Is CO2 a volatile or fixed acid?
Volatile
What is meant by a volatile acid?
One that can be eliminated from the body as a GAS
Eg. CO2 - all of which is eliminated by breathing out
What is a fixed acid?
An acid made in the body from sources other than carbon dioxide and is NOT excreted by lungs
What ions are consumed to buffer a weak acid?
Then how is it excreted?
At the expense of what ions?
Buffering a fixed acid consumes bicarbonate ions (HCO3-) but although CO2 will be excreted by ventilation, this will be at the expense of HCO3- so it’s conc will be lowered
To remove H+ effectively more HCO3- must be produced
Regulation of HCO3- conc is the job of the KIDNEYS - where H+ excretion and regeneration of HCO3- are linked
How do the KIDNEYS regulate acid base balance?
• reabsorb filtered HCO3- ions
• secrete FIXED acid
- secrete NON-HCO3- buffer in urine (mainly phosphate ion, PO4 3-)
- secrete NH4+ (ammonium) into urine
Formula for filtration if filtered bicarbonate ions?
[HCO3] x GFR = >4000 mmol/day
Where is most bicarbonate absorbed?
Proximal convoluted tubule
What can result if there is an inability to reabsorb filtered HCO3- ions?
Metabolic acidosis (Proximal tubular acidosis - failure to reabsorb bicarbonate)
Describe the generic mechanism for bicarbonate ion reabsorption?
Including the how it DIFFUSES into cell and what it’s broken down to in cell and where each of the products go and what enzyme is involved
Filtered HCO3- is broken down to water and carbon dioxide by CARBONIC ANHYDRASE (by brush border)
The water and CO2 diffuse from lumen into cell
Inside cell CARBONIC ANHYDRASE converts the water and CO2 into H+ ion and bicarbonate ion
The H+ ion is excreted back into the tubule lumen and the bicarbonate is reabsorb into interstitium then the blood
How much filtered HCO3- should be absorbed?
Almost 100%
How much filtered HCO3- should be absorbed?
Almost 100%
How can kidneys generate new HCO3-? (2 methods)
- excrete ammonium (NH4+) salts in urine
* excrete titratable acids in urine
Is bicarbonate reabsorption active or passive? ⚠️⚠️⚠️
Very active
In bicarbonate reabsorption is there any net loss of H+ or net gain of bicarbonate? ⚠️⚠️⚠️
No
How much fixed acid to we excrete per day?
Approx 70mmol/day
Secreting a fixed acid generates what? ⚠️⚠️⚠️
A new bicarbonate ion
How much fixed acid to we excrete per day?
Approx 70mmol/day
Is bicarbonate reabsorption active or passive? ⚠️⚠️⚠️
Very active
Secreting a fixed acid generates what?
A NEW bicarbonate ion
Secreting a fixed acid generates what?
A new bicarbonate ion
Where is carbonic anhydrase found in renal tubules?
Brush border
Fixed acids are not buffered by bicarbonate ions. What 2 substances can they be buffered by?
Filtered phosphate ions PO4 3- Ammonium ions (NH4+) secreted into urine
Titration of Filtered phosphate ions is dependent on what?
The deliver of filtered buffer so it’s relatively fixed
What happens to ammonium secretion in acidosis?
Unregulated to
Failure to be able to secrete fixed acids can cause what?
Acidosis
Distal tubular acidosis - Inability to excrete hydrogen ions
Difference between 1) proximal tubular acidosis and 2) distal tubular acidosis?
- Failure to reabsorb bicarbonate
2. Failure to secrete hydrogen ions
Describe the secretion of an H+ ion bus neutralisation (?) of phosphate? ⚠️⚠️⚠️
Filtered phosphate HPO4 2- is titration with H ion
The h ion is made in the tubular cell by H2O and CO2 conversion by carbonic anhydrase into a hydrogen ion and bicarbonate ion
The H+ ion is what is excreted into the tubule to titrate the HPO4 2- and he bicarbonate made is reabsrobed into interstitium (then blood)
i.e a bicarbonate has been created by excretion of one H+ ion
Secretion of H+ via glutamine metabolism and resulting excretion of an ammonium ion (NH4+)?
Also involves liver
This is why liver failure patients become acidotic
In PCT glutamine is broken into ammonium NH4+ and HCO
How is acid excreted?
Titration with phosphate
Or excretion of ammonium
What is the major non HCO3- buffer in urine?
PO4 3-
How much hydrogen ion excretion per day can be accounted to phosphate titration?
Approx 40 mmol/day
How is acid excreted?
Titration with phosphate
Or excretion of ammonium
What is the major non HCO3- buffer in urine?
PO4 3-
How much hydrogen ion excretion per day can be accounted to phosphate titration?
Approx 40 mmol/day
What controls ammonium secretion?
Metabolism of GLUTAMINE (amino acid)
How does acidosis affect ammonium excretion?
Upregulates it by stimulating glutamine transport and oxidation
In NORMAL conditions how much H+ secretion is due to ammonium excretion?
50-100mmol
But it can be increased
KEY CONCEPTS (3): For every H+ excreted from body what is generated?
A new HCO3- which is absorbed
KEY CONCEPTS (3): Name the 2 method of excreting fixed acids?
Excretion of titratable acid ⚠️⚠️
Excretion of ammonium ion
What components of blood biochemistry are affected by acid-base disorders?
HCO3- and CO2 blood levels
The primary disturbance in H+ concentration but it is soon buffered by a COMPENSATORY RESPONSE so it remains in normal range at expense of the other Bicarbonate ions and carbon dioxide
Why is H+ conc fairly normal in people with acid base disorders?
The primary disturbance in H+ concentration but it is soon buffered by a COMPENSATORY RESPONSE so it remains in normal range at expense of the other Bicarbonate ions and carbon dioxide
Is it easier to compensate for disturbed H+ via kidneys (absorption/excretion) or via lungs (increased or decreased ventilation)?
Via kidneys
Since There is a limit to how fast/hard you can breath
Difference between acidosis and acidaemia?
Acidosis - abnormal blood HCO3-
Acidaemia - reduced blood pH
What is more common acidosis or acidaemia?
Acidosis
How does metabolic acidosis affect:
- H+ conc
- Partial pressure of CO2
- Bicarbonate ion conc
- High or normal (ie low or norm pH)
- Low
- LOW
How does Respiratory acidosis affect:
- H+ conc
- CO2 partial pressure
- HCO3- conc
- High or normal (ie low or norm pH)
- HIGH
- High
How does metabolic alkalosis affect:
- H+ conc
- CO2 partial pressure
- Bicarbonate ion conc
- Low or normal (ie high/norm pH)
- High
- HIGH
How does respiratory alkalosis affect:
- H+ concentration
- CO2 partial pressure
- Bicarbonate ion conc
- Low or normal
- LOW
- Low
3 causes of metabolic acidosis?
Addition of extra acid
Failure to excrete acid
Loss of HCO3-
How can addition of extra acid come about (in relation to causes of metabolic acidosis)?
- production of organic acid through metabolism eg lactic acidosis / Keto acidosis
- acid ingestion eg methanol
What is the usual cause of failure to excrete acid?
Renal TUBULAR acidosis
How can bicarbonate ions be lost?
In diarrhoea (stool) In urine (renal tubular acidosis)
What condition would cause bicarbonate ion loss in urine?
Renal tubular acidosis
Give an example of metabolic acidosis?
DKA - diabetic Keto acidosis
What is the PRIMARY abnormality in metabolic acidosis?
FALL in plasma bicarbonate ion conc
Since it’s used up buffering H+ ions
What is the COMPENSATORY response to metabolic acidosis?
Fall in partial pressure of CO2 due to increased respiratory rate
Examples of general systemic effects of metabolic acidosis?
- CVS - arrhythmias, vasodilation
- Resp - high ventilation rate (hyperventilation) (KUSSMAUL’S breathing)
- Metabolic - protein wasting, resorption of Ca from bone
- Neutrophilia
What is the normal anion gap?
6-12 mmol/litre
What is diabetic Keto acidosis (DKA)?
In diabetic patients a shortage in insulin switches the body to burning FATTY ACIDS which produces ACIDIC ketones
What is the anion gap?
The difference between major cation (ie Na+) and major anions (Cl- and HCO3-)
Body is electrically neutral this gap is only present because there are UNMEASURED anions
What is the main reason to calculate the anion gap?
To identify the likely CAUSE of metabolic acidosis especially lactic acidosis or ingestion of acid
Anion gap measurement allows metabolic acidosis to be classified as _____ or ______?
Allows the metabolic acidosis to be classified as HIGH ANION or LOW ANION GAP acidosis
Equation for normal anion gap?
[Na+] - {[Cl-] + [HCO3-]} = 6-12 mmol/litre
If HCO3- ion conc decreases what will happen to the anion gap if a rise in Cl- cannot explain it?
Since body is electrically neutral if the HCO3- ion drops then EITHER the Cl- conc is raised OR there may be another anion (negative ion) present in which case the anion gap RISES because this other anion is not MEASURED (only na, HCO3 and chloride are)
4/5 examples of causes of metabolic acidosis that show and INCREASED anion gap?
Lactic acidosis
Ketoacidosis - due to starvation/diabetes
Ingestion - of methanol/aspirin…
Examples of metabolic acidosis caused by bicarbonate loss that gives a NORMAL anion gap?
Diarrhoea
Carbonic anhydrase inhibitors
How does chronic renal failure affect anion gap?
AG falls mostly but sometimes normal
Normal range of anion gap? ⚠️⚠️⚠️
9-16
How should you adjust anion gap when albumin is low?
Reduce AG by 2.5 for every 10g/litre fall in albumin concentration
How do we tell if there is co-existing RESPIRATORY acidosis along with the metabolic acidosis?
If partial pressure of CO2 does not reduce sufficiently via the respiratory compensation
__________________________________________________
(pCO2 should fall 0.125kPa (from 5) for every 1 mmol/litre fall in bicarbonate (from 25))
(5 and 25 are the approx normal values^)
In chronic renal failure, as renal function declines most patients become acidotic. Initially what type of acidosis is this?
Normal anion-gap acidosis
What causes the INITIAL normal anion gap acidosis in chronic renal failure?
Reduced renal secretion of ammonium
How is the titratable acid excretion initially preserved in chronic renal failure?
Due to increased PO4 excretion and decreased PO4 reabsorption in PCT
EVENTUALLY patients maybe develop high anion gap as PO4 3- are other anions accumulate
In chronic renal failure patients initially develop normal anion gap metabolic acidosis due to reduced renal ammonium secretion. EVENTUALLY it may become HIGH anion gap acidosis. Why?
As PO4 and other anions accumulate
LACTIC ACIDOSIS
How is lactic acid produced in body?
Through glycolytic metabolism of purification acid
LACTIC ACIDOSIS
What buffers lactic acid and what is it converted to in this process?
Bicarbonate ions
To lactate
Where is lactic acid metabolised?
Liver (and kidney)
What is lactic acidosis?
Buildup of lactate in the body which reduces blood pH. It’s a form of metabolic acidosis
What usually causes lactic acidosis?
Hypoperfusion (low blood flow) therefore Low oxygen so anaerobic respiration occurs which produces lactate
And reduced hepatic clearance - major problem in sepsis
Some medications can cause lactic acidosis. Give examples.
Metformin
Poisoning with cyanide or aspirin
EXAMPLE 65yr male with renal impairment. Has nocturia, hesitancy, post-micturition dribbling Na+ : norm K+ : very slightly high Cl- : very slightly high HCO3- : half the normal value Urea : very high eGFR : very low
Likely diagnosis? What’s the anion gap? What would you expect the pCO2 to be? What more info would be useful? Treatment?
- Renal failure due to OBSTRUCTION (urine symptoms), probably prostrate. Confirm diagnosis by ultrasound
- 136-(112+12) = 12
- Low due to respiratory compensation (high breathing rate)
- Arterial blood gases would confirm norm/high H+ ion conc & would exclude co existing resp acidosis (from pCO2)
- Relieve obstruction (Catheter) and consider oral bicarbonate
What is the primary abnormality in metabolic alkalosis?
Low H+ conc and high HCO3- conc
in metabolic alkalosis HCO3- is not being excreted
What’s the compensatory response in METABOLIC alkalosis?
HYPOventilation (low breathing rate) which INCREASES pCO2 to reduce blood pH
Main causes of metabolic alkalosis?
Gastric acid loss (vomiting) - single MAIN CAUSE Diuretics Hyperaldosteronism Cushing’s Profound K+ depletion
In metabolic alkalosis what happens to HCO3- that is not being excreted when there is a Cl- deficiency?
HCO3- is reabsorbed with Na+ when there’s a deficiency of Cl-
This is to stay ELECTRONEUTRAL
This is also promoted by aldosterone
?
In PCT bicarbonate reabsorption is mediated by H+ secretion but carbonic anhydrase in brush border breaks it down to CO2 and H2O
In DCT it is also mediated by H+ excretion but no carbonic anhydrase is present so bicarbonate accumulates in tubule fluid
Why does chloride depletion contribute to metabolic alkalosis? ⚠️⚠️⚠️⚠️
In DCT bicarbonate reabsorption requires Cl- SECRETION -
If tubular Cl- due is reduced due to depletion there is a gradient to absorb more HCO3-
?????
Why does volume depletion contribute to metabolic alkalosis?
If there’s volume depletion Na+ absorption increases
Na+ reabsorption drives HCO3- reabsorption (to remain electroneutral)
This is also promoted by aldosterone
Why does potassium depletion contribute to metabolic alkalosis?
Unclear but one example is :
H+ secretion out of blood into DISTAL tubule occurs in exchange for K+ which travels into blood
Therefore in K+ depletion, in an attempt to retain K+ ions, H+ will be excreted leading to bicarbonate reabsorption which contributes to alkalosis
What’s the treatment for metabolic alkalosis?
Treat underlying cause
Give fluids eg 0.9% NaCl for vomiting
What is respiratory acidosis?
And compensatory response
HYPOventilation therefore increased pCO2 with compensatory response to retain bicarbonate ions
Most H+ is buffered intracellularly With later renal compensation
What is respiratory alkalosis?
Hyperventilation thus reduced pCO2 with compensatory response to excrete bicarbonate
What happens to serum Ca2+ in ACUTE alkalosis?
There’s increased binding of Ca2+ to albumin therefore serum ionised Ca2+ DECREASES & TETANY results (muscular spasms/involuntary contractions)
What type of acidosis happens in shock?
Lactic acidosis
What type of acidosis can Metformin cause?
Lactic acidosis (Metformin increases anaerobic respiration therefore lactate is produced)
