Acid-Base Balance Flashcards
What does pH stand for?
potential of hydrogen
determined by molar concentration of OH- and H+
What is the definition of an acid?
substance which can donate an H+ ion
What is the definition of a base?
substance which can accept an H+ ion
What happens when an acid is added to water?
Dissociates reversibly according to reaction:
HA H+ + A-
What is a conjugate base?
A-
can combine with a H+ to form HA
Why is pH important in the body?
- controls speed of body’s biochemical reactions through controlling rate of enzyme activity and electrical reactions
How does pH affect speed of body’s electrical reactions?
- synaptic function depends on IC and EC pH gradients
- synaptic activity causes local pH gradients
What is normal blood pH?
Venous - 7.35 as more CO2
Arterial - 7.45
< 7.35 = acidosis (acidaemia)
> 7.45 = alkalosis (alkalaemia)
What is the fatal pH range?
<6.8
>8.0
What happens in blood pH is outside the normal range?
Disturbance of body functions
disruption to enzyme systems and ETC in mitochondria
still compatible with life
Where do H+ ions originate from in the blood?
Normal diet is almost neutral with small acid amounts (protein diets = more acid intake)
Cellular metabolism is largest source of H+, produces large amounts of carbonic, sulphuric, phosphoric and other acids
From there H+ continually added (breakdown of foods - proteins, carbonic acid + H20 = CO2, exercise lactic acid)
How do disease states affect H+ levels?
Even more production of H+
diabetes = keto acids
How much acid is produced/intaken?
aerobic respiration -> carbonic acid (15 mol/d)
anaerobic respiration -> lactic acid (1.5mol/d)
Acid from diet - oxidation of sulfur containing amino acids -> sulfuric acid, incomplete oxidation of fatty acids -> acidic ketone bodies, hydrolysis of phosphoproteins and nucleic acids -> phosphoric acid = 60mmol/d
What mechanisms limit pH changes? How quickly do they act?
1- chemical buffer systems in blood and ICF (immediate)
2- respiratory centre in brainstem (1-3 minutes)
3- renal mechanisms (hours to days)
What is a buffer?
solution that can resist pH change upon addition of acid or base, can neutralise small amounts of acid or base maintaining stable pH
acts quickly to bind/release H+
temporary
consist of a weak acid and salt of that acid (weak base)
What are the 3 major chemical buffer systems in the body?
- bicarbonate (HCO3-) in the buffer system (ECF)
- proteins (haemoglobin and albumin) (ICF and ECF)
- phosphate (ECF)
How do acid-base disturbances affect internal K+ distribution?
Acidemia = tissues release K+ = hyperkalemia alkalemia = cells take up K+ = hypokalemia -> dangerous for the heart (essentially H+ displaces K+ from cells/blood)
What are the causes of normal gap acidosis? (TOP 2)
severe diarrhoea chronic laxative abuse villous adenoma drainage of pancreatic/biliary secretions (e.g. fistulas) NG tube losses acidifying salts administration urinary diversions
What are the causes of elevated gap acidosis?
ketoacidosis
lactic acidosis
severe renal failure
toxic ingestions
What are the causes of low gap acidosis?
haemorrhage
nephrotic syndrome
intestinal obstruction
liver cirrhosis
How is the anion gap affected by alkalosis?
Metabolic alkalosis - small increment in anion gap, particularly if due to vomtiting/diuretic use
Respiratory does not cause change
What is the second and third line of defence in regulating blood pH?
second: Respiratory system
third: kidneys - renal control
What are the limitations of the respiratory and renal control of pH?
Kidneys can only rid body of metabolic acids such as phosphoric, uric, lactic acid and ketones preventing metabolic acidosis
Lungs only deal with volatile acids - CO2
What 2 tasks must the kidney accomplish in order to maintain acid base balance?
- reabsorption of all filtered bicarbonate
- excrete the daily acid load
How does the kidney maintain acid base balance?
Hydrogen secretion, bicarbonate reabsorption and excretion of hydrogen ions with urinary buffers
What is the Henderson-Hasselbach equation used to find?
- pH of a buffer solution
- ratio of conjugate base to acid of the system
Examples of pathological respiratory acidosis/alkalosis and metabolic acidosis/alkalosis?
Respiratory acidosis = hypoventilation (COPD)
Respiratory alkalosis = hyperventilation (anxiety/altitude)
Metabolic acidosis = diarrhoea, keto-acidosis, lactic acidosis
Metabolic alkalosis = vomiting, hypokalaemia, ingestion of HCO3-
What is the significance of albumin in the anion gap?
If no/low albumin production it reduces the anion gap too much producing a low gap even though it is unmeasured as it is the main plasma buffer protein
How does the kidney excrete acid form urine?
Phosphate buffer and ammonium buffer
What is hyperchloremic metabolic acidosis?
-Normal gap acidosis
Bicarbonate is lost in acidosis and so to compensate chloride ions enter cells through the bicarbonate-chloride co-transporter to maintain the negative anion charge
However chloride is meant to be in the ECF and so it gets released out of the cell via chloride channels
This results in the anion gap not being changed overall due to chloride compensation but there is still acidosis due to loss of bicarb.
- Another mechanism where kidneys are unable to excrete H+ alone so HCO3- has to combine with them to excrete it, still a loss of HCO3- required Cl- to compensate again
What is elevated gap acidosis?
Decrease in HCO3- and increase in unmeasured anions
Mostly when metabolism produces acid not gut so need to buffer it with bicarb, however this causes further acidosis as more bicarb loss
What are the main anions and cations?
Anion - chloride
Cation - sodium
What is the anion gap?
difference between the measured cations and measured anions
What is low gap acidosis?
Albumin loss (negatively charged protein) causing bicarbonate and Cl- retention to compensate electrical charge Very major plasma protein so to correct albumin loss to close anion gap
What are the normal anion gap values?
12-16 mEq/L if taking into account potassium
8-12 otherwise
What are some unmeasured anions?
Lactic acid
Glycolic acid
Acetoacetate
Formic acid
How is bicarbonate reabsorbed by the kidneys?
- First gets filtered through the glomerulus
- H+ and HCO3- combine to form H2CO3- in the lumen of the PCT
- carbonic anhydrase on membrane of tubular cell allows breakdown of H2CO3 into H20 and CO2 inside the tubular cell
- carbonic anhydrase inside the cell allows H2O and CO2 to combine to form HCO3- again
- HCO3- gets excreted through a co-transporter with chloride into the blood meaning chloride enters the cell (chloride shift to maintain the charge of the cell)
- as HCO3- has left the cell H+ also must leave to maintain the pH and so it gets excreted into the lumen of the PCT by ATPase or by sodium/H+ symporter (daily acid load)
How does daily acid load occur?
In parts of the DCT
- via intercalated cells which have reversed polarity:
alpha intercalated cells secrete acid via apical H+ ATPase and a H+/K+ exchanger
and resorb HCO3-via Cl-/HCO3- exchanger and resorb acid
- beta cells secrete bicarb via CL-/HCO3- exchanger and resorb acid via H+/ATPase
What is the significance of the glutamate pathway?
Allows you to produce bicarbonate (through production of alpha-ketoglutarate -> glucose giving side products of ammonia and bicarb)
Happens in acidosis to retain more bicarb
What does the kidney do in acidosis and alkalosis?
Acidosis - excretes H= and retain bicarb (with help of glutamate pathway)
Alkalosis - tubular cells secrete bicarb and reclaim hydrogen ions (using ATPases), also trade K+ with H+
What is the hormonal regulation of acid/base?
Aldosterone - increases pH
Angiotensin II- increases pH
Parathyroid hormones - prevent reabsorption of HPO32 increasing pH
What is the protein buffer system?
Acidic and basic side chains can give up or take up H+
- if pH rises = carboxyl group of amino acid acts as a weak acid
- if pH falls = amino group acts as weak base
What is the haemoglobin buffer system?
H+ + Hb HHb
When would you get a normal anion gap, high and low?
> High - acid has been added to the blood by metabolism, not gut = ketoacidosis, lactic acidosis, titrable from diet, ingested acid (poisoned yourself)
normal - hyperchloraemic metabolic acidosis, bicarb loss and compensatory chloride rise
low - acid lost (diarrhoea, diuretics, mineralocorticoid, vomiting)
What are the consequences of acidosis?
- acute/severe: negative ionotropic effects, confusion, Kussmaul’s breathing, hyperkalaemia
- chronic: bone reabsorption, calciruia, stones, insulin resistance, progressive renal impairment
