Anion Gap And Renal Tubular Acidosis Flashcards
What is metabolic acidosis?
Defined by a pH less than 7.35 and a decrease in plasma bicarbonate which is less than 24 mEQ/L, which results in a respiratory compensation with hypercapnia to offset CO2 levels
How is metabolic acidosis classified?
Based on anion gap, where anions like Cl- are high compared to Na+.
What are the features of metabolic acidosis?
Deep Kussmaul breathing -> due to compensatory increase in alveolar ventilation
Hypotension and pulmonary oedema -> due to acidosis causing decreased cardiac output and arterial dilatation
What is serum anion gap?
Used as an indicator between the balance of anions like Cl- and and cations like Na+.
Normal serum anion gap is between 4 to 12 mmol/L
What are the serum anions?
The primary serum anion is Sodium.
Potassium, calcium, magnesium and proteins form the remainder of serum anions.
What are the serum cations?
The primary serum anion is Chloride.
It includes bicarbonate, phosphate and sulphate ions.
How is the serum anion gap measured?
It is based on (Na+) subtracted from (Cl-) and HC03-) and the value represents the amount of unmeasured anions in the serum.
Normal serum anion gap is 4-12 mmol/L and is used to determine causes of metabolic acidosis.
What causes a rise in serum anion gap?
Rise in positive ions due to greater production of acids which occurs in:
-> Lactic acidosis, associated with hypoxia from conditions like heart failure
-> Diabetic ketoacidosis, associated with type 1 diabetes or excessive alcohol use and starvation
-> Ingestion of antifreeze
->Aspirin overdose
->Renal failure
-> Hyperphosphataemia
-> Hyperalbuminaemia
-> Mutiple myeloma with high IgA
What are the causes of lactic acidosis?
Associated with anaerobic metabolism due to hypoxia from:
-> Shock
->Excessive energy expenditure with seizures, hyperthermia or extreme exertion
->Liver failure that impairs lactate clearance
Intoxication with ethonal or carbon monoxide
Diagnosis is made on plasma lactate levels.
How does diabetic ketoacidosis affect anion gap?
Insufficiency of insulin causes ketogenesis to occur of ketoacidosis like B-hydroxybutyrate and Acetoacetate acids which disassociate and cause a rise in acid production and increase the anion gap metabolic acidosis.
Ppatients will have increased anion gap metabolic acidosis, hyperglycaemia and high serum ketoacids.
How does starvation affect the anion gap?
Reduction in caloric intake causes glucagon xcess and insulin deficiency, which accelerates hepatic ketogenesis, resulting in increased acid production and an increased anion gap..
How does aspirin affect the anion gap?
It stimulates the respiratory centres in the brain which causes respiratory alkalosis. However, it also inhibits action of the mitochondria for oxidative phosphorylation and overdose increases oxygen demand, resulting in lactic acidosis which increases acid and anion gap.
How does renal failure affect the anion gap?
Failure of the kidneys to excrete acid and this is more common in acute renal failure.
What is urinary anion gap?
Urinary anion gap is used to estimate the quantity of ammonium (NH4+) in the urine to determine the function of renal tubular h+ secretion. The value should be 0 or positive in the absence of metabolic acidosis due to low ammonium excretion and is based on the equation:
(Na+) + (K+) substracted by (Cl-)
The greater the NH4+, the lower the anion gap/ Low NH4+ causes a high anion gap. Urinary anion gap is used to differentiate renal from non-renal causes of metabolic acidosis.
What causes a high urinary anion gap in metabolic acidosis?
Metabolic acidosis where there is a low level of NH4+ excretion due to renal disease like renal tubular acidosis.
What causes a negative urinary anion gap in metabolic acidosis?
Metabolic acidosis typically causes a low or negative urinary anion gap where there is a Rise in NH4+ excretion due to GI losses of bicarbonate such as severe diarrhoea or fistula.
What causes a normal urinary gap?
Loss of bicarbonate ions
What are the causes of non-anion gap. Metabolic acidosis?
It is divided into
-> Gastrointestinal loss of HCO3-
-> Renal loss of HCO3-
-> Gain of H+ from renal diseases like Type 1 and 4 renal tubular acidosis, renal failure and hyperkalemia
What are the gastrointestinal causes of metabolic acidosis?
GI causes of normal anion gap metabolic acidosis result in hypochloremia due to:
->Diarrhoea which is the most common cause due to fluid loss and may result in lactic acidosis and result in an eventual increase in anion gap
-> Pancreatic damage
-> Fistula due to loss of bicarbonate rich fluid through the abrnoaml entry
-> Gastroointestinal damage
-> Excessive Ingestion of Calcium or magnesium which reacts with bicarbonate to form insoluble salts which reduces bicarbonate levels
What are the renal causes of normal anion gap metabolic acidosis?
Renal failure
Renal tubular acidosis
Carbonic anhydrase inhibitors
Hypoaldosteronism
K+ sparing diuretics
What is renal tubular acidosis?
A group of renal disorders where there is a disruption to the acid base balance, where there is deficient HCO3- absorption and H+ excretion, characterised by a normal anion gap metabolic acidosis
What is Type 2 renal tubular acidosis?
Proximal tubular acidosis where there is a defect in rebasorption of HCO3- in the PCT of the Na+/HCO3- cotransporter channels that is a major site for bicarbonate absorption. This causes loss of bicarbonate in urine, therefore the body compensates by increasing Cl- levels, resulting in a normal anion gap hyperchloremic metabolic acidosis.
What are the electrolyte changes in type 2 proximal renal tubular acidosis?
Low serum Bicarbonate
High urinary excretion of bicarbonate
Normal K+ or Hypokalemia
What is the cause of type 2 RTA?
Pathologies affecting the PCT for the action of the Na+/HCO3- cotransporter or Na+/H+ pump for H+ to combine with HCO3- and form carbonic acid for acid-base balance. This
includes:
Fanconi syndrome
How does type 2 RTA present?
Commonly occurs in adults with
Metabolic acidosis causing Leeching of calcium from bone, leading to osteomalacia
How is type 2 RTA treated?
High dose sodium bicarbonate to compensate for low level
Thiazide diuretics that cause volume depletion and increase bicarbonate reabsorption
What is the effect of aldosterone on the collecting duct?
Aldosterone activates Na+ channels to increase Na+ transport into the nephron from the lumen. It stimulates Na+/K+ ATPase pump on principal cells for Na+ uptake into the blood
What are the cells of the collecting duct?
Intercalated cells, which are involved in acid base balance by exchange of HCO3-/Cl- for HCO3- in blood. Intercalated cells also have a H+ /K+ ATPase pump for H+ excretion into the lumen for K+ uptake via stimulation by aldosterone, where it forms H2PO4 and NH4+ for removal into urine. They produce bicarbonate under stimulation of aldosterone.
Principal cells, which receive stimulation by aldosterone for Na+/K+ ATPase activity.
What is Type 1 RTA?
AKA Distal tubular acidosis, where there is a defect in the acidification of serum in the DCT commonly due to either:
-> impaired function of the H+ ATPase pump
-> back leak of H+ in epithelium
-> low aldosterone for generation of bicarbonate in intercalated cells
This causes a fall in K+ and reduces NH4+ excretion into urine for acid base balance, results in hypokalemic metabolic acidosis
It occurs most commonly in children and the acidosis can induce rickets.
What are the causes of hypokalemic Type 1 renal tubular acidosis?
Most commonly occurs in children due to:
Sjögren’s syndrome due to lymphocytic infiltration
Amphotecirin B due to damage to DCT cells causing back leak of H+
Hypercalcaemia,where calcium deposits can occur in the medulla or cortex and impair functioning of the DCT, in nephrocalcinosis
Multiple myeloma due to Bence-Jones obstruction
Lupus
What is Sjögren’s syndrome?
Chronic autoimmune condition occurring in the 40-60s where there is lymphocytic infiltration of the lacrimal and salivary glands, characterised. By a triad of:
-> Dry eyes
-> Dry mouth
-> Arthritis
These lymphocytes can infiltrate the DCT and cause Type 1 RTA?
Why does hyperkalemic Type 1 RTA occur?
Urinary obstruction affects K+ excretion
Autoimmune conditions such as lupus and sickle cell
Due to deficiency in aldosterone, which is importantly for stimulation of H+K+ ATPase pump of the intercalated cels for H+ excretion, associated with
Hypoaldosteronism with autoimmune conditions like Addiso’s disease
Diabetic nephropathy, where there is low renin release which reduces aldosterone release
How does Type 1 RTA present?
Commonly Occurs in children with:
Metabolic acidosis inducing rickets and osteomalacia due to leeching of calcium from bones
Increased risk of UTIs
Hypercalciuria and hypocitrituria that increases risk of kidney stones
How is Type 1 RTA treated?
Oral bicarbonate
What is the cause of backleak in Type 1 RTA?
Amphotecirin B
What is the cause of NH4+ defect in Type 1 RTA?
Hypoaldosteronism due to reduced H+/k+ ATPase activity for h+ excretion and combination with ammonia.
What is the cause of voltage defect in Type 1 RTA?
Amiloride is a thiazide diuretic which inhibits the na+/K+ ATPase pump for
What is Type 4 RTA?
Low levels or inhibition of aldosterone which is importantly for H+ excretion in the DCT, that results in hyponatremia, HYPERKALEMIA and metabolic acidosis due to reduced buffering capacity of ammonia and phosphate
What is the cause of Type 4 RTA?
This is most commonly associated with diabetic nephropathy, where there is hyporeninaemia with Hypoaldosteronism.
Drugs like K+ sparing diuretics, beta blockers, NSAIDs and ACE inhibitors and ARBs can induce this.
-> Treatment is with fludorcortisone
Which RTA has the highest urine pH?
Type 1 RTA due to loss of H+.
Which RTA has the highest excretion of bicarbonate?
Type 2 RTA
Which RTA causes high K+
Type 4 RTA
Which RTA is the only type with normal urine pH?
Type 4 RTA
What is parenterally alimentation?
Nutritional support directly through a vein which contains amino acid infusions, resulting in a hyperchloremic metabolic acidosis
How does renal failure cause metabolic acidosis?
Reduced ammonium excretion in the DCT causes a greater retainment of H+/
How do carbonic anhydrase inhibitors cause metabolic acidosis?
Use of these medications for conditions like glaucoma can result in reduced HCO3- absorption due to reduced disassociation of carbonic acid. This can also increase the risk of nephrolithiasis as a result of urine pH.
What is the effect of K+ on pH?
Hyperkalemia can result in metabolic acidosis due to the action of the H+/K+ exchanger in the DCT where high K+ intracellularly causes excretion of H+ into bloodstream.
How should normal anion gap metabolic acidosis be investigated?
Stop saline infusion temporarily
Assess kidney function
Assess serum K+ levels
Assess urine anion gap
Assess urine pH
How is metabolic acidosis treated?
Dependent on the underlying condition such as
Diabetic ketoacidosis: fluid resuscitation and insulin with K+
Sepsis: fluid resuscitation and antibiotics
Sodium bicarbonate adminstration
What is metabolic alkalosis?
Characterised by an increase in plasma bicarbonate, typically due to a net loss of H+ or increase in renal bicarbonate absorption.
What causes a net loss of h+?
Vomiting causes a loss of H+ through stomach fluid
Excess aldosterone, from tumours or conditions like Conn’s syndrome, which promotes the excretion of H+ by the intercalated cells of the DCT into the urine
What causes an increase of bicarbonate?
Intake of
Loss of extracellular fluid from use of diuretics or dehydration can induce contraction alkalosis
Hypokalemia can reduce the action of the H+/K+ pump in the DCT of the intercalated cells, that can occur with diuretic use or diarrhoea and activates the RAAS system for increased bicarbonate absorption
Intake of antacids like sodium bicarbonate
How does the body respond to metabolic alkalosis?
Chemoreceptors induce Respiratory compensation by reducing ventilation to retain more CO2
Excretion of bicarbonate into the urine
Buffering by the H+ ions combining with HCO3- to form carbonic acid and produce CO2
Which factors maintain/worsen metabolic alkalosis?
High levels of aldosterone
Hypercapnia due to loss of CO2
Chloride depletion
Decreases in arterial blood volume through vomiting or bleeding
What are the findings for metabolic alkalosis?
Hypokalemia
High plasma HCO3-
High PCO2
What is chlroide responsive metabolic alkalosis?
Metabolic alkalosis where there is a loss/secretion of chloride such as:
Vomiting
Diuretic use
Gastric drainage
Cystic fibrosis
What s chlroide resistant metabolic alkalosis?
Hyperaldosteronism
Cushing’s syndrome
Potassium depletion
Liquorice
How does cystic fibrosis affect pH?
Cystic fibrosis can impair the CFTR channel in the kidney for transport of Cl- which impairs the excretion of HCO3- and leads to metabolic alkalosis.
What is a common complication with diuretic use?
Metabolic alkalosis with hypokalemia due to volume depletion initiating contraction alkalosis by increasing bicarbonate reabsorption
How does Cushing’s syndrome affect pH?
Glucocorticoids have a similar structure to mineralcorticoids and can also act on the receptors and stimulate the alpha intercalated cells for bicarbonate reabsorption
How does liquorice affect body pH?
Liquorice inhibits the 11-beta hydroxyl are enzyme to inactivate cortisol which causes excessive activity on aldosterone in the alpha intercalated cells of the DCT for increased bicarbonate reabsorption
What is the treatment of metabolic alkalosis?
Fluid resuscitation
Administering HCL infusion and correcting PCO2
Potassium and magnesium depletion
