Renal: acid base balance disorders, renal tubular acidosis Flashcards
Metabolic acidosis
How do we differentiate if its due to loss of bicarbonate or excess metabolic acid?
Anion gap
What is the anion gap?
The anion gap represents the concentration of unmeasured anions in the serum.
AG = (Na + K) - (HCO3+Cl)
Usually between 8-16
Metabolic acidosis with normal anion gap
In patients with a normal AG metabolic acidosis, the primary problem is a loss of bicarbonate from the body. Loss of bicarbonate is nearly completely compensated for by a conservation of chloride. This situation is also known as hyperchloraemic metabolic acidosis.
Metabolic acidosis with normal anion gap - causes [4]
- GI loss of bicarbonate (including diarrhoea and enteric fistulae).
- Failure of renal conservation of bicarbonate (renal tubular acidosis).
- Drug ingestion (carbonic anhydrase inhibitors, e.g. acetazolamide).
- Excessive administration of normal saline in hospitalised patients.
FUSED CARS
Metabolic acidosis with normal anion gap MNEMONIC
FUSEDCARS
* Enteric Fistula; particularly entero-pancreatic as pancreatic juice is rich in HCO3–.
* Ureteroenteric fistula.
* Excessive IV Saline administration.
* Endocrine causes (e.g. hyperparathyroidism).
* Diarrhoea.
* Carbonic anhydrous inhibitors (e.g. acetazolamide).
* Ammonium chloride ingestion.
* Renal tubular acidosis.
* Spironolactone.
Metabolic acidosis with high anion gap
In high AG metabolic acidosis, the primary acid-base imbalance is an excess of organic acids, which are buffered by serum bicarbonate. The ‘extra’ acid is represented by an increase in the unmeasured anion (the AG).
‘MUDPILES’
* Methanol.
* Uraemia.
* Diabetic ketoacidosis. (Diabetic ketoacidosis is a relatively common condition compared to its less
common cousin, alcoholic ketoacidosis.)
* Paraldehyde poisoning.
* Iron toxicity and Infection.
* Lactic acidosis and Liver failure.
* Ethylene glycol poisoning.
* Salicylate toxicity.
Lactic acidosis
Lactic acid is a by-product of anaerobic metabolism. When present in excess (>5 mmol/L), lactic acid causes a high AG metabolic acidosis.
Sequelae of metabolic acidosis
Cardiac [3]
Respiratory [2]
Neurological [3]
Cardiac - hypotension, cariogenic shock, arrhythmias
Respiratory - hyperpnoea, Kussmaul breathing
Neurological - headache, confusion, coma
Sequelae of metabolic acidosis
Renal
Bone
Non specific
Renal - reduced GFR due to vascular constriction and reduced cardiac output
Bone - demineralisation if chronic
Non specific - malaise, muscle weakness, nausea, vomiting
Tubular disorders - Renal tubular acidosis
Normal Anion Gap metabolic acidosis
Type 1 distal RTA
Type 2 proximal RTA
Type 3 mixed renal tubular acidosis
Type 4 RTA - hypoaldosteronism
Type 1 distal RTA
Pathophysiology - Most mutations causing distal RTA affect the H+-ATPase (autosomal recessive) or the kidney anion exchanger (autosomal dominant) in the intercalated cells of the distal renal tubule.
Distal RTA results in a failure to excrete H+ into the tubular filtrate at the distal tubule, meaning that urine pH cannot be acidified below 5.5.
Hallmark -inappropriately alkaline urine in the context of systemic acidosis
Type 1 distal RTA
Biochemical abnormalities
Diagnostic test
- Hypokalaemia.
- Hypocitraturia.
- Hypercalciuria: calcification of the renal ultrastructure (nephrocalcinosis) and renal stones
(nephrolithiasis) are common, as well as osteomalacia from net calcium loss in the urine and chronic acidosis.
A diagnosis of distal RTA is established by a urinary acidification test. Failure to acidify the urine pH < 5.5 following ingestion of an acid load (usually ammonium chloride) confirms the diagnosis of dis- tal RTA.
Type 1 distal RTA management
Distal RTA responds to initiation of oral alkali therapy, usually bicarbonate or citrate salts. Correction of acidosis is usually sufficient to improve hypocitraturia, which in turn reduces the risk of renal stone for- mation.
Type 2 proximal RTA
What is the main biochemical problem?
How is Fanconi syndrome associated?
What are primary forms of Type 2?
Proximal RTA is due to incomplete bicarbonate reabsorption in the PCT.
Diseases causing global proximal tubular dysfunction can cause proximal RTA as part of Fanconi syndrome, the most common presentation of proximal RTA.
Primary forms of proximal RTA are rare, but include mutations in the sodium bicarbonate co-transporter (NBC1), which also includes an ophthalmic phenotype
Type 2 RTA presentation [3]
normal AG metabolic acidosis and osteomalacia
Patients universally have hypokalaemia due to hyperaldosteronism (from volume contraction) and high delivery of bicarbonate to the distal tubule. The urine calcium level is also high (one of the causes of osteomalacia).
Why can the urine acidity test be paradoxically normal in Type 2 RTA?
The metabolic acidosis is often self-limiting due to the ‘threshold’ effect. The proximal tubules retain some ability to reabsorb bicarbonate, reducing the filtrate bicarbonate concentration to a threshold level, usually ~5 mEq/L, resulting in complete reabsorption of filtered bicarbonate. Thus, the urinary acidification test can be ‘paradoxically’ normal in patients with proximal RTA.
Management of Type 2 RTA
- Alkali therapy: patients often require large quantities of alkali therapy daily, even more so when suffering from intercurrent illnesses.
- Potassium supplementation: as tubular bicarbonate concentrations rise above the threshold level, more bicarbonate reaches distal tubules causing potassium wasting.
- Thiazide diuretics: help to increase bicarbonate reabsorption from the proximal tubule by volume contraction. This can worsen hypokalaemia, so thiazides are usually prescribed with further potassium supplementation.
- Vitamin D therapy: to improve bone health and calcium/phosphate balance.
Type 3 RTA
Inherited mutation in carbonic anhydrase type II and is seen in infants, North Africa, Middle East.
Autosomal recessive inheritance
Guibaud-Vainsel syndrome
Cerebral calcification, mental retardation, osteoporosis
Type 4 RTA
Clinical features [2]
Describe acquired pathophysiology
Absolute deficiency of aldosterone or resistance to actions on renal tubules.
Hyporeninemia with adrenal failure
Aldosterone resistance can be either hereditary or acquired.
Acquired forms arise from chronic use of K sparing diuretics e.g., amiloride or chronic tubulointerstitial disease
Type 4 RTA Hereditary forms
Pseudohypoaldosteronism type I presents as severe salt wasting hyperkalaemia
High seram renin, high serum aldosterone
Mutation of ENCAC or mineralocorticoid receptor.
Cystinuria
Inheritance, mutation
Presentation
Diagnosis
Autosomal recessive disease
Mutation of dibasic amino acid transports e.g. cystine, lysine, arginine
Presentation - recurrent UTIs or CKD from chronic stone disease, corneal deposits of cystine on slit lamp, pigmentary retinopathy
Diagnosis: high urinary cystine concentration, presence of hexagonal urine crystals and imaging studies for stones
Management of cystinuria
Minimising risk of further stone formation, adequate daily hydration
Penicillamine to chelate cystine
Hartnups disease
Aetiology
Presentation [3]
Management
Mutation in transporter for neutral amino acid like tryptophan expressed in PCTs and intestine.
Tryptophan deficiency (required to make serotonin, melatonin, niacin)
- Pellagra-like dermatosis
- Neurological disease - cerebellar ataxia, nystagmus, tremor.
Management - high protein diet, nicotinamide supplement, sunlight avoidance
Bartter syndrome
Mutation in several transporter in the TAL of Henle
Failure of urine concentration
Chronic loop diuretic use
Volume depletion
Hypokalaemia
Hyperchloraemic metabolic alkalosis
Presentation of Bartter syndrome [6]
Presentation
- polyuria, polydipsia
- salt craving
- constipation
- growth retardation
- electrolyte abnormalities, hypercalciuria causing nephrocalcinosis and low Mg
- fever, diarrhoea
Why do patients with Type IV Bartter syndrome have sensorineural deafness?
‘Barttin’ is crucial for renal chloride reabsorption and inner ear potassium secretion. Barttin is the chloride channel beta-subunit
Gitelman syndrome
Mutation of sodium chloride cotransporter in distal tubule
Presentation- chronic thiazide use ie volume depletion and hypokalaemia.
Severe hypoMg
Muscle weakness, fatigability
Treatment
- supplement of electrolyte abnormalities
- antagonism of aldosterone and Angiotensin 2 with ACE inhibitor
- Indomethacin to limit prostaglandin secretion in kidneys
- Cure: transplant
Classification of renal diseases [6]
Mode of presentation
- Nephrotic syndrome
- Nephritic syndrome
- Non-nephrotic proteinuria
- Rapidly progressive glomerulonephritis
- Asymptomatic microscopic haematuria
- CKD
Aetiology
- Primary glomerural disease [5]
- Secondary glomerular disease [4]
Primary glomerular disease
- IgA nephropathy
- Primary focal segmental glomerulosclerosis
- Minimal change disease
- Idiopathic membranous nephropathy
- Hereditary nephritides
Secondary glomerular disease
- Immune complex deposition
- SLE
- Mixed essential cryoglobulinemia
- Plasma cell dycrasias like light chain deposits, amyloidosis
Classification of glomerular disease according to histopathological findings [7]
- Diffuse: >50%
- Focal: <50%
- Segmental: part of glomerulus
- Global: entire glomerulus involved
- Membranous: thickening of glomerular capillary wall
- Proliferative: increased number of cells in glomerulus, infiltrating inflammatory cells
- Crescentic: accumulation of inflammatory cells in Bowman’s space compressing the glomerulus
