Flashcards in Acid-Base physiology and renal tubule disorders Deck (36):
What is the effect of urinary alkalisation?
Reduces uric acid precipitation at renal tubules (coverts to rate)
increases calcium stones (CaPo4)
What are the three buffers?
- reabsorbed in proximal tubule (85%) & distal tubules (15%)
- neonatal HCO3 reabsorption is transiently reduced --> HCO3 wasting
- primary buffer system to be utilised
- actively reabsorbed in proximal tubules but mainly reabsorbed in distal tubule and collecting duct
- no secretion (buffering stops when all PO4 soaked up)
- secreted by distal tubule cells to generate HCO3 in the kidney
- buffers 1:1
How does urine acidification occur?
Normal kidney reabsorbs all HCO3
Distal tubule and CD also secretes H+ and NH4
What's the calculation for Anion Gap?
[Na} - [HCO3-Cl]
- normal is 10-12
- accounts for combined concentration of unmeasured anions including phosphate, sulphate, proteins, organic acids, exceeding those of unmeasured cations like K, Ca, Mg
What is the calculation for osmolarity?
2[Na+K] + Glucose + Urea
What is a significant anion gap?
- requires organic acid defect to be excluded
Modest increasing in anion gap (up to 20) can be seen in sick patients due to lactic acidosis from hypoxia or ketoacidosis in DKA
What conditions causes metabolic acidosis with normal anion gap?
Renal tubular acidosis
- losses of HCO3 due to reduced absorption in proximal tubule (type 2) --> urine pH <5.5 as distal tubular acidification is preserved
- reduced renal secretion of H+ in distal tubules (type 1)
Intestinal bicarbonate losses
- Stool losses (usually diarrhoea)
What are causes for metabolic acidosis with anion gap?
What are causes of metabolic alkalosis?
Assoc with hypochloraemia
- Cl usually moves app direction to HOC3 to balance net anion charge
- HCO3 generation in kidneys usually at cost of Cl loss
- Cl usually excreted with H+ in form ammonium
Assoc with hypoK
- due to K/H exchange in cells
What acid / base / electrolyte imbalance results in vomiting illness?
Metabolic alkalosis with hypoCl and hypoK
What acid / base / electrolyte imbalance results in acute diarrhoea?
Metabolic acidosis assoc with hypoK
(loss of Bicarb and K rich fluid)
Why is hyperkalaemia associated with metabolic acidosis?
Excess H in ECF needs to be buffered and so potassium is pulled out from cells
What are the effects of laxative abuse?
Acute: Metaboic acidosis
Chronic: Metabolic alkalosis with low Cl
- loss of K from diarrhoea causes hypoK which impairs intestinal reabsorption of chloride and diminishes bicarbonate secretion
- a/w hypoNa
What is Bartter Syndrome?
Autosomal Recessive condition caused by mutation of the Na-K-2Cl cotransporter
- singel gene defects
- Barttin gene defect assoc w sensorineural deafness and renal failure
- Hypochloraemic alkalosis
- Elevated renin and aldosterone
- HypoK stimulates synthesis of prostaglandins --> activates RAS system --> high renin / aldosterone
- High urine Na, K, Cl and Ca
Presents in first year of life with failure to thrive
- assoc with polyuria / polydipsia (concn defect)
- muscle weakness
- constipation (chronic vol depletion from renal salt losses)
- normal BP
- electrolyte supplements
- ACE inhibitor
- K sparing diuretic
What is Gitelman syndrome and how is that different from Bartter syndrome?
Autosomal recessive renal tubular salt-wasting disorder characterized by hypokalemic metabolic alkalosis with hypomagnesemia and hypocalciuria due to distal tubule defect
Gitelman syndrome is more common
Batter syndrome has HYPERCALCIURIA
What is Faconi syndrome?
Generalised impairment in proximal tubular function leading to urinary wasting of compounds normally reabsorbed in the proximal tubule.
- Metabolic acidosis
- Polyuria, rickets and growth failure
- Proximal RTA
What are inherited forms of Faconi syndrome?
Hereditary fructose intolerance
Medullary cystic disease
What are some acquired forms of Faconi syndrome?
- Lead, mercury, cadmium
- nephrotic syndrome
Excessive PTH hormal secretion (thought to inhibit carbonic anhydrase)
- Primary and secondary hyperparathyroidism
- Vitamin D deficient rickets
What is cystinosis (aka Lignac syndrome)?
Lysosomal storage disease
- Abnormality in the transport protein that normally removes cysteine from the lysosome
- One of the inherited cause of Faconi syndrome
- AR, mapped to chromosome 17
- growth retardation
- polyuria / polydipsia
- blood hair and fair skin from diminished pigmentation
- crystal deposits on cornea
- measure leukocyte cystine content
- prenatal testing available
- cysteamine may slow progression of disease
- renal transplant for ESRF
- CNS abnormalities, hypothyroidism, retinopathy, pancreatic insufficiency / diabetes, liver disease, muscle weakness
What's oculo-cerebral-renal syndrome of Lowe?
X-linked problem with transport vesicles into Golgi apparatus, one of the causes of inherited Fanconi
- Gene is OCRL-1
- mental retardation
- Fanconi syndrome
- growth failure
Progress: blindness and renal insufficiency eventually develops
Ix: CT and MRI show abnormalities in cerebral white matter
What is medullary sponge kidney?
A cause for distal RTA caused by cystic dilation of terminal portions of collecting ducts
- Renal function and life span usually normal
- Not inherited
What is the inheritance pattern for nephrogenic DI?
Mutation of AVPR2 x-linked recessive
- females less severely affected but also symptomatic in some cases
There are also mutations that are autosomal dominant / recessive
What causes nephrogenic DI?
Failure of collecting duct responding to ADH resulting in lack of renal concentration
Acquired cause includes lithium exposure
How does nephrogenic DI presents?
Growth retardation, polyuria and polydipsia
Findings include hypernatraemia and dilute urine
- give IM vasopressin the measuring serum and urine osmolality every hour for 4 hours
- dx confirmed if urine to plasma osmolality remains < 1.0
- Correct hypercalcaemia and hypokalaemia
- Low salt / protein diet
- Chlorothiazide paradoxically reduces UO
What causes renal tubular disorders?
Urinary tract obstruction
What are the acid / electrolyte disturbances from renal tubular disorders?
Hyponatraemia / hypokalaemia
- Due to excessive losses
Inappropriate dilute urine
- lack of concentrating mechanism
- Failure to absorb HCO3 / secrete Hypophosphateamia and rickets
- failure of phosphate reabsorption
What is renal tubular acidosis?
Clinical state of hypochloraemic acidosis resulting from impaired urinary acidification
- polyuria, dehydration
- anorexia, vomiting (most common), constipation
- If isolated RTA, usually present with growth failure toward the end of the first year of life
What are the types of RTA?
- Distal tubule
- Proximal tubule
- Combination of type 1 and 2
- Lack of or insensitivity to aldosterone
How is RTA diagnosed?
Exclude causes of systemic acidosis
Low serum HCO3
Normal anion gap
High serum chloride
What is the cause of proximal RTA (type 2)?
Failure to absorb HCO3 presumably due to deficiency carbonic anhydrase production or H secretion.
- inherited (usually autosomal dominant)
- Faconi syndrome a/w below
- Lowe syndrome
- Wilson disease
- Mitochondrial cytopathies
- Medullary cystic disease
What is the urinary pH proximal RTA?
pH < 5.6 as distal urinary acidification is preserved.
What is proximal RTA associated with?
Metabolic bone disease
- defective absorption of phosphate and production of vitamin D
What is the cause of distal RTA?
Inability of the distal tubule to secrete hydrogen.
- isolated, sporadic or inherited
- Reflux nephropathy
- Sickle cell nephropathy
- Ehlers-Dalos syndrome
- Medullary sponge kidney
- Obstructive nephropathy
- Disorders assoc w nephrocalcinosis like hypercalciuria, hyperparathyroidism, vit D intoxication
- Drugs / toxins like amphotericin B, mercury, lithium
What is the urinary pH in distal RTA?
pH > 5.8
Positive urinary anion gap
Hypercalciuria, nephrocalcinosis and nephrolithiasis may be present
What are the features of type 4 RTA?
HypoNa / hyperK acidosis
Urine pH <5.5 as urine acidification not impaired