Renal tubular acidosis
All three types of renal tubular acidosis (RTA) are associated with hyperchloraemic
metabolic acidosis (normal anion gap).
Type 1 RTA (distal)
● inability to generate acid urine (secrete H+) in distal tubule
● causes hypokalaemia
● complications include nephrocalcinosis and renal stones
● causes include idiopathic, rheumatoid arthritis, SLE, Sjogren's, amphotericin B
toxicity, analgesic nephropathy
●
Type 2 RTA (proximal)
● decreased HCO3- reabsorption in proximal tubule
● causes hypokalaemia
● complications include osteomalacia
● causes include idiopathic, as part of Fanconi syndrome, Wilson's disease,
cystinosis, outdated tetracyclines, carbonic anhydrase inhibitors
(acetazolamide, topiramate)
Type 3 RTA (mixed)
● extremely rare
● caused by carbonic anhydrase II deficiency
● results in hypokalaemia
Type 4 RTA (hyperkalaemic)
● reduction in aldosterone leads in turn to a reduction in proximal tubular
ammonium excretion
● causes hyperkalaemia
● causes include hypoaldosteronism, diabetes
●
,Water deprivation test
The water deprivation test is designed to help evaluate patients who have polydipsia.
Method
● prevent patient drinking water
● ask the patient to empty their bladder
● hourly urine and plasma osmolalities
Starting plasma Final urine Urine osm.
osm. osm. post-DDAVP
Normal Normal > 600 > 600
Psychogenic Low > 400 > 400
polydipsia
Cranial DI High < 300 > 600
Nephrogenic DI High < 300 < 300
Thyroid eye disease
Thyroid eye disease affects between 25-50% of patients with Graves' disease.
Pathophysiology
● it is thought to be caused by an autoimmune response against an
autoantigen, possibly the TSH receptor → retro-orbital inflammation
● the inflammation results in glycosaminoglycan and collagen deposition in the
muscles
Prevention
● smoking is the most important modifiable risk factor for the development of
thyroid eye disease
● radioiodine treatment may increase the inflammatory symptoms seen in
thyroid eye disease. In a recent study of patients with Graves' disease around
15% developed, or had worsening of, eye disease. Prednisolone may help
reduce the risk
,Features
● the patient may be eu-, hypo- or hyperthyroid at the time of presentation
● lid retraction (most common sign, seen in 90%)
○ sympathetic overactivity leading to overaction of the levator palpebrae
superioris and Müller’s muscle
○ → 'staring' appearance
● exophthalmos (most specific sign)
○ forward protrusion of the eyeball due to inflammation and oedema of
the extraocular muscles and orbital fat
● conjunctival oedema
● optic disc swelling
● ophthalmoplegia
● inability to close the eyelids may lead to sore, dry eyes. If severe and untreated
patients can be at risk of exposure keratopathy
Management
● smoking cessation
● topical lubricants may be needed to help prevent corneal inflammation
caused by exposure
● steroids
● radiotherapy
● surgery
Complications
Exposure keratopathy
● this is the most common complication of thyroid eye disease
● due to eyelid retraction and proptosis (exophthalmos) → cornea becomes
excessively exposed, disrupting the normal tear film → dryness, irritation, and
corneal ulceration
● symptoms include foreign body sensation, pain, and photophobia
● in severe cases, it can lead to corneal scarring and vision impairment.
Optic neuropathy
● one of the most serious complications of thyroid eye disease
● occurs when enlarged extraocular muscles compress the optic nerve at the
apex of the orbit → a reduction in visual acuity, colour vision deficits, and
visual field defect
● it requires urgent medical intervention to prevent permanent vision loss.
, Strabismus and diplopia
● fibrosis and enlargement of the extraocular muscles can result in restrictive
strabismus → misalignment of the eyes → double vision (diplopia)
● this not only affects visual function but can also significantly impair the
quality of life.
Monitoring patients with established thyroid eye disease
For patients with established thyroid eye disease the following symptoms/signs
should indicate the need for urgent review by an ophthalmologist (see EUGOGO
guidelines):
● unexplained deterioration in vision
● awareness of change in intensity or quality of colour vision in one or both
eyes
● history of eye suddenly 'popping out' (globe subluxation)
● obvious corneal opacity
● cornea still visible when the eyelids are closed
● disc swelling
Primary hyperaldosteronism
Primary hyperaldosteronism was previously thought to be most commonly caused
by an adrenal adenoma, termed Conn's syndrome. However, recent studies have
shown that bilateral idiopathic adrenal hyperplasia is the most common cause.
Differentiating between the two is important as this determines treatment.
Causes
● bilateral idiopathic adrenal hyperplasia: the cause of around 60-70% of cases
● adrenal adenoma: 20-30% of cases
● unilateral hyperplasia
● familial hyperaldosteronism
● adrenal carcinoma
Pathophysiology
● aldosterone is high
● renin is low (suppressed by volume expansion)
● consequences:
All three types of renal tubular acidosis (RTA) are associated with hyperchloraemic
metabolic acidosis (normal anion gap).
Type 1 RTA (distal)
● inability to generate acid urine (secrete H+) in distal tubule
● causes hypokalaemia
● complications include nephrocalcinosis and renal stones
● causes include idiopathic, rheumatoid arthritis, SLE, Sjogren's, amphotericin B
toxicity, analgesic nephropathy
●
Type 2 RTA (proximal)
● decreased HCO3- reabsorption in proximal tubule
● causes hypokalaemia
● complications include osteomalacia
● causes include idiopathic, as part of Fanconi syndrome, Wilson's disease,
cystinosis, outdated tetracyclines, carbonic anhydrase inhibitors
(acetazolamide, topiramate)
Type 3 RTA (mixed)
● extremely rare
● caused by carbonic anhydrase II deficiency
● results in hypokalaemia
Type 4 RTA (hyperkalaemic)
● reduction in aldosterone leads in turn to a reduction in proximal tubular
ammonium excretion
● causes hyperkalaemia
● causes include hypoaldosteronism, diabetes
●
,Water deprivation test
The water deprivation test is designed to help evaluate patients who have polydipsia.
Method
● prevent patient drinking water
● ask the patient to empty their bladder
● hourly urine and plasma osmolalities
Starting plasma Final urine Urine osm.
osm. osm. post-DDAVP
Normal Normal > 600 > 600
Psychogenic Low > 400 > 400
polydipsia
Cranial DI High < 300 > 600
Nephrogenic DI High < 300 < 300
Thyroid eye disease
Thyroid eye disease affects between 25-50% of patients with Graves' disease.
Pathophysiology
● it is thought to be caused by an autoimmune response against an
autoantigen, possibly the TSH receptor → retro-orbital inflammation
● the inflammation results in glycosaminoglycan and collagen deposition in the
muscles
Prevention
● smoking is the most important modifiable risk factor for the development of
thyroid eye disease
● radioiodine treatment may increase the inflammatory symptoms seen in
thyroid eye disease. In a recent study of patients with Graves' disease around
15% developed, or had worsening of, eye disease. Prednisolone may help
reduce the risk
,Features
● the patient may be eu-, hypo- or hyperthyroid at the time of presentation
● lid retraction (most common sign, seen in 90%)
○ sympathetic overactivity leading to overaction of the levator palpebrae
superioris and Müller’s muscle
○ → 'staring' appearance
● exophthalmos (most specific sign)
○ forward protrusion of the eyeball due to inflammation and oedema of
the extraocular muscles and orbital fat
● conjunctival oedema
● optic disc swelling
● ophthalmoplegia
● inability to close the eyelids may lead to sore, dry eyes. If severe and untreated
patients can be at risk of exposure keratopathy
Management
● smoking cessation
● topical lubricants may be needed to help prevent corneal inflammation
caused by exposure
● steroids
● radiotherapy
● surgery
Complications
Exposure keratopathy
● this is the most common complication of thyroid eye disease
● due to eyelid retraction and proptosis (exophthalmos) → cornea becomes
excessively exposed, disrupting the normal tear film → dryness, irritation, and
corneal ulceration
● symptoms include foreign body sensation, pain, and photophobia
● in severe cases, it can lead to corneal scarring and vision impairment.
Optic neuropathy
● one of the most serious complications of thyroid eye disease
● occurs when enlarged extraocular muscles compress the optic nerve at the
apex of the orbit → a reduction in visual acuity, colour vision deficits, and
visual field defect
● it requires urgent medical intervention to prevent permanent vision loss.
, Strabismus and diplopia
● fibrosis and enlargement of the extraocular muscles can result in restrictive
strabismus → misalignment of the eyes → double vision (diplopia)
● this not only affects visual function but can also significantly impair the
quality of life.
Monitoring patients with established thyroid eye disease
For patients with established thyroid eye disease the following symptoms/signs
should indicate the need for urgent review by an ophthalmologist (see EUGOGO
guidelines):
● unexplained deterioration in vision
● awareness of change in intensity or quality of colour vision in one or both
eyes
● history of eye suddenly 'popping out' (globe subluxation)
● obvious corneal opacity
● cornea still visible when the eyelids are closed
● disc swelling
Primary hyperaldosteronism
Primary hyperaldosteronism was previously thought to be most commonly caused
by an adrenal adenoma, termed Conn's syndrome. However, recent studies have
shown that bilateral idiopathic adrenal hyperplasia is the most common cause.
Differentiating between the two is important as this determines treatment.
Causes
● bilateral idiopathic adrenal hyperplasia: the cause of around 60-70% of cases
● adrenal adenoma: 20-30% of cases
● unilateral hyperplasia
● familial hyperaldosteronism
● adrenal carcinoma
Pathophysiology
● aldosterone is high
● renin is low (suppressed by volume expansion)
● consequences:
