Добавил:
Sekretar
kiopkiopkiop18@yandex.ru
t.me/Prokururor I Вовсе не секретарь, но почту проверяю
Опубликованный материал нарушает ваши авторские права? Сообщите нам.
Вуз:
Предмет:
Файл:Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_2826_Библиотеки_им_академика_М_И_Перельмана.pdf
Disorders of Potassium Regulation 333
Water loss relative to sodium occurs in diabetes insipidus, osmotic
diuresis and water loss from the lungs or skin. Usually in these situations,
serum sodium is maintained because an increase in plasma osmolality is a
potent stimulus to thirst; serum sodium only increases if thirst sensation is
abnormal or access to water is restricted.
Clinical features
Symptoms are non-specific and include nausea, vomiting, fever and
confusion.
Investigations
Simultaneous urine and plasma osmolality and sodium should be measured.
The passage of urine with an osmolality lower than that of plasma in this
situation is clearly abnormal and indicates diabetes insipidus (p. 629). If urine
osmolality is high, this suggests an osmotic diuresis or excessive extrarenal
water loss (e.g. heat stroke).
Management
Treatment is that of the underlying cause and replacement of water, either
orally if possible or intravenously with 5% dextrose. The aim is to correct
sodium concentration over 48 hours, as over-rapid correction may lead to
cerebral oedema. In severe hypernatraemia (>170 mmol/L), sodium chloride 0.9% (154 mmol/L) should be used to avoid too rapid a drop in serum
sodium. In addition, if there is clinical evidence of volume depletion, this
implies that there is a sodium deficit as well as a water deficit, and intravenous sodium chloride 0.9% should be used.
DISORDERS OF POTASSIUM REGULATION
Dietary intake of potassium varies between 80 and 150 mmol daily, most of
which is then excreted in the urine. Most of the body’s potassium (3500 mmol
in an adult man) is intracellular (see Table 8.2). Serum levels are controlled by:
• Uptake of K+ into cells
• Renal excretion – mainly controlled by aldosterone
• Extrarenal losses, e.g. gastrointestinal.
Hypokalaemia
This is a serum potassium concentration of <3.5 mmol/L.
Aetiology
The most common causes of hypokalaemia are diuretic treatment and
hyperaldosteronism (Table 8.6). Blood taken from a drip arm may produce
a spurious result.
334 Water, electrolytes and acid–base balance
Table 8.6 Causes of hypokalaemia
Increased renal excretion
(spot urinary K+ >20 mmol/L)
Gastrointestinal losses
(spot urinary K+ <20 mmol/L)
Redistribution into cells Increased activity of Na+/K+-ATPase
Reduced intake Severe dietary deficiency
*Hypokalaemia, primarily due to loss of gastric acid and associated metabolic alkalosis,
which leads to increased urinary loss of potassium and intracellular shift of potassium.
Diuretics, e.g. thiazides, loop diuretics
Solute diuresis, e.g. glycosuria
Hypomagnesaemia
Increased aldosterone secretion:
Liver failure
Heart failure
Nephrotic syndrome
Cushing’s syndrome
Conn’s syndrome
Exogenous mineralocorticoid:
Corticosteroids
Carbenoxolone
Liquorice
Renal disease
Renal tubular acidosis: types 1 and 2
Renal tubular damage
Rare syndromes with renal potassium
loss, e.g. Liddle’s syndrome
Prolonged vomiting,* profuse diarrhoea,
villous adenoma, fistulae, ileostomies
Alkalosis
β-Agonists
Insulin
Hypokalaemic periodic paralysis (rare,
episodic K+ movement into cells leads to
profound muscle weakness)
Inadequate replacement in i.v. fluids
Clinical features
Hypokalaemia is usually asymptomatic, although muscle weakness may
occur if it is severe. It results in an increased risk of cardiac arrhythmias,
particularly in patients with cardiac disease. Hypokalaemia also predisposes
to digoxin toxicity.
Disorders of Potassium Regulation 335
Management
The underlying cause should be identified and treated where possible.
Usually, withdrawal of purgatives, assessment of diuretic treatment, and
replacement with oral potassium chloride supplements, preferably as a
liquid or effervescent preparation (25–40 mmol/day in divided doses with
monitoring of serum K+ every 1–2 days) is all that is required (p. 337). Serum
magnesium concentrations should be normalized, as hypomagnesaemia
makes hypokalaemia difficult or impossible to correct. Indications for the
intravenous infusion of potassium chloride include hypokalaemic diabetic
ketoacidosis and severe hypokalaemia associated with cardiac arrhythmias
or muscle weakness. This should be performed slowly, and replacement at
rates of no greater than 10 mmol/hour via a peripheral line.
Hyperkalaemia
This is a serum potassium concentration >5.0 mmol/L. True hyperkalaemia
must be differentiated from artefactual hyperkalaemia, which results from
lysis of red cells during vigorous phlebotomy or in vitro release from abnormal red cells in some blood disorders, e.g. leukaemia.
Aetiology
The most common causes are renal impairment and drug interference with
potassium excretion (Table 8.7). An elevated serum potassium in the absence
of any of the listed causes should be confirmed before treatment, to exclude
an artefactual result.
Clinical features
Hyperkalaemia usually produces few symptoms or signs, until it is high
enough to cause cardiac arrest. Symptoms produced by hyperkalaemia
are related to impaired neuromuscular transmission and include muscle
weakness and paralysis. It may be associated with metabolic acidosis causing Kussmaul’s respiration (low, deep, sighing inspiration and expiration).
Hyperkalaemia may produce progressive abnormalities in the electrocardiogram (ECG) (Fig. 8.3).
Management
In the absence of any underlying cause (see Table 8.7) the serum potas-
sium should be rechecked to rule out spurious hyperkalaemia unless ECG
changes are present (see Fig. 8.3) that warrant emergency treatment. Mild to
moderate hyperkalaemia can be managed by dietary potassium restriction,
restriction of drugs causing hyperkalaemia and a loop diuretic (if appropriate) to increase urinary potassium excretion. Severe hyperkalaemia (>6.5
mmol/L) or hyperkalaemia (>6.0 mmol/L) with ECG changes (see Fig. 8.3) is
a medical emergency (Emergency Box 8.2).
336 Water, electrolytes and acid–base balance
(A
arrest)
(B
Table 8.7 Causes of hyperkalaemia
Decreased excretion
Acute kidney injury
Drugs (potassium-sparing diuretics, ACE inhibitors, NSAIDs, ciclosporin, heparin)
Addison’s disease
Hyporeninaemic hypoaldosteronism (type 4 renal tubular acidosis)
Redistribution (intracellular to extracellular fluid)
Diabetic ketoacidosis
Metabolic acidosis
Tissue necrosis or lysis (rhabdomyolysis, tumour lysis syndrome, severe burns)
Drugs (suxamethonium, digoxin toxicity)
Hyperkalaemic periodic paralysis
Increased extraneous load
Potassium chloride
Salt substitutes
Transfusion of stored blood
ACE, angiotensin-converting enzyme; NSAID, non-steroidal anti-inflammatory drug.
↓
widened QRS complex
↓
(D)
) Tented T wave (arrow)
Fig. 8.3 A–D Progressive electrocardiographic changes with increasing
hyperkalaemia.
'Sine wave' pattern (pre-cardiac
Disorders of Magnesium Regulation 337
Emergency Box 8.2 Management of hyperkalaemia
• Protect myocardium from hyperkalaemia (if K+ >6.5 mmol/L or
electrocardiographic (ECG) changes present):
• 10 mL of 10% calcium chloride bolus i.v. over 5–10 minutes with ECG
monitoring
• Repeat after 5 minutes if ECG changes persist
• Alternatively give up to 30 mL of 10% calcium gluconate
• NB: This treatment does not alter serum K
• Drive K+ into cells:
• Soluble insulin 10 units + 50 mL 50% dextrose i.v. over 15–30 minutes
and/or salbutamol nebulizer (5 mg) and/or correction of severe acidosis
(pH <6.9) with 1.26% sodium bicarbonate (500 mL i.v. over 60 minutes)*
• Effect of insulin lasts 1–2 hours; repeated doses may be necessary;
monitor K+ after treatment
• Deplete body K+ (after emergency treatment):
• Calcium resonium orally (15 g three times daily with laxatives) or
rectally (30 g) binds potassium
• Treat the cause
• Stop any extra source of potassium intake or potentiating drugs, e.g.
non-steroidal anti-inflammatory drugs and angiotensin-converting
enzyme (ACE) inhibitors
• Haemodialysis or peritoneal dialysis if conservative measures fail
• Monitor:
• Blood glucose (finger-prick stick testing) hourly during and for 6 hours
after insulin/dextrose infusion
• Serum K+ every 2–4 hours acutely and daily thereafter
*Not to be administered through the same line as calcium salts because of
a risk of precipitation.
+
DISORDERS OF MAGNESIUM REGULATION
Disturbance of magnesium balance is uncommon and usually associated with
more obvious fluid and electrolyte disturbance. Like potassium, magnesium
is mainly an intracellular cation (see Table 8.2) and balance is maintained
mainly via the kidney. The average daily magnesium intake is 15 mmol, about
one-third of which is absorbed in the small bowel; excretion is via the kidney.
Hypomagnesaemia
Aetiology
Low serum magnesium is most often caused by loss of magnesium
from the gut or kidney. Gastrointestinal causes include severe diarrhoea,
338 Water, electrolytes and acid–base balance
H
3
3
2
carbonic anhydrase
malabsorption, extensive bowel resection and intestinal fistulae. Excessive
renal loss of magnesium occurs with diuretics, alcohol misuse and with an
osmotic diuresis such as glycosuria in diabetes mellitus.
Clinical features
Hypomagnesaemia increases renal excretion of potassium, inhibits secretion
of parathyroid hormone and leads to parathyroid hormone resistance. Many
of the symptoms of hypomagnesaemia are therefore due to hypokalaemia (p.
332) and hypocalcaemia (p. 656).
Management
The underlying cause must be corrected where possible and oral supplements given (magnesium chloride 5–20 mmol daily or magnesium oxide
tablets 600 mg four times daily). Symptomatic severe magnesium deficiency
should be treated by intravenous infusion, particularly if there are seizures or
ventricular arrhythmias. Take care when interpreting repeat serum concentrations after treatment – the extracellular values may appear to normalize
quickly while the intracellular concentration requires longer to replenish (may
require up to 160 mmol over 5 days to correct).
Hypermagnesaemia
Hypermagnesaemia is rare and is usually iatrogenic, occurring in patients
with renal failure who have been given magnesium-containing laxatives or
antacids. Symptoms include neurological and cardiovascular depression,
with narcosis, respiratory depression and cardiac conduction defects. The
only treatment usually necessary is to stop magnesium treatment. In severe
cases, intravenous calcium gluconate may be necessary to reverse the cellular toxic effects of magnesium and dextrose/insulin (as for hyperkalaemia)
to lower the plasma magnesium level.
DISORDERS OF ACID–BASE BALANCE
The pH (the negative logarithm of [H+]) is maintained at 7.4 (normal range
7.35–7.45). The metabolism of food and endogenous body tissues produces
about 70–100 mmol of H+ each day, which is excreted by the kidneys.
Bicarbonate (HCO
It mops up free H+ ions and prevents increases in the H+ concentration
(Fig.8.4). Bicarbonate is filtered at the glomerulus but is then reabsorbed
Fig. 8.4 The carbonic anhydrase reaction.
-
) is the main plasma and extracellular fluid buffer.
3
+
–
+ HCO
H2CO
H2O+ CO
Disorders of Acid–Base Balance 339
in the proximal and distal renal tubule. The lungs also constantly regulate
acid–base balance through the excretion of CO2. Between production and
excretion of H+ ions there is an extremely effective buffering system maintaining a constant H+ ion concentration inside and outside the cell. Buffers
include haemoglobin proteins, bicarbonate and phosphate.
Acid–base disturbances may be caused by:
• Abnormal carbon dioxide removal in the lungs (‘respiratory’ acidosis and
alkalosis)
• Abnormalities in the regulation of bicarbonate and other buffers in the
blood (‘metabolic’ acidosis and alkalosis).
In general, the body compensates to some extent for changes in pH
by regulating renal bicarbonate excretion and altering the respiratory rate.
For instance, metabolic acidosis causes hyperventilation (via medullary
chemoreceptors), leading to increased removal of CO2 in the lungs and
partial compensation for the acidosis. Conversely, respiratory acidosis is
accompanied by renal bicarbonate retention, which could be mistaken for
primary metabolic alkalosis.
Measurement of pH, P
is present (Table 8.8). These measurements are made on an arterial blood
aco2
and [HCO
-
] will reveal which type of disturbance
3
sample using an automated blood gas analyser. Clinical history and examination
usually point to the correct diagnosis. In complicated patients, the Flenley acid–
base nomogram can be used to identify the acid–base disorder that is present
when arterial hydrogen ion concentration and P
are known (Fig. 8.5).
aco2
Respiratory acidosis
This is usually associated with ventilatory failure, with retention of carbon
dioxide. Treatment is of the underlying cause.
Table 8.8 Changes in arterial blood gases
pH P
aco2
Acidosis
Metabolic
Normal or reduced Normal or
reduced
Respiratory
Normal or reduced
Increased ++
Alkalosis
Metabolic
Respiratory
The pH may be at the limits of the normal range if the acidosis or alkalosis is compensated,
e.g. respiratory compensation (hyperventilation) of a metabolic acidosis. Theclue to the
abnormality from the blood gases will be the abnormal P
Normal or increased Increased
Normal or increased
Reduced ++
aco2
and HCO
-
HC0
3
Reduced ++
Normal or
increased
Increased ++
Reduced
-
.
3
340 Water, electrolytes and acid–base balance
6.9
+
21
120
100
80
] (nmol/L)
60
Arterial [H
40
20
Fig. 8.5 The Flenley acid–base nomogram. The central white box shows the
approximate limits of arterial pH and P co2 in normal individuals.
7.0
7.1
7.2
Arterial pH
7.3
7.4
7.5
7.6
M
e
t
a
b
o
l
i
c
a
c
i
d
o
s
i
s
Acute respiratory
acidosis
Chronic respiratory
(kPa)
2
(mmHg)
2
acidosis
00
Metabolic alkalosis
Respiratory
alkalosis
Arterial Pco
0 10 20 30 40 50 60 70 80 90
Arterial Pco
12864
Respiratory alkalosis
Hyperventilation results in increased removal of carbon dioxide, resulting in
a fall in P
aco2
and [H+].
Metabolic acidosis
This is the result of the accumulation of any acid other than carbonic acid.
The most common cause is lactic acidosis following shock or cardiac arrest.
Clinical features
These include hyperventilation, hypotension caused by arteriolar vasodilatation and the negative inotropic effect of acidosis, and cerebral dysfunction
associated with confusion and seizures.
Differential diagnosis (the anion gap)
The first step is to identify whether the acidosis is the result of retention of
HCl or of another acid. This is achieved by measurement of the anion gap.
Disorders of Acid–Base Balance 341
Table 8.9 Causes of metabolic acidosis with a normal anion gap
Increased gastrointestinal HCO
Diarrhoea
Ileostomy
Ureterosigmoidostomy
Increased HCO
-
renal loss
3
Acetazolamide ingestion
Proximal (type 2) renal tubular acidosis
Hyperparathyroidism
Tubular damage, e.g. drugs, heavy metals
Decreased renal H+ excretion
Distal (type 1) renal tubular acidosis
Type 4 renal tubular acidosis
Increased HCl production
Ammonium chloride ingestion
Increased catabolism of lysine, arginine
The main electrolytes measured in plasma are sodium, potassium, chloride
and bicarbonate. The sum of the cations, sodium and potassium, normally
exceeds that of chloride and bicarbonate by 6–12 mmol/L. This anion gap
is usually made up of negatively charged proteins, phosphate and organic
acids. If the anion gap is normal in the presence of acidosis, it can be concluded that HCl is being retained or NaHCO3 is being lost. The causes of a
normal anion gap acidosis are given in Table 8.9.
If the anion gap is increased (i.e. >12 mmol/L), the acidosis is the result
of an exogenous acid, e.g. salicylates or one of the acids normally present
in small unmeasured quantities, such as lactate. Causes of a high anion gap
acidosis are given in Table 8.10.
3
-
loss
Lactic acidosis
Increased production of lactic acid occurs when cellular respiration is abnormal, resulting from either lack of oxygen (type A) or a metabolic abnormality
(type B). The most common form in clinical practice is type A lactic acidosis,
occurring in septicaemic or cardiogenic shock.
Diabetic ketoacidosis
This is a high anion gap acidosis caused by the accumulation of acetoacetic
and hydroxybutyric acids.
342 Water, electrolytes and acid–base balance
Table 8.10 Causes of metabolic acidosis with an increased
anion gap: think GOLD MARK
• Glycols (ethylene and propylene): ingestions
• Oxoproline (pyroglutamic acid): chronic paracetamol ingestion
• L-lactate: type A and type B
• D-lactate: small bowel bacterial overgrowth
• Methanol: acute ingestion
• Aspirin: salicylate overdose
• Renal failure: accumulation of organic acids
• Ketoacidosis: diabetic, starvation, alcohol
a
Fe HCO3 = (urine bicarbonate × serum creatinine)/(serum bicarbonate/urine
creatinine) × 100.
(From Mehta AN, Emmett JB, Emmett M. GOLD MARK: an anion gap mnemonic for
the 21st century. Lancet 2008; 372(9642):892.)
Renal tubular acidosis
Renal tubular acidosis may occur in the absence of chronic kidney disease
and is a normal anion gap acidosis. There is failure of the kidney to acidify
the urine adequately. This group of disorders is uncommon and only rarely
a cause of significant clinical disease. There are four types, of which type 4
(also known as hyporeninaemic hypoaldosteronism) is the most common.
Typical features are acidosis and hyperkalaemia occurring in the setting of
mild chronic kidney disease, usually caused by tubulointerstitial disease or
diabetes. Plasma aldosterone and renin levels are low and do not respond
to stimulation. Treatment is with fludrocortisone, diuretics, sodium bicarbonate and ion exchange resins for the reduction of serum potassium.
Uraemic acidosis
Reduction of the capacity to secrete H+ and NH
ate wasting, contributes to the acidosis of chronic kidney disease. Acidosis
occurs particularly when there is tubular damage, such as reflux and
chronic obstructive nephropathy. It is associated with hypercalciuria and
renal osteodystrophy because H+ ions are buffered by bone in exchange
for calcium. Treatment is with calcium or sodium bicarbonate, although
acidosis in end-stage renal failure is only usually fully corrected by
adequate dialysis.
+
, in addition to bicarbon-
4
Metabolic alkalosis
This is much less common than acidosis and is often associated with potassium or volume depletion. The main causes are persistent vomiting, diuretic