8.01 Dehydration, diuretics, renal

Total body water (TBW) is approximately 50-70% body weight, or about 40L in a 70kg adult

Intracellular fluid (ICF, 30-40% of body weight, about 25 L)
Extracellular fluid (ECF, 20-30% of body weight, about 15 L)

Plasma volume (PV) compartment (3 L) and an interstitial fluid compartment (ISF, 12 L).

The blood volume (5 L) consists of the total red cell volume plus the plasma volume (3L). Cell membranes separate the ICF from the ECF, and capillary walls separate the plasma volume (containing proteins) from the interstitium.

Potassium is the main intracellular solute and sodium is the main extracellular solute. Even though the cell membranes are permeable to each solute, the separation is maintained by membrane-bound Na, K-ATPase which pumps sodium out and potassium into cells.

Two vary with temperature and humidity (insensible water losses, IWL)
33% through lungs
66% through skin
Also:
Stool losses
The kidney must also excrete an obligatory volume of urine each day to eliminate end products of metabolism and electrolytes

For both adults and children, by calories consumed per day. Insensible water loss 45mL/100cals expended, stool water 5mL/100cals. Visible sweating loses and additional amount of up to 50mL/100cals. Urinary losses vary according to dietary intake (50-75mL/100cal) and of these, 40-50mL/100cal are obligatory

Fluid drunk, water contained in food and the metabolic product of oxidation.

On balance a useful rule of thumb is that normally 100 ml of fluid is required per 100 Cals consumed per day. Normal daily requirements for electrolytes are about 2 mmol of Na, 1 mmol of potassium and 3 mmol of Cl per kg of body weight.

Oedema is due to excess fluid and salt in equal proportions resulting from kidney failure, or the escape of fluid to the ISF because of either reduced oncotic pressure of plasma (hypoalbuminaemia due to liver disease or renal loss of protein), or increased hydrostatic pressure in the capillaries, as in heart failure

- gain of water in excess of salt (hyponatraemic overhydration)
- loss of salt in excess water (hyponatraemic dehydration)
- gain of salt in excess water (sea water, hypernatraemic overhydration)
- loss of water in excess salt (hypernatraemic dehydration). hyponatraemic dehydration is always the result of initial isotonic dehydration followed by continued intake of water without salt.

They are clinically divided into a 4%, 7% or a 10% loss of body weight, described as mild, moderate and severe dehydration. A loss of 10% of body weight reduces the ECF from 270 ml/kg to 170 ml/kg, a level beyond which life-threatening irreversible shock is the rule rather than the exception.

By observing blood pressure (including postural BP drop), pulse rate, urine flow rate, accurate measurement of body weight, and assessment of the peripheral circulatory state and state of tissue and mucosal hydration

It acts to adjust the volume of the plasma, and thus of the ECF, by altering urinary sodium excretion. If the plasma volume is expanded, increased urinary sodium excretion occurs via a change in the balance between filtered sodium load and tubular sodium reabsorption (i.e. more filtration and/or less reabsorption), and vice versa.

Along the entire nephron but primarilly in the proximal tubule (60-65%), then 25-30% in the loop of Henle, 5-6% in the distal tubule and 2-4% in the collecting duct.

Na+-H+ countertransporter. It is stimulated by angiotensin

Aldosterone is an important regulator distally, where it stimulates sodium reabsorption by increasing epithelial sodium channel (ENaC) activity and Na-K-ATPase, simultaneously enhancing secretion of potassium and acid

Atrial natriuretic peptide (ANP) acts to inhibit sodium reabsorption

The bulk of filtered water is reabsorbed in the proximal tubule, and more water (alone) is reabsorbed in the descending limb if the loop of Henle driven by an osmolality between the tubule and the renal medullary interstitium

It increases the permeability of the tubule epithelium to water via aquaporins in the apical membranes of tubular cells, and to urea via urea transport proteins or carriers. In states of water excess, ADH levels fall and aquaporins are absent from the epithelial wall, thus water is not reabsorbed and polyuria ensues. In states of water deficiency, ADH secretion is increased and aquaporins are inserted in the tubular epithelium and urine flow is decreased.

0.5 L (insensible water loss) + urine output + sweat.

Visible losses occur from the gastrointestinal tract (mouth, fistulae, stomata, anus), kidneys, skin (e.g. burns) and blood stream.

Fluids sequestered around areas of inflammation (e.g. pancreatitis) or trauma (e.g. rhabdomyolysis), so-called third-spacing, and into serosal cavities (e.g. pleural, peritoneal) or interstitial tissues (oedema).

Sweat is hypotonic, with a Na+ and CI- concentration of less than 60-80 mmol/L

Gastric juice tends to be mildly hypotonic or isotonic, with a usual daily volume of 2-3 litres and an electrolyte composition dependent on the ratio of parietal cell (H+ 135-160 mmol/L, minimal Na+ , high CI- ) to nonparietal cell secretion (plasma-like). K+ concentration is 10-20 mmol/L

Hypokalaemia occurring with vomiting is due to kaliuresis: renal K+ loss accompanying HCO3-, rather than loss in the vomitus

It increases volume and ratio of HCO 3 - to CI - concentration of pancreatic juice

It causes extracellular hypertonicity with a resultant movement of water out of the cells

0.5 L (insensible water loss) + urine output + sweat.

It causes the movement of water into cells

Visible losses occur from the gastrointestinal tract (mouth, fistulae, stomata, anus), kidneys, skin (e.g. burns) and blood stream.

Fluids sequestered around areas of inflammation (e.g. pancreatitis) or trauma (e.g. rhabdomyolysis), so-called third-spacing, and into serosal cavities (e.g. pleural, peritoneal) or interstitial tissues (oedema).

Sweat is hypotonic, with a Na+ and CI- concentration of less than 60-80 mmol/L

Gastric juice tends to be mildly hypotonic or isotonic, with a usual daily volume of 2-3 litres and an electrolyte composition dependent on the ratio of parietal cell (H+ 135-160 mmol/L, minimal Na+ , high CI- ) to nonparietal cell secretion (plasma-like). K+ concentration is 10-20 mmol/L

Hypokalaemia occurring with vomiting is due to kaliuresis: renal K+ loss accompanying HCO3-, rather than loss in the vomitus

It increases volume and ratio of HCO 3 - to CI - concentration of pancreatic juice

It causes extracellular hypertonicity with a resultant movement of water out of the cells

It causes the movement of water into cells

- Blood
- Colloids (containing a macromolecular solute confined to the intravascular compartment)
- Crystalloids (electrolytes which will distribute initially throughout extracellular tissues)
- Dextrose-based solutions (providing water without electrolytes)

In part due to the resultant osmotic movement of fluid from extravascular tissue

- Hypertonic (e.g. 3 normal saline, 10% glucose)
- Isotonic (e.g. normal saline, 4% dextrose with 20% normal saline, 5% dextrose)
- Hypotonic (e.g. half normal saline)

By the type of fluid loss. Na+ and K+ are the predominant electrolytes that require replacement; other electrolytes that may require replacement include Ca2+ , Mg2+ and phosphate. In addition, fluids for parenteral nutrition may contain dextrose, amino acids, fats and trace elements

By a clinical assessment ofthe amount of fluid loss, plus a bit more to cover continuing physiological and pathological losses. The rate of fluid replacement is dependent on several factors - the rate and severity of fluid loss and need to restore vital organ function, the age and cardiac status of the patient and compensatory fluid shifts

Cardiac decompensation in patients with congestive cardiac failure, electrophysiological effects of potassium replacement and osmotic cell shrinkage (e.g. osmotic demyelination) with hypertonic saline.

The production of an ultrafiltrate of plasma (free of cellular elements or large protein molecules)

The hydrostatic pressure delivered from the heart into the glomerular capillary tufts

Variations in the tone (degree of constriction) in the afferent and efferent arterioles. Dilators on the afferent side (such as prostaglandin-E2) increase the filtration rate, while afferent constrictors (such as noradrenaline released from sympathetic nerve terrninals) decrease filtration. Note that efferent constrictors (such as angiotensin II released locally in low concentrations) act to maintain or increase the single nephron filtration rate

A complex local feedback mechanism that exists to relate the glomerular filtration rate of an individual nephron to the adequacy of sodium reabsorption in the tubular system of that nephron

At the level of the whole kidney, it is the stabilisation of the GRF despite variations over a wide range in the mean arterial blood pressure

The glomerular filtration rate is 150L/day
Urine is about 1.5L/day
Following filtration, some 99% of the filtered fluid is reabsorbed as it passes down the tubular system - giving rise to a 'fractional excretion' of fluid of around 1%.

Na+ ions are easily the most dominant ionic species available in the filtrate, and water movements are osmotically linked (directly or indirectly) to movements of sodium

Most sodium reabsorption (some 65%) takes place in the proximal tubules within the renal cortex, and at this site a similar proportion of filtered water is reabsorbed.

They undergo either no tubular transport after filtration (e.g. creatinine) or may actually be secreted by the tubules into the luminal fluid (e.g. organic acids and bases, and hydrogen ions themselves).

625 ml/min

T wave flattening, depression of the ST segment, and the appearance of prominent u waves.

Increasing extracellular K causes depolarisation. It stops the heart by preventing action potential generation in the sinoatrial node and by rendering the ventricular myocytes inexcitable. Once the membrane potential is excessively depolarized (more positive than - 60 mV) the Na current remains inactivated and the cell is inexcitable.

As extracellular K is lowered, the duration of the action potential is prolonged and this renders the heart liable to first ventricular tachycardia and then ventricular fibrillation. This is the same mechanism as occurs in the 'long QT' syndromes in which inherited mutations of various channels (K, Na and the intracellular Ca channel in the sarcoplasmic reticulum) can cause dangerous arrhythmias

Decreases

They are often asymptomatic, but may complain of malaise, weakness, leg cramps or rarely myalgia.

Rhabdomyolysis or paralysis.

A low intracellular K reduces intracellular glycogen synthesis and thus energy stores for exercising muscle.

Renal function is likely to be adversely affected by hypokalaemia, but do not usually cause symptoms in the patient. Specifically, hypokalaemia causes renal vasoconstriction, reduced renal blood flow and reduced glomerular filtration rate. If symptoms are present they relate to polyuria and secondary polydipsia due to a defect in tubular concentrating ability. K depletion additionally results in increased renal ammonia production in the proximal tubule. This may at least partly account for the metabolic alkalosis observed in severe hypokalaemia

Glucose intolerance. Reversal occurs with correction of hypokalaemia.
It also decreases plasma aldosterone by directly affecting the adrenal gland.

An increase in urinary water excretion by blocking reabsorption of Na at some point in the nephron, thus reducing the osmotic gradient for water reabsorption by increasing tubular osmolality. The consequent effects on water, K, Ca and H loss vary depending on the site and nature of the blocked transport systems

Diuretics which act earlier in the nephron increase delivery of Na to the late distal parts of the nephron, thereby enhancing K secretion there.
These can be either low potency (early distal tubule action, eg thiazides) or high potency (loop of Henle action, eg frusemide).

- Hypovolaemia
- Hyponatraemia (thiazides more than loop b/c more water lost with loop)
- Hypokalaemia (esp. in patients with high aldosterone)
- Alkalosis

- Hypercalcaemia: thiazides reduce renal Ca2+ secretion (Frusemide opposite effect)
- Hyperuricaemia: attacks of gout
- Hyperglycaemia
- Hyperlipidaemia: dose-dependent increase in cholerestol and triglycerides

Deafness

Hyperkalaemia, leading to cardiac arrhythmias and muscular weakness. Care must be taken in using these drugs in renal failure and with ACE inhibitors, which may also elevate potassium
Also spironolactone is not well tolerated and may cause GI upset, painful gynaecomastia and impotence

135 - 145 mmol/l

Mainly neurological: patients may be asymptomatic, or develop nausea and malaise, then headache, lethargy, confusion, obtundation and eventually seizures and coma.

Hyponatraemia may be spurious (false), dilutional, depletional or redistributional

Induction of osmotic demyelination (central pontine myelinolysis)

- Biochemcal error/ collection error (vein carrying an intravenous infusion)
- Spurious: hyperlipidaemia, hyperproteinaemia
- Solute excess: hyperglycaemia, mannitol

- With elevated extracellular volume: congestive cardiac failure, cirrhosis, nephrotic syndrome, renal failure, water overload
- Withour elevated extracellular volume: inappropriate ADH (syndrome of inappropriate antidiuretic hormone or SIADH)

It is a fascinating syndrome of excess ADH response not related to an aberration of body fluid osmolality or circulatory status. The classical example is the elaboration of ADH by tumours such as small cell carcinomas of the lung. The hyonatraemia can be severe in these patients. Other examples are head injury, cerebral metastatic cancer and lung tuberculosis.

- Adrenocortical failure
- Vomiting, diarrhoea, nasogastric or GIT fistula loss (especially with inappropriate fluid replacement)
- Diuretic abuse