Download Water and electrolyte د. احمد حسين جاسم

Water and electrolyte
‫ احمد حسين جاسم‬.‫د‬
Water and electrolyte distribution
In a typical adult male, total body water (TBW) is approximately 60% of body weight (somewhat
more for infants and less for women). Of a TBW of 40 L, more than half is located inside cells
(the intracellular fluid or ICF) while the remainder, some 15 L, is in the extracellular fluid (ECF)
compartment. Of the ECF, the plasma is itself a small fraction (some 3 L).
The dominant cation in the ICF is potassium, while the dominant cation in the ECF is sodium.
Phosphates and negatively charged proteins constitute the major intracellular anions, while
chloride and, to a lesser extent, bicarbonate dominate the ECF anions. An important difference
between the plasma and interstitial compartments of the ECF is that only plasma contains
significant concentrations of protein.
The major force maintaining the difference in cation concentration between the ICF and ECF is
the activity of the sodium-potassium pump (Na,K-activated ATPase) integral to all cell
membranes. Maintenance of the cation gradients across cell membranes is essential for many
cell processes, including the excitability of conducting tissues such as nerve and muscle. The
difference in protein content between the plasma and the interstitial fluid compartment is
maintained by the impermeability of the capillary wall to protein. This protein concentration
gradient (the colloid osmotic, or oncotic, pressure of the plasma) contributes to the balance of
forces across the capillary wall that favour fluid retention within the circulating plasma.
Functional anatomy and physiology of renal sodium handling
Since the great majority of the body's sodium content is located in the ECF, where it is by far the
most abundant cation, total body sodium is a principal determinant of ECF volume. Regulation of
sodium excretion by the kidney is crucially important in maintaining normal ECF volume, and
hence plasma volume, in the face of wide variations in sodium intake, typically in the range 50250 mmol/day.
The functional unit for renal excretion is the nephron. The glomerulus is the site of ultrafiltration of
the blood, resulting in the generation of a cell- and protein-free fluid, resembling plasma in
electrolyte composition, that is delivered into the initial part of the tubular system. The glomerular
filtration rate (GFR) is approximately 125 mL/min (equivalent to 180 L/day) in a typical adult.
Nephron segments
At least four different functional segments of the nephron can be defined in terms of their
mechanism for sodium reabsorption .
Proximal tubule
This is responsible for the reabsorption of some 65% of the filtered sodium load.. The basolateral
membrane contains a high density of Na,K-ATPase pump units which remove sodium from the
cell into the blood. The filtered sodium in the luminal fluid enters the cell via several transporters
in the apical membrane. Cotransporters couple sodium to the entry of glucose, amino acid,
phosphate and other organic molecules. A quantitatively more significant mechanism is the entry
of sodium by countertransport with H+ ions, using the sodium-hydrogen exchanger (NHE-3).
Water and electrolyte
‫ احمد حسين جاسم‬.‫د‬
Intracellular H+ ions are generated from carbonic acid, the product of the enzyme carbonic
anhydrase, which hydrates carbon dioxide. Overall, fluid and electrolyte reabsorption is almost
isotonic in this segment, as water reabsorption is matched very closely to sodium fluxes. A
component of this water flow also passes through the cells, via aquaporin-1 (AQP-1) water
channels, which are not sensitive to hormonal regulation.
The loop of Henle
The thick ascending limb of the loop of Henle reabsorbs a further 25% of the filtered sodium but is
impermeable to water, resulting in dilution of the luminal fluid. Again, the primary driving force for
sodium reabsorption is the Na,K-ATPase on the basolateral cell membrane, but in this segment
sodium enters the cell from the lumen via a specific carrier molecule, the Na,K,2Cl cotransporter
('triple cotransporter', or NKCC2), which allows electroneutral entry of these ions. Some of the
potassium accumulated inside the cell recirculates across the apical membrane back into the
lumen through a specific potassium channel (ROMK), providing a continuing supply of potassium
to match the high concentrations of sodium and chloride available in the lumen.
Early distal tubule
Some 6% of filtered sodium is reabsorbed in the early distal (also called distal convoluted) tubule,
again driven by the activity of the basolateral Na, K-ATPase. In this segment, entry of sodium into
the cell from the luminal fluid is via a sodium-chloride cotransport carrier (NCCT). This segment is
also impermeable to water, resulting in further dilution of the luminal fluid. There is no significant
transepithelial flux of potassium in this segment, but calcium is reabsorbed through the a
basolateral sodium-calcium exchanger leads to low intracellular concentrations of calcium,
promoting calcium entry from the luminal fluid through a calcium channel.
Late distal tubule and collecting ducts
The late distal tubule and cortical collecting duct are anatomically and functionally continuous.
Here sodium entry from the luminal fluid is via the epithelial sodium channel (ENaC) This sodium
reabsorptive flux is balanced by excretion of potassium and hydrogen ions and by reabsorption of
chloride ions. Potassium is accumulated in the cell by the basolateral Na,K-ATPase, and passes
into the luminal fluid down its electrochemical gradient, through an apical potassium channel
(ROMK). Chloride ions pass largely between cells. Hydrogen ion secretion is mediated by an H +ATPase located on the luminal membrane of the intercalated cells, which constitute
approximately one-third of the epithelial cells in this nephron segment. This part of the nephron
has a variable permeability to water, depending on the availability of antidiuretic hormone (ADH,
or vasopressin) in the circulation. All ion transport processes in this segment are stimulated by
the steroid hormone aldosterone. This can increase the sodium reabsorption in this segment to a
maximum of 2-3% of the filtered sodium load.
Less than 1% of sodium reabsorption occurs in the medullary collecting duct, where it is inhibited
by natriuretic peptides such as ANP (atrial) and BNP (brain).
Regulation of sodium transport
Water and electrolyte
‫ احمد حسين جاسم‬.‫د‬
Important sensing mechanisms include volume receptors in the cardiac atria and the intrathoracic
veins, as well as pressure receptors located in the central arterial tree (aortic arch and carotid
sinus) and the afferent arterioles within the kidney. A further afferent signal is generated within the
kidney itself; the enzyme renin is released from specialised smooth muscle cells in the walls of the
afferent and efferent arterioles, at the point where they make contact with the early distal tubule (at
the macula densa) to form the juxtaglomerular apparatus. Renin release is stimulated by:



reduced perfusion pressure in the afferent arteriole
increased sympathetic nerve activity
decreased sodium chloride concentration in the distal tubular fluid.
Renin released into the circulation activates the effector mechanisms for sodium retention which
are components of the renin-angiotensin-aldosterone (RAA) system. Renin acts on the peptide
substrate angiotensinogen (manufactured in the liver), producing angiotensin I in the circulation.
This in turn is cleaved by angiotensin-converting enzyme (ACE) into angiotensin II, largely in the
pulmonary capillary bed. Angiotensin II has multiple actions: stimulation of proximal tubular
sodium reabsorption, release of aldosterone from the zona glomerulosa of the adrenal cortex,
and direct vasoconstriction of small arterioles. Aldosterone acts to amplify sodium retention by its
action in the cortical collecting duct. The net effect is to restore ECF volume and blood pressure
towards normal, thereby correcting the initiating hypovolaemic stimulus.
The sympathetic nervous system also increases sodium retention, both through haemodynamic
mechanisms (afferent arteriolar vasoconstriction and GFR reduction) and by direct stimulation of
proximal tubular sodium reabsorption. Other humoral mediators, such as the natriuretic peptides,
inhibit sodium reabsorption, contributing to natriuresis during periods of sodium and volume
excess.
DISORDERS OF WATER BALANCE
Daily water intake can vary over a wide range, from 500 mL to several litres a day. While a
certain amount of water is lost ('insensible losses', approximately 800 mL/day) through the stool,
sweat and the respiratory tract, and some water is generated by oxidative metabolism ('metabolic
water', approximately 400 mL/day), the kidneys are chiefly responsible for adjusting water
excretion to maintain constancy of body water content and body fluid osmolality (normal range
280-295 mmol/kg).
Functional anatomy and physiology of renal water handling
While regulation of total ECF volume is largely achieved through the kidneys' control of sodium
excretion,
These functions are largely achieved by the properties of the loop of Henle and the collecting
ducts. The counter-current configuration of flow in adjacent limbs of the loop, involving osmotic
water movement from the descending limbs and solute reabsorption from neighbouring
ascending limbs, sets up a gradient of tissue osmolality from isotonic (like plasma) in the renal
Water and electrolyte
‫ احمد حسين جاسم‬.‫د‬
cortex through to hypertonic (around 1200 mmol/kg) in the inner part of the medulla. At the same
time, the fluid emerging from the thick ascending limb is hypotonic compared to plasma, because
it has been diluted by the reabsorption of sodium, but not water, from the thick ascending limb
and early distal tubule. As this dilute fluid passes from the cortex through the collecting duct
system to the renal pelvis, it traverses the medullary interstitial gradient of osmolality set up by
the operation of the loop of Henle, and water is avidly reabsorbed.
Further changes in the urine osmolality on passage through the collecting ducts depend on the
level in the plasma of the peptide ADH, which is released by the posterior pituitary gland under
conditions of increased plasma osmolality or other stimuli such as hypovolaemia.
Parallel to these changes in ADH release are changes in water-seeking behaviour triggered by
the sensation of thirst, which also becomes activated as plasma osmolality rises from normal to
above normal levels.
In summary, for adequate dilution of the urine there must be:



adequate solute delivery to the loop of Henle and early distal tubule
normal function of the loop of Henle and early distal tubule
no ADH in the circulation.
If any of these processes is faulty, water retention and hyponatraemia may result.
Conversely, to achieve concentration of the urine there must be:




adequate solute delivery to the loop of Henle
normal function of the loop of Henle
ADH release into the circulation
ADH action on the collecting ducts.
Failure of any of these steps may result in inappropriate water loss and hypernatraemia.