Learn — Renal system, body fluids & acid–base

6 notes · 16 questions on the topic

Types of solutions — isotonic/hyper/hypo

Tonicity is the effective osmolality of a fluid compared with plasma — the part of its osmolality made up of solutes that cannot cross the cell membrane, so it is what decides which way water moves once the fluid reaches the capillary. An isotonic fluid leaves cell volume unchanged and stays in the extracellular compartment, a hypertonic fluid pulls water out of cells, and a hypotonic fluid drives water into them, which makes the choice of bag a nursing decision with a cellular consequence.

  • Normal plasma osmolality is 275 to 295 mOsm/kg, so a fluid in the 270 to 310 mOsm/L band behaves as isotonic at the capillary.
  • Isotonic fluids: 0.9% sodium chloride (154 mEq/L each of sodium and chloride, about 308 mOsm/L) and Ringer's lactate (about 273 mOsm/L, with sodium 130, potassium 4, calcium 3, chloride 109 and lactate 28 mEq/L); both stay in the extracellular compartment and are the fluids of resuscitation.
  • 5% dextrose is isotonic only in the bag at about 252 mOsm/L; once the glucose is metabolised what is left is free water, so it distributes across all compartments and behaves as a hypotonic fluid — it must never be used to resuscitate a shocked patient.
  • Hypertonic fluids: 3% sodium chloride (513 mEq/L each of sodium and chloride, about 1026 mOsm/L), 10% and 25% dextrose and 20% mannitol; they draw water out of cells into the extracellular space, so they are given through a large vein or a central line, on a pump, with the serum sodium checked at fixed intervals.
  • Hypotonic fluids: 0.45% sodium chloride (77 mEq/L each, about 154 mOsm/L) and 5% dextrose after its glucose is used; they swell cells and are contraindicated in head injury, cerebral oedema and shock.
  • Only about a quarter of an infused isotonic crystalloid stays in the vessels after equilibration, because plasma is roughly a quarter of the extracellular fluid — one litre of normal saline expands the plasma by roughly 250 mL, which is the basis of the 3 mL of crystalloid for every 1 mL of blood lost.
  • Large volumes of 0.9% saline cause a hyperchloraemic metabolic acidosis because its chloride of 154 mEq/L is far above the plasma value of 98 to 106 mEq/L; Ringer's lactate avoids that but contains potassium and calcium, so it is not run with citrated blood and is used with care in renal failure.
  • In symptomatic hyponatraemia the serum sodium is raised by no more than 8 to 10 mEq/L in the first 24 hours, however low the starting value, because a faster correction risks osmotic demyelination.

Body fluid compartments

Body water is not one pool but a set of compartments separated by membranes that pass water freely and solutes selectively: about 60% of an adult man's weight is water, two-thirds of it inside cells and one-third outside them. Every fluid order, every deficit calculation and every electrolyte result is a statement about which compartment has gained or lost water, so the nurse who knows the compartments can predict what a bag of fluid will actually do.

  • Total body water is about 60% of body weight in an adult man and 50 to 55% in an adult woman, who has proportionally more fat; it is 75 to 80% in a newborn and falls to about 45 to 50% in old age, which is why infants and the elderly dehydrate fastest.
  • In a 70 kg man that is about 42 litres: 28 litres intracellular (40% of body weight, two-thirds of total body water) and 14 litres extracellular (20% of body weight).
  • The extracellular 14 litres divides into interstitial fluid of about 10.5 litres (15% of body weight) and plasma of about 3 litres (5% of body weight, roughly a quarter of the extracellular fluid), with 1 to 2 litres of transcellular fluid — cerebrospinal, pleural, peritoneal, synovial, intraocular and gastrointestinal secretions.
  • The main intracellular cation is potassium at about 140 to 150 mEq/L, balanced by phosphate and protein; the main extracellular cation is sodium at 135 to 145 mEq/L with chloride 98 to 106 and bicarbonate 22 to 26 mEq/L, and the sodium-potassium ATPase is what holds that difference.
  • Plasma differs from interstitial fluid chiefly by its protein of 6 to 8 g/dL, which generates the plasma colloid osmotic pressure of about 25 to 28 mmHg that holds water inside the vessels.
  • Compartments are measured by dilution: total body water with deuterium or antipyrine, extracellular fluid with inulin or mannitol, and plasma volume with Evans blue dye or radio-iodinated albumin; intracellular and interstitial volumes are never measured directly but obtained by subtraction.
  • Daily balance in an adult is about 2500 mL in (1500 mL drunk, 700 mL in food, 300 mL of metabolic water) against 2500 mL out (urine 1500 mL, insensible loss from skin about 500 mL and from lungs about 350 mL, faeces 150 mL); insensible loss rises sharply with fever, tachypnoea and burns.
  • Third-space fluid is fluid sequestered where it does no circulatory work — ascites, burns, bowel obstruction, pleural effusion — so the patient can be oedematous and hypovolaemic at the same time, and the circulation is judged by pulse, blood pressure and a urine output of at least 0.5 mL/kg/h rather than by weight.

Osmosis

Osmosis is the movement of water across a semipermeable membrane from the side of lower solute concentration to the side of higher solute concentration, driven by water's own gradient because the solute itself cannot cross. Osmotic pressure is the pressure that would have to be applied to the concentrated side to stop that movement, and it is the force behind tonicity, oedema formation and every intravenous fluid decision on the ward.

  • Water moves towards the higher solute concentration, so a cell placed in a hypertonic solution shrinks (crenates) and a cell in a hypotonic solution swells and may burst — a red cell haemolyses in distilled water, which is why nothing hypotonic is ever added to a blood unit.
  • Osmolarity is milliosmoles per litre of solution and osmolality is milliosmoles per kilogram of water; plasma osmolality is 275 to 295 mOsm/kg, and the two terms are used interchangeably in practice because plasma is mostly water.
  • Plasma osmolality can be estimated as 2 x sodium + glucose/18 + blood urea nitrogen/2.8 with the glucose and urea in mg/dL; sodium and its accompanying anions supply about 90 to 95% of the total, which is why the sodium is read as the osmolality.
  • Tonicity is not the same as osmolarity: urea and alcohol raise the measured osmolality but cross cell membranes freely, so they are ineffective osmoles and move no water — only solutes that stay outside the cell, chiefly sodium, exert tonicity.
  • The total osmotic pressure of plasma is about 5500 mmHg and comes mostly from sodium and chloride, but only 25 to 28 mmHg of it — the colloid osmotic (oncotic) pressure from the plasma proteins — acts across the capillary wall, because that wall passes small ions freely and protein hardly at all.
  • Starling's forces at the capillary: hydrostatic pressure pushes fluid out at about 30 to 35 mmHg at the arteriolar end, falling to about 10 to 15 mmHg at the venular end, against a constant oncotic pull of 25 to 28 mmHg — so fluid filters out proximally, is reabsorbed distally, and the small surplus returns as lymph.
  • Oedema follows any breach of that balance: raised hydrostatic pressure in heart failure and venous obstruction, fallen oncotic pressure in nephrotic syndrome, liver failure and kwashiorkor, increased permeability in burns and sepsis, and blocked lymphatics in filariasis or after axillary clearance.
  • Osmosis is used deliberately in treatment: 20% mannitol and 3% saline pull water out of swollen brain cells and lower intracranial pressure, glycerine drops the intraocular pressure, and hypertonic dressings draw exudate out of a wound.

Adrenal gland

The adrenal (suprarenal) glands are two retroperitoneal endocrine glands capping the upper poles of the kidneys — pyramidal on the right and semilunar on the left — each weighing only about 4 to 6 grams and yet essential to life. Each is two organs in one capsule: an outer cortex of mesodermal origin that makes steroid hormones under ACTH and the renin-angiotensin system, and an inner medulla of neural crest origin that is effectively a sympathetic ganglion secreting catecholamines into the blood, and that split explains everything from Addisonian crisis to phaeochromocytoma.

  • The cortex has three zones, remembered as GFR making Salt, Sugar and Sex: zona glomerulosa makes the mineralocorticoid aldosterone, zona fasciculata makes the glucocorticoid cortisol, and zona reticularis makes the androgens dehydroepiandrosterone and androstenedione.
  • Aldosterone is controlled by the renin-angiotensin system and by the plasma potassium rather than by ACTH; it acts on the distal tubule and collecting duct to reabsorb sodium and water and to excrete potassium and hydrogen — so excess (Conn's syndrome) gives hypertension with hypokalaemia and alkalosis, and deficiency gives hyponatraemia with hyperkalaemia.
  • Cortisol is released under ACTH from the anterior pituitary with a diurnal rhythm, highest at about 6 to 8 in the morning and lowest around midnight; it raises blood glucose by gluconeogenesis, breaks down protein and fat, and suppresses inflammation and immunity — which is why steroid doses are timed to the morning and why a steroid-treated patient masks the signs of infection.
  • The medulla's chromaffin cells secrete about 80% adrenaline and 20% noradrenaline under direct preganglionic sympathetic control through the greater splanchnic nerve, making it the only endocrine gland innervated by preganglionic sympathetic fibres; cortisol draining past it from the cortex is what induces the enzyme that converts noradrenaline into adrenaline.
  • Blood supply is unusually rich and threefold — superior suprarenal from the inferior phrenic artery, middle suprarenal from the abdominal aorta and inferior suprarenal from the renal artery — but venous drainage is by a single vein on each side: the short right suprarenal vein drains straight into the inferior vena cava and the left into the left renal vein.
  • Addison's disease is primary adrenal insufficiency, so both cortisol and aldosterone fail: fatigue, weight loss, anorexia, postural hypotension, salt craving, hyponatraemia, hyperkalaemia, hypoglycaemia and hyperpigmentation of the buccal mucosa, palmar creases and scars; secondary (pituitary) insufficiency spares aldosterone and produces no pigmentation.
  • Cushing's syndrome is cortisol excess: moon face, buffalo hump, truncal obesity with wasted limbs, purple striae, thin bruisable skin, hypertension, hyperglycaemia, hypokalaemia, osteoporosis, poor wound healing and susceptibility to infection; by far the commonest cause in practice is prescribed steroid, which is why steroids are tapered and never stopped abruptly.
  • Phaeochromocytoma is a catecholamine-secreting tumour of the medullary chromaffin cells — classically called the 10% tumour — presenting with episodic headache, palpitations, sweating and severe paroxysmal hypertension; it is diagnosed by plasma or 24-hour urinary metanephrines, and alpha blockade (phenoxybenzamine) must always precede beta blockade or unopposed alpha stimulation precipitates a hypertensive crisis.
  • Congenital adrenal hyperplasia, most often 21-hydroxylase deficiency, blocks cortisol and aldosterone synthesis and diverts precursors into androgens, so the newborn girl has ambiguous genitalia and either sex may present in the second week of life with a salt-losing crisis — vomiting, dehydration, hyponatraemia and hyperkalaemia.

Glomerular filtration rate (GFR)

The glomerular filtration rate is the volume of plasma filtered by all the glomeruli of both kidneys in one minute, normally about 125 mL per minute in a young adult, which comes to roughly 180 litres of filtrate a day. It is the single best measure of how much working kidney a patient has left, and because drug doses, contrast decisions and the whole staging of chronic kidney disease hang on it, a nurse reads it on every renal chart.

  • Normal GFR corrected for body size is about 90 to 120 mL per minute per 1.73 square metres; of the 180 litres filtered each day, more than 99 per cent is reabsorbed and only 1 to 2 litres appears as urine.
  • Filtration is driven by net filtration pressure: glomerular capillary hydrostatic pressure of about 60 mmHg pushing out, opposed by capsular hydrostatic pressure of about 18 mmHg and glomerular colloid osmotic pressure of about 32 mmHg, leaving a net outward pressure of roughly 10 mmHg.
  • Filtration fraction is GFR divided by renal plasma flow and is normally about 20 per cent, since the kidneys receive around a fifth of the cardiac output.
  • GFR is autoregulated across a mean arterial pressure of roughly 80 to 180 mmHg by the myogenic response of the afferent arteriole and by tubuloglomerular feedback from the macula densa, so it stays steady despite ordinary changes in blood pressure.
  • Two drug classes break that autoregulation in opposite ways: NSAIDs constrict the afferent arteriole by blocking prostaglandins and drop GFR, while ACE inhibitors and angiotensin receptor blockers dilate the efferent arteriole and drop filtration pressure, which is why the combination with a diuretic in a dehydrated patient is the classic triple whammy of acute kidney injury.
  • Inulin clearance is the gold standard because inulin is freely filtered and neither reabsorbed nor secreted; creatinine clearance is the practical substitute and slightly overestimates GFR because a little creatinine is secreted by the tubule.
  • In practice GFR is estimated from serum creatinine with the CKD-EPI or MDRD equation, while the Cockcroft-Gault equation, which uses age, weight and sex, is still the one many drug dosing tables are built on.
  • KDIGO stages chronic kidney disease by GFR: G1 is 90 or more with evidence of kidney damage, G2 is 60 to 89, G3a is 45 to 59, G3b is 30 to 44, G4 is 15 to 29 and G5 is under 15, which is kidney failure; albuminuria is staged alongside it as A1, A2 and A3.
  • Serum creatinine is a blunt instrument: GFR must fall by roughly half before creatinine rises above the reference range, and because creatinine comes from muscle, a normal value in a thin elderly woman can hide a badly reduced GFR.

Renal tubular absorption

Tubular reabsorption is the process by which the nephron reclaims water and solute from the 180 litres of glomerular filtrate made each day, returning more than 99 per cent of it to the blood so that only 1 to 2 litres is voided as urine. Each segment of the tubule reabsorbs different substances by different transporters, and because almost every diuretic and several important electrolyte disorders are named after one of those segments, the map of the nephron is the map of the drug chart.

  • The proximal convoluted tubule is the bulk reabsorber: about 65 to 70 per cent of filtered sodium and water, essentially all of the glucose and amino acids, most of the bicarbonate through carbonic anhydrase, most potassium and phosphate, and about half the urea; reabsorption here is isosmotic, so the fluid leaving is still iso-osmotic with plasma.
  • Glucose reabsorption in the proximal tubule is saturable: once plasma glucose exceeds the renal threshold of about 180 mg/dL the transporters are overwhelmed and glycosuria appears, which is why an untreated diabetic passes sugar and, with it, an osmotic diuresis.
  • The descending limb of the loop of Henle is permeable to water but not to solute, while the ascending limb is impermeable to water and actively reabsorbs about 25 per cent of the filtered sodium through the sodium-potassium-two-chloride cotransporter; together they run the counter-current multiplier that builds a medullary interstitial gradient reaching about 1200 mOsm per kg.
  • Loop diuretics such as furosemide block the sodium-potassium-two-chloride cotransporter in the thick ascending limb, which makes them the most powerful diuretics and also explains the losses they cause: potassium, magnesium and calcium, along with the risk of ototoxicity.
  • The distal convoluted tubule reabsorbs about 5 per cent of filtered sodium through the sodium-chloride cotransporter, which is the thiazide site; the same segment reabsorbs calcium under parathyroid hormone, so thiazides tend to raise serum calcium while loop diuretics lose it.
  • In the collecting duct, aldosterone acts on principal cells to reabsorb sodium and excrete potassium and hydrogen, which is the site blocked by spironolactone and amiloride, while antidiuretic hormone inserts aquaporin-2 water channels to make the final adjustment of urine concentration.
  • The engine behind all of it is the sodium-potassium ATPase pump on the basolateral membrane, which keeps intracellular sodium low so that sodium can enter from the lumen and drag glucose, amino acids and phosphate with it by secondary active transport.
  • The tubule also secretes: potassium and hydrogen ions in the collecting duct, ammonium for acid excretion, and organic acids and drugs such as penicillin in the proximal tubule, where probenecid competes for the same carrier.
  • The result is urine that can be varied from about 50 to 1200 mOsm per kg, with a specific gravity between 1.003 and 1.030 depending on how much antidiuretic hormone is acting.

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