Oxford Textbook of Fundamentals of Surgery

William E. G. Thomas (ed.) et al.

https://doi.org/10.1093/med/9780199665549.001.0001
Published: 2016 Online ISBN: 9780191810817 Print ISBN: 9780199665549

CHAPTER

1.2.9 Urinary 

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Aidan Bradford

https://doi.org/10.1093/med/9780199665549.003.0015 Pages 85–88

Published: July 2016

Abstract
This chapter begins with a description of the overall functions of the kidney, the general principles of
ltration, absorption, secretion, and urine formation, and the structural characteristics associated
with these processes such as the a erent and e erent arterioles, the glomerulus, Bowman’s capsule,
proximal tubule, loop of Henle, thick ascending limb, macula densa, distal tubule, collecting duct,
peritubular capillaries, and vasa recta. The mechanisms involved in the control of renal blood ow
through autoregulation are explained (i.e. the myogenic mechanism and tubuloglomerular feedback
involving the macula densa). The mechanisms involved in the generation of a concentrated medullary
interstitium are detailed such as the countercurrent multiplier and the countercurrent exchanger of
the vasa recta. Glomerular ltration rate and the Starling forces involved in ltration at the renal
corpuscle are de ned along with the concept of clearance and its measurement using creatinine. The
role of the kidneys in extracellular uid homeostasis is explained in relation to sodium, potassium,
water, and acid–base balance. The roles of renin, angiotensin, aldosterone, antidiuretic hormone, and
atrial natriuretic peptide are outlined and some of the causes of hyponatraemia, hypernatraemia,
hypokalaemia, hyperkalaemia, overhydration, and underhydration are given. The mechanism of
bicarbonate absorption by the renal tubular cell is detailed along with the mechanism of formation of
titratable acid and ammonium in the urine and the e ects of metabolic acidosis, metabolic alkalosis,
respiratory acidosis, and respiratory alkalosis on this process are explained. The chapter concludes
with a brief characterization of the pathophysiology of acute and chronic renal failure.

Keywords: nephron, renal blood flow, glomerular filtration rate, clearance, body fluid homeostasis, renal
failure
Subject: Surgery, Urology, Paediatric Surgery, Cardiothoracic Surgery, Peri-operative Care, Trauma and
Orthopaedic Surgery, Upper Gastrointestinal Surgery, Colorectal Surgery, Surgical Oncology, Neurosurgery,
Breast Surgery, Transplant Surgery, Vascular Surgery, Surgical Skills
Series: Oxford Textbooks in Surgery
Introduction

The functions of the kidney are to regulate the volume and composition of the extracellular uid (ECF). The
kidneys actually regulate the volume and composition of the plasma, maintaining a narrow plasma
osmolality between 285 and 295 mosmol/L which results in regulation of the volume and composition of the
entire ECF. They therefore play a crucial role in long-term control of blood pressure (BP). The kidneys
eliminate potentially toxic metabolic wastes and foreign compounds (urea, uric acid, drugs, etc.). They also
release renin, activate vitamin D, and secrete erythropoietin.

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The total body water is about 50–60% of body mass (females and males respectively): two-thirds is
intracellular uid (ICF) and one-third is ECF.

In a 70 kg body mass male:

◆ Total body water (TBW) = 42 L = 0.6 × body mass

◆ ICF = 28 L = 0.4 × body mass

◆ ECF = 14 L = 0.2 × body mass.

+ − + −
Na and Cl are the main ions in ECF and K and PO4 are the main ions in ICF.

In 24 hours, uid gain is by salt and water intake (~2 L) and metabolic water (~0.5 L). Fluid loss is through
urine (~1.5 L), insensible loss (skin ~0.5 L and lung ~0.5 L), sweat, and faeces (~0.1 L).

The nephron (Figure 1.2.9.1) is the functional unit of the kidney. Each nephron consists of a renal corpuscle
and a tubular system. The renal corpuscle consists of a tuft of capillaries or glomerulus and Bowman’s
capsule. The tubular system consists of the proximal tubule (PT), loop of Henle, distal tubule (DT), and
collecting duct (CD). The tubular system ‘loops down’ into the medulla and then returns to the cortex to join
a CD. The CD runs from the cortex to the inner medulla. Final urine forms in the CD. The process of urine
formation consists of ltration of blood at the glomerulus, tubular reabsorption, and secretion. Blood
reaches each nephron via an a erent arteriole. As blood ows through the glomerulus, a fraction of the
solutes and water is ltered across the capillary walls into Bowman’s capsule. This forms the tubular
ltrate. As the ltrate ows through the PT and loop of Henle, most of it is reabsorbed back into the blood.
The small volume which remains ows on to the DT and CD. Here, salt and water excretion is regulated so
that it matches salt and water intake and the nal urine is formed.
Fig. 1.2.9.1

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Structural characteristics of the renal nephron.

Reproduced from Reynard et al. (Eds), Oxford Handbook of Urology, Second Edition, Oxford University Press, Oxford, UK,
Copyright © 2009, with permission from Oxford University Press.

Blood flow

Blood ow to the two kidneys is approximately 1.2 L/min or one-quarter of cardiac output. In health, renal
blood ow (RBF) is held constant. Blood ow to the cortex is about 90% and blood ow to the medulla is
about 10% of total ow. Glomerular capillaries recombine to leave Bowman’s capsule as e erent arterioles.
E erent arterioles give rise to peritubular capillaries which surround the tubular system of each nephron.
These then recombine to form venules and the renal vein. These capillaries deliver nutrients and oxygen to
the epithelial cells lining the tubules and take up uid from the interstitium that has been reabsorbed from
the ltrate.

Over a range of 90–180 mmHg, RBF and hence glomerular ltration rate (GFR) is autoregulated, that is,
changes in mean BP have little e ect on RBF or GFR. This is by two mechanisms: (1) a myogenic mechanism
and (2) by tubuloglomerular feedback. The myogenic mechanism is due to the increase in BP causing stretch
of a erent arteriolar smooth muscle which then contracts, increasing a erent arteriole resistance and
preventing an increase in RBF. The tubuloglomerular feedback mechanism is due to an increase in BP
+
causing an increase in RBF, GFR, and the rate of uid ow through the tubules so that more Na reaches the
1
macula densa of the ascending limb of the loop of Henle and this causes constriction of the a erent
arteriole and a decrease in RBF. However, RBF can be altered by sympathetic nerve activity, hormones,
drugs, and so on.

GFR is the volume of plasma ltered per minute, that is, 120 mL/min. Filtration occurs due to a high
glomerular capillary hydrostatic pressure of 50 mmHg that is opposed by a lesser plasma colloid osmotic
pressure of 25 mmHg and a Bowman’s capsule hydrostatic pressure of 10 mmHg, leaving a net ltration
pressure of 15 mmHg (the oncotic pressure in Bowman’s capsule is 0 mmHg since no protein is ltered
normally). Filtration occurs through three layers: the fenestrated endothelium of glomerular capillaries, the
basement membrane, and the foot processes of epithelial cells (podocytes). The three layers contain
negatively charged glycoproteins. Proteins and cells are not ltered. In nephrotic syndrome, there is an
increase in the permeability of the glomerular capillaries to protein and there is protein loss in urine
(proteinuria), hypoproteinaemia, and oedema.
Clearance

Clearance is the volume of plasma cleared of a substance per minute or U × V/P (mL/min) where U and P are
the concentrations of a substance in the urine and the plasma respectively and V is the volume of urine
excreted in mL/min. It is used to measure GFR and GFR is an excellent measure of renal function. A decrease
in GFR is often the rst sign of renal disease.

The clearance of a substance which meets the following criteria will give a measure of GFR: freely ltered at
the glomerulus, not reabsorbed from the ltrate, not secreted into the ltrate, not metabolized by the

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tubular cells, and does not interfere with kidney function. Creatinine does not fully meet these criteria but is
2
used extensively to measure GFR and hence renal function. The Cockcroft and Gault formula allows
calculation of creatinine clearance by measuring plasma creatinine concentration, that is:

Creatinine clearance (mL/min) = (140 − age) × mass (kg) / (814 × plasma creatinine concentration)

For example, in a 40-year-old, 70 kg male with a normal creatinine concentration of 0.6mmol/L:

Creatinine clearance = (140 − 40) × 70/ (814 × 60) = 0.143 mL/min

(For females, the result must be multiplied by 0.85.)

Para-aminohippuric acid (PAH) is freely ltered but not absorbed. All of the PAH that escapes ltration is
secreted actively into the tubular uid. Therefore PAH is completely removed from all of the plasma that
ows through the kidneys. Therefore, the clearance of PAH equals the renal plasma ow (RPF) = 700
mL/min, therefore RBF = 700 mL/min × 1/0.58 (assuming a haematocrit of 0.42) = 1.2 L/min.
Control of extracellular fluid volume and electrolytes
Approximately 70% of the ltrate is reabsorbed in the PT and this is not regulated. In the loop of Henle, a
further 20% is reabsorbed and only 10% is left to enter the DT and CD. Here, salt and water reabsorption is
varied so that salt and water excretion is matched to intake. Sodium reabsorption is regulated by
aldosterone and water reabsorption is regulated by antidiuretic hormone (ADH, vasopressin). Normally
urine output is 1 mL/min or 1.5 L/day with urine osmolality depending on uid intake ranging from very
dilute at 50 mosmol/L to very concentrated at 1200 mosmol/L. The minimum normal urine output is 0.5
3
mL/min or 700 mL/day. ADH acts on a V2 receptor to incorporate aquaporin or water channels that make
the CD epithelium permeable to water. In its absence, the CD is impermeable to water. The hypertonic

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interstitium generated by the loop of Henle and the countercurrent multiplier (Figure 1.2.9.2) allows water
to move from the tubular lumen into the interstitium. The thick ascending limb of the loop is impermeable
+ + −
to water but has a Na /K /2 Cl pump (that is inhibited by loop diuretics) which moves these three ions into
the interstitium and creates an osmotic pressure of 1200 mosmol/L at the base of the loop. Urea absorption
also contributes to the high osmolarity. The vasa recta prevent loss of the osmotic gradient by
countercurrent exchange. Osmoreceptors located in the hypothalamus control thirst and ADH release from
the posterior pituitary. Loss of water causes an increase in plasma osmolarity resulting in ADH release and
thirst. In the syndrome of inappropriate ADH secretion (SIADH), for example, lung or brain tumours, there
is overhydration and decreased plasma osmolarity falling to as low as 260 mosmol/L. In central diabetes
insipidus, there is inadequate release of ADH from the posterior pituitary (e.g. head injury or brain
infection). In nephrogenic diabetes insipidus, the CD does not respond to ADH (e.g. lithium treatment).
These conditions cause polyuria and polydipsia and, when untreated, serum osmolality rises to higher than
320 mosmol/L and coma can develop.

Fig. 1.2.9.2

Diagrammatic representation of the countercurrent multiplier of the nephron and the countercurrent exchanger of the vasa
recta.

Reproduced from Pocock and Richards (Eds), Human Physiology: The Basis of Medicine, Third Edition, Oxford University Press,
Oxford, UK, Copyright © 2006, with permission from Oxford University Press.

When the ECF and, therefore, the blood volume falls, BP at the a erent arteriole falls and this causes renin
release. Circulating angiotensinogen is acted on by renin to produce angiotensin I which is changed to
+
angiotensin II in the lungs which causes aldosterone release from the adrenal cortex which increases Na
 +
absorption from the CD. The increase in plasma Na causes increased osmolarity and increased ADH release
so blood volume and BP rise. There are atrial receptors that are stimulated by increased blood volume and
cause reduced ADH release and inhibition of sympathetic nerve activity to the kidney. This reduces renin
release and also favours salt and water loss by dilating the a erent arteriole and increasing GFR.

4
The atria also release atrial natriuretic peptide which causes natriuresis and a decrease in blood volume and
pressure. In the normal plasma, sodium concentration is 135–148 mM/L. Sodium depletion can be caused by
+
severe diarrhoea, severe vomiting, haemorrhage, and adrenal insu ciency and Na retention can be caused
by chronic renal failure, heart failure, and excess adrenocortical hormones. Potassium homeostasis (normal
+ + +
plasma value is 3.5–5.0 mM/L) is controlled by the N /K pump in the CD cells. When plasma K increases,

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+ +
this causes aldosterone release which stimulates the pump, increasing CD cell K , and this K is then
secreted into the tubule for excretion. The pump is also directly stimulated by the increased ECF potassium
concentration. Hypokalaemia is caused by some diuretics, excess aldosterone secretion, metabolic alkalosis,
severe diarrhoea, and severe vomiting. Hyperkalaemia is caused by acute kidney injury, adrenal
insu ciency, acute acidosis, tissue destruction (burns, rhabdomyolysis, crush injury) and haemolysis. To
2+ +
treat hyperkalaemia, Ca is given to prevent arrhythmias, insulin and glucose are given to pump K into
+
cells, and ion exchange resins are given to remove K from the body through the GIT.

Acid–base balance
−
The kidneys play a major role in acid–base balance by regulating the HCO3 concentration of the plasma
− +
which is normally 24 mM. HCO3 regulates pH by bu ering H as follows:

+ −
H + HCO3 ↔ H2 CO3 ↔ H2 O + CO2

−
The tubule cells synthesize HCO3 and replenish that used up by bu ering, and add it to the blood (Figure
− + +
1.2.9.3). The cells make HCO3 and H from CO2 and H2O. H is secreted into the tubular lumen for excretion
− + −
and HCO3 enters the blood. The secreted H ion reacts with a HCO3 ion in the ltrate and ‘destroys’ it. For
− − −
each HCO3 ion ‘destroyed’, a HCO3 ion enters the blood so that the net e ect is as though the HCO3 in
the ltrate has passed through the cell into the blood. In this way, with a normal mixed diet, all of the
− −
ltered HCO3 is ‘reabsorbed’ and ‘new bicarbonate’ is then added to the blood to replenish HCO3 ‘used
− +
up’ by bu ering the acids generated by the mixed diet. This new HCO3 is accompanied by H secretion
+
which lowers the pH of the urine. These H ions are bu ered by ltered phosphate to form titratable acid
5 +
and by ammonia (NH3) made from glutamine in the tubular cell, to form ammonium (NH4 ).
Fig. 1.2.9.3

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+
Diagrammatic representation of the mechanism of bicarbonate absorption from the tubule lumen. For each H secreted by the
tubule cell that ʻdestroysʼ a bicarbonate ion in the filtrate, there is an associated bicarbonate ion that enters the plasma.

Reproduced from Reynard et al. (Eds), Oxford Handbook of Urology, Second Edition, Oxford University Press, Oxford, UK,
Copyright © 2009, with permission from Oxford University Press.

−
In metabolic acidosis, since the plasma, and therefore the ltered load of HCO3 is low, more ‘new
bicarbonate’ is added to the blood and the urine pH will be low.

−
In metabolic alkalosis, the plasma and ltered load of HCO3 is high so that not all of it is reabsorbed so
−
HCO3 is lost in the urine and the urine pH is high.

+ −
In respiratory acidosis, the blood PCO2 and tubular cell PCO2 is high so the cell makes more H and HCO3 so
that the urine pH is low and ‘new bicarbonate’ is formed.

+
In respiratory alkalosis, tubular cell PCO2 is low so insu cient H is formed and secreted in order to absorb
− −
all the ltered HCO3 so that HCO3 is excreted in the urine.
Renal failure

In acute kidney injury, there is a rapid, sudden decrease in renal function and GFR. In pre-renal failure, the
cause is cardiovascular such as heart failure, hypotension, or haemorrhage whereby RBF is inadequate. In
intrarenal failure, the cause is some abnormality within the kidney itself such as glomerulonephritis,
tubular necrosis, pyelonephritis, and so on. In post-renal failure, there is obstruction of the urinary tract
such as stones or high pressure urine retention. The e ects of acute kidney injury are hyperkalaemia,
metabolic acidosis, hypertension, oedema, increased plasma urea and creatinine, and uraemia. The causes
of chronic renal failure are vascular (atherosclerosis), infections (pyelonephritis), immunological

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(glomerulonephritis), diabetes mellitus, obstruction, polycystic kidney disease, and so on. The e ects are
similar to acute kidney injury but they occur more gradually. There is also anaemia due to the inability of the
kidney to produce erythropoietin and osteomalacia and hyperparathyroidism due to the inability to activate
vitamin D to 1,25-dihydoxycholecalciferol. Therefore plasma calcium falls due to reduced calcium
absorption from the gut.

Further reading
Barrett KE, Boitano S, Barman SM, et al. Ganongʼs Review of Medical Physiology (24th ed). New York: McGraw-Hill Education;
2012.
Google Scholar Google Preview WorldCat COPAC

Koeppen BM, Stanton BA. Berne & Levy Physiology (6th ed). St. Louis, MD: Elsevier Health Sciences; 2009.
Google Scholar Google Preview WorldCat COPAC

References
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2. Shoker A, Hossain MA, Koru-Sengul T, et al. Performance of creatinine clearance equations on the original Cockro –Gault
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4. Baxter JD, Lewicki JA, Gardner DG. Atrial natriuretic peptide. Nat Biotechnol 1988; 6:529–46. 10.1038/nbt0588-529
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