ANATOMY AND

PHYSIOLOGY OF
EXCRETORY
SYSTEM
 URINARY
SYSTEM
 The urinary system is the main
excretory system and consists of the
following structures:
 2 kidneys, which secrete urine.
 2 ureters, which convey the urine from
the kidneys to the urinary bladder.
 The urinary bladder where urine
collects and is temporarily stored.
 The urethra through which the urine
passes from the urinary bladder to the
exterior.
The urinary system plays a vital part in
maintaining homeostasis of water and
electrolyte concentrations within the body.
The kidneys produce urine that contains
metabolic waste products, including the
nitrogenous compounds urea and uric acid,
excess ions and some drugs.
The main functions of the kidneys are:
Formation and secretion of urine, which
regulates total body water, electrolyte and acid–
base balance and enables excretion of waste
products.
Production and secretion of erythropoietin, the
hormone that stimulates formation of red blood
cells.
Production and secretion of renin, an
important enzyme in the control of blood
pressure
Urine is stored in the bladder and excreted by
the process of micturition.
 ANTERIOR VIEW OF THE
KIDNEY
 The kidneys lie on the posterior abdominal wall, one on each side
of the vertebral column, behind the peritoneum and below the
diaphragm.
 They extend from the level of the 12th thoracic vertebra to the 3rd
lumbar vertebra, receiving some protection from the lower rib
cage.
 The right kidney is usually slightly lower than the left, probably
because of the considerable space occupied by the liver
 Kidneys are bean-shaped organs, about 11 cm long, 6 cm wide, 3
cm thick and weigh 150 g.
 They are embedded in, and held in position by, a mass of fat. A
sheath of fibrous connective tissue, also known as the renal fascia,
encloses the kidney and the renal fat.
 As the kidneys lie on either side of the vertebral column, each is
associated with a different group of structures.
POSTERIOR VIEW OF THE
KIDNEY
 LOCATION OF THE KIDNEY

Right kidney
 Superiorly – the right adrenal gland
 Anteriorly – the right lobe of the liver, the
duodenum and the hepatic flexure of the
colon
 Posteriorly – the diaphragm, and muscles of
the posterior abdominal wall
Left kidney
 Superiorly – the left adrenal gland
 Anteriorly – the spleen, stomach, pancreas,
jejunum and splenic flexure of the colon
 Posteriorly – the diaphragm and muscles of
the posterior abdominal wall
 GROSS STRUCTURE OF THE KIDNEY
There are three areas of tissue that can be
distinguished when a longitudinal section of the
kidney is viewed with the naked eye
 an outer fibrous capsule, surrounding the
kidney
 the cortex, a reddish-brown layer of tissue
immediately below the capsule and outside
the pyramids
 the medulla, the innermost layer, consisting
of pale conical-shaped striations, the renal
pyramids.
 The hilum is the concave medial border of the kidney where the renal blood and lymph
vessels, the ureter and nerves enter.
 The renal pelvis is the funnel-shaped structure that collects urine formed by the kidney.
 Urine formed in the kidney passes through a renal papilla at the apex of a pyramid into a
minor calyx, then into a major calyx before passing through the renal pelvis into the ureter.
 The walls of the pelvis contain smooth muscle and are lined with transitional epithelium.
 Peristalsis of the smooth muscle originating in pacemaker cells in the walls of the calyces
propels urine through the renal pelvis and ureters to the bladder.
 This is an intrinsic property of the smooth muscle, and is not under nerve control.
 MICROSCOPIC STRUCTURE OF THE
KIDNEY
 The kidney is composed of about 1–2 million
functional units, the nephrons, and a smaller
number of collecting ducts.
 The collecting ducts transport urine through
the pyramids to the calyces and renal pelvis,
giving the pyramids their striped appearance.
 The collecting ducts are supported by a small
amount of connective tissue, containing
blood vessels, nerves and lymph vessels.
 The nephron consists of a tubule closed at one end,
the other end opening into a collecting tubule. The
closed or blind end is indented to form the cup-
shaped glomerular capsule (Bowman’s capsule),
which almost completely encloses a network of tiny
arterial capillaries, the glomerulus. These resemble a
coiled tuft.
 Continuing from the glomerular capsule, the
remainder of the nephron is about 3 cm long and is
described in three parts:
the proximal convoluted tubule
the medullary loop (loop of Henle)
the distal convoluted tubule, leading into a collecting
duct.
 The collecting ducts unite, forming larger ducts that
empty into the minor calyces.
 The kidneys receive about 20% of the cardiac output.
 After entering the kidney at the hilum the renal artery
divides into smaller arteries and arterioles.
 In the cortex an arteriole, the afferent arteriole, enters
each glomerular capsule and then subdivides into a
cluster of tiny arterial capillaries, forming the glomerulus.
 Between these capillary loops are connective tissue
phagocytic mesangial cells, which are part of the
monocyte–macrophage system. The blood vessel leading
away from the glomerulus is the efferent arteriole.
 The afferent arteriole has a larger diameter than the efferent
arteriole, which increases pressure inside the glomerulus and
drives filtration across the glomerular capillary walls.
 The efferent arteriole divides into a second peritubular (meaning
‘around tubules’) capillary network, which wraps around the
remainder of the tubule, allowing exchange between the fluid in
the tubule and the bloodstream.
 This maintains the supply of oxygen and nutrients to the local
tissues and removes waste products.
 Venous blood drained from this capillary bed eventually leaves the
kidney in the renal vein, which empties into the inferior vena
cava.
 The blood vessels of the kidney are supplied by both sympathetic
and parasympathetic nerves.
 The presence of both branches of the autonomic nervous system
controls renal blood vessel diameter and renal blood flow
independently of autoregulation
 The walls of the glomerulus and the glomerular
capsule consist of a single layer of flattened
epithelial cells.
 The glomerular walls are more permeable than those
of other capillaries.
 The remainder of the nephron and the collecting
duct are formed by a single layer of simple
squamous epithelium.
 FUNCTIONS OF THE KIDNEY

FORMATION OF URINE
The kidneys form urine, which passes through the ureters to the bladder for storage prior to
excretion.
The composition of urine reflects exchange of substances between the nephron and the blood
in the renal capillaries.
Waste products of protein metabolism are excreted, electrolyte levels are controlled and pH
(acid–base balance) is maintained by excretion of hydrogen ions.
There are three processes involved in the formation of urine:
 Filtration
 Selective reabsorption
 Secretion.
 FILTRATION
 This takes place through the semipermeable walls of
the glomerulus and glomerular capsule.
 Water and other small molecules pass through,
although some are reabsorbed later.
 Blood cells, plasma proteins and other large molecules
are too large to filter through and therefore remain in
the capillaries.
 The filtrate in the glomerulus is very similar in
composition to plasma with the important exceptions
of plasma proteins and blood cells.
Constituents of glomerular filtrate and glomerular capillaries

Blood constituents in glomerular Blood constituents remaining in

filtrate glomerular capillaries

 Water  Leukocytes
 Mineral salts  Erythrocytes
 Amino acids  Platelets
 Ketoacids  Plasma proteins
 Glucose  Some drugs (large molecules)
 Some hormones
 Creatinine
 Urea
 Uric acid
 Some drugs (small molecules)
 Filtration takes place because there is a difference between the blood pressure in the
glomerulus and the pressure of the filtrate in the glomerular capsule.
 Because the efferent arteriole is narrower than the afferent arteriole, a capillary
hydrostatic pressure of about 7.3 kPa (55 mmHg) builds up in the glomerulus.
 This pressure is opposed by the osmotic pressure of the blood, provided mainly by
plasma proteins, about 4 kPa (30 mmHg), and by filtrate hydrostatic pressure of
about 2 kPa (15 mmHg) in the glomerular capsule.
 The net filtration pressure is, therefore:
 The volume of filtrate formed by both kidneys each minute is called the glomerular
filtration rate (GFR). In a healthy adult the GFR is about 125 ml/min, i.e. 180 litres of
filtrate are formed each day by the two kidneys.
 Nearly all of the filtrate is later reabsorbed from the kidney tubules with less than 1%, i.e. 1
to 1.5 litres, excreted as urine.
 The differences in volume and concentration are due to selective reabsorption of some
filtrate constituents and tubular secretion of others.
 AUTOREGULATION OF FILTRATION

 Renal blood flow is protected by a mechanism called autoregulation, whereby renal blood
flow is maintained at a constant pressure across a wide range of systolic blood pressures
(from around 80 to 200 mmHg).
 Autoregulation operates independently of nervous control, i.e. if the nerve supply to the
renal blood vessels is interrupted, autoregulation continues to operate.
 It is therefore a property inherent in renal blood vessels; it may be stimulated by changes in
blood pressure in the renal arteries or by fluctuating levels of certain metabolites, e.g.
prostaglandins.
 In severe shock, when the systolic blood pressure falls below 80 mmHg, autoregulation fails
and renal blood flow and the hydrostatic pressure decrease, impairing filtration within the
nephrons.
 SELECTIVE REABSORPTION
 Most reabsorption from the filtrate back into the blood takes place in the proximal
convoluted tubule, whose walls are lined with microvilli to increase surface area for
absorption.
 Materials essential to the body are reabsorbed here, including some water,
electrolytes and organic nutrients such as glucose.
 Some reabsorption is passive, but some substances are transported actively.
 Only 60–70% of filtrate reaches the loop of the nephron.
 Much of this, especially water, sodium and chloride, is reabsorbed in the loop, so
only 15–20% of the original filtrate reaches the distal convoluted tubule, and the
composition of the filtrate is now very different from its starting values.
 More electrolytes are reabsorbed here, especially sodium, so the filtrate entering the
collecting ducts is actually quite dilute.
 The main function of the collecting ducts therefore is to reabsorb as much water as
the body needs.
 Active transport takes place at carrier sites in the epithelial membrane, using chemical energy to transport
substances against their concentration gradients.
 Some ions, e.g. sodium and chloride, can be absorbed by both active and passive mechanisms depending
on the site in the nephron.
 Some constituents of glomerular filtrate (e.g. glucose, amino acids) do not normally appear in urine
because they are completely reabsorbed unless blood levels are excessive.
 Reabsorption of nitrogenous waste products, such as urea, uric acid and creatinine is very limited.
 The kidneys’ maximum capacity for reabsorption of a substance is the transport maximum, or renal
threshold.
 For example, the normal blood glucose level is 3.5 to 8 mmol/l (63 to 144 mg/100 ml) and if this rises
above the transport maximum of about 9 mmol/l (160 mg/100 ml), glucose appears in the urine. This
occurs because all the carrier sites are occupied and the mechanism for active transport out of the tubules
is overloaded. Other substances reabsorbed by active transport include sodium, calcium, potassium,
phosphate and chloride.
 The transport maximum, or renal threshold, of some substances varies according to body need at a
particular time, and in some cases reabsorption is regulated by hormones.
 HORMONES THAT INFLUENCE SELECTIVE
REABSORPTION
Parathyroid hormone
• This comes from the parathyroid glands and together
with calcitonin from the thyroid gland regulates the
reabsorption of calcium and phosphate from the distal
collecting tubules.
Antidiuretic hormone
• Also known as ADH, this is secreted by the posterior lobe of
the pituitary gland and increases the permeability of the distal
convoluted tubules and collecting tubules, increasing water
reabsorption. Secretion of ADH is controlled by a negative
feedback system
Aldosterone
• Secreted by the adrenal cortex, this hormone increases
the reabsorption of sodium and water, and the
excretion of potassium. Secretion is regulated through
a negative feedback system
Atrial natriuretic peptide
 Also known as ANP, this hormone is secreted by
the atria of the heart in response to stretching of
the atrial wall.
 It decreases reabsorption of sodium and water
from the proximal convoluted tubules and
collecting ducts.
 Secretion of ANP is also regulated by a negative
feedback system
 TUBULAR SECRETION
 Filtration occurs as the blood flows through the glomerulus.
 Substances not required and foreign materials, e.g. drugs including penicillin and
aspirin, may not be cleared from the blood by filtration because of the short time it
remains in the glomerulus.
 Such substances are cleared by secretion from the peritubular capillaries into the
convoluted tubules and excreted from the body in the urine.
 Tubular secretion of hydrogen ions (H+) is important in maintaining normal blood
pH.
THREE PROCESS THAT FORM
URINE
 COMPOSITION OF URINE

Water 96%
Urea 2%
 Urine is clear and amber in colour due to the presence of urobilin, a bile pigment altered in
the intestine, reabsorbed then excreted by the kidneys.
 The specific gravity is between 1020 and 1030, and the pH is around 6 (normal range of 4.5
to 8).
 A healthy adult passes 1000 to 1500 ml per day.
 The amount of urine produced and the specific gravity vary according to fluid intake and the
amount of solute excreted.
 Urine production is decreased during sleep and exercise.
 WATER BALANCE AND URINE
OUTPUT
 Water is excreted as the main constituent of urine, in expired air, faeces and through the skin
as sweat.
 The amount lost in expired air and faeces is fairly constant, and the amount of sweat
produced is associated with environmental and body temperatures.
 The balance between fluid intake and output is controlled by the kidneys.
 The minimum urinary output, i.e. the smallest volume required to excrete body waste
products, is about 500 ml per day.
Changes in the concentration of electrolytes in the body fluids may be due to changes
in:
• the body water content, or
• electrolyte levels.
• There are several mechanisms that maintain the balance between water and
electrolyte concentration.
Sodium and potassium balance
 Sodium is the most common cation (positively charged ion) in extracellular fluid and
potassium is the most common intracellular cation.
 Sodium is a constituent of almost all foods and salt is often added to food during cooking.
This means that intake is usually in excess of the body’s needs. It is excreted mainly in urine
and sweat.
Renin–angiotensin–aldosterone system
• Sodium is a normal constituent of urine and the amount excreted is regulated by the
hormone aldosterone, secreted by the adrenal cortex.
• Cells in the afferent arteriole of the nephron release the enzyme renin in response to
sympathetic stimulation, low blood volume or by low arterial blood pressure.
• Renin converts the plasma protein angiotensinogen, produced by the liver, to angiotensin
1. Angiotensin converting enzyme (ACE), formed in small quantities in the lungs, proximal
convoluted tubules and other tissues, converts angiotensin 1 into angiotensin 2, which is a
very potent vasoconstrictor and increases blood pressure.
• Renin and raised blood potassium levels also stimulate the adrenal gland to secrete
aldosterone. Water is reabsorbed with sodium and together they increase the blood volume,
leading to reduced renin secretion through the negative feedback mechanism. When sodium
reabsorption is increased potassium excretion is increased, indirectly reducing intracellular
potassium.
CALCIUM BALANCE
• Regulation of calcium levels is
achieved by coordinated secretion
of parathyroid hormone and
calcitonin. The distal collecting
tubules reabsorb more calcium in
response to PTH secretion, and
reabsorb less calcium in response
to secretion of calcitonin.
pH balance
 In order to maintain the normal blood pH (acid–base balance), the cells of the proximal
convoluted tubules secrete hydrogen ions. In the filtrate they combine with buffers:
 Bicarbonate, forming carbonic acid

 Ammonia, forming ammonium ions

 hydrogen phosphate, forming dihydrogen phosphate.
 The normal pH of urine varies from 4.5 to 8 depending on diet, time of day and a number of
other factors. Individuals whose diet contains a large amount of animal proteins tend to
produce more acidic urine (lower pH) than vegetarians.
 URETERS
 The ureters are the tubes that carry urine from the kidneys to the
urinary bladder.
 They are about 25 to 30 cm long with a diameter of about 3 mm.
 The ureter is continuous with the funnel-shaped renal pelvis.
 It passes downwards through the abdominal cavity,
behind the peritoneum in front of the psoas muscle into
the pelvic cavity, and passes obliquely through the
posterior wall of the bladder.
 Because of this arrangement, when urine accumulates
and the pressure in the bladder rises, the ureters are
compressed and the openings occluded.
 This prevents reflux of urine into the ureters (towards the
kidneys) as the bladder fills and during micturition, when
pressure increases as the muscular bladder wall contracts
The walls of the ureters consist of three layers of
tissue.
 an outer covering of fibrous tissue, continuous
with the fibrous capsule of the kidney
a middle muscular layer consisting of
interlacing smooth muscle fibres that form a
functional unit round the ureter and an
additional outer longitudinal layer in the lower
third
 an inner layer, the mucosa, composed of
transitional epithelium
 URETERS - FUNCTION
 The ureters propel urine from the kidneys into the bladder by peristaltic contraction
of the smooth muscle layer.
 This is an intrinsic property of the smooth muscle and is not under autonomic nerve
control.
 Peristalsis originates in a pacemaker in the minor calyces.
 Peristaltic waves occur several times per minute, increasing in frequency with the
volume of urine produced, sending little spurts of urine into the bladder.
 URINARY BLADDER
 The urinary bladder is a reservoir for urine. It lies in the
pelvic cavity and its size and position vary, depending on
the volume of urine it contains. When distended, the
bladder rises into the abdominal cavity.
 The bladder is roughly pear shaped, but becomes more
oval as it fills with urine. The posterior surface is
the base. The bladder opens into the urethra at its lowest
point, the neck.
 The peritoneum covers only the superior surface before it
turns upwards as the parietal peritoneum, lining the
anterior abdominal wall. Posteriorly it surrounds the
uterus in the female and the rectum in the male.
The bladder wall is composed of three layers:
 the outer layer of loose connective tissue, containing blood and lymphatic vessels and
nerves, covered on the upper surface by the peritoneum
 the middle layer, consisting of interlacing smooth muscle fibres and elastic tissue loosely
arranged in three layers. This is called the detrusor muscle and when it contracts, it empties
the bladder
 the mucosa, composed of transitional epithelium, that readily permits distension of the
bladder as it fills with urine.
 When the bladder is empty the inner lining is arranged in folds, or rugae, which gradually
disappear as it fills.
 The bladder is distensible but when it contains 300 to 400 ml, awareness of the need to pass
urine is felt. The total capacity is rarely more than about 600 ml.
 The three orifices in the bladder wall form a triangle or trigone.
 The upper two orifices on the posterior wall are the openings of the ureters.
 The lower orifice is the opening into the urethra. The internal urethral sphincter, a thickening
of the urethral smooth muscle layer in the upper part of the urethra, controls outflow of urine
from the bladder. This sphincter is not under voluntary control.
 URETHRA
 The urethra is a canal extending from the neck of the bladder to the exterior, at the external
urethral orifice. It is longer in the male than in the female.
 The male urethra is associated with the urinary and the reproductive systems,
 The female urethra is approximately 4 cm long and 6 mm in diameter.
 It runs downwards and forwards behind the symphysis pubis and opens at the external
urethral orifice just in front of the vagina. The external urethral orifice is guarded by
the external urethral sphincter, which is under voluntary control.
 The wall of the female urethra has two main layers: an outer muscle layer and an inner lining
of mucosa, which is continuous with that of the bladder.
 The muscle layer has two parts, an inner layer of smooth muscle that is under autonomic
nerve control, and an outer layer of striated muscle surrounding it.
 The striated muscle forms the external urethral sphincter and is under voluntary control.
 The mucosa is supported by loose fibroelastic connective tissue containing blood vessels and
nerves.
 Proximally it consists of transitional epithelium while distally it is composed of stratified
epithelium
 MICTURITION
 When 300 to 400 ml of urine have
accumulated in the bladder, afferent autonomic
nerve fibres in the bladder wall sensitive to
stretch are stimulated.
 In the infant this initiates a spinal reflex and
micturition occurs.
 Urine passed in the response to
parasympathetic stimulation of the bladder,
causing contraction of the detrusor muscle and
relaxation of the internal urethral sphincter.
 Urine is expelled from the bladder and passes
through the urethra before leaving the body.
CONTROL OF MICTURITION AFTER BLADDER
CONTROL
 When the nervous system is fully developed, the micturition
reflex is stimulated but sensory impulses also pass upwards to
the brain and there is awareness of the need to pass urine.
 By learned and conscious effort, contraction of the external
urethral sphincter and muscles of the pelvic floor can inhibit
micturition until it is convenient to empty the bladder.
 In adults, urine is passed when the detrusor muscle
contracts, and there is reflex relaxation of the internal
sphincter and voluntary relaxation of the external sphincter.
 It can be assisted by increasing the pressure
within the pelvic cavity, achieved by lowering
the diaphragm and contracting the abdominal
muscles (Valsalva’s manoeuvre).
 Overdistension of the bladder is extremely
painful, and when this stage is reached there is
a tendency for involuntary relaxation of the
external sphincter to occur allowing a small
amount of urine to escape, provided there is no
mechanical obstruction. Involuntary loss of
urine is known as incontinence.
 DISEASES OF THE KIDNEYS
Common signs and symptoms of disorders of the urinary system
Sign/symptom Definition and description
Oliguria Urine output less than 400 ml per day
Haematuria Presence of blood in the urine. Leaky glomeruli allow red blood cells to escape from the
glomerular capillaries and they cannot be reabsorbed from the filtrate as they are too large.
Bleeding in the urinary tract also causes hematuria
Proteinuria Presence of protein in the urine. This is abnormal and occurs when leaky glomeruli allow
plasma proteins to escape into the filtrate but they are too large to be reabsorbed
Anuria Absence of urine
Dysuria Pain on passing urine, often described as a burning sensation
Glycosuria Presence of sugar in the urine. This is abnormal and occurs in diabetes mellitus
Ketonuria Presence of ketones in the urine. This is abnormal and occurs in, e.g., starvation, diabetes
mellitus
Nocturia Passing urine during the night
Polyuria Passing unusually large amounts of urine
Frequency of Requiring to pass, often small amounts of, urine frequently
micturition
Incontinence Involuntary loss of urine
 GLOMERULONEPHRITIS
 Inflammatory conditions of the glomerulus.
 These are formed when antigens and antibodies combine either within the kidney or
elsewhere in the body, and they circulate in the blood. When immune complexes lodge in the
walls of the glomeruli they often cause an inflammatory response that impairs glomerular
function.
Classification of GN is complex and based on a number of features: the cause, immunological
characteristics and findings on microscopy.
The extent of damage:
– diffuse: affecting all glomeruli
– focal: affecting some glomeruli
Appearance:
– proliferative: increased number of cells in the glomeruli
– membranous: thickening of the glomerular basement membrane.
EFFECTS OF GLOMERULAR NEPHRITIS
Haematuria
Asymptomatic proteinuria
Acute nephritis is characterized by the presence of:
 oliguria (<400 ml urine/day in adults)
 hypertension
 hematuria
 uremia
 Loin pain, headache and malaise are also common
 NEPHROTIC SYNDROME
This is not a disease in itself but is an important feature of several kidney diseases. The main characteristics are:
• marked proteinuria
• hypoalbuminemia
• generalised oedema
• hyperlipidemia.
 When glomeruli are damaged, the permeability of the glomerular membrane is increased and plasma proteins pass
through into the filtrate.
 Albumin is the main protein lost because it is the most common and is the smallest of the plasma proteins.
 When the daily loss exceeds the rate of production by the liver there is a significant fall in the total plasma protein
level. The consequent low plasma osmotic pressure leads to widespread oedema and reduced plasma volume. This
reduces the renal blood flow and stimulates the renin–angiotensin–aldosterone system, causing increased
reabsorption of water and sodium from the renal tubules. The reabsorbed water further reduces the osmotic
pressure, increasing the oedema.
 The key factor is the loss of albumin across the glomerular membrane and as long as this continues, the vicious
circle is perpetuated. Levels of nitrogenous waste products, i.e. uric acid, urea and creatinine, usually remain
normal.
 Hyperlipidemia, especially hypercholesterolemia, also occurs but the cause is unknown.
 STAGES OF DEVELOPMENT OF NEPHROTIC
SYNDROME
Nephrotic syndrome occurs in a number of
diseases. In children the most common cause is
minimal-change glomerulonephritis. In adults it
may complicate:
 Most forms of glomerulonephritis
 Diabetic nephropathy
 Systemic lupus erythematosus
 Infections, e.g. malaria, syphilis, hepatitis B
 Drugs, e.g. penicillamine, gold, captopril,
phenytoin.
 DIABETIC NEPHROPATHY
 Renal failure is the commonest cause of death in young people with diabetes mellitus and is
more common if hypertension and severe, long-standing hyperglycemia are present.
Diabetes causes damage to large and small blood vessels throughout the body, although the
effects vary considerably between individuals. In the kidney, these are known collectively
as diabetic nephropathy or diabetic kidney and include:
 progressive damage of glomeruli, proteinuria and nephrotic syndrome
 ascending infection leading to acute pyelonephritis, sometimes complicated by renal
papillary necrosis
 atheroma of the renal arteries and their branches leading to renal ischemia and hypertension
 chronic renal failure.
 HYPERTENSION AND THE KIDNEYS
Hypertension can be the cause or the result of renal disease. Essential and secondary hypertension both affect the
kidneys when there is renal blood vessel damage, causing ischemia. The reduced blood flow stimulates the renin–
angiotensin–aldosterone system, raising the blood pressure still further.
Essential hypertension
Benign hypertension
• This causes gradual and progressive damage to the glomeruli, which may lead to renal failure after the renal
reserve has been lost or to malignant hypertension.
Malignant hypertension
• This causes arteriolosclerosis which spreads to the glomeruli with subsequent destruction of nephrons, leading
to a further rise in blood pressure and a variable degree of renal impairment in most people. In a few people
there are more serious effects; increased permeability of the glomeruli allows escape of plasma proteins and red
blood cells into the filtrate causing proteinuria and hematuria, which may progress to renal failure.
Secondary hypertension
• This is caused by long-standing kidney diseases and may lead to chronic renal ischemia, worsening
hypertension and renal failure.
Acute pyelonephritis
 This is acute bacterial infection of the renal pelvis and calyces, spreading to the kidney substance
causing formation of small abscesses.
 The infection may travel up the urinary tract from the perineum or be blood-borne. It is
accompanied by fever, malaise and loin pain.
Ascending infection
 Upward spread of microbes from the bladder, is the most common cause of this condition.
 Abnormal reflux of infected urine into the ureters when the bladder contracts during micturition
predisposes to upward spread of infection to the renal pelvis and kidney substance.
Blood-borne infection
 The source of microbes may be from septicemia or elsewhere in the body, e.g. respiratory tract
infections, infected wounds or abscesses.
 Due to their large blood flow (20% of cardiac output) the kidneys are susceptible to infection by
blood-borne microbes.
PATHOPHYSIOLOGY
 When the infection spreads into the kidney tissue it causes suppuration and destruction of
nephrons.
 The prognosis depends on the amount of healthy kidney remaining after the infection
subsides.
 Necrotic tissue is eventually replaced by fibrous tissue but there may be some hypertrophy
of healthy nephrons.
 There are a number of outcomes: healing, recurrence, especially if there is a structural
abnormality of the urinary tract, and reflux nephropathy.
 Perinephric abscess and papillary necrosis are complications, usually if the condition is
untreated.
 REFLUX NEPHROPATHY
 Previously known as chronic pyelonephritis, this is almost always associated with reflux of
urine from the bladder to the ureter allowing spread of infection upwards towards the
kidneys.
 A congenital abnormality of the angle of insertion of the ureter into the bladder predisposes
to reflux of urine, but it is sometimes caused by an obstruction that develops later in life.
 Progressive damage to the renal papillae and collecting ducts leads to chronic renal failure
and concurrent hypertension is common.
 RENAL FAILURE

• Acute renal failure

• There is a sudden and severe reduction in the glomerular filtration rate and kidney
function that is often reversible over days or weeks if treated. There is oliguria or anuria
accompanied by metabolic acidosis due to retention of H+; electrolyte imbalance;
accumulation of other mainly nitrogenous waste products; and, if not associated with
severe fluid loss, retention of water, i.e. substances normally excreted in urine are
retained in the body. This occurs as a complication of a variety of conditions not
necessarily associated with the kidneys. The causes of acute renal failure are classified as:
• • prerenal: the result of reduced renal blood flow, especially as a consequence of, e.g.,
severe and prolonged shock
• • renal: occurs due to damage to the kidney itself due to, e.g., acute tubular necrosis,
glomerulonephritis
• • postrenal: arises from obstruction to the outflow of urine, e.g. disease of the prostate
gland, tumour of the bladder, uterus or cervix, large calculus (stone) in the renal pelvis.
 ACUTE TUBULAR NECROSIS (ATN)

This is the most common cause of acute renal failure. There is severe damage to the tubular epithelial cells caused by ischemia or,
less often, by nephrotoxic substances.
causes of ATN
 Ischemia – severe shock, dehydration, hemorrhage, trauma; extensive burns; myocardial infarction; prolonged and complex
surgery, especially in older people
 Drugs – e.g. aminoglycoside antibiotics, non-steroidal anti-inflammatory drugs (NSAIDs), ACE inhibitors, lithium
compounds, paracetamol overdose
 Hemoglobinemia – accumulation of hemoglobin, released by haemolysis of red blood cells, e.g. incompatible blood
transfusion, malaria
 Myoglobinaemia – accumulation of myoglobin released from damaged muscle raises blood levels, e.g. following crush injury .
 Oliguria, severe oliguria (less than 100 ml of urine per day in adults) or anuria may last for a few weeks, followed by
profound diuresis. There is reduced glomerular filtration and selective reabsorption and secretion by the tubules, leading to:
 heart failure due to fluid overload
 generalised and pulmonary oedema
 accumulation of urea and other metabolic waste products
 electrolyte imbalance which may be exacerbated by the retention of potassium (hyperkalaemia) released from damaged cells
anywhere in the body
 acidosis due to hydrogen ion retention.
 Profound diuresis (the diuretic phase) occurs during the healing process when the epithelial cells of the tubules have
regenerated but are still incapable of selective reabsorption and secretion. Diuresis may lead to acute dehydration, complicating
the existing high plasma urea, acidosis and electrolyte imbalance. If the patient survives the initial acute phase, a considerable
degree of renal function is usually restored over several weeks (the recovery phase).
 CHRONIC RENAL FAILURE
 This occurs when the renal reserve is lost and there is irreversible damage to about 75% of
nephrons.
 Onset is usually slow and asymptomatic, progressing over several years. The main causes are
diabetes mellitus, glomerulonephritis and hypertension.
 The effects on glomerular filtration rate (GFR), selective reabsorption and tubular secretion
are significant.
 GFR and filtrate volumes are greatly reduced, and reabsorption of water is seriously impaired.
This results in production of up to 10 litres of urine per day. Reduced glomerular filtration
leads to accumulation of waste substances in the blood, notably urea and creatinine. When
renal failure becomes evident, blood urea levels are raised and this is referred to as uremia.
Some of the signs and symptoms that may accompany this condition include nausea,
vomiting, gastrointestinal bleeding, anemia and pruritus (itching). Others are explained below.
Polyuria in chronic renal failure
Polyuria
Large volumes of dilute urine (with a low specific gravity) are passed, because
water reabsorption is impaired. Nocturia is a common presenting symptom.
Normal kidney End-stage kidney

GFR 125 ml/min or 180 l/day 10 ml/min or 14 l/day

Reabsorption of water >99% Approx. 30%

Urine output <1 ml/min or 1.5 l/day Approx. 7 ml/min or 10 l/day

Acidosis
• As the kidney buffer system that normally controls the pH of body fluids fails, hydrogen
ions accumulate.
Electrolyte imbalance
• This is also the result of impaired tubular reabsorption and secretion.
Anemia
• Deficiency of erythropoietin occurs after a few months, causing anemia that is usually
exacerbated by hemodialysis which damages red blood cells. If untreated, anemia results in
fatigue, and may also lead to dyspnea and cardiac failure. Tiredness and breathlessness are
sometimes the initial symptoms of chronic renal failure.
 END-STAGE RENAL FAILURE
 When death is likely without renal replacement therapy, such as hemodialysis,
peritoneal dialysis or a kidney transplant, the condition is referred to as end-stage
renal failure.
 The excretory functions of the kidneys are lost, acid–base balance cannot be
maintained and endocrine functions of the kidney are disrupted.
 Towards the end of life anorexia, nausea and very deep (Kussmaul’s) respirations
occur as uraemia progresses.
 In the final stages there may be hiccoughs, itching, vomiting, muscle twitching,
seizures, drowsiness and coma.
 RENAL CALCULI
 Calculi (stones) form in the kidneys and bladder when urinary constituents normally
in solution are precipitated.
 The solutes involved are usually oxalates and phosphates.
 They are more common in males and after 30 years of age and the condition is often
recurrent.
 Most originate in the collecting tubules or renal papillae.
 They then pass into the renal pelvis where they may increase in size. Some become
too large to pass through the ureter and may obstruct the outflow of urine, causing
kidney damage.
 Others pass to the bladder and are either excreted or increase in size and obstruct the
urethra
Sometimes stones originate in the bladder, usually in developing countries and often in
children. Predisposing factors include:
 Dehydration. This leads to increased reabsorption of water from the tubules but does not
change solute reabsorption, resulting in a reduced volume of highly concentrated filtrate in
the collecting tubules.
 pH of urine. When the normally acid filtrate becomes alkaline, some substances may be
precipitated, e.g. phosphates. This occurs when the kidney buffering system is impaired and
in some infections.
 Infection. Necrotic material and pus provide foci upon which solutes in the filtrate may be
deposited and the products of infection may alter the pH of the urine. Infection sometimes
leads to alkaline urine (see above).
 Metabolic conditions. These include hyperparathyroidism and gout.
Congenital abnormalities of the kidneys
• Misplaced (ectopic) kidney
One or both kidneys may develop in abnormally low positions. Misplaced kidneys function
normally if the blood vessels are long enough to provide an adequate blood supply but a
kidney in the pelvic cavity may cause problems during pregnancy as the expanding uterus
compresses renal blood vessels or the ureters. If the ureters become kinked there is increased
risk of infection as there is a tendency for reflux and backflow to the kidney. There may also
be difficulties during childbirth.
• Polycystic disease
The infantile form is very rare and is usually fatal in early childhood.
Autosomal dominant polycystic kidney disease (ADPKD)
 This is inherited as an autosomal dominant condition that may become apparent any
time between childhood and late adult life. Both kidneys are affected.
 Dilations (cysts) form at the junction of the distal convoluted tubules and collecting
ducts.
 The cysts slowly enlarge and pressure causes ischemia and destruction of nephrons.
 The disease is progressive and secondary hypertension is common; chronic renal
failure affects about 50% of patients.
 TUMOURS OF THE KIDNEY

Benign tumours are relatively uncommon.

Malignant tumours
• These are most common in the bladder or kidney.
Renal cell carcinoma
• Previously known as hypernephroma or Grawitz’s tumour, this tumour of tubular
epithelium is more common after 50 years of age, especially in males.
Nephroblastoma (Wilms’ tumour)
• This is one of the most common malignant tumours in children under 10 years,
usually occurring in the first 4 years
 DISEASES OF THE RENAL PELVIS,
URETERS, BLADDER AND URETHRA
Obstruction to the outflow of urine
Hydronephrosis
This is dilation of the renal pelvis and calyces caused by accumulation of urine above
an obstruction in the urinary tract. It leads to destruction of the nephrons, fibrosis and
atrophy of the kidney.
Complete sustained obstruction
In this condition hydronephrosis develops quickly, pressure in the nephrons rises and
urine production stops. The most common causes are a large calculus or tumour. The
outcome depends on whether one or both kidneys are involved
Partial or intermittent obstruction
 This may progress undetected for many years. It leads to progressive hydronephrosis
and is caused by, e.g.:
 a succession of renal calculi in a ureter, eventually moved onwards by peristalsis
 constriction of a ureter or the urethra by fibrous tissue, following epithelial
inflammation caused by the passage of a stone or by infection
 a tumour in the urinary tract or in the abdominal or pelvic cavity
 enlarged prostate gland in the male.
Spinal lesions
 When there is damage to the nerve supply to the bladder, e.g. transverse spinal cord lesions,
micturition does not occur.
 When the bladder fills, the rise in pressure causes overflow incontinence, back pressure into
the ureters and hydronephrosis.
 Reflex micturition is usually re-established after a time, but loss of voluntary control may be
irreversible.
 Pressure on the spinal cord and other abnormalities, e.g. spina bifida, can also impair
micturition.
Urethritis
 This is inflammation of the urethra
 TUMOURS OF THE BLADDER

Tumours are often multiple and recurrence is common. Predisposing factors include cigarette
smoking, taking high doses of analgesics over a long period and occupational exposure to some
chemicals, e.g. aniline dyes used in the textile and printing industries.
Transitional cell carcinomas
These tumours, also known as papillomas, arise from transitional epithelium and are often benign.
They consist of a stalk with fine-branching fronds, which tend to break off causing painless
bleeding and hematuria. Papillomas commonly recur, even when benign.
Solid tumours
These are all malignant to some degree. At an early stage the more malignant and solid tumours
rapidly invade the bladder wall and spread in lymph and blood to other parts of the body. If the
surface ulcerates there may be haemorrhage and necrosis.
 URINARY INCONTINENCE
• In this condition normal micturition is affected and there is involuntary loss of urine.
Several types are recognized.
Stress incontinence
• This is leakage of urine when intra-abdominal pressure is raised, e.g. on coughing,
laughing, sneezing or lifting. It usually affects women when there is weakness of the
pelvic floor muscles or pelvic ligaments, e.g. after childbirth or as part of the ageing
process. It occurs physiologically in young children before bladder control is
achieved.
Urge incontinence
• Leakage of urine follows a sudden and intense urge to void and there is inability to
delay passing urine. This may be due to a urinary tract infection, calculus, tumour or
overactivity of the detrusor muscle.
Overflow incontinence
This occurs when there is overfilling of the bladder and may be due to:
 retention of urine due to obstruction of urinary outflow, e.g. enlarged prostate gland
or urethral stricture, or
 a neurological abnormality affecting the nerves involved in micturition, e.g. stroke,
spinal cord injury or multiple sclerosis.
 The bladder becomes distended and when the pressure inside overcomes the
resistance of the external urethral sphincter, urine dribbles from the urethra. The
individual may be unable to initiate and/or maintain micturition.