Urinary System

Urinary system
2023-2024
Second year
MSBP-CP
Contents
1 Anatomy and development of Kidney and Ureter 1
2 Histology of Glomerulous and renal tubules 21
3 Functions of the kidney 33

3.1 General functions of the kidney . . . . . . . . . . . . . . . . . . . . . . . . . . 33
3.2 Metabolic function of the kidney . . . . . . . . . . . . . . . . . . . . . . . . . . 35
4 Tubular functions 39
5 Role of Kidney in Acid Base Balance 61
6 Diuretics 67
7 Glomerular diseases in children 81

7.1 Acute Post-streptococcal Glomerulonephritis (APSGN) . . . . . . . . . . . . . 81
7.2 Nephrotic syndrome in children (NS) . . . . . . . . . . . . . . . . . . . . . . . 84
8 Pathology of glomerular diseases 89
9 Proteinuria 99
10 Diabetic nephropathy 103
11 Chronic Kidney disease 105
12 Laboratory assessment of renal functions 109
13 Drug induced kidney injury 115
14 Acute kidney injury 119
15 Pathology of different renal diseases 123
16 Anatomy and development of urinary bladder and urethra 127
17 Histology of excretory passages 143
18 Physiology of urinary bladder 147
i
ii CONTENTS
19 Nucleotide Metabolism 151
20 Imaging of urinary system 159
21 Urinary tract symptoms 165
22 Urolithiasis (Urinary Calculi) 171
23 Microbiology of urinary tract infections 177
24 Urinary tract infections 189
25 Diseases of urinary bladder 195
26 Urinary antiseptics 197
27 Parasites affecting The Urinary system 201
28 Tumors of urinary system 211
29 Obstructive uropathy 217
30 Hematuria 223
31 Urinary incontinence 229

31.1 Urinary incontinence . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 229
31.2 Drug and urinary incontinence . . . . . . . . . . . . . . . . . . . . . . . . . . 234
List of Figures
1.1 Renal system organs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1

1.2 Right and left kidneys . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2
1.3 The positions of the kidneys in male and female . . . . . . . . . . . . . . . . 3
1.4 Longitudinal section in the kidney . . . . . . . . . . . . . . . . . . . . . . . . 4
1.5 Coverings of the kidney . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5
1.6 Anterior relations of right and left kidneys . . . . . . . . . . . . . . . . . . . 5
1.7 Posterior relations of the right and left kidneys . . . . . . . . . . . . . . . . . 6
1.8 Pathway of the blood through the kidney . . . . . . . . . . . . . . . . . . . . 7
1.9 The segmentation of the kidney based on segmental 5 arteries . . . . . . . 8
1.10 parts and course of the two ureters . . . . . . . . . . . . . . . . . . . . . . . 8
1.11 Anterior relations of the right and left ureters . . . . . . . . . . . . . . . . . . 9
1.12 Pelvic part of the ureter. A:in female B: in male Pelvis . . . . . . . . . . . . . 11
1.13 Sites of constrictions of the ureter . . . . . . . . . . . . . . . . . . . . . . . . 11
1.14 Arterial supply of the ureter . . . . . . . . . . . . . . . . . . . . . . . . . . . 12
1.15 The intermediate mesoderm and cloaca . . . . . . . . . . . . . . . . . . . . 12
1.16 The nephric tubules and neprogenic cord . . . . . . . . . . . . . . . . . . . 13
1.17 Different stages of development of the kidney . . . . . . . . . . . . . . . . . 14
1.18 The origin of permanent kidney from ureteric bud and metanephric cap . . . 16
1.19 Development of the collecting tubules . . . . . . . . . . . . . . . . . . . . . 16
1.20 Development of excretory part of the nephron . . . . . . . . . . . . . . . . . 17
1.21 The different location of the kidney during development . . . . . . . . . . . . 17
1.22 The different blood supply of the kidney during development . . . . . . . . . 18
1.23 Different congenital anomalies (agenesis, pelvic and horseshoe) . . . . . . 19
1.24 Polycystic kidney, double kidney and double ureter . . . . . . . . . . . . . . 19
1.25 Different anomalies of the ureter . . . . . . . . . . . . . . . . . . . . . . . . 20
2.1 Diagram showing nephron components . . . . . . . . . . . . . . . . . . . . 22

2.2 Podocyte and blood renal barrier . . . . . . . . . . . . . . . . . . . . . . . . 24
2.3 Intraglomerular mesangial cell . . . . . . . . . . . . . . . . . . . . . . . . . . 26
2.4 Sections in the components of uriniferous tubules . . . . . . . . . . . . . . . 26
2.5 EM for a proximal convoluted tubules cell (a) and distal convoluted tubule
cell (b) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 27
2.6 EM of an epithelial cell of thin limb of Henle’s loop . . . . . . . . . . . . . . 28
2.7 Section of cortex in kidney . . . . . . . . . . . . . . . . . . . . . . . . . . . . 30
2.8 Juxtaglomerular apparatus . . . . . . . . . . . . . . . . . . . . . . . . . . . . 30
iii
iv LIST OF FIGURES
3.1 Metabolic interrelationships of tissues in kidney failure. . . . . . . . . . . . . 38
4.1 Tubular functions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 39

4.2 Transport of sodium in PCTs . . . . . . . . . . . . . . . . . . . . . . . . . . 41
4.3 Glucose absorption . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 42
4.4 Bicarbonate transport in PCT . . . . . . . . . . . . . . . . . . . . . . . . . . 44
4.5 The Renal Counter Current Mechanism . . . . . . . . . . . . . . . . . . . . 48
4.6 The transport of Na+ , K+ , Cl in thick ascending limb of loop of Henle . . . 48
4.7 Vasa recta as a countercurrent exchanger system . . . . . . . . . . . . . . 49
4.8 The action of aldosterone in the DCTs . . . . . . . . . . . . . . . . . . . . . 53
4.9 Buffering of the hydrogen ion . . . . . . . . . . . . . . . . . . . . . . . . . . 56
4.10 Intracellular mechanism of action of ADH in the CDs . . . . . . . . . . . . . 58
5.1 pH value in the body . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 62

5.2 Body’s buffering of blood pH levels . . . . . . . . . . . . . . . . . . . . . . . 63
5.3 Physiologic buffer systems . . . . . . . . . . . . . . . . . . . . . . . . . . . . 63
5.4 Bicarbonate conservation . . . . . . . . . . . . . . . . . . . . . . . . . . . . 64
5.5 Acid Base disturbances . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 66
7.1 Degrees of proteinuria in children . . . . . . . . . . . . . . . . . . . . . . . . 87
8.1 Focal glomerulonephritis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 92

8.2 Crescentic glomerulonephritis . . . . . . . . . . . . . . . . . . . . . . . . . . 93
8.3 Minimal change disease . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 94
8.4 Membranous glomerulonephritis . . . . . . . . . . . . . . . . . . . . . . . . 95
8.5 Membranoproliferative glomerulonephritis . . . . . . . . . . . . . . . . . . . 96
16.1 Position of the urinary bladder in male and female Pelvis. . . . . . . . . . . 127
16.2 Different parts and surfaces of the urinary bladder . . . . . . . . . . . . . . 128
16.3 Structures related to the base of urinary bladder in male . . . . . . . . . . . 129
16.4 Different ligaments support the urinary bladder . . . . . . . . . . . . . . . . 131
16.5 The interior of the urinary bladder . . . . . . . . . . . . . . . . . . . . . . . . 131
16.6 Nerve supply of the urinary bladder . . . . . . . . . . . . . . . . . . . . . . . 133
16.7 Different parts of male urethra . . . . . . . . . . . . . . . . . . . . . . . . . . 133
16.8 Structures in the posterior surface of prostatic urethra in male . . . . . . . . 134
16.9 The internal and external urethral sphincter . . . . . . . . . . . . . . . . . . 136
16.10 Course of female urethra in the pelvis . . . . . . . . . . . . . . . . . . . . . 136
16.11 The cloaca and its divisions . . . . . . . . . . . . . . . . . . . . . . . . . . . 137
16.12 The formation of vesicourethral canal and definitive urogenital sinus . . . . 138
16.13 Absorption of the mesonephric ducts and formation of the trigon of the uri-
nary bladder . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 138
16.14 Different anomalies of urachus . . . . . . . . . . . . . . . . . . . . . . . . . 139
16.15 Ectopia vesica anomalies of urinary bladder . . . . . . . . . . . . . . . . . . 140
16.16 The origin of the different parts of male urethra . . . . . . . . . . . . . . . . 141
LIST OF FIGURES v
17.1 Ureter . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 144

17.2 Transverse section of Urinary Bladder . . . . . . . . . . . . . . . . . . . . . 145
17.3 Superficial cells of transitional epithelium . . . . . . . . . . . . . . . . . . . . 145
18.1 Cystometrogram . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 148
19.1 Nucleotides . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 151

19.2 Source of atoms in the purine ring . . . . . . . . . . . . . . . . . . . . . . . 152
19.3 Synthesis of IMP . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 153
19.4 Step of reduction in deoxyribonucleotide biosynthesis . . . . . . . . . . . . 154
19.5 Salvage pathway for purines . . . . . . . . . . . . . . . . . . . . . . . . . . . 155
19.6 Purine catabolism . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 156
19.7 Sources of atoms for pyrimidine ring . . . . . . . . . . . . . . . . . . . . . . 157
19.8 Steps of pyrimidine nucleotides biosynthesis . . . . . . . . . . . . . . . . . . 158
20.1 Normal PUT . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 160

20.2 Normal IVU . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 161
20.3 Urethrogram . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 162
27.1 Adult S. haematobium . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 204

27.2 Life cycle of Schistosoma . . . . . . . . . . . . . . . . . . . . . . . . . . . . 206
28.1 Renal cell carcinoma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 212

28.2 Papillary transitional cell carcinoma . . . . . . . . . . . . . . . . . . . . . . . 216
28.3 Squamous cell carcinoma . . . . . . . . . . . . . . . . . . . . . . . . . . . . 216
29.1 Differential diagnosis of lower urinary tract obstruction . . . . . . . . . . . . 218

29.2 Causes of unilateral ureteric obstruction . . . . . . . . . . . . . . . . . . . . 218
29.3 Causes of bilateral urinary tract obstruction . . . . . . . . . . . . . . . . . . 218
29.4 Grading of Hydronephrosis by ultrasound . . . . . . . . . . . . . . . . . . . 221
vi LIST OF FIGURES
List of Tables
4.1 Difference between water and osmotic diuresis: . . . . . . . . . . . . . . . . 60
23.1 IMVC formula . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 181
26.1 Drug that alter Urine pH . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 200
vii
Chapter 1
Anatomy and development of Kidney and Ureter
The renal system(urinary system) is responsible for filtering out excess fluid
and other substances from the blood stream.
The renal system organs include the kidneys, ureters, bladder, and ure-
thra. Figure:1.1
Figure 1.1: Renal system organs
1
2
1. Kidney
Shape and size:
The kidneys are a pair of bean-shaped organs approximately 12 cm
long, 6 cm in breadth and 3cm in thickness.
It has:
2 poles; upper and lower.
2 surfaces; anterior and posterior
2 borders; lateral convex and medial concave with a hilum in its middle
The hilum transmits from front backward renal vein, renal artery and the
ureter that directed downward
Vein ; anteriorly
Artery ; intermediate
Ureter ; posterior and is directed downwards Figure 1.2
Figure 1.2: Right and left kidneys

Chapter 1. Anatomy and development of Kidney and Ureter 3
Position
• They lie:
– On the posterior abdominal wall.
– Behind the peritoneum
– On each side of the vertebral column
• They extend from the level of the 12th thoracic vertebra to the level
of the 3rd lumbar vertebra
• The left kidney lies in an upper position than the right because of its
relation to the liver.
– The left kidney reaches up to the 11th rib
– The right kidney reaches up to the 11th space
• They lie sloping in the para-vertebral gutters so that the hilum faces
somewhat forwards as well as medially
• They lie obliquely with their upper poles nearer to the median plane
than the lower ones.
Figure 1.3: The positions of the kidneys in male and female

4
Longitudinal section Kidney
Figure 1.4
• It is composed of an outer cortex and inner medulla.

• The medulla consists of conical masses called renal pyramids (10
to 18), the base of which are directed towards the renal cortex while
their apices (renal papillae) are directed towards the renal sinus.
• Minor calyx surrounds one or more renal papillae.
• The minor calyces (10 to 12 in number) unit to form 2 or 3 major
calyces, which unite together forming the renal pelvis inside the
renal sinus.
• Sinus of the kidney is a central recess within the hilum of the kid-
ney, which contains renal vessels and pelvis.
• Cortical tissue extends between the pyramids to form the renal columns.
• Each pyramid with its covering cortex forms a renal lobe.
Figure 1.4: Longitudinal section in the kidney
Coverings of the kidney
The kidneys have the following coverings from inside to outside:

1 Fibrous capsule: This surrounds the kidney and is Closely applied to
its outer surface.
2 Perirenal fat: This covers the fibrous capsule.
3 Renal fascia: This is a condensation of connective tissue that lies out-
side the perirenal fat and encloses the kidneys and suprarenal glands;
it is continuous laterally with the fascia transversalis.
4 Pararenal fat: This lies external to the renal fascia and is often in
large quantity. It forms part of the retroperitoneal fat.
The perirenal fat, renal fascia, and pararenal fat support the kidneys and
hold them in position on the posterior abdominal wall
Figure 1.5: Coverings of the kidney
Relations to the kidney
Anterior relations of right and left kidneys

Right kidney Left kidney
-Right suprarenal gland -left suprarenal gland
-right lobe of liver -stomach
-2nd part of duodenum -spleen -pancreas
-right colic flexure -left colic flexure
-coils of jejunum -coils of jejunum
Figure 1.6: Anterior relations of right and left kidneys

6
Posterior relations of the right and left kidneys

Left kidney Right kidney
-11th and 12th ribs -12th rib
-diaphragm
-psoas major muscle
-qudratus lumborum muscle
-subcostal nerve and vessels
-iliohypogastric nerve
-ilioinguinal nerve
Figure 1.7: Posterior relations of the right and left kidneys
Blood supply of the kidney
There is a network of blood vessels throughout the kidneys
• The kidneys receive blood from the aorta via the renal arteries.
• the renal arteries branch into the segmental arteries, the lobar
arteries, and the interlobar arteries
• The interlobar arteries branch to form the arcuate arteries.
• The arcuate arteries branch off into interlobular arteries
• The interlobular arteries branch off into the afferent arterioles.
• The afferent arterioles lead into the glomerulus
• Efferent arterioles leave the glomerulus to form peritubular capil-
laries surrounding the collecting tubules at the renal nephron
• When the blood leaves the nephron it travels to the the interlobular
veins, arcuate veins and then the Interlobar veins.
• There are no segmental veins like the segmental arteries. Blood

leaves the kidney via the renal veins
An outline of the pathway of blood through the kidneys is as follows
Figure 1.8: Pathway of the blood through the kidney
1-Renal artery 2-Segmental arteries

3-Lobar arteries 4- Interlobar arteries
5-Arcuate arteries 6-Interlobular arteries
7-Afferent arterioles (Arteries = Afferent) 8-Glomerulus (capillaries)
9- Efferent arterioles (Exit vein = Efferent) 10-Peritubular capillaries
11-Interlobular veins 12-Arcuate veins
13- Interlobar veins 14-Renal vein
Renal vascular segments
Renal artery usually gives into 5 segmental based on the distribution of

five segmental branches of renal artery, each kidney is divided into five
vascular segment
• Apical/ superior
• Upper anterior
• Middle anterior
• Caudal/ inferior
• posterior
8
Figure 1.9: The segmentation of the kidney based on segmental 5 arteries
2. Ureter
• Each ureter is a long tube of about 10 inches long.

• The two ureters are muscular tubes that extend from the kidneys to
the posterior surface of the urinary bladder. The urine is propelled
along the ureter by peristaltic contractions of the muscle coat, as-
sisted by the filtration pressure of the glomeruli
• Its upper12 lies in the abdomen & its lower 1
2 in the pelvis
Figure 1.10: parts and course of the two ureters
Abdominal part of the ureter
Course
• Begins inside the renal sinus as the pelvis of the ureter

• The pelvis is the funnel shaped expanded upper end of the ureter. It
receives 2,3 major calyces.
• The ureter emerges from the hilum of the kidney and descends ver-
tically behind the peritoneum, on the psoas major opposite the tips
of the transverse processes of the lower 4 lumbar vertebrae
• It enters the pelvis by crossing the bifurcation of the common iliac
artery in front of the sacroiliac joint.
Relations
Right ureter Left ureter

Medially:
-Inferior vena cava - Inferior mesenteric vein
Anteriorly:
- 2nd part of the duodenum. -Left colic vessels
- Right colic vessels -Left gonadal vessels
- Gonadal vessels - sigmoid colon
- Iliocolic vessels - Simoid mesocolon
- Root of the mesentery
Posteriorly of both right and left ureters

-Psoas major muscle
-Genitofemoral nerve
-Bifurcation of common iliac artery
Figure 1.11: Anterior relations of the right and left ureters

10
Pelvic part of the ureter
Course and relations
• It enters the pelvic:

– Opposite the sacroiliac joint.
– Crossing in front of the bifurcation of common iliac artery
• Its course is divided into 3 parts.
1 From the pelvic brim to the ischial spine:
– It passes downwards and backwards along the anterior mar-
gin of greater sciatic foramen
It crosses the following from above downwards:
* External iliac vessels.

* Superior vesical artery & obliterated umbilical art.
* Obturator nerve & vessels
* Inferior vesical artery.
* Middle rectal artery
– In female forms the posterior border of ovarian fossa
2 From the ischial spine to the urinary bladder:
At the ischial spine the ureter changes its direction to run for-
wards and medially on the floor of the pelvis to reach the postero-
superior angle of the urinary bladder
– In male:
It is crossed by the vas deferens
– In female:
- It passes closely lateral to the upper end of vagina
- is crossed by the uterine artery from lateral to medial.
3 Intramural part of the ureter:
- It runs a very oblique course through the bladder wall to open
at the supero-lateral angle of the trigone.
Figure 1.12: Pelvic part of the ureter. A:in female B: in male Pelvis
Constrictions of the ureter
Along its course it has 3 constrictions:
1 At the pelvi-ureteric junction

2 As it crosses the pelvic brim
3 As it pierces the bladder wall (intramural part)
Figure 1.13: Sites of constrictions of the ureter
Blood supply
1 Arteries: The ureter is supplied along its course as follows:

• Abdominal aorta, renal, gonadal, common iliac & Internal iliac ar-
teries.
• Inferior vesical and middle rectal arteries in males.
• Twigs from the vaginal and uterine arteries in females
2 Veins: corresponds to the arteries
3 Lymph Drainage: The lymph drains to the lateral aortic nodes and
the iliac nodes.
12
4 Nerve Supply:
The nerve supply is the renal, testicular (or ovarian), and hypogastric
plexuses (in the pelvis). Afferent fibers travel with the sympathetic
nerves and enter the spinal cord in the 1st and 2nd lumbar segments
Figure 1.14: Arterial supply of the ureter
Development of the Kidneys and Ureters
The urinary system develops from:
• Intermediate mesoderm
• Part of cloaca (urogenital sinus)
Figure 1.15: The intermediate mesoderm and cloaca

• The urogenital ridge is formed from the intermediate mesoderm
• At the 4th week, the intermediate mesoderm in the cervical region loses
its contact with the somite and forms segmentally arranged cell clusters,
known as the nephrotomes
• It grows in a lateral direction and obtains a lumen (nephric tubules).
• The nephric tubules open medially into the intra-embyronic coelom and
laterally grow in a caudal direction.
• During the caudal growth, the tubules of succeeding segments unite and
form a longitudinal duct on each side of the embryo (pronephric duct).
Both ducts open caudally into the cloaca
Figure 1.16: The nephric tubules and neprogenic cord
Development of the Kidney
Three different, slightly overlapping kidney systems are formed during in-
trauterine life in humans:
1. Pronephros (rudimentary and non-functional)
2. Mesonephros (may function for a short time during the early fetal period).
3. Metanephros (permanent kidney)
• Pronephros:
It is the first kidney to appear.

It is represented by 7-10 solid cell groups (nephrotomes) in the cer-
vical region. As they obtain lumina, they form 7-10 rudimentary
pronephric tubules.
14
The medial end of each tubule opens into the coelomic cavity.
The other lateral ends of the tubules join into a longitudinal duct
called the pronephric duct which extends downwards to open into
the cloaca
It is segmental in arrangement i.e. one pronephric unit develops
opposite each somite
The pronephric tubules degenerate early at the end of the 4th week
and the pronephric duct persists to the next stage where it is called
the mesonephric duct.
Figure 1.17: Different stages of development of the kidney
• Mesonephros:
It is the second kidney to appear.

During regression of the pronephric system, the first excretory tubules
of the mesonephros appear.
It develops in the intermediate mesoderm of the thoracic, lumbar
and upper sacral regions opposite the 14- 28 somites
The intermediate mesoderm undergo segmentation into about 70
solid clusters, on each side. They elongate greatly and become
canalized to form S-shaped tubules called the mesonephric tubules.
The lateral ends of the mesonephric tubules open into the mesonephric
duct (previous pronephric duct).
The medial end of each tubule is invaginated by a tuft of capillaries
forming an internal glomerulus.
While the caudal tubules are still differentiating, the cranial tubules
and glomeruli show degenerative changes until they disappear by
the end of the 2nd month
Parts of the mesonephros persist to form very important derivatives:
The derivatives of the mesonephros in male:
1) Vasa efferentia
2) Epididymis
3) Vas deferens
4) Seminal vesicle
5) Ejaculatory duct
6) Trigone of the urinary bladder
7) Upper part of the posterior wall of the prostatic urethra
8) Ureteric bud and its derivatives
The derivatives of the mesonephros in female:
1) Paroophoron
2) Epoophoron and its duct (Gartener’s duct)
3) Trigone of the urinary bladder
4) Ureteric bud and its derivatives
• Metanephros:
It is the permanent kidney

It develops from 2 separate primordia:
1. The ureteric bud:
Arise from a diverticulum of the mesonephric duct (collecting
units) which gives rise to the entire collecting duct system.
2. The metanephric cap:
Arise from the intermediate cell mass of the lower lumbar region,
below the 26th somite and the sacral regions (excretory units)
nephrons.
The ureteric bud:
It arises as an outgrowth of the caudal part of the mesonephric duct

close to its entrance into the cloaca
16
The bud grows dorsocranially invading the mesoderm of the intermedi-

ate cell mass, which condenses around it to form the metanephrogenic
cap.
Figure 1.18: The origin of permanent kidney from ureteric bud and metanephric cap
Development of collecting ducts
The ureteric bud forms the ureter, which dilates at this upper end to
form the pelvis of the ureter.
Later the pelvis gives off branches that form the major calyces, and
these in turn divide and branch repeatedly until 12-14 order of branches
are established, they form the minor calyces and the collecting tubules.
New collecting tubules continue to be formed until the end of the fifth
month of fetal life.
Figure 1.19: Development of the collecting tubules
The metanephric cap:(excretory part)
The mesoderm is segmented into cell clusters in relation to the termina-

tion of the collecting tubules.
These cell clusters change into renal vesicles which elongate to form
the different parts of nephron which are:
• Bowman’s capsule,
• Proximal convoluted tubule,
• Loop of Henle and
• Distal convoluted tubule.
The proximal glomerular capsule becomes invaginated by a cluster of

capillaries that form the glomerulus.
The distal convoluted tubule joins the nearest collecting tubule to form a
complete uriniferous tubule.
Figure 1.20: Development of excretory part of the nephron
More signs of kidney development:
• Location
Figure 1.21: The different location of the kidney during development

18
In the early stages of development, the kidney is located in the pelvic

region, later it moves upwards until it finally lies in front of the upper part
of the posterior abdominal wall. This ascent is caused by a diminution
of the body curvature and the growth of the body in the lumbar and sacral
regions
• Blood supply
The kidney changes its blood supply during the ascent.
At first it receives its blood supply from the median sacral and the com-
mon iliac arteries and then from the lower part of the abdominal aorta.
Figure 1.22: The different blood supply of the kidney during development
• Shape
The fetal kidney is lobulated with an irregular surface. This lobula-
tion usually disappear before birth as a result of further growth of the
nephrons.
• Position
In the early stages, the convex border of the kidney look posteriorly and
its hilum looks ventrally. Later it rotates about 90 degree medially so that
the hilum becomes directed medially
Congenital anomalies of the kidney:
1) Renal Agenesis: (Bilateral and unilateral):

Occurs when the ureteric bud fails to develop.
2) Anomalies of position:
• Pelvic kidney: Occurs when one or both kidneys fail to ascend and
remain in the pelvis or lower lumbar area.
• Abnormal rotation of the kidney
Figure 1.23: Different congenital anomalies (agenesis, pelvic and horseshoe)
3) Anomalies of shape
Horseshoe kidney: Occurs when the inferior poles of the kidneys

fuse together.
Polycystic kidney: The kidney shows many small cysts which be-
come full with urine due to failure of nephrons to join the collecting
tubules
Persistence of fetal lobulation
Figure 1.24: Polycystic kidney, double kidney and double ureter
4) Anomalies of urinary tract:
Duplication of the urinary tract:

Occurs when the ureteric bud prematurely divides before penetrating
the metanephric blastema. It results in either double kidney or dupli-
cated ureter and renal pelvis.
20
Ectopic ureteric orifice:

* In males the ureter may open into
-The lower part of the trigone -The prostatic urethra,
-The ejaculatory duct -The seminal vesicles.
* In females , the ureter may open into:
- The vagina - The urethra - The vestibule
Post-caval ureter:
The ureter is present posterior to I.V.C
Atresia of the ureter :
May occur at the ureteric orifice of bladder
5) Anomalies of blood supply:

Multiple renal arteries -Accessory renal artery
Figure 1.25: Different anomalies of the ureter

Chapter 2
Histological structure of glomerular apparatus and renal tubules
kidney is divided into:
1. Stroma: Connective tissue is very scanty between renal lobes and lobules
and also around blood vessels.
2. Parenchyma: It is a compound tubular gland, which is highly vascular and

formed of uriniferous tubules.
The uriniferous tubules consist of:
a. Nephrons which produce urine.

b. Collecting ducts that concentrate urine
Both components of urinephrous tubules have different embryological
origins.
Nephron
Definition: It is the structural and the functional unit of the kidney.
Each kidney is formed of 1-3 million nephrons.

Two or three nephrons can be drained by one collecting tubule that
join others to form duct of Bellini.
Types of Nephrons
There are two types of nephrons;
I Subcapsular or cortical nephrons which are present high up in cortex

under the capsule.
II Juxtamedullary nephrons are near the medulla.
21
22
- Each nephron consists of: Figure 2.1
1 Renal corpuscle (Malpighian corpuscle).

2 Proximal convoluted tubule.
3 Loop of Henle
4 Distal convoluted tubule.
Figure 2.1: Diagram showing nephron components (Mescher. 2013)
1- Renal corpuscle (Malpighian corpuscle)

- It is found in the cortex and is formed of:
a) The glomerulus (tortuous tuft of capillaries)
b) Bowman’s capsule (epithelial capsule covering the glomerulus)
It has two poles; vascular and urinary.
- The vascular pole is the site where the afferent arteriole enters
and efferent arteriole leaves.
- The urinary pole is the site where the proximal convoluted tubule
begins.
a) Glomerulus:
- It is a tuft of anastomosing capillaries formed from the afferent ar-
teriole that enters the renal corpuscle at its vascular pole and gives
Chapter 2. Histology of Glomerulous and renal tubules 23
capillary loops of the glomerulus and unite to form efferent arteriole.

Structure
• The glomerular capillaries are lined by fenestrated endothelium
that has no diaphragm and rests on thick basement mem-
brane 300nm thick that appear by EM formed of three layers
(Figure 2.2);
o The middle is the lamina densa which is formed of collagen
type IV.
o The outer and inner layers are less electron dense called lam-
inae rarae and are formed of laminin, fibronectin and proteo-
glycans
b) Bowman’s capsule is formed of two layers: Figures 2.7, 2.8
• The outer is the parietal layer and is lined with simple squamous
epithelium.
• The inner visceral layer is lined with modified cells called podocytes
which are adherent to glomerular capillaries.
• The space between parietal and visceral layers
is called capsular space/ urinary space which receives the glomeru-
lar filtrate and is continuous with the lumen of the proximal con-
voluted tubule.
Podocyte
– L/M
Podocyte is star shaped with multiple processes
The basement membrane is well developed and can be demon-
strated as PAS+ve line (formed of glycoprotein).
– E/M Figure2.2
It is a large cell that consists of body, primary processes (major)
and secondary processes (minor).
The cell body consists of cytoplasm and central nucleus with ex-
tended chromatin. The cytoplasm contains mitochondria, Golgi
body, rough endoplasmic reticulum, microtubules and microfila-
ments.
24
The cell body gives rise to several primary processes that extend
parallel to long axis of blood capillaries.
Each primary (major) process gives rise to secondary foot pro-

cesses / the pedicels that implanted on the basement mem-
brane of glomerular blood capillaries.
The pedicels from one podocyte embrace more than one capil-
lary and the pedicels of two podocytes alternate in position on a
single capillary.
Pedicels contain only microtubules & microfilaments.
Pedicels have a well-developed glycocalyx composed of nega-

tively charged proteins.
In between the pedicels there are filtration slits that are covered
with slit diaphragms.
Slit diaphragms are a highly specialized type of intercellular

junctions mainly formed by nephrin.
Podocytes are separated from glomerular capillaries by sub-

podocytic space.
– Function of podocyte
It has an important function in the blood renal barrier and in regen-
eration of basement membrane.
Figure 2.2: Podocyte and blood renal barrier

) Blood-renal barrier is formed of Figure 2.2

1. Fenestrated endothelium of blood capillaries
2. Thick basement membrane, which is the only continuous layer of the
filtration barrier.
3. Filtration slits (60-100nm) with their covering diaphragms.
Function of Blood-renal barrier
- The principle function of the barrier is formation of the glomerular
filtrate.
- When blood is filtered through the glomerular capillaries, plasma
passes through the fenestrae holding back red blood corpuscles,
white blood cells and blood platelets.
- Protein with high molecular weight (> 68,000 D) cannot pass through
the thick basement membrane but protein with small molecular weight,
sugar, amino acids can pass with the filtrate.
- Filtration slits and the overlying diaphragms prevent the passage of
molecules according to their electrostatic charge.
Intraglomerular Mesangial cells (Figure 2.3):
Site: In between the loops of capillaries in the places that lack the
podocytes.
Function:
1- Give support to the capillaries (like pericytes).
2- Phagocytosis of proteins (antigen-antibody complexes) that adhere
to the basement membrane.
26
3- Secretion of factors important for immune defense (eg, cytokines)

4- May be contractile because they respond to the vasoactive sub-
stances (angiotensin II) to reduce the blood flow into the glomerulus.
Figure 2.3: Intraglomerular mesangial cell
2- Proximal convoluted tubules

- It begins in the cortex at the urinary pole of renal corpuscle.
- It is at first highly convoluted then straightens to become continuous
with descending thick segment of loop of Henle in the medulla.
- Each tubule is 60um in diameter and 14mm long with small lumen.
By L/M Figure 2.4, cross section of proximal convoluted tubule
shows that:
It is formed of 4-5 pyramidal cells.
The cells are strongly acidophilic.
The nuclei are rounded and central.
The apical surface shows brush border.
The basal part has acidophilic striation.
The cell boundaries are indistinct.
The lumen is narrow.
Figure 2.4: Sections in the components of uriniferous tubules

By E/M shows the characters of ion transporting cells Figure 2.5
The apical surface has long microvilli and numerous vesicles at

their bases.
The basal part has basal invaginations (basal striation).
Numerous long mitochondria in between the basal invaginations
(which is the cause of acidophilia).
Lateral cell membrane interdigitations (indistinct border by LM).
There is tight junction that seals the intercellular space from the
lumen of the tubule, and zonula adherence that maintain the ad-
hesion between neighboring cells.
The nuclei are central rounded with extended chromatin.
The cytoplasm contains Golgi, rER, lysosomes and endocytotic
vesicles in the apical part.
Both brush border and basolateral folds contain many types of
transmembrane proteins that mediate tubular reabsorption and
secretion
Figure 2.5: EM for a proximal convoluted tubules cell (a) and distal convoluted tubule cell (b)
28
3- Loop of Henle
- It is U shaped tube present mainly in medulla.
- It consists of four parts:
1. Thick descending part:
It starts in the cortex and extends to the medulla.
It is similar to proximal convoluted tubule in structure and func-
tion.
2. Thin descending part:
Present in the medulla.
Lined with simple squamous epithelium
Cross section of the thin limb is similar to blood capillary wall,
but its lumen contains no blood cells and its nuclei protrudes
slightly into the lumen Figures 2.4 and 2.6.
Figure 2.6: EM of an epithelial cell of thin limb of Henle’s loop
3. Thin ascending part:

It is in the medulla.
It is lined with simple squamous epithelium.
4. Thick ascending part:
It starts in the medulla and extends to the cortex.
It is similar to the distal convoluted tubule in structure and func-
tion.
N.B. Both thin descending and thin ascending parts are similar
by LM and EM.
*EM of thin parts
- The cells lining them have few short stubby microvilli on the
luminal surface.
- They have few mitochondria in the cytoplasm surrounding the

nuclei.
- Numerous processes project from the basal portion of the cells

to interdigitated with neighboring cells.
4- Distal convoluted tubules
- It is the continuation of thick ascending loop of Henle in the corti-

comedullary zone.
- There are three parts of distal convoluted tubule.
1. Straight part is continuous with ascending thick limb of the loop

of Henle.
2. Macula densa is present between the afferent and efferent arte-

rioles and it is a part of the juxtaglomerular apparatus.
3. Convoluted part opens in the collecting tubule.
By L/M (Figure 2.4) cross section of distal convoluted tubule shows:
It is formed of 5-8 simple cuboidal cells.
The cells are acidophilic but less than PCT.
Their nuclei are rounded and nearly apical.
Their apical surface has no brush border.
The basal part has acidophilic striation.
Their cell boundaries are more distinct than PCT.
Their lumens are wide.

E/M (Figure 2.5) shows that:
The apical part has few club-shaped short microvilli and api-
cal canaliculi.
Their nuclei are rounded and nearly apical with extended chro-
matin.
Their basal parts contain mitochondria in-between basal invagi-

nations less than PCT.
30
Figure 2.7: Eroschinko V. (2008): diFiore’s Atlas of Histology with Functional Correlations. 11th ED. Chapter
16. Urinary System.p 365.
Juxtaglomerular apparatus
It is composed of (Figure 2.8):

1- Juxtaglomerular cells.
2- Macula densa.
3- Polar cushion or lacis cells or extraglomerular mesangial cells.
Figure 2.8: Juxtaglomerular apparatus
1- Juxtaglomerular cells
They are modified smooth muscle cells of the tunica media of the
afferent arteriole.
Structure
1- LM
- The cells are large cubical cells with rounded nuclei.
- The cytoplasm contains many secretory granules which are
(PAS) +ve.
2- EM
- The cytoplasm contains rER, Golgi apparatus, mitochondria and
secretory granules with renin.
- The internal elastic lamina is absent, so the juxtaglomerular
cells are in contact with the endothelium and blood from one side
and with cells of macula densa on the other side due to the ab-
sence of the basement membrane of macula densa.
2- Macula densa
It is the part of distal convoluted tubule present in the concavity be-
tween afferent and efferent arterioles of the same nephron.
Structure:
o LM: The cells appear columnar, tall and narrow with packed nu-
clei.
o E/M: the cytoplasm has small mitochondria, infranuclear Golgi ap-
paratus and numerous microvilli.
- Absence of basement membrane.
3- Extraglomerular mesangial cells, (Polar cushion or Lacis cells)
Structure: The cells are pale staining and occupying the space be-
tween afferent and efferent arterioles and macula densa.
Function: May be phagocytic.
Collecting tubules
- Collecting tubules are not a part of the nephron.

- Collecting tubules have three recognized regions:
o Cortical.
o Medullary.
o Papillary.
-Cortical collecting tubules: which start at the medullary rays in the
cortex by union of two or three distal convoluted tubules and enter the
32
medullary pyramid.
- Medullary collecting tubules: they are larger in caliber as they formed
by union of several cortical collecting tubules.
- Papillary collecting tubules (ducts of Bellini): formed from union of
the medullary tubules that open on the apex of renal papillae into a minor
calyx. Two to four minor calyces join to form a major calyx that opens in
the renal pelvis.
Structure: By L/M : Figure 2.4
The tubules are lined with simple cubical epithelium (in small tubules)
or simple columnar epithelium (in large tubules).
The cytoplasm is pale acidophilic.
The cell borders are distinct.
The lumens are wide.
The nuclei are dark and central.
E/M:
The cytoplasm has few organelles, oval centrally rounded nuclei and
few mitochondria.
Interdigitations between the cells are not marked.
There are few microvilli and numerous basal infoldings.
Renal interstitial tissue:
1) The kidney is invested by collagenous connective tissue capsule with

some elastic fibers in between.
2) The cortical interstitial connective tissue is rich in fibroblasts and macrophages.
3) The interstitial cells are more numerous between straight collecting
ducts and ducts of Bellini.
4) They have elongated nuclei and numerous lipid droplets.
5) They appeared to be placed like rugs of a ladder one on top of other.
6) These cells synthesize medullipin I that is converted in the liver into
medullipin II, which is a potent vasodilator lowering blood pressure.
Chapter 3
Functions of the kidney
3.1 General functions of the kidney
(1) Role of the kidney in homeostasis:
I The kidney maintains the internal environment (extracellular fluid) al-

ways constant.
I This action is exerted by the following mechanisms of the kidney.
a- Regulation of the extracellular fluid volume:

In overhydration ) the urine will be increased.
In dehydration ) the urine volume will be decreased.
This function is adjusted by antidiuretic hormone
b- Regulation of the blood level of electrolytes: e.g.:
V By adjustment of Na+ & K+ excretion in the urine.
V This function is adjusted by the aldosterone.
c- Regulation of blood pH:
I The kidney can regulate pH through:
i- Secretion of nonvolatile acids or alkalies.
ii- Formation of NH3 & excretion of other buffer system ) (e.g.) phos-
phate & bicarbonate.
(2) Reabsorption:
The kidney reabsorbs useful nutrient substances & other elements es-
sential for body functions
(3) Excretory function

VThe kidney has a role in excretion of:
33
34 3.1. General functions of the kidney
i- Waste products formed in the body ) (e.g.) uric acid & creatinine.
ii- Foreign substances after their detoxification in the liver by conjuga-
tion ) (e.g.) drugs & toxins.
iii- Excess amounts of essential substances ) (e.g.) excess water,
electrolytes & H+ .
(4) Regulation of the Arterial blood pressure (ABP):
I In conditions of shock or hemorrhage ) renal ischemia occurs.

I Renal ischemia leads to ) stimulation of juxtaglomerular appara-
tus) to secrete renin.
I Then, renin acts on angiotensinogen formed by the liver to ) form
angiotensin I.
I Angiotensin I is converted to angiotensin II by the convertase en-
zyme (angiotensin converting enzyme).
I Angiotensin II causes a powerful vasoconstriction of the blood
vessels) increase ABP.
I In addition, angiotensin II is stimulant for the secretion of aldos-
terone hormone) which leads to Na+ & water retention ) increase
the blood volume ) increase ABP.
(5) Erythropoiesis:
Hypoxia stimulates the kidney to secrete ) erythropoietin from en-

dothelial cells of the peritubular capillaries in the renal cortex.
Erythropoietin is a powerful stimulant to the bone marrow to ) pro-
duce RBCs.
(6) Prostaglandins:
V The kidney secretes prostaglandins (E2 & I2).

V Prostaglandins play a minor role in regulation of the renal blood flow
& protection of the kidney from excess renal V.C. during severe car-
diovascular stress such as hemorrhage.
(7) Endocrine function of the kidney:

VThe kidneys are endocrine organs they secrete the following:
Chapter 3. Functions of the kidney 35
1. Renin
2. Erythropoietin
3. Kinins (unknown function).
4. Prostaglandins.
5. 1, 25 dihydroxycholecalciferol (1,25-DHCC).
I1,25-DHCC is the active form of the vitamin D.
3.2 Metabolic function of the kidney
- Despite that the kidney tissue represents less than 0.5% of the body
weight, it receives 25% of the cardiac output & 10% of O2 are consumed
by it.
- This is required for the synthesis of ATP needed to reabsorb most of the
solutes filtered through glomerular membranes. However, its stores of
glycogen, phosphocreatine and lipids are very low, so kidney must get
its energy requirement from circulating fuel substrates (as glucose, fatty
acids & ketone bodies)
- Beside its known excretory functions, kidney has many metabolic func-
tions.
1. Carbohydrate Metabolism in the kidney
- Gluconeogenesis: Synthesis of glucose from non-carbohydrate sources

as lactate, glycerol & amino acids (esp. glutamine)
- Glucose oxidation (Glycolysis), citric acid cycle & HMP shunt
Kidney & glucose homeostasis

- Regarding glucose homeostasis, the kidney can be considered as
2 organs due to the differences in the distribution of various en-
zymes in renal medulla & renal cortex
- Cells of the cortex have considerable amounts gluconeogenic en-
zymes, BUT have little hexokinase. So, the release of glucose by
36 3.2. Metabolic function of the kidney
the normal kidney is exclusively, a result of renal cortical gluconeo-

genesis. The most important substrates for renal gluconeogenesis
are glutamine, lactate & glycerol.
- Cells of the medulla have considerable amounts of hexokinase and
other enzymes of glycolysis. So, they can take up, phosphorylate
& metabolize glucose through glycolysis BUT: don’t have gluco-
neogenic enzymes nor glucose 6- phosphatase, so they can form
glycogen (limited amounts), but cannot release free glucose into
the circulation.
Renal gluconeogenesis paradoxically increases postprandi-

ally due to postprandial increases in sympathetic nervous system
activity availability of gluconeogenic precursors (e.g., lactate and
amino acids). This increase in renal gluconeogenesis help liver
glycogen repletion by suppression of hepatic glucose release.
Kidney & Glucose Metabolism in Fasting
* Early fasting (first hours): source of glucose in blood is mainly

by liver glycogenolysis.
* 18 – 60 hours of fasting: source of blood glucose is mainly

gluconeogenesis (in liver & kidneys).
* After 60 hours of fasting: Liver gluconeogenesis release is

decreased by 25%. So, liver cannot compensate for the kidney
to preserve normal blood glucose levels in patients with renal
insufficiency during prolonged fasting. This may explain why
patients with renal failure develop hypoglycemia.
2. Lipid Metabolism in the Kidney Lipid metabolic pathways occur in the

kidneys:
1. Beta-oxidation of fatty acids.

2. Synthesis of carnitine: for transport of FA to mitochondria for oxidation.
3. De-novo synthesis of fatty acids.
4. De-novo synthesis of cholesterol.
Chapter 3. Functions of the kidney 37
5. Activation of glycerol to glycerol 3-phosphate (by glycerol kinase)
3. Protein Metabolism in the Kidney Amino acid metabolic pathways occur

in the kidneys:
1. Excretion of ammonia & urea to urine.

2. Degradation of glutamine by glutaminase enzyme. Glutamine produced
in most organs (from amino acid metabolism) are degraded into gluta-
mate & ammonia in the kidney. Ammonia produced is important in acid
base balance.
3. Amino acids deamination.
4. Creatine synthesis (first step) from amino acids glycine & arginine:
a. Formation of guanido acetic acid from amino acids glycine & arge-
nine occurs in the kidney.
b. Methylation of guanido acetic acid to creatine occurs in the liver.
4. Production of Erythropoietin
It is a glycoprotein hormone that controls erythropoiesis. It is produced by
the renal cortex in response to low oxygen levels in the blood.
5. Activation of vitamin D in the Kidney
- Renal 1 hydroxylase: The key regulatory enzyme in vitamin D acti-

vation is the 1 hydroxylase enzyme produced by the kidney.
- Vitamin D3 (cholecalceferol) is hydroxylated in the liver to 25 hydrox-
ycholecalciferols. Then, the renal 1 hydroxylase converts 25 hydrox-
ycholecalciferols to 1, 25 dihydroxycholecalciferol which is the active
form of vitamin D in the kidney.
Metabolic interrelations of tissues in kidney diseases
1. In chronic kidney diseases levels of amino acids (proline, glutamin, gly-

sine and citrulline) normally metabolized by kidney are increased, ni-
trogen end product accumulates (urea, uric acid, creatinine) which are
normally metabolized by the kidney.
2. High protein intake or increased proteolysis worsens kidney function.

38 3.2. Metabolic function of the kidney
3. In kidney failure protein intake except for essential amino acids should be
limited as much as possible, but carbohydrate should be increased which
may delay the need for dialysis
4. Patients under dialysis have an increased risk of cardiac and skeletal my-
opathy due to impaired fatty acid oxidation as a result of carnitine de-
ficiency as:
- Carnitine is removed from blood during dialysis.

- Dietary source of carnitine (meat) is reduced.
- Functional kidney mass is reduced.
Figure 3.1: Metabolic interrelationships of tissues in kidney failure.

Chapter 4
Tubular functions
In the renal tubules, the glomerular filtrate is changed to urine through the
processes of:
1. Reabsorption. 2. Secretion.
1. Reabsorption
V This process is either passive or active:
Passive reabsorption Active reabsorption
• This occurs by simple or facilitated dif- • It requires energy.

fusion. • It occurs against a concentration, electri-
• It requires no energy. cal or osmotic gradients.
• It occurs down a concentration, electrical • It needs enzymatic activity & specific car-
or osmotic gradients. riers.
• It is either primary or secondary ) (see
later for differentiation between them).
2. Secretion.
I This process is almost only active.

I The secreted substances may be:
a. Derived from the blood stream ) e.g. creatinine & K+ .
b. Synthesized in the tubular cells then secreted ) e.g. H+ &
NH3.
Figure 4.1: Tubular functions
39
40
~The tubular functions include:

I. Functions of PCTs. II. Functions of Loop of Henle.
III. Functions of DCTs. IV. Functions of collecting ducts.
Functions of the proximal convoluted tubules (PCTs)
I. Reabsorption in the PCTs:
1. Sodium reabsorption:
V Na+ reabsorption in the PCTs occurs as following:
a. Primary active transport at the basolateral borders of the cells of
the PCTs.
Na+ is reabsorbed by primary active transport as follows:
I Na+ is pumped at the basolateral borders of the cells into the
interstitial fluid.
I The required energy is obtained directly from ATP breakdown
by the activity of the Na+ -K+ ATPase enzyme.
I This energy pump 3 Na+ outside the cells in exchange with 2
K+ pumped inside the cells.
I K+ diffuse almost immediately back again into the interstitium
b. Passive diffusion at the brush borders of the cells of the PCTs.
I The primary active transport of Na+ at the basolateral borders)
leads to decrease the intracellular Na+ concentration & the po-
tential inside the cells is kept at about -70mV.
I This negative intracellular voltage as well as the low concen-
tration of Na+ inside the epithelial cells ) cause Na+ to diffuse
passively from the tubular lumen into the cells by the so called
electrochemical gradient.
I The passive diffusion of Na+ into the cells also occurs by fa-
cilitated diffusion ) (i.e.) Na+ binds to a special Na+ carrier
protein at the brush borders of the cells.
2. Water reabsorption:
I The PCTs are highly permeable to water.
I Water is reabsorbed by passive diffusion (osmosis) following
Na+ reabsorption.
Chapter 4. Tubular functions 41
I This is called obligatory water reabsorption. (See later).

I It is about 65% of water in the glomerular filtrate.
3. Chloride reabsorption:
About 65% of Cl is reabsorbed by passive diffusion in the PCTs
secondary to active reabsorption of Na+ ) to maintain electrical neu-
trality.
Figure 4.2: Transport of sodium in PCTs
4. Glucose reabsorption:
V This is usually complete in normal condition.
V It occurs only in the PCTs.
V Glucose reabsorption at the brush borders occurs by the sec-
ondary active transport.
V Then, Glucose reabsorption at the basolateral borders of the cells
of PCTs to the interstitium occurs by facilitated diffusion.
V Secondary active transport as following:
I The energy of the secondary active transport is not directly
provided by breakdown of ATP.
I But it is provided by the primary active transport of Na+ out
of the renal tubular cells into the interstitial fluid as follows:
* The outward Na+ pump greatly decreases the intracellular

Na+ concentration) this creates a large concentration gra-
dient for Na+ diffusion from the tubular lumen into the tubular
cells.
42
* This gradient represents diffusion energy ) because the

increased Na+ diffusion also energizes the transport of other
substances along with Na+ through the cell membrane.
+
* Both Na & glucose are co-transported into the cells by
binding to a symport carrier in the brush borders of the cells.
* Then, glucose moves to the interstitial fluid by facilitated dif-

fusion (type of passive diffusion).
Figure 4.3: Glucose absorption
5. Amino acids reabsorption:

I Normally, amino acids & other substances of nutritional value (e.g.
protein & vitamins) are completely reabsorbed.
I Amino acids are reabsorbed by secondary active transport at
the brush borders of PCTs into the cells.
I Then, they are transported at the basolateral borders of the cells
of PCTs to the interstitium occurs by facilitated diffusion.
I Protein is reabsorbed in by pinocytosis through the brush border
of the epithelial cells ) then, they are digested into amino acids.
6. K+ reabsorption:
I 65% K+ of glomerular filtrate is reabsorbed in the PCTs.
I At the brush borders of the tubular cells ) K+ reabsorption oc-
curs by secondary active transport with Na+ (co-transport with
Na+ ).
I At the basolateral borders of the tubular cells ) K+ reabsorp-
tion occurs by passive diffuse into the interstitium ) then, to the
blood in the peritubular capillaries.
7. Calcium reabsorption:
I About 60% of filtered Ca++ is reabsorbed in the PCTs.
I Ca++ transport occurs by secondary active transport at the brush
borders of the tubular cells.
I Then, by passive diffusion at the basolateral borders of the tubu-
lar cells.
8. Phosphate reabsorption:
I Phosphate is reabsorbed only in the PCTs.
I It occurs by secondary active transport.
I It is inhibited by the parathyroid hormone.
9. Bicarbonate (HCO3 ) reabsorption:
V The renal tubules are poorly permeable to HCO3
V However, HCO3 is primary reabsorbed in the form of CO2 as
follow:
a. H+ is formed inside the tubular cells ) then, secreted in the tubular
fluid.
b. H+ combines with HCO3 in the tubular fluid ) forming H2CO3.
c. By activity of carbonic anhydrase enzyme (C.A.) at the brush
borders of the tubular cells ) H2CO3 dissociates into CO2 & H2O
(the later excreted).
d. CO2 diffuses into the cells where it combines with H2O by activity
of an intracellular C.A. ) forming H2CO3.
e. H2CO3 dissociates into HCO3 and H+ .
f. HCO3 passively diffuses into the interstitial fluid ) (then to
the blood).
g. While, H+ is secreted into the tubular fluid to help more reabsorp-
tion of HCO3
44
Figure 4.4: Bicarbonate transport in PCT
10. Urea reabsorption:

About 50% of the filtered urea is passively reabsorbed in the PCTs
) (because their walls are partially permeable to urea).
11. Uric acid reabsorption:
I Uric acid is reabsorbed only in the PCTs.
I This occurs by passive diffusion.
I It is also slightly secreted.
I Its absorption is more than that of urea ) (so uric acid clearance
is only 14 ml/min.).
II. Secretion in the PCTs:

+
ions:
I H+ ions are actively secreted by secondary active transport (counter-

transport with Na+ ) in the PCTs.
I This secretion is controlled by H+ ions level in the blood.
1. Secretion of creatinine:
Small quantities of creatinine are secreted by the PCTs.
2. Secretion of foreign substances:
e.g. PAHA, penicillin & metabolites as steroids degradation.
III. Synthesis in the PCTs:
V Synthesis & secretion of NH3 occur in all the renal tubules with the
exception of the thin segment of loop of Henle.
V The ammonia (NH3) reacts with H+ to form ammonium ions (NH4+ ).

V Then NH4+ is excreted into the urine in combination with Cl ions )
to from ammonium chloride which is a weak acid.
Functions of the loops of Henle
Loops of Henle act as countercurrent system.
V The loops of Henle of the cortical nephrons ) are concerned with

conservation of water & electrolytes.
V While, the loops of Henle of the juxtamedullary nephrons ) are es-

sential for urine concentration.
, N.B.: (A countercurrent system)
~ It is a system where there is two currents flowing parallel, opposite and

adjacent to each other.
~ There are two types of the countercurrent system include:
1. Countercurrent multiplier system:

I It is a system that operates actively to create an osmotic or
chemical gradient.
I The loop of Henle is an example of this type which creates an
osmotic gradient in the renal medullary interstitium.
2. Countercurrent exchanger system:
I It a system that operates passively to maintain an osmotic,
thermal or chemical gradient.
I Examples for countercurrent exchanger system include:
The vasa recta are an example of the countercurrent osmotic
exchanger system.
The renal countercurrent mechanism
V This is the mechanism by which urine is concentrated in the kidneys.
V It depends on the production & maintenance of a state of hypersomo-

larity in the renal medullary interstitium by the action of the structures
that pass in the renal medulla.
46
V These structures include the following:
1. The loop of Henle of the juxtamedullary nephrons:

I These constitute a countercurrent multiplier system.
I It acts to increase progressively hyperosmolarity in the renal
medulla.
I So that the osmolarity of the medullary interstitium gradually in-
crease from (300 mOsm/liter) in the renal cortex ) to (1200-
1400 mOsm/liter) at the renal papillae.
2. The vasa recta:
V These constitute a countercurrent exchanger system that op-
erates passively ) to maintain the hyperosmolarity of the medullary
interstitium.
3. The medullary collecting ducts:
I These establish an osmotic equilibrium between the tubular
fluid & the renal medullary interstitium.
I Thus, it is considered as an osmotic equilibrating device.
The countercurrent multiplier system (The loop of Henle)
I This system consists of the loop of Henle of the juxtamedullary nephrons

(which penetrate deeply in the renal medulla).
I It is concerned with graded hyperosmolarity in the medullary intersti-

tium by the following mechanism:
1. The descending limb of loop of Henle:
It receives isotonic fluid from the PCTs.

Its wall is:
(a) Highly permeable to water.
(b) Poorly permeable to solutes (Na+ , Cl and urea).
Accordingly, water passively diffuse outward down an osmotic gra-
dient into the medullary interstitium.
As a result, the tubular fluid because hypertonic.
Its hypertonicity increase gradually as the tabular fluid flows down-

wards ) reaching (1200 up to 1400 mOsm/liter) at the tips of the
renal pyramids.
The amount of the reabsorbed water in the loop of Henle is about 15%
of the filtered water in the glomeruli & it is an obligatory reabsorption
as that occurring in the PCTs.
2. The ascending limb of loop of Henle:
V It receives hypertonic fluid from the descending limb.

V Then, the following changes occur:
a. The initial thin part is:
i. Impermeable to water.
ii. Poorly permeable to urea.
iii. Highly permeable to Na+ and Cl :
I Accordingly, Na+ & Cl diffuse passively down their con-
centration gradients into the medullary interstitium.
I Therefore, the tonicity of the tubular fluid progressively de-
creases as it moves up (becoming iso then hypotonic).
I While, hyperosmolarity is developed in the medullary intersti-
tium.
b. The distal thick part is:
i. Impermeable to water.
ii. Poorly permeable to all solutes.
iii. However, both Na+ & Cl are actively transported from the
tubular fluid into the medullary interstitium. This produces:
V Hyperosmolarity in the medullary interstitium.
V The tubular fluid becomes more hypotonic with an osmolar-
ity about 150 mOsm/liter when delivered to the DCTs.
48
Figure 4.5: The Renal Counter Current Mechanism
Mechanism of Na+ & Cl- transport in the distal thick part of the ascend-
ing limb of loop of Henle:
a) Secondary active transport as following:
I One Na+ , one K+ and 2Cl are co-transported from the tubular lu-
men into the cells.
I This transport needs a symport carrier.
b) Primary active transport of Na+
I Na+ is actively pumped out from the cells into the medullary intersti-
tium by ATPase in exchange for K+ .
I Then, K+ passively diffuses into the tubular fluid.
c) Transport of Cl- from the cells into interstitium:
I One Cl is co-transported with the absorbed K+ into the medullary

interstitium.
I The other Cl diffuses passively into the interstitium.
Figure 4.6: The transport of Na+ , K+ , Cl in thick ascending limb of loop of Henle
The vasa recta
I The main function of vasa recta is to maintain the medullary intersti-

tium hyperosmolarity.
I This is achieved by operating as a countercurrent osmotic exchanger

system as following:
a. It provides a trapping (holding) mechanism for Na+ , Cl & urea in the

medullary interstitium.
b. It removes excess water from the medullary interstitium.
~Such effects occur as following:
1. In the descending limb:
I The solutes diffuse from the medullary interstitium into the blood)
(because the concentration of these solutes is higher in medullary
interstitium).
I Water diffuses from the blood to the medullary interstitium ) (so the
blood osmolarity rises).
2. In the ascending limb:
I The solutes diffuse from the blood into the medullary interstitium.
I Water diffuses from the medullary interstitium to the blood ) (so the
blood osmolarity falls).
Figure 4.7: Vasa recta as a countercurrent exchanger system

50
, N.B.1:
~The excess water comes from 2 sources:
i. Water that diffuses from the descending limbs of both vasa recta & loop
of Henle.
ii. Water that is reabsorbed from the collecting ducts ) (see later).
, N.B.2:
~The countercurrent exchanger function of the vasa recta is helped by:
1. They are highly-permeable to both solutes and water.
2. They constitute a low pressure system of capillaries ) at which the

blood flow is small (about 2% of the renal blood flow) & sluggish. Proper-
ties in 1 &2) allow:
• Maximal diffusion of the solutes from the ascending limbs of the

vasa recta into the medullary interstitium.
• Diffusion of water in the opposite direction.
Na+ & Cl cycle
Na+ & Cl are first transported into the medullary interstitium from the
ascending limbs of both the loop of Henle & vasa recta.
Then, they passively diffuse into the descending limbs of the vasa recta.
Finally, it is transported from the ascending limbs of the vasa recta into
the medullary interstitium.
The cycle is repeated.
Role of urea in concentration of urine

(Urea cycle)
I Urea accumulates within the medullary interstitium.
I About half of the 1200 mOsm/liter found at the tip of the medullary
pyramid is caused by urea.
I The accumulation of urea in the medullary interstitium is caused by re-

circulation in the following cycle:
The urea first diffuses passively from the medullary collecting

duct into the medullary interstitium.
Then, it diffuses into the descending limb of vasa recta & slightly
into the thin limb of loop of Henle.
Finally, it diffuses from the ascending limb of the vasa recta and
from the medullary collecting duct into the medullary interstitium.
And the cycle is repeated.
Renal handling of urea through

the different parts of the renal tubules
a. In the PCTs:
I The permeability of the PCTs to urea is high.

I Urea follows Na+ , Cl & water by passive diffusion.
b. In the descending limb of loop of Henle:
I The permeability to urea is low.

I Thus, the fluid that reaches the tip loop of Henle has high urea.
c. In the DCTs & the cortical part of the collecting duct.
I The tubule is almost impermeable to urea.

I Thus, urea becomes concentrated in this segment.
d. In the medullary part of the collecting ducts:
I The permeability to urea is high.

I Urea diffuses passively from the collecting duct into the medullary
interstitium.
I Once urea inters the medullary interstitium ) it is trapped there by the
countercurrent exchange between the ascending & descending limbs
of the vasa recta.
Causes of medullary interstitium hyperosmolarity
1. Na+ and Cl transport from the ascending limb of loop of Henle: (the
most important cause):
52
I Passively at their lower thin parts.

I Actively at their upper thick parts.
2. Small amounts of Na+ & Cl transported from the medullary collecting

ducts:
I Na+ by primary active transport.

I Cl by passive diffusion.
3. Urea:
I The medullary collecting ducts are partially permeable to urea as the

PCTs.
I They become highly permeable to urea in the presence of ADH.
I Therefore, urea diffuses passively from the medullary collecting ducts
to the medullary interstitium.
N.B.:
~ The cortical interstitium is iso-osmotic (have an osmolarity about 300

mOsm/liter).
~ This is due to the much greater blood flow rate in the cortical peritubular
capillaries (as compared with that in the vasa recta).
~ So, the peritubular capillaries drain excess solutes from the cortical in-
terstitium.
Functions of the distal convoluted tubules (DCTs)
I The DCTs receive hypotonic fluid from the ascending limbs of the
loops of Henle.
I Functionally, they are divided into 2 parts:
a. The initial part:

This has the same characteristics as the thick segment of the
ascending limbs of loop of Henle.
It is almost impermeable to both water & solutes (urea, Na+
&Cl ).
But, Na+ is reabsorbed by primary active transport & Cl fol-

lows it passively.
The tubular fluid becomes more hypotonic (about 100 mOsm/liter).
Thus, this part is called the diluting segment of the nephron.
The initial parts of DCTs secrete H+ mainly by secondary active
transport.
b. The late part:
VThis part performs the following functions:
I. Reabsorption:
(1) Na+ reabsorption:
This occurs by primary active transport.
It is controlled mainly by aldosterone hormone.
It is followed by passive reabsorption of Cl & water.
About only 5% of the filtered water is reabsorbed in the
DCTs, as they poorly permeable to water.
There is no urea reabsorption, because the DCTs are nor-
mally poorly permeable to urea.
The fluid delivered from the DCTs into the collecting ducts
is hypotonic.
(2) Ca++ reabsorption:
This also occurs by primary active transport.
It is increased by the parathyroid hormone.
Figure 4.8: The action of aldosterone in the DCTs
II. Secretion:
54
(1) H+ secretion:
I This occurs mainly by secondary active transport by Na+ -
H+ antiport carrier.
I However certain cells called (intercalated, dark or brown
cells) ) start to appear in this segment (and become more
abundant in the collecting ducts).
I These cells secrete H+ independent of Na+ (by primary
active transport) against high concentration gradient by
specific uniport carrier protein & H+ -ATPase. Secretion
of buffers for excess H+ in the DCTs:
The kidney often excrete urine at pH as low as 4.5 in
acidosis or as high as 8 in alkalosis.
In acidosis, the urine is buffered by the following buffer
systems to prevent marked decrease of pH below 4.5.
a. Bicarbonate buffer:
I The HCO3 ions & H+ are normally titrate each other in
the tubules mainly in the PCTs.
I The remaining excess H+ in the tubular fluid is buffered
by the phosphate & ammonia buffers.
b. Phosphate buffer:
) This buffer is a much more powerful in the tubular
fluid than in blood (due to its high concentration in the
urine).
c. Ammonia buffer
(2) K+ secretion:
I This occurs actively as follows:
a. K+ is transported inside the tubular cells by the Na+ - K+
pump at their basolateral borders.
b. Then, it is secreted by counter-transport mechanism at
their luminal borders of the principle cells, (which start to
appear in this segment), into the tubular fluid in exchange
for Na+ reabsorption (utilizing an antiport carrier).
I K+ secretion in the DCTs and cortical collecting ducts is
increased by:
i. Increase The extracellular K+ level.
ii. Increase Aldosterone level.
N.B.:
~ K+ & H+ compete for secretion in the DCTs and cortical
collecting ducts.
~ So, an increase of any of these ions in the tubular cells
favours its secretion.
Acidification of urine
(H+ secretion) by the renal tubules
Urine acidification occurs by secretion of H+ into the tubular lumen.
This mostly occurs in the PCTs, DCTs & collecting ducts.
To lesser extent in the ascending limbs of loop of Henle.
It occurs as following:
1) H+ is formed inside the renal tubular cells as a result of dissociation

of H2CO3. ) (The later is formed by combination of CO2 and H2O
under the influence of C.A enzyme).
2) Then, H+ is secreted by either:
a. Secondary active transport:

I In exchange for Na+ reabsorption (i.e. by counter-transport
utilizing an antiport carrier).
I It occurs in the PCTs, loop of Henle, DCTs & collecting ducts.
b. Primary active transport:
I This occurs against high H+ concentration gradient by the in-
tercalated cells.
I These cells are abundant in the late parts of the DCTs & the
collecting ducts.
I It occurs only in the late DCTs & collecting tubules.
56
Figure 4.9: Buffering of the hydrogen ion
Functions of the collecting ducts (CTs)
I The collecting ducts receive hypotonic fluid from the DCTs
I Functionally, they are divided into 2 parts:
1. Cortical part.
2. Medullary part.
I They perform the following functions:
I. Reabsorption:
1. Na+ reabsorption:
This occurs by primary active transport all over the CDs.
It increases by aldosterone ) only in the cortical CDs.
It is followed by passive diffusion of Cl & water.
It is coupled with K+ secretion.
2. Urea reabsorption:
This occurs by passive diffusion only in the inner parts of
the medullary CDs ) (because these parts are partially
permeable to urea) especially in the presence of ADH.
Urea is not reabsorbed in both cortical CDs and outer parts

of medullary CDs ) (because these parts are impermeable
to urea).
3. Water reabsorption in the CDs:
The CDs are relatively impermeable to water in absence of
ADH.
However, in the presence of ADH ) the CDs become highly
permeable to water ) (due to activation of water channels in
that segment which are called aquaporins [AQP2 & AQP3]).
Water reabsorption in the CDs and to some extent also in the
DCTs ) is called facultative water reabsorption ) (be-
cause it depends on the blood level of ADH).
Water reabsorption in the cortical CDs occurs as follow-
ing:
I The cortical CDs receive hypotonic fluid from the DCTs.
I At the normal rate of ADH secretion) about 10% of the fil-
tered water is passively reabsorbed ) into the iso-osmotic
cortical interstitium in excess of Na+ reabsorption.
I So, the tubular fluid becomes isotonic at the end of the
cortical CDs.
Water reabsorption in the medullary CDs occurs as fol-
lowing:
I This isotonic fluid enters the medullary CDs,
I Then, an additional 4.7% of H2O is reabsorbed by the hy-
perosmotic medullary interstitium.
II. Secretion:
1. K+ secretion:
I This occurs only in the cortical CDs in exchange for Na+ re-
absorption.
I It is increased by the aldosterone hormone.
2. H+ secretion:
I It is secreted all over the CDs:
58
I In the cortical CDs ) it occurs by both primary and sec-

ondary active transport.
I In the medullary CDs ) it occurs mainly by primary active
transport.
3. Secretion of buffers: As in DCTs.
N.B.1: Summary of water reabsorption through the different parts of
the renal tubules:
I Normally, about 99.7% of the filtered water is reabsorbed in the renal
tubules as follows:
(1) 65% in the PCTs.

(2) 15% in the descending limb loop of Henle.
(3) 5% in the DCTs.
(4) 10% in the cortical CDs.
(5) 4.7% in the medullary CDs.
I Only, 0.3% of the glomerular filtrations excreted producing) about 1.5

liters urine daily with osmolarity about 400 mOsm/liter.
N.B.2: Aquaporins (AQP):
~ They are water protein channels.
~ There are many types of them as following:

a) AQP1, AQP2 & AQP3are found in the kidneys.
~ The vasopressin-responsive water channels in the CDs is AQP2 & AQP3.
Figure 4.10: Intracellular mechanism of action of ADH in the CDs

Urine concentration and dilution
(1) Mechanism of urine concentration:
V This occurs in:

a. Hypovolemia ) (e.g. in dehydration & hemorrhage).
b. Blood hypertonicity) (e.g. due to excessive salt intake).
V This mechanism depends only on the facultative water reabsorp-
tion in the CDs which is determined by 2 main factors:
1. Blood level of ADH:
I When it increases in (hypovolemia or hypertonicity) ) in-
crease the permeability for water reabsorption in the CDs and
to the little extent the late part of DCTs.
I Increase ADH secretion) larger part of the medullary CDs
become water-permeable) so, more water is reabsorbed )
result in excretion of concentrated urine.
2. The hyperosmolarity of medullary interstitium:
It is increased by countercurrent mechanism ) which causes
passive diffusion of water from the CDs into the medulla.
V The net effect is excretion of small volume of concentrated urine
) (0.5 liter daily with an osmolarity about (1400 mOsm/liter).
(2) Mechanism of urine dilution:
This occurs in:

a. Hypervolemia.
b. Blood hypotonicity.
The following occurs:
1. Inhibition of secretion ADH.
I This decreases the water permeability of the CDs) decrease
the reabsorption of water.
2. Decrease the osmolarity of medullary interstitium.
The net effect is the excretion of large volume of diluted urine with
an osmolality less than 80 mOsm/liter.
60
e.g. in diabetes insipidus ) complete absence of ADH ) so, the

urine volume 23.3 liter/day with osmolarity is about 30 mOsm/liter.
Diuresis
Definitions:
Diuresis means increasing the rate of urine output.
Types (methods) of diuresis:
I. Water Diuresis:
I This is produced by drinking of a large amount of water) which

increase the urine volume after about 15 minutes.
I The maximal diuresis occurs within 40–45 min.
I While, the ingested amount completely excreted after 2 hours.
II. Osmotic diuresis:
This is produced by administration of osmotically active substances

that are not readily absorbed in the PCTs.
e.g. mannitol & sucrose.
Table 4.1: Difference between water and osmotic diuresis:
Water diuresis Osmotic diuresis

1-Water reabsorption Facultative water Obligatory & facultative
reabsorption only # water reabsorption are #
2- ADH secretion # Normal
3- Na+ excretion Normal "
4-Tonicity of urine Hypotonic Isotonic
III. Pressure diuresis:
I The changes in the ABP within the autoregulation level ) have a

little effect on GFR with parallel changes in urine volume.
I Marked increase in ABP ) increase urine output.
I Drop in the mean ABP below 50mmHg ) stop urine formation.
Chapter 5
Role of Kidney in Acid Base Balance &

Metabolic acid base disorders
Acids and bases:

A hydrogen ion is a single free proton released from a hydrogen atom.
• Acids are molecules containing hydrogen atoms that can release hy-
drogen ions in solutions. An example is hydrochloric acid (HCl), which
ionizes in water to form hydrogen ions (H+ ) and chloride ions (Cl). Like-
wise, carbonic acid (H2CO3) ionizes in water to form H+ and bicarbonate
ions (HCO3 ).
• A base is an ion or a molecule that can accept an H+ For example,

HCO3 is a base because it can combine with H+ to form H2CO3.
pH
The hydrogen Ion concentration [H+ ] can be expressed in a simpler form by
using the pH expression.
The pH is the negative logarithm (base 10) of H+ concentration.
pH = -log[H+ ]
So, if the (H+ ) is 10 7gram/ion/liter, the pH will be 7.
The pH of acidic solutions ranges from 0 – 7, of neutral solution is 7 and of
alkaline solutions ranges from 7 – 14.
• Precise H+ regulation is essential because the activities of almost all
enzyme systems in the body are influenced by it. Therefore, changes in
hydrogen concentration alter virtually all cell and body functions.
• About 50 to 100 millimoles of hydrogen ions are released from cells

into extracellular fluid each day. However; the extracellular hydrogen ion
concentration ([H+ ]) is maintained between about 35 and 45 nanomol/L
(40 nmol/L = pH 7.40).
61
62
• There are three primary systems that regulate the H+ concentration in

the body fluids to prevent acidosis or alkalosis:
(1) The chemical acid-base buffer systems of the body fluids, which im-
mediately combine with acid or base to prevent excessive changes
in H+ concentration;
(2) The respiratory center, which regulates the removal of CO2 (and,
therefore, H2CO3) from the extracellular fluid;
(3) The kidneys, which can excrete either acid or alkaline urine, thereby
readjusting the extracellular fluid H+ concentration toward normal
during acidosis or alkalosis.
Figure 5.1: pH value in the body
Buffers and buffering system

Definition:
A buffer is an aqueous solution that resists changes in pH upon adding strong
Acids or alkalies.ie. if we add 1 ml of HCl to pure water, pH drops Significantly
where as if we add the same amount of HCl to a buffer solution pH will drop
slightly.
Buffer solution consists of a mixture of a weak acid and its conjugate of strong
base or a weak base and its conjugate acid.
. e.g. buffer solution consists of acetic acid (weak acid) + sodium acetate
(conjugate base).
• If strong alkali is added to solution it releases (OH ) which combines

with acetic acid and so pH doesn’t rise.
CH3COOH (aq) + OH-(aq) CH3COO-(aq) + H2O (aq)
Chapter 5. Role of Kidney in Acid Base Balance 63
• If a strong Acid is added it releases H+ which combines with CH3COO-

to form Weak acid so pH doesn’t drop. CH3COO (aq) + H+ (aq) CH3COOH
(aq)
Figure 5.2: Body’s buffering of blood pH levels
Physiologic buffer systems (in our body)

Are important to keep the pH suitable for enzymatic reactions and for keeping
the pH of blood within normal range (7.3 – 7.5) since any marked change in
pH of blood is fatal.
1. Plasma proteins (amino acids in proteins are amphoteric ie contain basic

NH3 group which can receive H+ and acidic COOH group which can lose
H+ and become COO ).
2. Bicarbonate buffer system. (H2CO3/NaHCO3).
3. Phosphate buffer system (NaH2PO4/Na2HPO4).
4. Hemoglobin (when it releases Oxygen, H+ binds to NH3 in this protein)
Figure 5.3: Physiologic buffer systems
Respiratory system:
Quick way to respond, takes minutes to hours to correct pH
Eliminate volatile respiratory acids such as CO2

Doesn’t affect fixed acids like lactic acid
Body pH can be adjusted by changing rate and depth of breathing.
Urinary system:
64
– Only the kidneys can rid the body of metabolic acids (phosphoric,
uric, and lactic acids and ketones) and prevent metabolic acidosis.
– The most important renal mechanisms for regulating acid-base bal-
ance are conserving bicarbonate ions and excreting bicarbonate
ions.
* Losing a bicarbonate ion is the same as gaining a hydrogen ion;

* Conserving a bicarbonate ion is the same as losing a hydrogen ion
Conserving of Bicarbonate:
Plasma bicarbonate is freely filtered at the glomerulus.
Carbonic acid formed in filtrate dissociates to release carbon dioxide and

water
Carbon dioxide then diffuses into tubule cells, where it acts to trigger
further hydrogen ion secretion
For each hydrogen ion secreted, a sodium ion and a bicarbonate ion are
conserved
Secreted hydrogen ions form carbonic acid
Thus, bicarbonate disappears from filtrate at the same rate that it enters
the peritubular capillary blood.
The term renal tubular acidosis (RTA) is applied to a group of transport

defects in the conservation of bicarbonate (HCO3 ), the excretion of
hydrogen ion (H+ ), or both.
In its responses to alkalosis, the kidneys may excrete more bicarbonate

by decreasing hydrogen ion secretion from the tubular epithelial cells.
Figure 5.4: Tubular cells are not permeable to bicarbonate; thus, bicarbonate is conserved
rather than reabsorbed. Steps 1 and 2 of bicarbonate conservation are indicated.
Chapter 5. Role of Kidney in Acid Base Balance 65
Metabolic acid base disorders
I. Metabolic acidosis
• In metabolic acidosis the primary problem is a reduction in the bicar-

bonate concentration of the extracellular fluid.
• Compensatory mechanism: The drop in pH stimulates ventilation
Anion Gap
Anion gap is equal to the difference between the plasma concen-
trations of the major cation (Na+) and the major measured anions
(Cl +HCO3 ).
Anion Gap = Na+ – (Cl + HCO3 )
It ranges between 4 to 12mmol/L
– Normally; blood is neutral with net charge equals zero, this gap is
caused by the presence of serum phosphate and serum albumin
that carry negative charges and not measured or considered in
this equation.
– An increased anion gap usually is caused by an increase in un-
measured anions, and that most commonly occurs when there is
an increase in unmeasured organic acids, that is, an acidosis.
– If anion gap > 30 mmol/L then metabolic acidosis invariably present.
II. Metabolic alkalosis
• The causes of a metabolic alkalosis are:

a. Loss of hydrogen ion in gastric fluid during vomiting. This is
especially seen when there is pyloric stenosis preventing parallel
loss of bicarbonate-rich secretions from the duodenum.
b. Ingestion of an absorbable alkali such as sodium bicarbon-
ate. Very large doses are required to cause a metabolic alkalosis
unless there is renal impairment.
• Compensatory mechanism: Similar to a metabolic acidosis, the
respiratory system is the first-line compensatory mechanism. Venti-
lation decreases to retain CO2.
66
Respiratory acid–base disorders
I. Respiratory acidosis:
• The primary problem in acute respiratory acidosis is alveolar hy-

poventilation. If airflow is completely or partially reduced, the PCO2
in the blood will rise immediately and the [H+ ] will rise quickly
• Compensatory mechanisms: The kidneys compensate by con-
serving HCO3 and eliminating H+ , but the kidneys take days to fully
compensate.
II. Respiratory alkalosis:
• Respiratory alkalosis is much less common than acidosis but can

occur when respiration is stimulated
• Compensation: The kidneys compensate by eliminating HCO3
and conserving H+ , but the kidneys take days to fully compensate.
Figure 5.5: Acid Base disturbances

Chapter 6
Diuretics
Diuretics: drugs that increase urine volume

Natriuretic: is an agent which increase sodium excretion and hence water
excretion
Aquaretic: agent that increase solute free water excretion
Classification according to efficacy:
1. High: loop diuretics
2. Medium: thiazide diuretics
3. Low: K sparing diuretics and carbonic anhydrase inhibitors
Loop diuretics
I. Members: frusemide, torsemide and bumetanide
II. Pharmacokinetics:
• Rapidly absorbed with torsemide (1 hour) versus frusemide (2-3

hours), oral bioavailability of torsemide is high, while frusemide is
variable
• Bound to plasma proteins
• Duration of torsemide 4-6 hours, frusemide is 2-3 hours, while, half
life depends on renal function
• Torsemide and bumetanide have significant hepatic metabolism
• Eliminated via glomerular filtration and tubular secretion
67
68
III. Pharmacodynamics:
Mode of action:
– Secreted in proximal convoluted tubules and inhibit luminal Na+ /K+ /2Cl
transporter in Thick ascending limb of loop of Henle
– Weak carbonic anhydrase inhibitors
Effects:
– Reduce NaCl reabsorption 25% (natriuretic)

– Reduce Mg++ and Ca++ reabsorption and increase their excre-
tion
– Enhance secretion of K+ and H+ due to delivery of Na to collect-
ing tubule that lead to increased secretion of K+ and H+
– Increase renal blood flow through induction of synthesis of prostaglandin
– Frusemide causes VD of peripheral vessels especially veins via
direct effect + PG production
IV. Clinical indications:
1. Acute pulmonary edema (IV) due to vasodilation and diuretic effect

7 ! #
preload and pulmonary congestion
2. Other refractory edematous conditions (renal (e.g. nephrotic syn-

drome), hepatic, cardiac (congestive heart failure)) if severe combined
with thiazide
3. Can be used in hypertension (by its diuretic effect only)
a. Emergency hypertension
b. With mild renal impairment
c. Resistant hypertension
4. Acute hypercalcemia: it is a medical emergency (saline should be

administered to avoid volume contraction)
5. Hyperkalemia, the response is enhanced by NaCl and water admin-

istration
6. Acute renal failure as they increase renal blood flow and reduce K+
Chapter 6. Diuretics 69
7. Bromide, fluoride and iodide overdose as they are reabsorbed in

thick ascending limb of Henle’s loop (saline should be given to the
patient to avoid volume depletion)
V. Adverse effect:
1. Severe dehydration and hypovolemia

2. Hyponatremia may develop from thirst induced increased water in-
take.
3. Hypokalemic metabolic alkalosis
4. Hypomagnesemia with risk of arrhythmia
5. Hypercalciuria with resultant mild Hypocalcemia
6. Hyperuricemia due to hypovolemia induced enhanced reabsorption
of uric acid
7. Hyperglycemia and diabetes (infrequent than thiazides)
8. Hyperlipidemia ! " LDL-C and TG, # HDL-C
9. Ototoxicity: reversible dose related especially in impaired renal func-
tions and use of other ototoxic drugs frequently with rapid IV injection
than oral route
10. Allergic reactions: with sulfonamide loop diuretics
VI. Contraindications:
• Patients allergic to sulfonamide drugs as there is cross allergy

• Postmenopausal osteopenia as it affects bone metabolism
• Pregnancy
• Excessive use should be avoided in :
– Borderline renal failure
– Hepatic cirrhosis
– Heart failure
Excessive use of diuretics may lead to reduced venous
return and impaired cardiac output, which cause conse-
quently impaired renal perfusion
70
Hypokalemia that results from diuretic use may exacerbate

arrhythmia and enhance digitalis toxicity
VII. Drug interactions:
1. Increase oral anticoagulant effect via displacing warfarin from plasma

protein
2. Increase digitalis toxicity due to hypokalemia
3. Increase plasma level of lithium due to reduced clearance
4. Probenecid antagonize its diuretic action via decreasing renal tubu-
lar excretion
5. NSAIDs decrease its diuretic effect
6. Thiazide diuretic synergize diuretic action
7. Aminoglycosides and other ototoxic drugs increase ototoxicity
8. Aminoglycoside, amphotericin and cephalosporin increase nephro-
toxicity
Thiazides diuretics
I. Members: hydrochlorothiazide, chlorthalidone, indapamide, metolazone
II. They have sulfonamide group
III. Pharmacokinetics:
• Administered orally, hydrochlorothiazide is used in lower doses, chlorthali-

done is absorbed slowly and has long duration of action
• Indapamide is excreted mainly in biliary system
• All of them are excreted by organic acid secretory system in proxi-
mal tubules including indapamide to act on distal convoluting tubules
(site of action)
IV. Pharmacodynamics:
Mode of action:
– They act from inside tubule on Na+ /Cl transporter in early part
of distal convoluted tubules to exert their diuretic effect.
– Weak inhibition of carbonic anhydrase enzyme (chlorothiazide)

Effects:
– Inhibit NaCl reabsorption 10% (natriuretic)
– Enhance secretion of K+ and H+
– Enhance Ca++ reabsorption due to:
I Volume depletion lead to increased sodium reabsorption with
passive Ca++ reabsorption in proximal tubules
I Lowering of intracellular Ca++ due to block of Na entry in dis-
tal convoluted tubules enhance Na+ /Ca++ exchanger in baso-
lateral membrane
– Thiazide diuretics may NOT act sufficiently if GFR is <30 ml/min
and they decrease GFR so not used in renal impairment
– Antihypertensive effect even in sub-diuretic doses due to direct
arteriolar VD
V. Clinical indications:
1. Hypertension
• Thiazides are preferred than loop due to VD effect in addition to
diuretic effect
• Moderate salt restriction can potentiate the effect of diuretic and
lessen K+ loss
• Patients treated with powerful vasodilators as hydralazine or mi-
noxidil require diuretics as these drugs cause salt and water re-
tention
2. Mild congestive heart failure due to diuresis (#preload) and arterial
VD (#afterload)
3. Nephrolithiasis due to idiopathic hypercalciuria
4. Nephrogenic diabetes insipidus due to volume contraction and re-
duction of GFR which lead to enhanced Na+ reabsorption
72
VI. Adverse effects:
1. Hypokalemic metabolic alkalosis

2. Hyponatremia: (due to hypovolemia induced thirst and elevation of
ADH, so reduced by limiting water intake)
3. Hypomagnesemia and mild hypercalcemia
4. Hyperuricemia due to decreased uric acid excretion
5. Hyperglycemia: especially in patients with diabetes and impaired
glucose tolerance, it occurs due to impaired insulin secretion and is
exacerbated by hypokalemia
6. Hyperlipidemia: total cholesterol and LDL
7. Allergy: cross allergy with sulfonamide group, photosensitivity, throm-
bocytopenia, hemolytic anemia but rare
8. Impotence due to volume depletion
9. Weakness and paresthesia due to carbonic anhydrase enzyme in-
hibition
VII. Contraindications:
1. Renal failure as it tends to reduce GFR (NB.: metolazone is used

even in severe renal failure)
2. Gout and diabetes
3. Pregnancy
4. Excessive use is dangerous in:
a. cirrhotic patients as fluid and electrolyte disturbances may lead
to hepatic encephalopathy
b. borderline renal failure
c. heart failure
VIII. Drug interactions:
1. # efficacy of uricosuric agents

2. # efficacy of hypoglycemics and insulin
3. " effects of digitalis due to hypokalemia
4. " effect of vit D due to hypercalcemia

5. " effect of lithium due to reduced clearance
6. NSAIDs decrease its diuretic effect
7. Corticosteroids increase hypokalemia
8. Fetal arrhythmia with drugs prolonging QT interval
Potassium sparing diuretics
Classification
• Aldosterone antagonists: spironolactone, eplerenone
• Non-aldosterone antagonists: amiloride, triamterene
Spironolactone and eplerenone
I. Pharmacokinetics:
• Absorbed orally
• Slow onset; several days before effect appear as it is determined by
aldosterone kinetics in response tissue
• Metabolized in liver
II. Pharmacodynamics:
Mode of action: competitively antagonize aldosterone in collecting

tubule which control Na+ reabsorption and K+ excretion
Effects:
– Inhibition of Na+ reabsorption
– Decrease K+ secretion so cause hyperkalemia
– Decrease H+ secretion causing metabolic acidosis
– Increase Ca++ excretion
74
III. Clinical indications:
1. Hyperaldosteronism as primary (Conn’s syndrome) or secondary

due to (heart failure, hepatic cirrhosis, nephrotic syndrome)
2. Can reduce mortality in patients with mild to moderate heart fail-
ure.
3. Spironolactone and eplerenone usually of choice in cirrhotic patients
but caution if there is also renal impairment to avoid hyperkalemia
4. In combination with other diuretics to combat hypokalemia and
produce synergism
IV. Adverse effects:
1. Hyperkalemia: especially in renal impairment and drugs which in-

crease K+
2. Hyperchloremic metabolic acidosis
3. Gynecomastia and impotence due to antagonism of androgen re-
ceptors, this effect doesn’t occur with eplerenone as it selective only
for aldosterone receptors
V. Contraindications:
• Chronic renal insufficiency due to hyperkalemia

• With other agents that increase K+ as: oral K supplementation,
beta blockers, ACEIs, ARBs
• Patients with liver disease has impaired metabolism of spironolac-
tone
VI. Drug interactions:strong CYP3A4 inhibitors as erythromycin can markedly

elevate levels of eplerenone not spironolactone
Triamterene and amiloride
• Taken orally
• Triamterene is extensively metabolized in liver (short half-life), while,
amiloride is not metabolized
• Renal excretion is the major route of elimination of the drug and its
metabolite
Mode of action: both drugs directly block epithelial Na+ channels in

collecting tubules!
– Inhibit Na+ reabsorption
– Decrease H+ and K+ secretion
The same effects as spironolactone, but decrease Ca++ excretion in
urine
III. Clinical indications: as spironolactone + amiloride is of choice in lithium

induced diabetes insipidus
1. Hyperkalemia, Hyperchloremic metabolic acidosis

2. Acute renal failure: occurs in combination of triamterene with in-
domethacin
3. Triamterene may cause kidney stones as it is slightly soluble
V. Contraindications: impaired renal functions, drugs that increases K+

levels, patient with liver disease may impair metabolism of triamterene
Carbonic anhydrase inhibitors

(acetazolamide)
• Well absorbed orally

• Secreted by proximal tubule (dose must be reduced in renal insuffi-
ciency)
• Onset of alkaline urine is 30 minutes, peak 2 hours and duration 12
hours after single dose
Mode of action and effects: inhibit carbonic anhydrase enzyme in
proximal convoluted tubules (PCT)!
76
• Inhibit HCO3 reabsorption in PCT
• Na+ and HCO3 loss in urine
• Excess Na+ delivery to distal tubules exchange with K+ only as ex-

cretion of H+ is inhibited so lead to K+ depletion
• Self-limited diuretic effect as HCO3 loss lead to enhanced NaCl

reabsorption by other sites of nephron so the diuretic effect of them
decrease overtime, also development of acidosis limits its diuretic
activity to 2-3 days only.
NB.: because of self-limited diuretic effect of carbonic anhy-
drase inhibitors, they are used when carbonic anhydrase en-
zyme needed to be inhibited in other sites in body
III. Clinical indications:
1. Glaucoma: as HCO3 is secreted into aqueous humor of eye by ac-

tion of carbonic anhydrase, inhibition of this enzyme can lower intraoc-
ular pressure and this is the most common indication of this drug, to
avoid renal systemic effects eye drop preparations are used as (dor-
zolamide and brinzolamide)
2. Urine alkalinization: to enhance solubility of uric acid and cysteine

as they form stones in acidic urine, but this needs oral bicarbonate if
the therapy is prolonged as alkalinization lasts for 2-3days only
3. Metabolic alkalosis: if it occurs due to diuretics in patients with se-

vere heart failure
4. Acute mountain sickness: decrease pH of CSF and brain lead to

reduction of CSF formation ! increase ventilation and diminish symp-
toms as headache, insomnia, dizziness and weakness associated
with mountain sickness
5. Others: adjuvant in epilepsy (raise seizure threshold) and hypokalemic

periodic paralysis
1. Hyperchloremic metabolic acidosis

2. Renal stones: calcium phosphate stone as they are insoluble in al-

kaline urine
3. Hypokalemia
4. Drowsiness, weakness and paresthesia after large doses
5. Hypersensitivity reaction (fever, rash, bone marrow depression)
6. Neural toxicity in renal failure patients
V. Contraindications:liver cirrhosis as it leads to hepatic encephalopathy

because NH3 is not converted to urea due to diminished H in urine
Aquaretic
Drugs that alter water excretion
• Osmotic diuretics
• Antidiuretic hormone antagonists
Osmotic diuretics
(mannitol)
I. Criteria of ideal osmotic diuretic: Pharmacologically inert, Freely fil-

tered in glomerulus, Not reabsorbed
II. Pharmacokinetics:
• Poorly absorbed orally (NB: if taken orally cause osmotic diarrhea)

• Not metabolized
• Excreted in kidney by glomerular filtration, not reabsorbed, not se-
creted by renal tubules
III. Pharmacodynamics:
Mode of action: as it is not reabsorbed, it will prevent water re-

absorption by its osmotic force in two sites (proximal tubules and
descending limb of Henle’s loop) as they are freely permeable to
water
Effects:
– Increase urine volume
78
– Reduce sodium as well as water reabsorption due to increased

urine flow which decrease contact time between fluid and tubular
epithelium
– Natriuresis is less than water excretion so leads to severe
water loss and hypernatremia
– If taken IV, they increase osmotic pressure in blood vessels
and remove excess fluid from cells
IV. Clinical indications:
1. Reduction of intracranial pressure in cerebral edema

2. Reduction of intraocular pressure during acute attack of glaucoma
or before ophthalmic preparation
3. Enhance urinary excretion of salicylates, barbiturates, bromides,
and lithium following overdose
4. Treatment of dialysis disequilibrium: as dialysis remove solutes
so causes reduction of extracellular osmolality so water move inside
cells and cause (headache, nausea, muscle cramps, restlessness
and convulsion), mannitol shift fluids back to extracellular compart-
ment
V. Adverse effects:
1. Extracellular volume expansion which lead to complications in heart

failure as pulmonary edema
2. Headache, nausea, vomiting
3. Dehydration and hypernatremia
4. Hyperkalemia due to extraction of water from cells which elevate in-
tracellular K+ with loss of cell and hyperkalemia
5. Hyponatremia: in patients with severe renal impairment
VI. Contraindications:
1. Acute renal failure due to expansion of Extracellular volume with no

filtration
2. Active Cerebral hemorrhage as it increases intracranial pressure
Antidiuretic hormone antagonists
Lithium - Demeclocycline- ADH receptor antagonists (vaptans)
I. Pharmacodynamics:
Mode of action:they inhibit the effect of ADH in collecting tubule
II. Clinical indications:
1. Syndrome of inappropriate ADH secretion(SIADH)

2. Other causes of elevated ADH as: heart failure which may lead to
hyponatremia
III. Adverse effects:
1. Nephrogenic diabetes insipidus

2. Acute renal failure, lithium may cause chronic interstitial nephritis
3. Dry mouth and thirst
Diuretic combinations:
1. Combination of loop and thiazide diuretics has additive effect as they

act on two different sites in the nephron so reduce sodium reabsorption,
but this combination may cause marked hypokalemia and can mobilize
large amount of fluid so hemodynamic and electrolytes monitoring is im-
portant
2. Combination of loop or thiazide diuretics and K sparing diuretics may

be needed to antagonize hypokalemia but should be avoided in renally
impaired patients and in patients taking drugs increasing K+ level
Role of diuretic in Kidney diseases and renal failure:
Patients with mild degree of renal impairment may need diuretic to de-
crease fluid accumulation
Diuretics may help in short term fluid management of acute renal fail-
ure, of choice is loop diuretic (thiazides are ineffective, mannitol cause
volume expansion, K sparing cause hyperkalemia), but loop diuretics
sometime worsen renal functions due to reduction of preload
80
Thiazide or loop diuretics may treat hyperkalemia associated with dia-

betic nephropathy
Carbonic anhydrase inhibitors may cause acidosis due to loss of bicar-

bonate so should be avoided in renal patients
Potassium spring diuretics should be avoided in renal patients due to

hyperkalemia
Excessive use of diuretics may impair renal functions and is more dan-
gerous in patients with underlying renal disease as they may result in
prerenal failure
Chapter 7
Glomerular diseases in children
7.1 Acute Post-streptococcal Glomerulonephritis (APSGN)
• It is the most common form of nephritis in childhood.
• Characterized by sudden onset of:
Gross hematuria.
Significant proteinuria.
Mild to moderate edema.
Hypertension.
Variable degrees of impaired renal function.
• Epidemiology
APSGN follows infection of the upper respiratory tract (Pharyngitis,

nasopharyngitis, or otitis media) or skin infection (impetigo, acne,
or erysipelas) with certain nephritogenic strains of group A beta -
hemolytic sterptococci.
A seasonal variation in the incidence of attacks of APSGN due to
either streptococcal pharyngitis (winter and early spring) or strepto-
coccal pyoderma (summer and early fall) has been observed.
Epidemics of nephritis have been described in association with both
throat (Serotype 12) and skin (Serotype 49) infections.
A latent period between the preceding streptococcal infection and
the onset of APSGN of 7 to 21 days (average 10 days) in throat
infection and 14 to 28 days (average 20 days) in pyoderma is usually
present.
• Pathogenesis:
81
82 7.1. Acute Post-streptococcal Glomerulonephritis (APSGN)
1. Decreased glomerular filtration rate (GFR).

2. Increased permeability of glomerular capillaries leading to escape
of RBCs (hematuria) and passing of serum albumin (albuminuria).
3. Edema: Due to salt and water retention and circulatory overload
leading to the expansion of extracellular fluid compartment.
4. Hypertension: In addition to salt and water retention and circula-
tory overload (circulatory congestion), renal ischemia also shares
in getting hypertension, hypertensive heart failure, hypertensive en-
cephalopathy and retinal exudate and hemorrhages are the compli-
cations of hypertension.
5. Impaired renal function: Decreased renal perfusion due to narrowing
of glomerular capillaries leads to oliguria, retention of potassium,
non-protein nitrogen and results in acute kidney failure.
• Clinical presentation:
Age at onset is 3 - 10 years.

More common in males, male to female ratio 2: 1.
Asymptomatic cases: The disease may be so mild to be passed
unnoticed.
1. General manifestations: anorexia, nausea, fever (usually low
grade) and abdominal pain (loin pain).
2. Urinary manifestations:
a. Hematuria:
* Occurs in 100% of cases

* Ranges from microscopic to gross hematuria.
* Gross hematuria occurs in 50% of cases, persists for 1 - 14
days.
* Most of RBCs are lysed causing tea color, cola color, smoky
urine or dark red colored urine.
b. Decreased urine volume and oliguria in cases of acute kid-
ney failure (AKF).
3. Edema:
Chapter 7. Glomerular diseases in children 83
Present in over 75% of cases.

Mild to moderate edema.
Usually starts in the face in the morning.
Severe edema occurs in: CHF, and secondary nephrotic syn-
drome.
4. Hypertension:
Mild to moderate hypertension but may be severe enough to
cause hypertensive HF and hypertensive encephalopathy.
Occurs in 50%-60% of cases, occurs during acute phase (first
3 weeks).
Blood pressure usually returns to normal within two weeks.
5. Manifestations of complications:
a. Hypertensive heart failure:
Due to circulatory congestion and the hypertension.
Dyspnea and congested pulsating neck veins, cardiomegaly,
tachycardia, pulmonary edema, hepatomegaly and increas-
ing generalized edema.
b. Hypertensive encephalopathy: The child gets severe headache,
nausea, vomiting, drowsiness, papilledema and convulsions
may occur.
c. Acute kidney failure: The child develops progressive olig-
uria and even anuria with increasing edema, with nausea,
vomiting, drowsiness and even convulsions may occur.
• Differential Diagnosis:
Other causes of hematuria in children:
Congenital polycystic kidney.

Trauma: Blunt trauma and urinary stones and crystaluria (oxaluria).
Infection: Urinary tract infection, Renal T.B, and Urinary Bilharziasis.
Blood diseases: Coagulation defects (Hemophilia), Thrombocytope-
nia (I.T.P.), and Sickle cell anemia,
Malignancy: Leukemia, and Renal tumors (Wilm’s tumor).
84 7.2. Nephrotic syndrome in children (NS)
Drugs: Anticoagulants(Heparin).
• Prevention:
No available vaccine.
Avoid contact with children suffering from streptococcal throat or
skin infections.
Avoid overcrowding during cold weather.
Adequate skin hygiene during summer.
Antibiotic prophylaxis is not justified.
7.2 Nephrotic syndrome in children (NS)
The nephrotic syndrome is a clinical complex characterized by:
1. Proteinuria of nephrotic range (>40 mg/m2/h)
2. Hypoalbuminemia (< 2.5 g/dl)
3. Generalized massive edema
4. Hyperlipidemia (Total cholesterol > 250 mg/dl)
5. Recurrence
The nephrotic syndrome can be classified according to the etiology

into:
I. Primary (Idiopathic) nephrotic syndrome: where the etiology is un-

known, the most prevalent glomerular injury in childhood forms 90% of
cases of nephrotic syndrome in childhood.
The categories of primary NS are:
• Minimal change disease (MCD) 85%.

• Focal segmental glomerulosclerosis (FSGS) 10%.
• Mesangial proliferative nephropathy (MPN) 5%.
II. Secondary nephrotic syndrome: forms 10% of childhood nephrotic

syndrome where it is secondary to another disease as:
• Acute post streptococcal glomerulonephritis (APSGN).

• Henoch - Schonlein Purpura (HSP).
• Systemic Lupus Erythematosus (SLE).
• Hodgkin’s Lymphoma.
• Juvenile Diabetes Mellitus (JDM).
• Infective endocarditis.
III. Congenital nephrotic syndrome: Occurs in the first 3 months of life

may be hereditary disease (Finnish type) or secondary to congenital
infection (Toxoplasmosis or syphilis).
Pathophysiology:The underlying abnormality in nephrotic syndrome is an

increase in permeability of the glomerular capillary wall, which leads to mas-
sive proteinuria and hypoalbuminemia. The cause of the increased perme-
ability is not well understood.
• In minimal change disease, it is possible that T-cell dysfunction leads

to alteration of cytokines, which causes a loss of negatively charged
glycoproteins within the glomerular capillary wall. The role of immune-
mediated process in the etiology of MCD was supported by the response
to immunosuppressive drugs.
• In focal segmental glomerulosclerosis, a plasma factor, perhaps pro-

duced by lymphocytes, may be responsible for the increase in capillary
wall permeability. Alternately, mutations in podocyte proteins (podocin,
-actinin4) are associated with focal segmental glomerulosclerosis
Minimal Change Disease (MCD) (Nil disease)
It is the most common form of nephrotic syndrome in childhood.

MCD is common in boys, with male to female ratio of 2:1.
Age: It is a disease of young children with a peak incidence from 2 to 5 years
of age.
• Etiology:The etiology of MCD remains unknown.
• Pathogenesis:The glomerular leakage of serum proteins mainly albu-

min results in:
1. Hypoalbuminemia.
2. Edema: It is the increase in the extra vascular (interstitial) compo-
nent of the extracellular fluid volume. It results from:
i. The hypoalbuminemia and the decrease in the oncotic pressure
of the blood (underfill theory).
ii. Decrease in plasma volume leads to the activation of the renin
angiotensin - aldosterone axis with salt and water retention (over-
fill theory).
3. Hyperlipidemia:
i. It is mainly due to increase in serum cholesterol and triglyc-
erides.
ii. This is due to increased liver synthesis of cholesterol and triglyc-
erides and also due to the decrease in peripheral catabolism of
lipids.
4. Increased susceptibility to infection: This is due to:
i. Decrease in serum immunoglobulins and complement, which are
lost in urine.
ii. Edema fluid acts as good bacterial culture media.
iii. Protein deficiency and decreased bactericidal activity of leuko-
cytes.
iv. Defective opsonization of bacteria due to Loss of properdin factor
B in urine
5. Hypercoagulability:
i. Due to increased plasma levels of certain coagulation factors
such as factor V, VII and fibrinogen. While plasma level of an-
tithrombin III is decreased. In addition to increased blood viscos-
ity.
ii. Tendency for thrombosis is less common in children.
• Clinical Picture:
The onset is usually gradual in a child of 2-5 years of age often following
influenza like syndrome.
Edema:
– It may be mild at first around the eyes (periorbital edema). Then

progresses to become generalized with increase in body weight and
decreased amount of urine.
– Generalized edema may be severe up to anasarca (Hydrothorax and
ascites) leading to dyspnea.
– Gastrointestinal disturbances as nausea, vomiting, diarrhea and ab-
dominal pain due to edema of gastrointestinal wall.
Figure 7.1: Degrees of proteinuria in children
• Complications of nephrotic syndrome:
1. Infections:
– Bacterial and viral infections are common due to increased li-
ability of nephrotic patients to infection and the use of steroid
therapy.
– The most common organisms are pneumococcus and gram -ve
(E. coli).
– Peritonitis is the most common site of infection but pneumonia,
Skin infection (cellulitis) and urinary infections are not uncom-
mon.
– All children with nephrotic syndrome should receive polyvalent
pneumococcal vaccine (if not previously immunized) and Influenza
vaccine annually.
2. Hypovolemic shock: It occurs in severe cases with massive pro-
teinuria, septicemia and aggressive diuretic therapy especially if serum
albumin below 1.5 g/dl.
3. Arterial and venous thrombosis:
– Due to hypercoagulability state, it is less common in children

than adults.
– Its possibility increases when associated with dehydration, sep-
ticemia and serum albumin below 1.5 g/dl.
4. Muscle wasting: Due to hypoproteinemia and the steroid therapy.
5. Side effects of therapy
• Differential diagnosis (other causes of proteinuria and edema in chil-

dren):
Nephrotic syndrome must be differentiated from:
I. Acute post streptococcal glomerulonephritis.

II. Generalized edema.
– Nutritional.
– Cardiac edema as in cases of right sided or congestive heart
failure and constrictive pericarditis.
– Hepatic edema, in late cases of chronic liver diseases with as-
cites.
– Allergic edema as in angioneurotic edema.
III. Other causes of nephrotic syndrome. A diagnosis other than MCNS
should be considered in the presence of age <1 yr, presence of fam-
ily history of NS, extrarenal findings (arthritis, rash, anemia), hyper-
tension, acute or chronic renal insufficiency, and gross hematuria.
Chapter 8
Pathology of glomerular diseases
The role of humoral immunity in the pathogenesis of glomerular diseases:
1- In-situ immune complexes: antibodies are directed against endogenous

antigen in the glomerular basement membrane. The classical example is
in Goodpasture’s syndrome.
2- Antibodies are formed to non-glomerular antigens. Circulating antigen

antibody complexes are formed and carried to the glomeruli resulting in
their damage, It may be endogenous, as in the GN associated with sys-
temic lupus erythematosus, or it may be exogenous, as in the GN that fol-
lows certain bacterial (streptococcal), viral (hepatitis B), e.g. acute post
streptococcal glomerulonephritis. The pattern and location of im-
mune complex deposition are helpful in distinguishing among vari-
ous types of GN. Immune complexes show a granular pattern of de-
position.
Immune complexes and antibodies cause injury by complement activation
and leukocyte recruitment, with release of various mediators, and some-
times by direct podocyte damage.
Complement fixation
. &
Chemotaxis of neutrophils Activation of complement factors
# #
Release of enzymes Formation of cell membrane
& .
Vascular damage
89
90
Classification of glomerular diseases:
Syndrome Common primary causes Common secondary causes

Nephritic IgA nephropathy Poststreptococcal
Mesangiocapillary Vasculitis
Hereditary nephritis Systemic lupus erythromatosis (SLE)
Anti-GBM disease (Goodpasture’s)
Cryoglobulinemia
Nephrotic Membranous Diabetes
Minimal change SLE(class V nephritis)
Focal segmental glomerulosclerosis Amyloid
Mesangiocapillary Hepatitis B/C
Clinical classification of glomerular disease
• Nephritic syndrome
– Acute glomerulonephritis: Abrupt onset of hematuria, non-nephrotic-

range proteinuria, hypertension, edema and transient renal impair-
ment.
– Rapidly progressive glomerulonephritis: focal necrosis with or
without crescents with features of acute nephritis and rapidly pro-
gressive renal failure over weeks
• Nephrotic syndrome: massive proteinuria, hypoalbuminemia, edema,

hyperlipidemia and lipiduria, it is related to pododcyte injury or malfunc-
tion
• Mixed nephritic/nephrotic presentation: glomerulonephritis is part of

systemic disease as (lupus nephritis, Henoch-schönlein purpura), it is a
nephritic often associated with nephrotic
• Asymptomatic hematuria, proteinuria or both
A. Acute nephritic syndrome: could be manifested in the following:
1. Acute post-streptococcal glomerulonephritis:

Synonyms: acute diffuse glomerulonephritis, endocapillary prolif-
erative glomerulonephritis.
Chapter 8. Pathology of glomerular diseases 91
Pathological features:
Gross picture: as in all nephritic syndromes,
– Both kidneys are enlarged; the capsule is tense and strips eas-
ily.
– The cortex is broad and pale, the medulla is congested.
Microscopic picture:
1. The glomeruli are swollen and cellular that affects nearly all
glomeruli—hence the term diffuse. This is due to swelling and
proliferation of endothelial cells as well as leucocytic infiltration.
2. The convoluted tubules show cloudy swelling of their lining cells,
hydropic degeneration and fatty change.
3. The collecting tubules contain casts in their lumen (mainly blood
casts).
4. The interstitial tissue is edematous, hyperemic and shows leu-
cocytic infiltration.
Immunofluorescence: granular deposits of immunoglobulin IgG
and C3 in the capillary walls.
• Electron microscopy: subepithelial immune complex deposits (be-
tween the basement membrane and podocytes) of dense granular
substance or humps.
2. Acute non-streptococcal glomerulonephritis: may also develop on

top of other bacterial or viral infections.
3. IgA nephropathy (Berger’s disease) :
Age: in any age particularly between 6 and 12 years.
Immunofluorescence: shows granular mesangial deposits of IgA.
4. Hereditary nephritis (Alport’s disease):
Clinical picture: a familial disease characterized by hematuria
92
which is frequently associated with nerve deafness and ocular ab-

normalities.
Electron microscopy: shows attenuation and splitting of the glomeru-
lar basement membrane.
5. Focal glomerulonephritis:
Gross picture: kidneys may show minute areas of hemorrhage
(flea-bitten kidney).
Some of the glomeruli are affected, others are normal.
The lesion in the affected glomeruli is limited to one or two lob-
ules.
There is mesangial proliferation, capillary thrombosis and hem-
orrhage in the Bowman’s capsule.
Immunofluorescence: mesangial deposition of IgM and comple-
ment C3.
Figure 8.1: Focal glomerulonephritis
B. Rapidly progressive glomerulonephritis (RPGN):

Manifested in the following:
RPGN is commonly associated with severe glomerular injury with

necrosis and GBM breaks and subsequent proliferation of parietal
epithelium (crescents).
RPGN may be immune-mediated, as when autoantibodies to the GBM
develop in anti-GBM antibody disease or when it arises consequent
to immune complex deposition.
1. Crescentic (rapidly progressive) glomerulonephritis

Synonyms: crescentic glomerulonephritis, subacute diffuse glomeru-

lonephritis.
Etiology: idiopathic: unknown cause.
It may follow acute glomerulonephritis
As a manifestation of other diseases as Goodpasture’s syn-
drome and polyarteritis nodosa
Gross picture: both kidneys are enlarged, pale and have smooth
surface.
1- Most of the glomeruli show crescent formation due to prolifera-
tion of the parietal layer of the Bowman’s capsule.
2- The crescents formed by the proliferating epithelial cells enlarge,
compress the capillary tufts and ultimately become replaced by
fibrous tissue.
3- Thrombosis in the capillary loops and adhesions between the
tuft and the capsule.
4- There is focal necrosis of the tubules and interstitial inflamma-
tory cellular infiltration. Tubular lumen contains red cells, hyaline
and cellular casts.
Immunofluorescence: shows the characteristic granular pattern
of immune complex disease
Figure 8.2: Crescentic glomerulonephritis
2. Goodpasture’s syndrome:
Pathogenesis: due to formation of antibodies against the base-
ment membranes of the kidneys and the lungs.
94
Clinically: characterized by pulmonary hemorrhagic lesions and

renal lesions.
Immunofluorescence: shows linear pattern of deposition of anti-
bodies along the glomerular basement membranes.
C. Nephrotic syndrome:
(1) Minimal change disease:

Synonym: lipoid nephrosis.
Pathologic features:
Gross picture: no gross pathologic changes.
Microscopic picture: no or minimal changes in the form of lipid
droplets in the cells of the convoluted tubules, this feature is sec-
ondary to tubular reabsorption of the lipoproteins passing through
the diseased glomeruli. The glomeruli appear normal, thus giving
rise to the name “minimal-change disease”
Immunofluorescence: no immunoglobulins are detected.
Electron microscopy: fusion (effacement) of the foot processes
of epithelial cells (Podocytes). With reversal of the changes in
the podocytes (e.g., in response to corticosteroids), the proteinuria
regress.
Figure 8.3: Minimal change disease
(2) Membranous glomerulonephritis:

Gross picture: kidneys are enlarged and pale.
Microscopic picture: diffuse hyaline thickening and formation of
spikes giving hair comb appearance of the basement membrane.
Immunofluorescence: granular immune complex deposits con-
taining IgG and C3.
Electron microscopy: subepithelial electron dense deposits, which

nestle against the GBM and are separated from each other by
small, spike like protrusions of GBM matrix that form in reaction to
the deposits (spike and dome pattern).
Figure 8.4: Membranous glomerulonephritis
(3) Focal segmental glomerulosclerosis:

Etiology:
1- Idiopathic.
2- Secondary: due to heroin abuse, AIDS and analgesic abuse.
Injury to the podocytes is thought to represent the initiating
event of primary FSGS.
The deposition of hyaline masses in the glomeruli represents
the entrapment of plasma proteins and lipids in foci of injury
where sclerosis develops.
The condition starts in the juxtamedullary glomeruli.
Focal = some glomeruli become sclerosed.
Segmental = some segments (lobules of the glomerular tuft of
the same glomerulus) are affected. The affected glomeruli ex-
hibit increased mesangial matrix, obliterated capillary lumens,
and deposition of hyaline masses (hyalinosis) and lipid droplets.
Immunofluorescence: focal mesangial deposition of IgM, C3 and
C4.
Electron microscopy: increased mesangial matrix and the podocytes
exhibit effacement of foot processes, as in minimal change dis-
ease.
96
(4) Membranoproliferative glomerulonephritis:

Synonym: mesangiocapillary glomerulonephritis
Etiology: an immune-mediated disease involving both classical
and alternate pathway of complement activation.
Primary: idiopathic.
Secondary: to other diseases as systemic lupus erythemato-
sus, AIDS, schistosomiasis and tumors.
Types: three types:
Type 1: is the most common caused by immune complexes
deposition and associated with classic complement pathway
characterized by subendothelial deposits.
Type 2: is less common and is known as dense deposit dis-
ease. It is associated with alternative complement pathway.
Type 3: very rare. It is a mixture of type 1 with subepithelial
deposits.
Pathologic features: Microscopic picture:
Enlarged hypercellular lobulated glomeruli and show prolifer-
ation of mesangial and endothelial cells as well as infiltrating
leukocytes
There is thickening of the capillary walls with double contour
appearance best demonstrated by silver or PAS stain.
Immunofluorescence: Deposition of C3, C1q and properdin.
Electron microscopy: There is subendothelial interposition of
mesangial cells which is responsible for the formation of double
layers of basement membrane. This picture is called double con-
tour of the basement membrane.
Figure 8.5: Membranoproliferative glomerulonephritis

D. Asymptomatic hematuria and/or proteinuria:

As in benign recurrent hematuria:
Pathology: the majority of glomeruli exhibited normal or slightly pro-

liferative changes in the form of mild diffuse mesangial hypercellular-
ity.
Chronic (slowly progressive) glomerulonephritis:
Definition: the final stage of different forms of glomerulonephritis where

sclerosis has destroyed many glomeruli and their associated tubules.
End stage kidney disease usually follow chronic glomerulonephritis
Gross picture:
1. The kidneys are small in size and firm.

The surface is finely granular and the capsule is adherent and dif-
ficult to strip with decortication, diffusely granular when the under-
lying disorder affects blood vessels or glomeruli. Kidneys damaged
by chronic pyelonephritis are typically unevenly involved and have
deep scars.
2. The cut surface shows that the cortex is narrowed and not demar-
cated from the medulla. The peripelvic fat is increased.
1. Many glomeruli are sclerosed with adhesion between the glomerular

tuft and Bowman’s capsule.
2. The tubules connected to the fibrosed glomeruli are atrophied and
those connected to the functioning glomeruli show compensatory
hypertrophy, dilatation and cyst formation. The tubular lumen con-
tains hyaline and granular casts.
3. There is interstitial fibrosis and infiltration by chronic inflammatory
cells.
4. The medium sized and small arteries show intimal thickening (en-
darteritic changes).
98
Chapter 9
Proteinuria
Definition: Urinary protein excretion more than 150 mg/ day (10% albumin,
the rest derived from renal cells)
Albuminuria: (normally <30 mg/day) may be:
• Micro-albuminuria (30-300mg/day)
• Macro-albuminuria (>300mg/day).
Micro-albuminuria is strong predictor for microvascular disease damage es-

pecially as diabetic nephropathy
Protective mechanisms against proteinuria:
• Electrostatic barrier: negative charge in glomerular basement mem-

brane glycosaminoglycan has a repelling action against negatively charged
circulating macromolecule (albumin)
• Structural barrier: blood renal barrier allows only passage of water and
water-soluble substances.
Selectivity of proteinuria:
Selective Non-selective
>85% albumin (LMW) in urine Equal amounts of albumin (LMW) and
globulin (HMW) in urine
loss of electrostatic barrier loss of structural barrier
Minimal lesion glomerulonephritis Focal, segment, and mesangocapil-
lary glomerulonephritis.
Good prognosis Poor prognosis
99
100
Causes:
I. Physiological: orthostatic(postural), functional
II. Pathological: overflow, glomerular, tubular
Orthostatic (postural) proteinuria (mild, reversible with good prognosis)
• Increased protein excretion in the urine in upright position (standing or

ambulant) but becomes normal in recumbent position.
• Mechanism: increased venous congestion of both kidneys
• More common in tall lordotic children and adolescent
• Related to exercise, disappear at rest, proteinuria +ve by day -ve by night
Functional proteinuria:
• Secondary to systemic disease without real renal disease e.g. heart

failure, hypertension, blood diseases, fever, burn, etc.
• Disappear rapidly with successful treatment of the disease
• Mechanism: hemodynamic change and change in glomerular pores
Overflow (overproduction) proteinuria:
• Excessive protein filtration abnormally large amount of small (low MW)

protein present in the serum that exceeds the capacity of normal tubular
reabsorption (glomeruli are normal)
• Causes: hemoglobinuria, myoglobinuria, etc.
Glomerular proteinuria
• Causes: any glomerular disease
• Mechanism: loss of electrostatic charge of basement membrane, dam-

age of structural barrier caused by inflammation which affect size and
selectivity of pores, Increase intraglomerular pressure due to hemody-
namic changes
Tubular proteinuria:
Chapter 9. Proteinuria 101
• Causes: acute and chronic injuries involving the renal tubulointerstitial

region
• Mechanism: Increased protein loss by injured tubules of small MW pro-

tein filtered by the glomeruli as B2 microglobin or increased secretion of
cellular enzyme by damaged tubules
Differential diagnosis:
• False proteinuria: if associated with hematuria or urinary tract infection

(pyuria)
• Different causes of proteinuria
Investigation:
Routine urine examination:
• Present or not: boiling test (urine clot by boiling), dipstick change color
to yellow if above 300 mg/L, urine protein electrophoresis (type of pro-
tein)
• Amount of protein: 24-hour collection to measure amount in protein-

uria and albuminuria
• Character of protein:
– Glomerular: foamy urine, albuminuria, more than 1-2g/day, associ-

ated with hematuria and casts
– Tubular: mainly small MW protein as B2 microglobin, less than 1-
2g/day
Blood: renal function tests, hypoproteinemia and hyperlipidemia with glomeru-

lar proteinuria
Radiological imaging: renal or extrarenal e.g. bone, chest.
Renal biopsy: It the best answer for diagnosis
Investigation of the cause
Treatment:
1. Specific treatment; Successful treatment of the cause will remain the

corner stone of therapy.
102
2. Non-Specific treatment:
• Dietary protein intake. (+) to 0.6gm/day+ urine loss.

• ACE inhibitors: It should be avoided of the serum creatinine is above
2.7mg/dl or increasing by its use.
• ARBs: may be superior to ACE inhibitors.
Chapter 10
Diabetic nephropathy
Definition: a clinical syndrome characterized by persistent albuminuria (>300

mg/ 24 hours) is confirmed on at least 2 occasions 3-6 months apart, pro-
gressive decline in glomerular filtration rate (GFR) and hypertension
• It is a glomerulopathy related to duration and control of diabetes
• It is the commonest cause of end stage renal disease (ESRD)
• It may be part for diabetic triopathy: Neuropathy, Retinopathy, and Nephropa-

thy
Pathophysiology:
• Early: renal hypertrophy and glomerular hyperfiltration
• Vasodilation of afferent arteriole that leads to increase in intraglomeru-

lar filtration pressure ! damage of glomerular capillaries ! glomerular
sclerosis
Pathology:
1. Nodular glomerulosclerosis which results in nephrotic syndrome plus dia-

betes mellitus (Kimmelsteil-Wilson syndrome).
2. Thickening of glomerular basement membrane.
3. Hyaline arteriolosclerosis of the basement membrane of the afferent and

efferent arterioles.
Sequence of events in diabetic nephropathy: Hyperfiltration (raised GFR

above normal) related to bad glycemic control (hyperglycemia) ! Microalbu-
minuria ! Gross proteinuria with or without nephrotic ! Renal impairment
(gradual decline in GFR) after onset of proteinuria ! End stage renal disease
103
104
Diagnosis:
• Diabetic patients with history of: passing foamy urine, unexplained

proteinuria, diabetic retinopathy, fatigue and foot edema due to (hypoal-
buminemia if nephrotic syndrome is present), other associated diseases
as hypertension
• Physical examination:
– Early diagnosis: microalbuminuria detection by special dipstick

– Measurement of albuminuria with exclusion of other causes of albu-
minuria by albumin creatine ration
– Physical finding of long-standing diabetes mellitus: hyperten-
sion, peripheral vascular disease, evidence of diabetic neuropathy
or retinopathy, non-healing ulcer, etc...
– Renal biopsy is not indicated unless another kidney disease is sus-
pected or presence of atypical feature
Differential diagnosis: other glomerulopathies that may affect diabetic pa-

tients
Treatment:
1. Control of blood sugar
2. Control of blood pressure with reduction of dietary salt intake
3. ACE inhibitors (must be used early at stage of microalbuminuria):
• Vasodilation of efferent arteriole

• # intraglomerular pressure (decrease proteinuria)
• # glomerulosclerosis so decrease progression of renal disease
Chapter 11
Chronic Kidney Disease:
Definition: gradual slowly progressive irreversible deterioration of kidney

function with development of clinical syndrome of uremia which finally pro-
gresses to end stage renal disease
Etiology:
• Diabetes mellitus (long standing)
• Hypertension (long duration)
• Non diabetic:
Glomerular Tubulointerstitial Vascular Transplant Cystic

-Lupus or vas- -Myeloma -Hypertension -Chronic rejec-
culitis -Pyleonephritis -Renal artery tion
-Hepatitis or -Obstruction stenosis -Medications
HIV -BPH -Renal vasculi- -Chronic dis-
-Endocarditis -Tumor tis ease
-Amyloidosis -Chronic reflux -Sickle cell -Low-flow
-Medications -Sarcoidosis -HUS states
-Lithium (hemolytic ure- -Cirrhosis, CHF,
mic syndrome etc.
)
Pathogenesis and clinical picture:
• Hypervolemia: failure to excrete Na and water when GFR<10-15 ml/min

! edema and hypertension, pulmonary edema, ascites
• Hyperkalemia: due to decreased renal ability of K+ excretion, observed

with sudden load of K (diet, drugs, hemolysis, infection, trauma, lack of
insulin and acidosis)
– Normally asymptomatic
105
106
– In severe cases > 7mmol/L ! tingling around tips & fingers, loss of
tendon jerk, abdominal distention, arrhythmia
– ECG changes in form of prolonged PR interval, prolonged QRS, tall

T wave
• Metabolic acidosis: Inability to produce enough NH3 in prox. Tubules,

decreased bicarbonate reabsorption
– In advanced cases, accumulation of PO4, SO4& another organic

anion cause the high anion gap metabolic acidosis.
– Clinically manifested by Hyperventilation, respiratory distress, fa-

tigue, reduced cardiac output, confusion & drowsy
• Hematologic:
– Normochromic, normocytic anemia: mainly due to low production

of erythropoietin, low erythropoiesis in addition to inhibition of bone
marrow by toxic uremia, decreased intake and absorption of iron
and blood loss in dialysis and bleeding
– Increase susceptibility to infection due to suppression of leuko-

cytes
– Bleeding tendency due to platelet dysfunction
• Mineral and bone disorder: Abnormalities of calcium, phosphorus,

PTH, or vitamin D metabolism. Abnormalities in bone turnover, mineral-
ization, volume, linear growth, or strength. Vascular or other soft tissue
calcification. Secondary hyperparathyroidism
Causes:
– Hyperphosphatemia: Suppresses hydroxylation of 25-OH vit.D to

1,25 diOH vit.D
– Hypocalcemia: due to decreased intestinal calcium absorption
– Calcium binding to high plasma levels of phosphate
– Decreased renal production of 1,25 diOH vit.D

Chapter 11. Chronic Kidney disease 107
Alteration and manifestation:

Neurological system: Peripheral neuropathy, insomnia, legs pain, confu-
sion, seizure, coma
Respiratory system: acidotic air hunger (Kussmaul’s respiration), pul-
monary congestion ! dyspnea, cough, recurrent chest infection. Cardiovas-
cular system: hypertension, peripheral edema, arrhythmia ("K) Gastroin-
testinal: anorexia, nausea, vomiting, ammonia odor, hiccough, GIT bleed-
ing, abdominal distension due to hyperkalemia
Renal system
Acid base: Metabolic acidosis
Electrolytes: hyperkalemia, hypocalcemia, hyperphosphatemia
Excretory: azotemia, hematuria and proteinuria
Other manifestations of uremia in ESRD
Pericarditis ! cardiac tamponade
Skin manifestations: Pallor, Dryness, Pruritus, Ecchymosis
Easy fatiguability, failure to thrive
Malnutrition due to decreased protein intake and catabolism
Erectile dysfunction, decreased libido, amenorrhea.
Management:
Chronic kidney failure cannot be cured but there are four goals of therapy:
• Slow the progression of disease.
• Treat underlying causes and contributing factors.
• Treat complications of disease.
• Replace lost kidney functions
This can be achieved by:
• Blood glucose and blood pressure control (ACEI)
• Diet: low protein diet (controversial)
• Treatment of hyperlipidemia.
• Avoidance of nephrotoxins such as: IV radiocontrast, NSAIDs, Amino-

glycosides.
108
Treating the complications:

• Fluid retention by diuretics
• Anemia by injections of erythropoietic stimulating agents.
• Low calcium by calcium supplements
• Hyperphosphatemia with dietary phosphate binders and dietary phos-

phate restriction.
• Hyperpathayroidism with calcitriol or vitamin D analogues or calcimimet-

ics.
• Metabolic acidosis with oral alkali supplements.

Timing the initiation of Renal Replacement therapy (RRT)
• Symptoms or signs attributable to kidney failure: (serositis, acid-base or
electrolyte abnormalities, pruritus);
• Inability to control volume status or blood pressure;
• A progressive deterioration in nutritional status refractory to dietary in-

tervention;
• Cognitive impairment.
• This often but not invariably occurs in the GFR range between 5 and
10ml/min (2B)
Treating the uremic manifestations by the following:
• Hemodialysis: takes 3-4 hours and usually performed about 3 times a
week.
• Peritoneal dialysis:
– It is done by putting 2 Liters of dialysis fluid into the abdominal cavity

through a catheter.
– The fluid will balance out electrolytes and toxic waste products and
it needs to be exchanged 4 times a day.
• Kidney transplant: can be from living related donors, living unrelated

donors or cadavers.
Chapter 12
Laboratory assessment of renal functions
Laboratory tests aiding in the evaluation of kidney function
I. Glomerular function
1. Those measuring the glomerular filtrate. It is the most useful general

index for assessing the severity and progress of renal damage as it is
inflating phase of nephron function, these are inulin clearance, urea
clearance and creatinine clearance.
2. Those assessing the Glomerular permeability
3. Determination of Non-protein Nitrogen Containing Compounds (NPN).
II. Tubular function:
1. Concentration and dilution tests.

2. Urine titerable acidity.
3. PSP excretion test.
4. Serum and urine osmolality
5. Excretory and re-absorptive capacity.
III. Those measuring renal blood flow
Glomerular function
1. Those measuring the glomerular filtrate.

Clearance tests:
Clearance of a substance means the volume of plasma from which the
substance is completely removed by the kidneys per unit time.
UxV x1:73
C=
P
• U = concentration of this substance in urine mg/dl
109
110
• V = volume of the urine voided / min

• P = concentration of this substance in plasma in mg/dl
• 1.73 is generally accepted average of body surface area in square
meters
The clearance tests provide more sensitive measure for renal function
than the estimation of NPN.
~ Creatinine clearance: is less accurate in measuring GFR than inulin

clearance but more accurate than urea its advantages:
– It is an endogenous subs. e.g. need not to be injected.
– Its estimation is simple & easy.
– It is less influenced by rate of urine flow.
– Its level is independent of protein intake.
Disadvantages: A small fraction is secreted by tubules especial when
its plasma level increase above normal, therefore, creatinine clear-
ance value may be greater than actual GFR.
It’s Normal value: males (85-125 ml/min), in females (75-115 ml/min).
~ Urea clearance:
Advantage: it is of greatest value in assessing renal function in pa-
tient with normal or with slight increase in plasma urea and in patient
with urine volume equal to or more than 2 ml/min.
Disadvantages:
– It is dependent on rate of urine flow.
– It is useful only in cases at urine flow rate 2 ml/min or more.
– Urea level is significantly affected by diet.
Factors affecting the GFR (clearance value):
(1) Renal blood flow. (2) Glomerular damage. (3) Increased cap-
sular pressure. (4) Altered plasma colloid or osmotic pressure.
2. Assessment of Glomerular permeability:
When proteinuria exists, the following measurement should be carried

Chapter 12. Laboratory assessment of renal functions 111
out: Its excretion rate, its type whether selective or not & if possible elec-
trophoretic separation.
3. Determination of NPN: Its major component is urea nitrogen, amino

acids, uric acid, creatinine, creatine and ammonia.
Tubular function:
1. Concentration and Dilution tests of renal function:

The usual tests consist of:
Concentration test: Patient is given protein meal with 200 ml water at 6
p.m. with no more fluid after. All urine voided is discarded. Collect urine
samples at 8 a.m. and at 9 a.m. measure specific gravity & /or osmolality
of each specimen. One of these specimens should have a sp. Gr. > 1020
or osmolality > 850 mOsm/kg to be considered normal.
Dilution test: No fluid is taken after mid night, at 7 a.m. patient empties
his bladder completely. Then drinks 1200 ml water within 1/2h Urine is
then collected hourly for 4 hours. For the result to be normal, there should
be all volume is excreted in these 4 hours. Specific gravity and osmo-
lality of one of these specimens should be about 1002 or 50 mOsmol/kg
respectively.
2. Serum and urine Osmolality:

Simultaneous measurements of serum and urine osmolality and calculat-
ing ratio of urine/serum Osm gives ratio of concentration of osmotically
active particles in urine (Na, Cl, HCO3 & to less extent urea & glucose) to
that in serum. It expresses the actual degree to which kidney has concen-
trating GF.
3. Secretory and re-absorptive capacity
4. Urine titerable acidity

112
Measurement of Non-protein Nitrogen Containing Compounds (NPN)
1. Urea:
~ Clinical Utility: An elevated concentration of urea in the blood is

called azotemia. Very high concentration accompanied by renal failure
is called uremia or Uremic syndrome. Conditions causing elevation of
plasma urea are classified according to the cause into three main cat-
egories:
– pre-renal azotemia: caused by

a. Reduced renal blood flow less blood and urea is delivered
to the kidney less urea is filtrated as in (Congestive heart
failure – shock – hemorrhage – dehydration and other factors
resulting in blood volume).
b. Amount of protein metabolism as in (high-protein diet – pro-
tein catabolism – muscle wasting (as in starvation) – re-absorption
of blood proteins after a gastrointestinal hemorrhage – treat-
ment with cortisol or its synthetic analogues)
In all of the above pre-renal, situations, the plasma creatinine
concentration will be normal.
– Renal azotemia: caused by renal function urea concen-
tration as a result of compromised urea excretion as in (acute and
chronic renal failure – glomerulonephritis – tubular necrosis and
other intrinsic renal disease.
In all of the above renal, situations, the plasma urea and creatinine
concentration will .
– post-renal azotemia: caused by obstruction to the flow of urine
anywhere in the urinary tract by (renal calculi – malignancy of the
bladder or prostate – sever infection), both the plasma creatinine
and urea levels will be increased; in these situations there is often
a greater increased in the plasma urea than in the plasma creati-
nine because of the increased back-diffusion of the urea.
– urea level caused by ( protein intake and sever liver disease,
pregnancy and transfusion.
Chapter 12. Laboratory assessment of renal functions 113
~ Reference Intervals: Urea nitrogen in adult:

! serum or plasma = 6 – 20 mg/dL (2.1 – 7.1 mmol/L urea).
! urine 24-hour =12 – 20 g/day (0.43 – 0.71 mol/day urea).
2. Creatinine:
~ Clinical Utility: Conditions causing elevation of serum creatinine

– non-renal causes:
subject with a large muscle mass, high protein intake, transient
increase after vigorous exercises and some drugs.
– Renal causes: as
Impaired renal perfusion (e.g. reduced blood, fluid depletion,
renal artery stenosis)
Diseases lead to loss of the functioning nephrons (e.g. acute
and chronic glomerulonephritis)
– post-renal causes as: caused by obstruction to the flow of urine
anywhere in the urinary tract by (renal calculi – malignancy of the
bladder or prostate – severe infection)
– serum creatinine is found in: children, wasting diseases, star-
vation and patients treated by corticosteroid due to their catabolic
effect.
~ Reference Intervals:
Serum creatinine in male: 0.6 – 1.4 mg/dL.
Serum creatinine in female: 0.5 - 1.3 mg/dL.
Serum creatinine in children: 0.2 – 0.7 mg/dL.
114
Chapter 13
Drug induced kidney injury
• It is elevation of renal functions as serum creatinine and blood urea ni-

trogen during treatment with potentially harmful drug to the kidney
• It is preventable by avoiding these potentially toxic drugs in high risk

patients
• Kidney injury is often reversible after stopping the drug but may turn from
acute kidney injury to chronic kidney disease
Drug induced kidney injury:
1. Acute tubular necrosis:
• Most common type

• Injury occurs mainly in proximal and distal tubule, hence the name
• Causative drugs: Aminoglycosides, Radiographic contrast media,
outdated tetracycline, Cisplatin, Amphotericin B, Tacrolimus and cy-
closporin, Adefovir, cidofovir
Important examples:
Aminoglycosides
Mechanism of kidney injury: the drug bind to proximal tubules then up

taken by cells + renal vasoconstriction so cell death results.
Risk factors:
• Risk is increased with neomycin and gentamicin and least with amikacin
• Prolonged course more than 7-10 days
• Use with other nephrotoxic drugs
115
116
• Chronic kidney disease and old age
Ways to minimize injury
• Once daily dosing

• Reduce duration of therapy
• Maintain low serum levels
• Use third generation cephalosporin or quinolones as alternatives
• Avoid successive courses
Care in case of evident injury:
• The drug should be stopped

• Adequate hydration
• Stop other nephrotoxic drugs
Radio-contrast agents
Mechanism of kidney injury: renal ischemia and obstruction of renal

tubules, direct tubular toxicity
Risk factors:
• High dose
• Use with other nephrotoxic drugs
• GFR<60ml/min
• Diabetes, dehydration, old age
Ways to minimize injury
• Expansion of extracellular volume by isotonic saline or sodium bicar-

bonate (but with caution in cardiac and advanced renal disease pa-
tient)
• Non-ionic is preferred than ionic contrast agents
• Use low amount of the contrast
Care in case of evident injury:

• Supportive
Chapter 13. Drug induced kidney injury 117
2. Obstructive nephropathy
Adequate hydration and alkalization of urine can prevent this injury if used
before drug administration
Mechanism of kidney injury:
• Direct: precipitation of the drug or its metabolites due to low solubility

in either acidic or alkaline urine
• Indirect: when tumor lysis syndrome and hyperuricemia occur due to
use of antineoplastic drugs
Causative drugs:
a. Intratubular obstruction: Sulfonamides, methotrexate (both precipi-

tate in acidic urine), Acyclovir, vitamin C overdose (oxalate nephropa-
thy), etc.
b. Nephrocalcinosis: oral sodium phosphate solution
c. Nephrolithiasis: Sulfonamides, Indinavir, Triamterene.
3. Hemodynamic mediated kidney injury

Causative drugs: Angiotensin converting enzyme inhibitors(ACEIs), An-
giotensin receptor blockers (ARBs), non-steroidal anti-inflammatory in-
hibitors(NSAIDs), Cyclosporin and tacrolimus
NB: In reduction of GFR, dilation of afferent and constriction of efferent
occurs aiming at redistribution of renal blood flow inside glomerulus to
maintain glomerular filtration pressure.
ACEIs, ARBs:
Mechanism of kidney injury: ACEI causes dilation of efferent arterioles,

so results in reduction of glomerular filtration
Risk factors:
• Renal artery stenosis

• Conditions of reduced renal blood flow: severe heart failure, volume
depletion
• Preexisting renal dysfunction involving diabetic nephropathy
How to minimize or avoid injury?
118
• Begin with low doses and increase gradually

• Avoid agents and conditions causing hypovolemia or reduce perfusion
of kidney as dehydration, hypotensive drugs, diuretics and NSAIDs
NSAIDs
Mechanism of kidney injury: inhibition of vasodilator prostaglandins E2

and I2, so VC of afferent arteriole occurs leading to prerenal injury
Risk factors:
• Same as ACEIs risk factors

• Simultaneous use of ACEI and diuretics
• Hepatic diseases, systemic lupus erythromatosis (SLE), advanced
age
How to minimize or avoid injury:
• Avoid potent NSAIDs as indomethacin
• Use paracetamol as it does not inhibit VD prostaglandins
• Shorten duration of use as possible
4. Glomerular disease: Causative drug: Gold, Lithium, NSAIDs including

COX 2 inhibitors, etc. Mechanism of kidney injury: immune mediated,
uncommon
5. Tubulointerstitial diseases
a. Acute allergic interstitial nephritis: Penicillin, NSAIDs including COX

2 inhibitors, Loop diuretics, etc. treated by stopping treatment and cor-
ticosteroid administration
b. Chronic interstitial nephritis: cyclosporin, lithium
c. Papillary necrosis: NSAIDs, Combined analgesics (aspirin and phenacetin),
Caffeine analgesics
6. Renal thrombosis and emboli

Causative drugs:
• Hydralazine, Propylthiouracil, Allopurinol, etc.,

• Cholesterol emboli with warfarin
Chapter 14
Acute kidney injury
Definition: a clinical syndrome characterized by rapid deterioration in kidney

function over 48 hours with or without oliguria
Etiology:
I. Prerenal (#renal perfusion)
II. Renal
III. Postrenal (urinary outflow obstruction)

Prerenal:
• Hypovolemia: hemorrhage, dehydration, cardiogenic shock, burn, etc.
• Acute renal artery occlusion
• Sudden peripheral VD as septicemia, drugs, etc. and sudden # in car-

diac output as in massive myocardial infarction, etc.
Renal (intrinsic):
• Tubular: acute tubular necrosis (most common), acute interstitial
nephritis, acute tubular obstruction (crystals, drugs, hemoglobin, etc.),
etc.
• Glomerular: rapidly progressive glomerulonephritis, collagen diseases,

etc.
• Vascular: malignant hypertension, thromboembolism, etc.

Postrenal:
• Bilateral ureteric obstruction
• Unilateral ureteric obstruction with contralateral non-functioning kidney
• Obstruction of bladder or urethra
119
120
Acute tubular necrosis (ATN)
Causes:
• Ischemic: prerenal factors if NOT corrected rapidly
• Toxic: drugs as aminoglycosides, sulphonamide, etc., endogenous toxin

as hemoglobin, myoglobin, uric acid, etc., exogenous as insecticides,
mercury, lead, ionized radiographic contrast agents, etc.
Pathophysiology and clinical picture:
I. Oliguric phase:
• Reduction of urine output due to tubular damage and obstruction

by necrotic cells in addition to reflex VC by substances released from
damaged tubules
• It ranges from days to weeks
• Leads to manifestation of hypervolemia as: headache, pulmonary
edema, edema, congested neck veins
• Na retention ! volume expansion and hypertension, dilutional hy-
ponatremia may occur if increased intake of fluids
• Potassium retention ! weakness, nausea, vomiting, ECG changes
and arrhythmia
• Hydrogen retention: acidosis ! rapid deep respiration
• " urea and creatinine ! manifestation of uremia (anorexia, nausea,
vomiting, hiccough, bleeding, convulsions, confusion, coma, death)
II. Diuretic phase
• Occurs due to partial regeneration of tubules but still unable to con-

centrate urine
• Urine output increase may reach 5-10 L/day
• Manifested by improved general condition, dehydration,
III. Recovery phase (may take 3-12 months): Gradual return of renal func-
tion to normal with improvement of general health
Chapter 14. Acute kidney injury 121
Diagnosis of acute kidney injury

• Differentiate from chronic or acute on top of chronic
• Differentiate prerenal form other causes by history, clinical examination,

urine analysis and renal function tests
• Urinary catheter to exclude postrenal causes

Investigation of acute kidney injury:
Urine analysis:
• Volume: <400ml/d, anuric in obstruction, increase in diuretic phase
• Low fixed specific gravity at 1010 (>1020 in prerenal)
• Casts and cells in renal causes
• Urine osmolarity: >500 in prerenal, <400 in renal and postrenal
• Urine Na: <20 mEq/L in prerenal, >40 mEq/L in renal and postrenal
Blood: hyperkalemia, hyponatremia, acidosis, hyperphosphatemia
Renal function test: " urea and creatinine, #creatinine clearance
Renal imaging: helpful in postrenal causes
Investigation of the cause
Treatment:
I. Treatment of cause:
• Prerenal: correction of hypovolemia

• Postrenal: catheterization then treatment of cause
• Renal (ATN)
– Prevention: proper treatment of prerenal causes, avoid nephro-
toxins
– Treatment during initiation phase (1-2days of exposure): cor-
rection of cause, stop nephrotoxic drugs, induction of diuresis to
convert oliguria to non-oliguria
Furosemide: If mannitol fails to induce diuresis furosemide can
be used as either single large dose 80-320 mg IV or regular
hourly doses at 100 mg/hour/IV infusion.
122
II. Treatment of oliguric phase:
• Hypervolemia: restriction of salt and fluid, antihypertensives, treat-

ment of heart failure, dialysis if needed
• Treatment of hyperkalemia
• Treatment of hyperphosphatemia and hypocalcemia
• Treatment of acidosis: protein restriction, NaHco3, dialysis
• Treatment of uremia:
– Diet: protein restriction, CHO increase
– Drugs for symptoms (convulsion, vomiting, hiccough, infection,
etc.)
– Dialysis (hemodialysis or peritoneal dialysis)
III. Treatment of diuretic phase: fluid intake and electrolyte replacement.

Chapter 15
Pathology of different renal diseases
RENAL CYSTS
1. Simple solitary cyst:

It is common finding in adults. The size of the cyst is variable and con-
tains serous or hemorrhagic fluid. There are no associated genitourinary
diseases. On microscopic examination, these membranes are seen to be
composed of a single layer of cuboidal or flattened cuboidal epithelium,
2. Retention cyst: occurs in advanced glomerulonephritis or hypertensive

kidneys. They are usually multiple and are due to compensatory tubular
dilatation.
3. Congenital polycystic kidneys:
a. Childhood (autosomal recessive) type:

• Rare fatal type, which is, inherited as autosomal recessive trait.
• Both kidneys are enlarged. The cut section is spongy and cystic.
• The condition is due to dilatation of the collecting tubules and is
usually associated with cystic fibrotic liver.
• Death occurs early during infancy due to renal failure.
b. Adult (autosomal dominant) type:
• Common type and occurs in adults due to autosomal dominant in-
heritance.
• Both kidneys are enlarged, the cysts are found in the cortex and
medulla.
• They are variable is size but larger than those of the autosomal
recessive type and contain serous or brownish fluid.
123
124
• The cysts are due to abnormal dilatation of tubules at any level of

the nephrons and collecting ducts, the pressure of the expanding
cysts leads to ischemic atrophy of the intervening renal substance.
• The condition becomes manifest in the third and fourth decades by
gradual renal failure and hypertension.
RENAL LESIONS IN DIABETES MELLITUS
1. Nodular glomerulosclerosis which results in nephrotic syndrome plus dia-

betes mellitus (Kimmelsteil-Wilson syndrome).
2. Thickening of glomerular basement membrane.
3. Hyaline arteriolosclerosis of the basement membrane of the afferent and

efferent arterioles.
4. Pyelonephritis.
5. Necrosis of the renal papillae.
6. Glycogen deposition in the cells of convoluted tubules.
RENAL LESIONS IN HYPERTENSION
1. Benign essential hypertension:

*Gross picture:
• In long standing cases the kidneys are reduced in size, contracted and
firm.
• The surface is finely granular showing retention cysts and the capsule
is adherent.
• The cut surface shows atrophy of the cortex and there is loss of de-
marcation between the cortex and medulla. There is relative increase
of the perinephric fat.
*Microscopic picture:
• The interlobular arteries show fibroelastic thickening of the intima, the

afferent arterioles show hyaline subendothelial material.
Chapter 15. Pathology of different renal diseases 125
• There is fibrosis of the Bowman’s capsule together with thickening of

the glomerular capillary walls followed by atrophy and hyalinosis of the
whole glomeruli.
• The tubules connected to the fibrotic glomeruli undergo atrophy while
those connected to the functioning glomeruli show compensatory di-
latation forming retention cysts.
• There is increased interstitial tissue and infiltration by lymphocytes.
2. Malignant hypertension:
*Gross picture: kidneys are normal in size, the capsule strips easily and
the outer surface is smooth. The vessels are thick, narrow and promi-
nent. The cut surface shows areas of hemorrhage. kidneys are normal
in size or slightly shrunken, depending on the duration and severity of the
hypertensive disease. Small, pinpoint petechial hemorrhages may appear
on the cortical surface from rupture of arterioles or glomerular capillaries
• The interlobular arterioles show concentric subintimal fibrosis, the af-

ferent arterioles show fibrinoid necrosis.
• The Bowman’s capsules show hemorrhage and crescent formation.
Diseases of The Renal Tubules and Interstitial Tissue
Tubulo-interstitial nephritis
*Definition: a condition characterized by some tubular atrophy and fibrosis
as well as infiltration of the interstitial tissues by acute and chronic inflamma-
tory cells.
The glomeruli are normal.
*Causes: Acute bacterial pyelonephritis, drug induced hypersensitivity re-
actions to antibiotics, non-steroidal antirheumatics and diuretics, acute viral
infections and Idiopathic.
Acute tubular necrosis
types
1. Anoxic tubular necrosis:

*Pathology: there is necrosis at multiple hemorrhagic points along the
126
nephron. The tubular lumen is occluded by necrotic tissue and casts.

There is interstitial hyperemia and edema.
2. Toxic tubular necrosis:

*Pathology: proximal convoluted tubules show extensive necrosis and
their lumen is occluded by necrotic tissue.
PYELONEPHRITIS
*Definition: the most common form of renal disease It denotes inflammation

of the renal pelvis and parenchyma. It may be either acute or chronic.
1. Acute pyelonephritis: see chapter 24
2. Chronic pyelonephritis: see chapter 24
URINARY CALCULI (UROLITHIASIS, STONES)
Types and pathology of renal stones (see chapter 22)

Chapter 16
Anatomy and development of urinary bladder and urethra
Urinary Bladder
It is a hollow viscus with strong muscular wall that acts as a reservoir for
urine.
Position
• In children:
- The bladder lies almost in the abdominal cavity.
• At puberty:
- The bladder lies within the lesser pelvis.
• In adult:
- Empty bladder lies in the lower and anterior part of the lesser pelvis
- Distended bladder ascends upwards, may reach the level of the
umbilicus.
Figure 16.1: Position of the urinary bladder in male and female Pelvis.
127
128
Shape
• Distended bladder :
Is spherical or ovoid in shape.
• Empty bladder:
Is in the form of three-sided pyramid having:
– Apex: directed anteriorly and formed by the meeting of the superior

and 2 inferolateral surfaces .
– Base: directed posteriorly and is triangular in shape.
Three surfaces:
- Superior surface; triangular in shape.
- 2 inferolateral surfaces; meet together anteriorly.
Figure 16.2: Different parts and surfaces of the urinary bladder
– Neck: Directed downwards and it lies at the meeting of the base

with the 2 infero-lateral surfaces .
Relations
Apex:
- Lies immediately behind the upper border of the symphysis pubis.
- It is continuous with the median umbilical ligament (obliterated urachus).
Base (fundus):
Its supero-lateral angles receive the ureters.

Chapter 16. Anatomy and development of urinary bladder and urethra 129
In male:
* The upper part is:

Related to the rectum
Separated from it by : Rectovesical pouch,contents of coils of
ileum
* The lower part is:

Related to the rectum
Separated by ampulla of vas deferens and seminal vesicles
In female
It is related directly to the anterior wall of vagina
Figure 16.3: Structures related to the base of urinary bladder in male
Superior surface:
– In male
Related to the sigmoid colon and loops of ileum
– In female
Is related to the vesical surface of uterus.
- Is separated from it by the uterovesical pouch
The posterior end of the superior surface
- Is related directly to the supravaginal part of cervix
Inferolateral surfaces:
Related to the retro-pubic fat (in the space of Retzius)
Neck:
130
It is the lowest and most fixed part of urinary bladder.

It lies 1 inch behind the lower part of symphysis pubis
In male:
- It rests on the upper surface of prostate.
- It gives attachment to the pubo-prostatic ligament
In female
- It rests on the pelvic fascia
- It gives attachment to the pubo-vesical ligament
- It is related posteriorly to the anterior wall of vagina
Ligaments of the urinary bladder:
Median umbilical ligament :

- From the apex of bladder to the umbilicus
Pubo-prostatic and pubovesical ligaments:
– They are 2 on each side of the midline

– In male:Puboprostatic ligaments:
- Extends from the back of the pubic bone to the anterior surface of
the sheath of the prostate .
– In female :Pubovesical ligaments:
- Extends from the back of the pubic bones to the urethra and neck
of the bladder.
Lateral ligaments of the bladder:

- They are 1 on each side of the midline
- Extend from the side of the bladder to the tendinous arch of the fascia
covering obturator internus.
Posterior ligaments:
- They are 1 on each side of the midline
- Extend from the lateral edge of the base of the bladder to the posterior
wall of the pelvis.
- It lodges the veins draining the bladder
Figure 16.4: Different ligaments support the urinary bladder
Interior of the bladder:
• Trigone:
- It is a small smooth triangular area that lies in the posterior wall of the
bladder
- It is bounded by 3 lines joining the 2 ureteric orifices and the internal
urethral meatus.
- Its mucosa is smooth and adherent to the muscle coat
- It is more sensitive & vascular than the rest of bladder
Figure 16.5: The interior of the urinary bladder
• Ureteric orifices:
- They are 2 slits at the postero-superior angle of trigone
- Inter-ureteric crest (ridge):
- It is a transverse ridge at the superior boundary of trigone
- It lies between the two ureteric orifices.
132
• Uvula vesicae:
- It is an elevation of the mucous membrane behind the internal urethral
orifice
- It is produced by the median lobe of prostate.
- With senility, the enlarged prostate produces an enlargement of the
uvula leading to difficulty in micturition.
• Internal urethral meatus:

- An opening situated at the lowest part of the bladder.
- It is surrounded by the sphincter vesicae which is formed of involun-
tary smooth muscle fibers.
Arterial supply of the bladder:
• Superior vesical artery:

- Arises from the proximal patent part of the obliterated umbilical artery .
• Inferior vesical artery:

- Arises from the anterior division of the internal iliac
- This artery is replaced by the vaginal artery in female
Venous drainage of the bladder:
- The veins of the bladder form the vesical venous plexus on each infero-
lateral surface
- This plexus communicates inferiorly with :

In male ; the prostatic venous plexus
In female ; the vaginal venous plexus
- Final drainage is to the internal iliac veins.
Nerve supply:
Arises from the pelvic plexuses
Sympathetic ( T11,12 & L1,2 ):

- Inhibitory to the detrusor muscle
- Stimulant to the sphincter vesicae.
Parasympathetic ( S2 , 3 & 4 ):
- Motor to the detrusor muscle
- Inhibitory to the sphincter vesicae.
Sensory:
- Conveys the sense of distension and pain.
- The majority pass through the pelvic splanchnic nerve
- Some fibers travel via the hypogastric plexus.
Figure 16.6: Nerve supply of the urinary bladder
Male Urethra
Shape & length:

- It is a long S shaped canal (20cm long) which conveys urine and semen
to the outside of the body.
Extension:
- From the internal urethral meatus at the neck of the urinary bladder to
the external urethral meatus at the tip of glans penis
Figure 16.7: Different parts of male urethra

134
Divisions: divided into 3 parts:
1. Prostatic urethra:
Begins at the neck of the bladder. It is about 1 inch long
It is the widest and most dilatable part of the urethra.
It passes through the substance of the prostate
The posterior wall shows the following features :
* The urethral crest:

- It is a median longitudinal spindle shaped ridge
* The prostatic sinuses :

- The shallow grooves along the sides of urethral crest that
receive the openings of prostate gland
* The seminal colliculus

- It is a rounded elevation at the middle of urethral crest
- It has 3 openings:
1 Opening of the prostatic utricle
2 Openings of the ejaculatory ducts on each side
Figure 16.8: Structures in the posterior surface of prostatic urethra in male
2. Membranous urethra:
It is about ½ an inch long.
It is the narrowest and least dilatable part of urethra.
It passes vertically downwards
It is surrounded by the external urethral sphincter
3. Spongy (penile) part:
It is the longest part of urethra , about 6 inches long
It passes through the bulb of penis and the corpus spongiosum

and ends at the external urethral meatus .
It receives the openings of the ducts of the bulbo-urethral glands
External urethral orifice:
- It is the narrowest part of the whole urethra.
Sphincters of the urethra:
Internal urethral sphincter
Site :
-Lies in the pelvis around the internal urethral orifice and the neck of
bladder .
Structure
-Formed of involuntary smooth muscle fibers
Nerve supply
-Autonomic fibers from inferior hypogastric plexus
Function
-It is well developed in male than in female.
-It acts involuntary. It maintain continence of urine and prevents
reflux of semen into the urinary bladder
External urethral sphincter
Site
-Lies in the perineum around the membranous urethra in the deep
perineal pouch
Structure
-Formed of striated muscle fibers
Nerve supply
- Somatic from the perineal branch of pudendal nerve
Function
- It is well developed in male and female.
- It acts voluntary.
- It maintain continence of urine
136
Figure 16.9: The internal and external urethral sphincter
Female Urethra
It is about 4cm long.
It is wider , (6 mm in diameter ) and more dilatable than the male ure-

thra.
It begins at the internal urethral meatus.
It is embedded in the anterior wall of the vagina.
It descends downwards and forwards traversing the deep and superficial

perineal pouches.
It ends at the external urethral meatus in the vestibule in front of the

vaginal orifice.
Figure 16.10: Course of female urethra in the pelvis

Development of the urinary Bladder
• The cloaca is a dilatation in the terminal part of the hindgut. Its floor is
closed by the cloacal membrane.
• The cloaca receives three openings: The allanto-enteric diverticulum

ventrally and the mesonephric duct on each side.
• During the 4th and the 7th weeks of development, a septum of meso-
derm (the urorectal septum) divides the cloaca into the anorectal canal
and primitive urogenital sinus.
• The cloacal membrane itself is then divided into urogenital membrane

anteriorly and the anal membrane posteriorly
Figure 16.11: The cloaca and its divisions
• The primitive urogenital sinus receives the allanto-enteric diverticulum

and the two mesonephric ducts.
• The entrance of the distal ends of the mesonephric ducts into the primi-
tive urogenital sinus divides it into:
1. Upper part called the vesico-urethral canal.

2. Lower part called the definitive urogenital sinus
138
which is further subdivided into:
a. Pelvic part
b. Phallic part which is closed by the uro-genital membrane.
In male, the vesicourethral canal gives rise to:
1) Major part of the urinary bladder
2) The upper part of the urethra above the prostatic utricle.

In female, the vesico urethral canal gives rise to:
1) Major part of the urinary bladder except the trigone.
2) Nearly the whole of the female urethra
Figure 16.12: The formation of vesicourethral canal and definitive urogenital sinus
• The caudal ends of the mesonephric ducts become absorbed into the
lower part of the bladder, so that the ureters and ducts have individual
openings in its dorsal wall.
• With differential growth of the dorsal bladder wall, the ureters come to
open through the lateral angels of the bladder and the mesonephric
ducts open close together in the future urethra.
Figure 16.13: Absorption of the mesonephric ducts and formation of the trigon of the urinary
bladder
So the urinary bladder is developed from 4 sources
1. The greater part of the urinary bladder is developed from the upper part
of the vesico-urethral canal.
2. The apical part is developed from the proximal part of the allanto-enteric
diverticulum.
3. The distal part of the diverticulum is called urachus which becomes oblit-
erated and fibrosed to form the median umbilical ligament.
4. The trigone of the bladder:

- Is mesodermal in origin in contrast to the remaining part which is endo-
dermal.
Congenital anomalies of the urinary bladder:
1. Urachal fistula:
- The allantois fails to become obliterated and the urine passes out of the
patent urachus to the umbilicus
2. Urachal cyst:
- Occurs when a localized area of the allantois persists.
3. Urachal sinus:
- The proximal part of the urachus is obliterated and fibrosed, while its
distal part remain patent.
- This leads to the formation of a sinus which discharge serous fluid through
the umbilicus
Figure 16.14: Different anomalies of urachus

140
4. Ectopia vesica:
- Occurs when the posterior wall of the urinary bladder is exposed to the
exterior.
- It is caused by the failure of the anterior abdominal wall and anterior wall
of the bladder to develop.
- This defect is due to inability of the mesoderm of the primitive streak to
migrate around the cloacal membrane.
Figure 16.15: Ectopia vesica anomalies of urinary bladder
Development of the urethra
In female
The urethra develops from the vesico-urethral canal
In male
The urethra is formed of many parts which develop from different regions.
= The upper part of the prostatic urethra (above the prostatic utricle)
develops from the vesico-urethral canal
= The lower part of the prostatic urethra and the membranous urethra
develop from the pelvic part of the definitive urogenital sinus.
= The penile urethra develops from the phallic part of the definitive uro-
genital sinus.
Figure 16.16: The origin of the different parts of male urethra
Congenital anomalies of urethra
1. Hypospadias
Hypospadias is the most common congenital anomaly affecting the male
urethra. The external meatus is situated on the ventral or undersur-
face of the penis anywhere between the glans and the perineum. Five
degrees of severity may occur, the first of which is the most common: (1)
glandular, (2) coronal, (3) penile, (4) penoscrotal, and (5) perineal. In all
except the first type, the penis is curved in a downward or ventral direction,
a condition referred to as chordee
2. Epispadius
The urethra opens in the dorsal aspect of penis between the glans and
the anterior abdominal wall. The most severe type is associated with
exstrophy of the bladder. It is caused by failure of the embryonic mes-
enchyme to develop in the lower part of the anterior abdominal wall, so
that when the cloacal membrane breaks down the urogenital sinus opens
onto the surface of the cranial aspect of the penis
142
Chapter 17
Histology of excretory passages
- They are formed of minor calyces, major calyces, renal pelvis, ureter, uri-
nary bladder and urethra.
- Their walls consist of three layers:
1. Mucosa, which consists of:
a. Epithelium: Transitional epithelium (urinary epithelium).

b. Lamina propria: Formed of loose connective tissue.
2. Muscle layer of smooth muscle that becomes thicker from minor calyces
to the renal pelvis.
3. Adventitia: A connective tissue layer covering the urinary passages ex-

cept for the upper part of the urinary bladder which is covered by peri-
toneum.
URETER
- It starts from renal pelvis and ends in urinary bladder.

- It has thin wall and its lumen is stellate or star shaped.
Histological structure Figure 17.1
1. Mucosa: is thrown into longitudinal folds and consists of:
a. Epithelium: transitional
b. Lamina propria: is formed of dense CT, blood vessels and lymphatic
nodules.
2. Muscle layer is formed of smooth muscles arranged in the upper two

thirds of ureter as inner longitudinal and outer circular, and in the lower
third there is an additional outer longitudinal layer.
3. Adventitia is formed of fibroblastic CT.
143
144
Figure 17.1: Ureter
URINARY BLADDER
Histological structure Figure 17.2
1. Mucosa is arranged in numerous folds which disappear when the bladder
becomes distended with urine. It consists of:
a. Urothelium or Transitional epithelium:.

It is a special type of stratified epithelium where the numbers of
layers are changeable according to the state of the organ distended
or empty.
In the empty bladder the transitional epithelium has several layers
(6-8 layers) and in distended bladder the epithelium has two or three
layers.
The superficial cells (dome-shaped or umbrella cells):
- They are large polyhedral cells with one or two nuclei that bulge
into the lumen.
-These cells are highly differentiated to protect the underlying cells
against cytotoxic effect of urine (blood-urine barrier).
- During distention the large dome-shaped cells become stretched
and flattened.
The intermediate cell layer contain pear-shaped cells that are con-
nected to each other and to the overlying domes shaped cells by
desmosomes.
Chapter 17. Histology of excretory passages 145
The basal cell layer consists of small cells that bind to the base-
ment membrane with hemidesmosomes. This layer contains stem
cells for the urothelium.
b. Lamina propria: It is wide and formed of superficial and deep connec-
tive tissues.
The accommodation of the superficial cell shape:
• The unique upper cell plasma membrane composed of specialized
rigid thickened regions called rigid plaques interposed by normal
membrane regions called interplaque regions.
• When the bladder is empty the plaque regions are folded inside the
cytoplasm into irregular angular contour which disappear when the
cells become stretched (Figure. 17.3)
2. Muscular layer is thick and formed of ill-defined three layers arranged into
inner and outer longitudinal and middle circular layers, collectively called
detrusor muscle.
3. Adventitia is formed of dense connective tissue. The upper surface of the

bladder is covered by peritoneum.
Figure 17.2: Transverse section of Urinary Figure 17.3: Superficial cells of transitional
Bladder epithelium
146
URETHRA
Urethra of female differs from urethra of male in structure and in length.

Urethra of female:
Histological structure:
1. Mucosa:
a. Epithelium: It is lined with transitional epithelium near urinary bladder

at the internal orifice, stratified squamous at the external orifice and in
between with stratified columnar epithelium.
b. Lamina propria is fibroelastic along its length.
2. Muscle layer: is arranged in the form of inner longitudinal and outer cir-
cular smooth muscle. As the urethra pierces the uro-genital diaphragm,
skeletal muscle forms an external sphincter around the urethra that gives
voluntary control of micturition.
Urethra of male:
- It consists of three parts:
1. Prostatic urethra
• It is lined by transitional epithelium
2. Membranous urethra: Lined by stratified columnar epithelium interposed

with patches of pseudostratified columnar epithelium.
3. Penile urethra: It is the longest part of the urethra
a. Bulbous urethra:
• lined by pseudostratified or stratified columnar epithelium
b. Pendulous urethra:
• Pendulus urethra is lined mostly by stratified squamous epithelium
Chapter 18
Physiology of urinary bladder
Functions of the urinary bladder
I. It acts as a reservoir.
II. Micturition.
I. It acts as a reservoir.
I Urine enters the bladder without producing much increase in the in-
travesical pressure till the bladder becomes well-filled.
I This is due to:
a. Plasticity of the Detrusor muscle:
Like other smooth muscles, when this muscle is slowly stretched
) the tension that initially produced is not maintained.
b. Laplace’s law:
I This law states that: the pressure in a spherical viscus equals
twice the wall tension divided by its radius (P=2T/r).
I As the urinary bladder fills) the tension & radius increase
together and the intravesical pressure increase only slightly.
I But, at certain volume ) the tension markedly increase & the
intravesical pressure increase sharply.
I The relation between the intra-vesical pressure and bladder
volume can be recorded as curve (cystometrogram) which
composed of 3 components:
1. Stage I a:
V The curve shows an initial slight rise in pressure up to
10 cm 3H2O, when the first increase in volume is produced
by about 10-50 ml.
147
148
2. Stage I b:
V Nearly flat segment, as further volume increase.
V This phase is adjusted by Laplace law.
3. The stage II: VSudden sharp rise in pressure which give
the first sensation of fullness at 300- 400 ml.
I The urethral sphincters resist a pressure of 70-100 cm 3H2O.
I The pressure within the bladder rise up to 130 cm 3H2O at the
start of micturition.
Figure 18.1: Cystometrogram
Urinary bladder sensations:
a. The first desire for micturition:

• It is felt at a bladder volume of about 150ml.
• It can easily be voluntarily inhibited.
b. The sense of bladder fullness:
• This normally initiates reflex micturition.
• It is felt at a volume of 300-400ml.
• It can also be voluntarily inhibited.
c. A sense of bladder discomfort:
• It is felt at volumes between 400 - 600ml.
• The micturition reflex can still be voluntarily inhibited.
d. A sense of bladder pain:
• It is felt at volumes exceeding 600ml.
• It can hardly be voluntarily inhibited.
Chapter 18. Physiology of urinary bladder 149
• When, the volume becomes about 700ml ) (urination become

urgent & obligatory micturition occurs).
II. Micturition.
A. Unconditioned micturition: V Increase of the intravesical pressure

) leads to the following reflexes (spinal reflexes):
1. Rise of the intravesical pressure:
• Leads to contraction of the detrusor muscle.
• Its afferent & efferent nerves are present in the pelvic nerves.
• Its center is the LHCs of 2, 3, &4 sacral segments in the spinal
cord.
• Leads to relaxation of the internal urethral sphincter.
• Its afferent & efferent nerves and its center are the same as
in reflex 1.
• Leads to relaxation of the external urethral sphincter.
• Its afferent nerves are present in the pelvic nerves.
• Its efferent nerves are present in the pudendal nerves.
• Its center is the AHCs of 2, 3, & 4 sacral segments in the
spinal cord.
4. Flow of urine through the urethra:
• Leads to more contraction of the detrusor of muscle.
• Its afferent nerves are present in the pudendal nerves.
• Its efferent nerves are present in the pelvic nerves.
• Its center is the LHCs of 2, 3, &4 sacral segments in the spinal
cord.
• Leads to further relaxation of the internal urethral sphinc-
ter.
• Its afferent & efferent nerves and its center are the same as
in reflex 4.
150

• Leads to further relaxation of the external urethral sphinc-
ter.
• Its afferent & efferent nerves are present in the pudendal
nerves.
• Its center is AHCs of 2, 3, &4 sacral segments in the spinal
cord.
B. Voluntary (conditioned) micturition:
The reflex micturition is spinal reflex.
So, it is adjusted by supraspinal facilitatory & inhibitory im-
pulses as follow:
i. Facilitatory:
1. In pontine area.
2. In the hypothalamus.
ii. Inhibitory:
1. In the mid brain.
2. In some suppressor areas of cerebral cortex.
The role of higher centers in controlling micturition include the
follow:
1. Supraspinal inhibition which is powerful control for the spinal
center.
2. The supraspinal inhibition is increased and inhibits micturition
) when the condition is unfavorable.
3. It can stop micturition even after its start.
4. Facilitate the sacral centers ) when the condition is favorable.
5. Inhibition of the external urethral sphincter during micturition.
6. Voluntary increase in the intraabdominal pressure during mic-
turition.
Chapter 19
Nucleotide Metabolism
Nucleotides, nucleosides, and deoxynucleotides

Nucleotides are composed of a base, a sugar, and phosphate. In the nucleo-
side, the nitrogenous base is linked to a sugar, either ribose or deoxyribose.
In deoxynucleotides, the prefix “d” precedes the abbreviation. For example,
dATP is deoxyadenosine triphosphate (the base adenine attached to a de-
oxyribose with three phosphate groups).
Figure 19.1: Nucleotides
- Because of the minimal dietary uptake of these important molecules,

nearly all organisms synthesize purines and pyrimidines de novo (“a
new”).
- Many organisms also "salvage" purines and pyrimidines that allow the
reuse of the preformed bases resulting from normal cell turnover or to a
much less extent from the diet.
151
152
Purine Metabolism
De novo purine nucleotides biosynthesis:

The purine bases are produced de novo by pathways that use amino acids
as precursors and produce nucleotides. Most de novo synthesis occurs in
the liver, and the nitrogenous bases and nucleosides are then transported to
other tissues by red blood cells.
Sources of atoms in the purine ring:

The atoms of the purine ring are contributed by: the amino acids aspartic
(N1), glycine (C4, C5, N7), and glutamine (N3, N9), CO2 (C6) and derivatives
of tetrahydrofolic acid (C2,C8).
Figure 19.2: Source of atoms in the purine ring
Steps of purine biosynthesis:
Synthesis of IMP:
– As purines are built on a ribose base. 5-Phosphoribosyl-1-pyrophosphate

(PRPP) is the activated source of the ribose moiety. It is synthesized
from ATP and ribose 5-phosphate, which is produced from glucose
through the pentose phosphate pathway, catalyzed by PRPP syn-
thetase.
– In the first committed step of the purine biosynthetic pathway, PRPP
reacts with glutamine to form phosphoribosylamine. This reaction,
produces nitrogen 9 of the purine ring, and is catalyzed by glutamine
phosphoribosyl amidotransferase, a highly regulated enzyme.
– In the next step of the pathway, the entire glycine molecule is added
to the growing precursor. Glycine provides carbons 4 and 5 and
nitrogen 7 of the purine ring. Subsequently, carbon 8 is provided
Chapter 19. Nucleotide Metabolism 153
by N10-methenyl FH4, nitrogen 3 by glutamine, carbon 6 by CO2,

nitrogen 1 by aspartate, and carbon 2 by formyl tetrahydrofolate.
– Six molecules of ATP are required to synthesize the first purine nu-
cleotide, inosine monophosphate (IMP). This nucleotide contains
the base hypoxanthine.
Figure 19.3: Synthesis of IMP
Conversion of IMP to AMP:

- Addition of aspartate to IMP forms adenylosuccinate using the enzyme
adenylsuccinate synthetase. Then ,release of fumarate forming adeno-
sine 5‘-monophosphate (AMP) is catalyzed by adenylsuccinase.
Conversion of IMP to GMP:

- Oxidation of IMP by NAD, catalyzed by IMP dehydrogenase forms xan-
thosine monophosphate (XMP), then transamination by the amide nitro-
gen of glutamine forms guanosine monophosphate (GMP).
- Conversion of AMP and GMP to their respective nucleoside di- and

triphosphates involves successive phosphoryl transfer from ATP, cat-
alyzed by nucleoside monophosphate kinase and nucleoside diphos-
phate kinase respectively.
154
Biosynthesis of deoxyribonucleotides:
-The nucleotides required for DNA synthesis are 2‘-deoxyribonucleotide, which
are produced from ribonucleoside diphosphate by direct reduction at 2‘-carbon
in the ribose moiety, catalyzed by the ribonucleotide reductase complex. Re-
duction requires thioredoxin (a protein cofactor), thioredoxin reductase (a
flavoprotein) and NADPH.
Figure 19.4: Step of reduction in deoxyribonucleotide biosynthesis
Regulation of purine biosynthesis:
a. The major determinant of the overall rate of de novo purine nucleotide

biosynthesis is the concentration of PRPP intracellularly.
b. PRPP amidotransferase is sensitive to feedback inhibition by purine nu-

cleotides (AMP, GMP). These are competitive inhibitor of the substrate
PRPP.
c. Inhibiting formation of tetrahydrofolate compounds can block purine syn-

thesis (e.g. by using the anticancer medication “Methotrexate”).
d. AMP feedback regulates adenylosuccinate synthetase, and GMP feedback-

inhibits IMP dehydrogenase.
Purine salvage pathway:
- Most of the de novo synthesis of the bases of nucleotides occurs in the

liver. Within the liver, nucleotides can be converted to nucleosides or
free bases, which can be transported to other tissues.
- In addition, the small amounts of dietary bases or nucleosides that are

absorbed also enter cells in this form. Most cells can re-use these bases
to generate nucleotides for RNA and DNA synthesis. This is referred to
as “salvage pathway” for purine, that require far less energy than does
de novo synthesis. The salvage pathway occurs primarily in extrahepatic
tissues.
The most important mechanism involves phosphoribosylation of a free

purine base by PRPP, forming a purine 5‘-mononucleotide catalyzed
by 1-adenine phosphoribosyltransferase (converts adenine to AMP). 2-
hypoxanthine guanine phosphoribosyltransferase (HGPRT) (converts hy-
poxanthine or guanine to IMP or GMP).
Figure 19.5: Salvage pathway for purines
A second salvage mechanism involves direct phosphorylation of purine

ribonucleoside by ATP using kinase enzyme.
PURINE CATABOLISM
- Uric acid is the end product of purine catabolism.
- Adenosine is first deaminated to inosine by adenosine deaminase, then

phosphorolysis of N-glycosidic bonds of inosine and guanosine, cat-
alyzed by purine nucleoside phosphorylase, release ribose 1-phosphate
and a purine base.
156
- Hypoxanthine and guanine next form xanthine in reactions catalyze by

xanthine oxidase and guanase, respectively. Xanthine is then oxidized
to uric acid in a reaction catalyzed by xanthine oxidase.
Figure 19.6: Purine catabolism
Disorders of Purine Metabolism:
1. Hyperuricemia: is the presence of high levels of uric acid in the blood,

which may progress to gouty arthritis if uric acid is deposited in joints and
surrounding soft tissues. Hyperuricemia may be produced by overproduc-
tion or underexcretion of uric acid by the kidneys. Hyperuricemia and gout
often accompany the following conditions:
• HGPRT deficiency (Lesch-Nyhan syndrome).

• Increased activity of PRPP synthetase.
• Purine-rich diet: A diet rich in meats, organ foods and alcohol.
• Increased nucleic acid turnover: as in hemolytic anemia and lym-
phoma.
• Some glycogen storage disease such as von Gierke’s disease.
2. Lesch-Nyhan Syndrome: is an X-linked recessive condition involving

deficiency of HGPRT activity, hyperuricemia, mental retardation, spastic
cerebral palsy with compulsive biting of hands and lips, death often oc-
curs in the first decade.
3. Adenosine deaminase (ADA) deficiency: It is an autosomal recessive

disorder, causes a type of severe combined immunodeficiency (SCID).
Lacking both B-cell and T-cell function, children are infected with many
organisms and do not survive without treatment.
Pyrimidine Metabolism
Sources of atoms for pyrimidine ring: The sources of atoms of pyrimidine

ring are carbamoyl phosphate and aspartic acid.
Figure 19.7: Sources of atoms for pyrimidine ring
Steps of pyrimidine nucleotides biosynthesis:
1. Pyrimidine biosynthesis begins with the formation of carbamoyl phosphate

from glutamine, ATP and CO2. This reaction is catalyzed by cytosolic car-
bamoyl phosphate synthetase (CPS II), committed step in mammals in-
cluding human.
N.B. Unlike the purine ring, the pyrimidine ring is synthesized before being
attached to ribose-5-phosphate, which is donated by PRPP.
2. Condensation of carbamoyl phosphate with aspartate forms carbamoyl

aspartate in a reaction catalyzed by aspartate transcarbamoylase.
3. Ring closure via loss of water, catalyzed by dihydroorotase, forms dihy-

droorotic acid.
4. Abstraction of hydrogens from C5 and C6 by NAD+ introduce a dou-

ble bond, forming orotic acid, a reaction catalyzed by mitochondrial dihy-
droorotate dehydrogenase. All other enzymes of pyrimidine biosynthesis
are cytosolic.
158
5. Transfer of a ribose phosphate moiety from PRPP forming orotidine monophos-

phate (OMP), which is catalyzed by orotate phosphoribosyl transferase.
6. Decarboxylation of orotidylate forms uridine monophosphate (UMP), the

first true pyrimidine ribonucleotide.
Figure 19.8: Steps of pyrimidine nucleotides biosynthesis
N.B.: The reaction catalyzed by CPSII is inhibited by UMP and stimulated by PRPP.
Pyrimidine catabolism:
Catabolism of pyrimidine occurs mainly in the liver to CO2, NH3,
-alanine
and
-aminoisobutyrate.
Clinical disorders of pyrimidine metabolism
Orotic aciduria: It is a genetic disorder caused by deficiency of:
1. Orotate phosphoribosyltransferase.
2. Orotodylic acid decarboxylase (OMP decarboxylase).
• So, orotic acid becomes accumulated in the blood and excreted in

urine.
• Characterized by: Growth retardation, mental retardation, and ane-
mia.
• Oral uridine and cytidine can treat this clinical disorder.
Chapter 20
Imaging of urinary system
Methods of Imaging of the Urinary Tract
1. Plain radiography (PUT/KUB)
2. Intravenous Urography (IVU)
3. Ascending Urography
4. Ultrasound
5. Angiography
6. Computed tomography
7. MRI
8. Nuclear Imaging studies
PLAIN RADIOGRAPHY OF THE URINARY TRACT (PUT)
Synonym: KUB (Kidney Ureter Bladder)
• Used as a general evaluation of the abdomen or the urinary tract
• Serve a role as preliminary films (scouts) prior to an examination such

as an intravenous urography
PUT should include:
• Last 2 or 3 dorsal vertebra and the lower 2 ribs
• One inch below the symphisis pubis
Evaluate:
• Abnormalities in the skeleton
159
160
• Soft tissue margins of the renal outline, liver, spleen, and psoas regions
• The gas pattern in the bowel
• Calcifications.
Of particular interest are those calcifications that project or overlie the

region where you expect to find kidneys, ureters, and bladder
Figure 20.1: Showing normal PUT with important Landmarks on PUT (open arrows point to
the normal renal soft tissue shadow “outline”)
INTRAVENOUS UROGRAPHY (IVU)
Also known as intravenous pyelography (or more commonly, the IVP)
• IVU remains an important study for some urinary tract disease pro-
cesses.
Technique:
• Bowel preparation by clear liquids and laxatives.
• Scout KUB.
Detection of calcifications (which may be obscured after contrast

material is injected)
Assurance of proper technique (patient positioning, exposure pa-
rameters, proper patient preparation) prior to contrast administration
Exclusion of contraindications to the study (retained barium, etc.).
Chapter 20. Imaging of urinary system 161
• Intravenously injected iodinated contrast (excreted primarily by glomeru-

lar filtration in the kidney causing opacification of the urinary tract)
• Sequential radiographs are taken after contrast injection.
Nephrogram: a few minutes (1-5 mins) after contrast administration
Pelvicalyceal system: 5-10 minutes after contrast administration
Ureters: 10 -20 mins.
Urinary bladder: 30 mins.
Post voiding film: after bladder emptying

Evaluate:
Kidneys Ureters Urinary bladder
Site, size, shape Caliber Site, size (volume), shape
Renal collecting sys- Course Masses (filling defects)
tem (size, shape, fill- Filling defects Diverticulae
ing defects) Residual urine volume
CONTRAINDICATIONS:
• Sensitivity to contrast material
• Impaired renal function (It is advisable to do renal function testing prior

to any study where IV contrast administration is required as its main
excretion is by the kidneys)
• Pregnancy
Figure 20.2: showing normal IVU with important Landmarks on the IVU
162
RETROGRADE PYELOGRAPHY/CYSTOGRAPHY/ URETHROGRAPHY

- Direct injection of water-soluble iodinated contrast material
- Retrograde pyelography
Performed by placing a small catheter into the distal ureters (By cystscopy).
Contrast material is then injected through this catheter into one or both
ureters.
Fluoroscopy and conventional radiographs should then be obtained.

- Cystogram (UB)
A catheter is placed into the bladder and contrast material is then in-
jected.
- Urethrography
Could be evaluated during voiding, often following a cystogram (voiding
cystourethrogram or VCUG).
Retrograde study may be performed (Ascending urethrogram by injec-

tion of contrast through the urethral opening).
Figure 20.3: showing normal (A)Ascending and (B)Voiding uretherogram with important
Landmarks on the film (PU: Penile urethra, BU: Bulbar urethra, B: Bladder)
Chapter 20. Imaging of urinary system 163
ULTRASONOGRAPHY
- Ultrasonography is a useful technique for evaluation of the urinary tract,
Ease of use and availability, non-invasive
Lack of complications (no contrast material or ionizing radiation).
COMPUTED TOMOGRAPHY
CT is now the dominant radiologic imaging modality for evaluation of the

urinary tract.
- CT scans of the urinary tract may be performed
With intravenous iodinated contrast material depending on the indica-

tions.
Without intravenous iodinated contrast material
Or both one after the other (i.e. Precontrast then Postcontrast

scan)
Noncontrast studies (CT urography)
To evaluate stone disease and other calcifications.

Serve as a baseline to evaluate for lesion enhancement after con-
trast administration, a critical factor in mass evaluation.
MAGNETIC RESONANCE IMAGING
- Just like CT, technical advances in magnetic resonance (MR) imaging have
led to increasing use in urinary imaging.
Advantages
• Multiplaner imaging (Axial, Coronal and Sagittal Imaging)
• Lack of ionizing radiation
• MRU is a study which can be used for evaluation of the urinary tract giv-
ing images like those of IVU without the use of contrast material (Bene-
ficial in patients with renal failure where IV contrast is contraindicated)
164
Disadvantages
- Cost
- Contraindication (e.g. pacemaker, metallic prosthesis)
NUCLEAR MEDICINE
Its main role is to asses renal function through obtaining data which can be
quantified. The patient is injected by a radio-active isotope which is excreted
by the kidney. The exact dose of radiation emitted by the kidney could be
calculated and plotted hence giving an idea about the renal function.
Chapter 21
Urinary tract symptoms
Pain
Pain arising from the GU tract may be quite severe and is usually associated
with either:
Urinary tract obstruction or Inflammation
Large non-obstructing stone Vs Small obstructing stone
• Inflammation of the GU tract usually cause severe when it involves the

parenchyma of a GU organ due to edema and distention of the capsule.
• Thus pyelonephritis, prostatitis, and epididymitis are typically quite painful.
• Inflammation of the mucosa of a hollow viscus such as the bladder or

urethra usually produces discomfort, but the pain is not so severe
• Tumors in the GU tract usually do not cause pain unless they produce
obstruction or extend beyond the primary organ to involve adjacent nerves.
• Thus pain associated with GU malignancies is usually a late manifesta-

tion and a sign of advanced disease
I. Renal pain: Caused by acute distension of the renal capsule e.g:
• acute pyelonephritis (steady pain)

• ureteral obstruction (fluctuates in intensity)
• Slowly progressive renal disease (e.g. polycystic kidney, cancer,
chronic pyelonephritis and staghorn stones) may be painless.
Character: Dull aching and constant

Site: Ipsilateral costovertebral angle. May radiate across the flank to-
wards upper abdomen and umbilicus, lower abdominal quadrant or testis
165
166
(in males)
Associated symptoms: GIT symptoms in the form of pain, distension,
nausea and vomiting (reflex celiac ganglion stimulation and peritoneal
irritation)
II. Ureteral colic:

Caused by acute ureteric obstruction (passage of stone or blood clot) )
spasm of renal pelvis and ureteric muscle.
Character: Sever colicky pain (patient is rolling in bed), accompanied
by renal dull ache.
Site: it’s a radiating pain felt from the costovertebral angle along the
course of the ureter to the suprapubic region and referred according to
irritation of the genitofemoral nerve to ipsilateral groin and scrotum.
Associated symptoms: similar to renal pain.
Lower Urinary Tract Symptoms (LUTS)
Irritative Symptoms (Storage Symptoms)

Dysuria is painful urination that is usually caused by inflammation.
Urgency is a sudden desire of micturation at an unsuitable time and place.
Strangury is an intense discomfort or pain associated with passage of small
amounts of urine.
Precipitancy means that the patient can not withhold the urine aganist the
desire.
Frequency The normal adult voids 3 to five times per day and 0 to1 time per
night.
• Increase frequency with large amounts means polyuria and should be

evaluated for diabetes mellitus, diabetes insipidus, or excessive fluid in-
gestion.
• Increased frequency with normal or low amounts means bladder irritabil-

ity (infection, stones, BPH, neurogenic bladder)
Nocturia is nocturnal frequency.
• Nocturia with increased urine output as in polyurea (D.M)
• Nocturia with normal urine output in BPH

Chapter 21. Urinary tract symptoms 167
Obstructive Symptoms (Voiding Symptoms)
• Decreased force and caliber of urination is usually secondary to blad-

der outlet obstruction and commonly results from benign prostatic hyper-
plasia (BPH) or a urethral stricture.
• Weak stream and prolonged voiding time are usually due to myogenic
or neurogenic causes in the bladder or due to bladder outlet obstruction.
• Urinary hesitancy refers to difficulty in starting the act of micturation. in

bladder outlet obstruction.
• Intermittency refers to difficulty in maintaining the act of micturation (in

BPH)
• Postvoid dribbling refers to difficulty in ending the act of micturation is

often an early symptom of urethral obstruction related to BPH.
• Straining refers to the use of abdominal musculature to urinate. Nor-

mally, it is unnecessary for a man to perform a Valsalva maneuver ex-
cept at the end of urination. Increased straining during micturition is a
symptom of bladder outlet obstruction.
• Bifurcation of the urinary stream, indicates uretheral pathology e.g.

stone.
• Interruption of the urinary stream, indicates mobile stone in the blad-

der.
• Double micturation, means passage of gush of urine after the act has
been completed and indicates bladder diveticulum.
• Urinary Retention: This means inability to evacuate a full bladder,

which may be acute urinary retention; chronic urinary retention or re-
tention with overflow.
• Acute urinary retention: defined as inability to pass urine at all, it has

a sudden onset and accompanied by severe agonizing suprapubic pain.
• Chronic urinary retention: defined as the presence of postvoiding

residual urine in the bladder.
168
• Retention with overflow (paradoxical incontinence): in which urine

may dribble out in small amounts as the bladder overflows.
Incontinence
Urinary incontinence is the involuntary loss of urine. Urinary incontinence

can be subdivided into four categories (see chapter 31)
Enuresis (automatic voiding)
It occurs normally in children up to 3 years of age but persists in about 15%

of children at age 5 and about 1% of children at age 15. Enuresis must be
distinguished from continuous incontinence, which in a young girl, usually
indicates the presence of an ectopic ureter.
Changes in the gross appearance of urine:
1. Cloudy urine:
• Crystalluria
• Pyuria means presence of more than 5 WBCs/ high power field in
urine.
• Chyluria means the presence of lymphatic fluid or chyle and is noted
by the patient as passage of milky white urine. Chyluria represents a
lymphatic urinary system fistula. The fat in the chyle is stained with fat
stains and extracted with ether.
• Proteinuria: presence of proteins in urine. It coagulates by heating
the mouth of the test tube.
2. Hematuria see chapter 30
3. Pneumaturia Is the passage of gas in the urine. due to
1. A fistula between the intestine and the bladder. Common causes in-
clude diverticulitis, carcinoma of the sigmoid colon, and regional enteri-
tis (Crohn’s disease).
2. infection with gas forming organisms.
3. Iatrogenic after catheter and cystoscopy.
Chapter 21. Urinary tract symptoms 169
4. Necroturia Means passage of necrotic tissues per urethera In cases of

neoplasms.
Changes in urine volume
• Oliguria means deceased urine output below 400 cc/day.
• Anuria means complete cessation of urine formation or urine output be-

low 100 cc/day.
• Polyuria means increased amount of urine output above 3500 cc/day.
Urethral Discharge
Urethral discharge is the most common symptom of venereal infection. A

purulent discharge that is thick, profuse, and yellow to gray is typical of gono-
coccal urethritis; the discharge in patients with nonspecific urethritis is usu-
ally scant and watery. A bloody discharge is suggestive of carcinoma of the
urethra.
General symptoms:
• General manifestation of infection of parenchymatous organs. (fever,

malaise and GIT symptoms)
• General manifestation of malignancy (cachexia, loss of weight and ane-

mia)
• General manifestation of uremia

170
Chapter 22
Urolithiasis (Urinary Calculi)
Stone disease is very common worldwide, with overall male to female ratio
2:1, renal stones usually occur in the upper urinary tract while bladder stones
are usually associated with stasis, abnormal flow, infection and presence of
nidus for stone formation
Stone types
Calcium oxalate 73% Uric acid 7%

Calcium phosphate 8% Cystine 1%
Struvite 9% Others 2%
Pathology
1- Calcium stone: composed of calcium oxalate and/or calcium phosphate.

It is hard in consistency, rough surface which causes injury and bleeding,
and brown in color due to blood pigments.
2- Calcium magnesium ammonium phosphate stone (mixed stone): sec-

ondary stone, friable, soft in consistency and has smooth white surface.
3- Uric acid stone: hard in consistency, light brown in color and smooth
outer surface. A Large urate stone may develop in the renal pelvis and
calyces and it is known as stag horn stone.
4- Cystine stone: very rare, yellowish and waxy.
Risk factors:
• Living or working in a hot environment and dehydration
• Metabolic: hypercalcemia, hypercalciuria, hyperoxaluria, hyperuricemia,

hyperuricosuria and cystinuria
171
172
• Recurrent urinary tract infections, renal tubular acidosis, polycystic kid-

neys
• Drugs: as loop diuretics, vitamin D and C, indinavir and sulfadiazine
Many people have none of these and develop stones (Idiopathic stone for-
mers)
Factors predisposing to stone formation in idiopathic stone formers
• Supersaturation of urine with ions of crystal components
• Modifiers of crystallization such as promoters, inhibitors, and matrix
• Intra-renal anatomic sites of crystal retention and growth
Examples of modifiers
INHIBITORS: Citrate, Magnesium, Nephrocalcin, Pyrophosphate, Glycosamino-
glycans, Osteopontin, Crystal matrix protein
PROMOTERS: Matrix, Tamm-Horsefall protein
Dietary influence
Increase incidence Decrease incidence

Protein Fish oil
Sodium Potassium
Oxalate Dietary calcium
Sucrose
Supplement Ca
Juice
Role of dietary calcium and CaOx urolithiasis hypothesis
Decreased dietary calcium 7 ! Decreased binding to dietary oxalate 7 !

Increased intestinal oxalate absorption 7 ! Increased urinary oxalate
Effect more pronounced than decreased urinary calcium.

~ Natural Ca in diet is valuable for decreasing stone formation
~ On contrary to dietary Ca; supplementary Ca ( in drugs) increases the
chances of stone formation.
Foods increase urinary oxalate spinach, beets, nuts, chocolate, tea, wheat
Chapter 22. Urolithiasis (Urinary Calculi) 173
bran, strawberries, coca cola ‘dark’, most foods that have seeds
(a) Nucleation and aggregation (b) Anatomic sites of initial kidney stone formation
Strategies to decrease urine supersaturation

Increase urine volume &:
• Decrease ingestion &/or absorption
• Decrease metabolic production
• Use complexing agents that will decrease the free ionic concentration
• Change urine pH to favor the dissolution of stone crystals
Epidemiology
• Kidney stones (Symptomatic Vs asymptomatic)
• Ureteral stones (Symptomatic)
• Bladder stones: endemic for children in developing countries stone

composition similar to upper tract stones etiology; decreased cereal con-
tents in diet.
Effects and complications:
1. Renal colic due to contraction of the ureteric muscle to move the small
stone down the ureteric lumen.
2. Hematuria.
3. Secondary infection.
4. Obstruction leads to hydroureter and hydronephrosis.

174
5. Chronic irritation leads to squamous metaplasia and malignant changes

(squamous cell carcinoma) may occur.
Diagnosis
History:
• Frequency of stone disease Family history of nephrolithiasis
• Past medical and surgical history Dietary history
• List of medications Stone analysis
Examination:
• General examination for manifestations of hyper-parathyroidism
• Examination of genitourinary tract for organic obstructive cause or any

complications; large kidney or renal failure.
Laboratory work up:
• Complete urine test looking for infection, blood in urine and abnormal
crystals.
• General blood work up; renal function tests including uric acid level.
• Specific blood work up; indicated in specific groups and in specific

situation: e.g. children and recurrent cases or solitary kidney.
Radiological investigations
• Plain urinary tract X-ray and U/S examination of the abdomen and
pelvis are the initial studies for cases with stones
• NCCT; non-contrast spiral CT of the abdomen and pelvis is the corner

stone for evaluation of a stone in the urinary tract today.
• Other radiological tests are tailored to detect a cause or predict any

complications for the stone disease.
Medical Treatment
• Varies from watchful waiting to invasive lines of treatment.

Chapter 22. Urolithiasis (Urinary Calculi) 175
• Medical treatment of patients with urinary stone depends on the type of

the patients as well as the criteria of the stone.
• The cooperative the patient the better the chance of stone passage.
• The smaller the stone the better the chance of successful medical treat-
ment. Stones < 5mm has 75% chance
• Also, the lower down in the urinary tract the better the outcome. 75% of
distal ureteric stones and 79% of ureterovesical junction
• Watchful waiting for spontaneous stone passage:

Intake of a lot of fluid; oral fluid
Analgesics when indicated
Walking when possible.
• MET(Medical Expulsive Therapy) for urinary stones
Medical Expulsive therapy (MET) to help stone passage:
• Use of certain medications to help, accelerate and or makes stone pas-

sage less painful.
• The better chances for such kind of treatment when the stone locate at
the lower ureter.
• It can be used for not more than 4 weeks and if not successful, another
line of treatment should be followed
Medications available include

Diuretic Ca channel blocker; nifedpine.
Spasmolytic Alpha-1- blockers:
Steroids Non-selective
NSAIDs/ Anticox II Selective
Progesterone Super selective
The most commonly used pharmaceutical agents are:

Tamsulsin HCL; e.g. Tamsulin, omnic-ocas
Sildosine: e.g. Sildocare, flopadex
Diuretics: A rational to MET is to increase peristaltic activity by more fluid
176
intake to increase volume transported via the ureter and augment hydrostatic
pressure above the stone. In case of obstruction; high diuresis is likely to
counteract stone pass and increase pain.
Non-Medical Treatment
• Minimally invasive procedures as Extra-Corporeal Shock Wave Lithotripsy

(SWL) is one of the most commonly used lines of treatment today.
• A less invasive endoscopic procedures as ureteroscopy and percu-

taneous nephroscopy are used to extract and/or fragment stones that
nor amenable for SWL.
• Open surgery is indicated in selective cases that can not managed by

one or both SWL and Endoscopic lines
Chapter 23
Microbiology of urinary tract infections
Overview
– The healthy urinary tract -except urethral mucosa- is resistant to bacte-

rial colonization with the ability to eliminate microorganisms rapidly and
efficiently. The acidic PH, chemical content and flushing mechanism of
urine help to dispose of organisms in the urethra.
– Urinary tract infection (UTI) is an infection in any part of urinary system

kidneys, ureters, bladder and urethra. Most infections involve the lower
urinary tract -the bladder and the urethra. It occurs predominantly by
ascension of normal enteric flora through the urethra into the bladder
or less commonly, through hematogenous spread from other sites of
infection such as endocarditis.
– These infections more frequently affect women due to anatomic differ-

ences including a shorter urethra.
– Diagnosis is made by identifying related clinical symptoms in combina-

tion with an abnormal urinalysis and growth on urine culture. Antibiotics
are often effective therapy, although antibiotic resistance is increasing.
The most common microorganisms that cause upper and lower urinary
tract infection
A Bacteria:
• Escherichia coli(E-coli; 60-90% of cases)

• Proteus and Klebsiella 30%
• Pseudomonas ((especially Healthcare associated infection; HCAIs).
• Staphylococci:
177
178
– Mainly Staph saprophyticus

– Staph aureus (hemotogenous spread).
• Enterococcus species.
• Mycobacterium tuberculosis (T.B) (hemotogenous spread).
• Mycoplasma & Chlamydia (non-gonococcal urethritis).
B Non-bacterial causes include:
• Fungi: Candida
• Viruses: herpes simplex, cytomegalo- and adeno- viruses
• Others: Histoplasma and Trichomonas
Healthcare associated (Nosocomial) urinary tract infections

Healthcare associated infections of urinary tract are UTIs, which are nei-
ther present nor incubating at admission and appear more than 48 hours
after admission. Also include those acquired in the hospital but appear after
discharge E. coli is the commonest cause. Others include Klebsiella, Pseu-
domonas and Proteus.
Bacteriuria
Normally urinary tract and urine are sterile. Presence of bacteria in urine
samples may be classified as:
• Insignificant bacteriuria: meaning bacterial count less than 104 colony

forming unit (CFU)/ ml urine that usually involves the presence of more
than one species. It is due to contamination of urine from external ure-
thra and skin of genitalia during collection of samples.
• Significant bacteriuria: is considered when count exceeds 105 CFU/

ml in a properly collected midstream urine sample or 1 X 102 CFU/mL
urine of samples collected from catheterization.
Pyuria:
Pyuria is the presence of white blood cells (WBCs) or pus in urine. It is
defined as the presence of 6-10 or more neutrophils per high power field of
unspun, voided mid-stream urine (Leukocyturia). It may be classified as:
• Septic pyuria: Pyuria associated with significant bacteriuria and indi-

cates UTI or sepsis.
Chapter 23. Microbiology of urinary tract infections 179
• Aseptic (sterile) pyuria: it is the presence of elevated numbers of

WBCs in a urine sample without a detected presence of bacteria (ster-
ile) using standard culture techniques. Sterile pyuria is common and has
many causes:
Infection related Non-infection related

Current antibiotics – even one dose Presence of catheter or recent
of antibiotic before collection of urine catheterization
specimen Recent cystoscopy or urinary tract
Use of an antiseptic to clean urethra surgery
prior to collection of urine Urinary tract stones
Prostatitis Physiological pyuria of pregnancy
UTI with ’fastidious’ or slow growing Urinary tract neoplasm
organism e.g M.tuberculosis
Viral infections of the lower genitouri-
nary tract
Schistosoma haematobium
Laboratory diagnosis of urinary tract infection:

Samples collection: urine samples (mid-stream or from sterile catheters)
are obtained according to standardized procedure (see practical handout)
Urine samples examination:
• Physical Appearance: usually turbid urine
• Urine dipsticks: use different chemicals reagents on a strip that is dipped

in urine to diagnose urinary tract diseases. Certain dipstick test results
are suggestive of infection, namely positive leukocyte esterase, positive
nitrite, and positive hemoglobin.
• Microscopic examination:
– WBC count: 6-10 or more WBCs/HPF

– Gram stained films: Bacteria characteristic morphology + pus cells
can be seen.
• Culture: using calibrated loop (or dip slide method) 1 to 10 l is inoc-

ulated onto suitable culture media at suitable temperature and gas re-
quirements and for suitable duration according to the characters of the
causative organism. This is done for:
180
1. Colony count: numeric threshold of colony-forming units (CFUs)

per milliliter has established to confirm infection.
2. Colony identification: colonies are identified by the following ac-
cording to the characters of the causative organism:
– Colony morphology,
– Gram stained film,
– Biochemical reactions according to the suspected organism.
– Serological: through agglutination, Immunofluorescence, using
specific antisera.
– Antibiotic susceptibility test.
• Molecular: using DNA probes or PCR either for detecting DNA directly
in samples or from colonies.
• Serology:
– Detection of IgM or IgG by ELISA or complement fixation.

– Detection of cold agglutination (Uroplasma)
• Detection of the source of HCAIs: Typing as phage typing in Staph

aureus
Most common causes of UTI
1. Escherichia coli
Escherichia coli account for 60-70% of cases of urinary tract infection

Characteristics of uropathogenic E.coli include:
• Production of hemolysin and aerobactin (iron chelating agent).
• Expression of fimbriae and cytotoxic necrotizing factor.
• k antigens.
Distinguishing diagnostic features:

Morphology: Gram-negative bacilli, non-sporing and motile. Some strains
are capsulated.
Culture characters:
• Gas requirements: aerobe facultative anaerobe.
• Incubation temperature: 37°C.
• Incubation time: 24-48 hours.
• Culture media and colony morphology:
– It can grow on ordinary media.

– On MacConkey’s agar they produce discrete rose pink lactose fer-
menting colonies.
Biochemical reactions:
• Fermentation of glucose, lactose, sucrose, maltose, and mannite with

production of acid and gas.
• IMVC formula: table 23.1
Table 23.1: IMVC formula
Indole MR VP Citrate
E.coli + + - -
Klebseilla - - + +
2. Klebsiella

Morphology: Gram-negative bacilli, non-motile and capsulated.
Culture characters:
- The same as E-coli except on MacConkey’s agar, they produce large
pink lactose fermenting mucoid colonies (due to the production of abun-
dant extracellular slime).
Biochemical reaction:
• Fermentation of glucose, lactose, sucrose, maltose, and mannite with

production of acid and gas.
• IMVC formula: table 23.1

182
3. Proteus
Proteus is a common cause of urinary tract infection due to:
• High motility and ability to swarm over surfaces,
• production of urease which raises the PH of urine.

Morphology: Gram-negative bacilli, usually pleomorphic, non-capsulated
and non-sporing. Highly motile with peritrichate flagella.
Culture characters:
- Gas requirements: aerobe facultative anaerobe.
- Incubation temperature: 37°C.
- Incubation time: 24-48 hours.
- Culture media & colony morphology:
– It can grow on ordinary media giving a spreading growth in several

waves (swarming).
– On MacConkey’s agar they produce pale yellow non-lactose fer-
menting colonies.
– Proteus cultures are usually characterized by their fishy odour.
Biochemical reactions: ferment glucose with production of acid and gas

and produce H2s also it is urease test positive
4. Pseudomonas aeruginosa

Morphology: Gram-negative bacilli, motile, non-sporing and some strains
are capsulated.
Culture characters:
- Gas requirements: strict aerobe.

– It can grow on ordinary media where the media turn greenish blue
due to diffusible exopigments.
– MacConkey’s agar where they produce pale yellow non-lactose fer-

menting colonies.
– On blood agar, Most strains produce hemolysis
Biochemical reactions: no sugar fermentation and oxidase test positive
5. Staphylococci
A. Staphylococcus aureus
Distinguishing diagnostic features: Morphology:
Staphylococci are gram-positive spherical cells, non-motile, non-spore
forming, usually non-capsulated and arranged in irregular grape like clus-
ters.
Culture characters:
- Gas requirements: aerobe facultative anaerobe
– Nutrient agar: Colonies are grey to deep golden yellow (endopig-

ment).
– Blood agar: colonies surrounded by a zone of beta hemolysis.
– Mannitol salt agar (selective differential medium for Staphylococci):
containing 10-15% NaCL (halophilic), the colonies are yellow.
Biochemical reactions:
I. Catalase Test: All Staphylococci produce catalase enzyme that break

down toxic substance (H2O2) into water and O2.
184
II. Coagulase Test: Staphylococcus aureus is characterized by produc-

tion of coagulase enzyme (cell bound or free) which convert fibrino-
gen into fibrin that deposit around the organisms and the produced
lesions.
III. Ferment mannite with production of acid only
Phage typing:
Cell wall of Staph aureus contains receptors for a set of phages that can
be utilized in phage typing to trace the source of infection in HCAIs.
N.B) Methicillin resistant Staphylococcus aureus (MRSA)

MRSA are They are responsible for 25% of HCAIs. The drug of choice
in treatment of infections caused by MRSA is vancomycin, but now there
are resistant strains to vancomycin (VRSA).
B. Staphylococcus saprophyticus:
• It causes urinary tract infections in young women.

Non-hemolytic on blood agar
Coagulase negative
Dose not Ferment manitol on manitol salt agar
6. Mycobacterium tuberculosis
Two species could cause urinary tuberculosis:
• Mycobacterium tuberculosis
• Mycobacterium bovis

Sampling: Urine is collected for 5 consecutive morning or urine for 24 hours
then decontaminated and centrifuged before staining and cultivation.
Morphology and staining:
• Slender, straight or slightly curved rods (3X 0.3 µ) which may show bead-
ing, non-motile, non-sporing and non capsulated.
• They are acid and alcohol fast as demonstrated by Zeihl- Neelsen tech-
nique of staining. They appear as thin pink rods, single or in small group
against blue background.
• Using flourochrome stains (e.g.) auramine and examined under ultravi-

olet microscope, it appears as golden yellow rods against a dark back-
ground.
Cultural characters:
– Gas requirements: strict aerobe
– Incubation temperature: 37°C.
– Incubation time: 2-6 weeks and Culture is considered negative if

there was no growth after 8 weeks
– Culture media & colony morphology:
– Can’t grow on ordinary media

– It needs protein enriched medium like Lowenstein Jensen (LJ) or
Dorset egg media
– Addition of 5% glycerin favors the growth of human type (eugenic)
while it disfavors the growth of bovine type (dysgenic).
– Colony of human type is raised, dry, cream (tough, rough, buff,
tenacious).
– Bovine type is thin, smooth, slightly moist and easily broken.
Biochemical reaction:
• In general, not recommended in routine identification.
BACTC Technique: it is a rapid radiometric detection method for identifica-
tion of growth within 4days to 14 days.
The polymerase chain reaction (PCR) for rapid detection of mycobacterium
DNA directly in the pathological samples.
Non-gonococcal urethritis
Symptoms of discharge and dysuria clinically indistinguishable from gonor-
rhea caused by organisms other than N. gonorrhea is called non-gonococcal
urethritis (NGU).
186
Etiology:
1. 20-40% chlamydia trachomatis
2. 20-30% genital mycoplasmas (Ureaplasma urealyticum, Mycoplasma gen-

italium and Mycoplasma hominis).
3. Others: viruses, fungus and parasites
7. Chlamydia trachomatis
Types of chlamydial infections:
• Genital trachoma: serotypes D-K In male cause non gonococcal urethri-

tis and epididymitis and in female cause urethritis, cervicitis, salpingitis
and pelvic inflammatory disease.
• Lymphogranuloma venereum: serotypes L1-L3
Diagnosis of chlamydial infections:
A. Direct diagnosis:
1. Specimen: obtained from the site of the lesion: urethral or cervical

discharge/ lymph node aspirate.
2. Smears:
• Stained with Giemsa: basophilic intra- cytoplasmic inclusions (col-
lection of Gram- negative small non-motile bacteria).
• Direct immunofluorescence: cytoplasmic inclusions.
3. Culture (Obligate intracellular parasites): The exudate is inoculated on
cell cultures treated with cycloheximide. Intra-cytoplasmic inclusions
are detected by Giemsa stain or by immunofluorescence. These are
suggestive of C. trachomatis.
4. ELISA to detect chlamydial antigens.
5. PCR.
B. Serological diagnosis: By ELISA or indirect micro immunofluorescence

to detect IgM and IgG formed against chlamydia.
8. Mycoplasma
They are the smallest free-living organisms that lack the cell wall resulting in
being pleomorphic, stain poorly with Gram and are resistant to the cell wall
inhibitors. They are the only bacterium that contain cholesterol in their cell
membrane.
Morphology:
Minute (0.2 µm), pleomorphic organisms. They are stained with Giemsa and
are poorly stained with Gram.
Culture characters:
– Gas requirements: 10% CO2
– Incubation temperature: 37°C.
– Incubation time: 3-10 days
– Culture media & colony morphology:
– Can’t grow on ordinary media

– It can grow on complex artificial media. On agar media, they have
a fried egg appearance. The whole colony is examined microscopi-
cally.
Biochemical reaction: urease positive

Direct detection of the organism by:
• Immunofluorescence.
• DNA probes or PCR.
Serology test: for antibody detection.
Other causes of urinary tract infection

Candida: oval unicellular fungi which reproduce by budding and in immuno-
suppressed individuals, Candida may cause urinary tract infection.
Viruses: uncommon cause of urinary tract infection in an immunocompetent
host, however BK virus, Adenovirus and cytomegalovirus may cause hemor-
rhagic cystitis among immunocompromised patients.
188
Chapter 24
Urinary tract infections
Classification of UTIs
• Non specific • Isolated infection
• Specific: • Recurrent infection:
– Bacterial: TB – Unresolved infection

– Fungal: actinomycosis – Bacterial persistence
– Parasitic: bilharziasis – Reinfection
Diagnosis of UTIs: see chapter 23
Acute pyelonephritis
• Inflammation of renal pelvis and parenchyma due to bacteria
• Causative organism: E coli (80%)
• Routes of infection:
1- Ascending: from the lower urinary tract following urinary obstruction

by stones, enlarged prostate, pregnant uterus and tumors.
2- Blood borne and direct spread (rare)
Predisposing factors:
– Obstruction
– Septic focus
– Vesico-Ureteral reflux
– Instrumentation
189
190
– Diabetes mellitus
– Immunosupression
Pathological features
Gross picture:
• The kidney is enlarged, and the outer surface shows multiple small ab-
scesses.
• The pelvis and parenchyma of the kidney are swollen, congested and
contain purulent exudate.
• Pale streaks of pus surrounded by areas of congestion are seen in the

medullary rays.
• Patches of interstitial suppuration are found in the cortex and medulla.
• The tubules show degeneration and contain leucocytic casts.
Diagnosis
• C/P:
– High grade fever

– Flank pain
– Lower urinary tract symptoms (dysuria, urgency and frequency)
– Nausea, vomiting and malaise
Examination Lab Imaging tests

-Looks ill -Blood leucocytosis -US: To detect the pres-
-Tender renal -Increased blood urea & ence of obstruction
angle serum creatinine in bilat- -IVU: to detect cause of in-
eral cases fection
-Urinalysis: pyruia, hema- -VCUG: To detect VU re-
turea flux
-Urine culture and sensitiv-
ity
Chapter 24. Urinary tract infections 191
Complications Renal abscess, Perinephric abscess, Renal insufficiency in

bilateral cases
Treatment:
• Obstruction must be relieved with ureteral catheter or PCN
• Rest in bed
• Plenty of fluids oral or parentral if vomiting is present
• Antibiotics:(10-14 days)
– Ampicillin + gentamycin or
– Fluroquinolones or
– Third generation chephalosporins
Chronic pyelonephritis
• Renal insufficiency due to renal scarring
• Incidence Adults 18%, Childhood 30%
• Predisposing factors:
Diabetes mellitus, Obstruction, VU reflux, Analgesic nephropathy
• Pathological features
*Gross picture:
– The affected kidney is usually small in size with very irregular surface
due to multiple U-shaped fibrous scars.
– The capsule is thickened and adherent.
– The cut surface shows that the cortex is narrowed; the pelvis and
calyces are thickened, dilated and distorted.
– The blood vessels are prominent.
– There are patches of interstitial fibrosis and inflammatory cellular

infiltration formed of plasma cells, lymphocytes and macrophages.
192
– The glomeruli show focal periglomerular fibrosis and even complete

hyalinization.
– Some of the tubules are atrophied; others are dilated and contain
colloid casts leading to thyroid-like appearance.
– The blood vessels show endarteritis obliterans.
• Diagnosis
C/P Lab Radiological

-Asymptomatic -Urine analysis -KUB: small sized with ir-
-Hypertension (pyuria, bacteri- regular outlines
-Manifestations of uria & proteinuria) -IVU: small atrophic, im-
renal failure -Blood urea and paired excretion, disturbed
serum creatinine arrangement of calyces
may be elevated -VCUG
• Treatment:
– Correction of underling abnormalities

– Long term prophylactic antibiotic
– Nephrectomy in unilateral atrophic kid
Acute cystitis
More in women due to ascending infection from short urethra

E coli 60%
• C/P:
– Irritative LUTS : Frequency, urgency, dysurea

– Hematuria
– Suprapubic pain
• Pathologic features:
Gross picture: mucosal hyperemia with superficial minute ulceration.
The lamina propria shows infiltration by neutrophils with congested blood
vessels and may be hemorrhage.
Chapter 24. Urinary tract infections 193
• Lab: Urinalysis and culture
• Radiological KUB & US (differential diagnosis: bladder stone)
• Treatment:
– Antibiotics: trimethoprim+sulfamethoxazole or nitrofurantoin or fluro-

quinolones
– Increase fluid intake
– Vaginal douche by antiseptic solution
Chronic cystitis
• Due to bacterial persistence or reinfection
• Predisposing factors: Calculi, Diverticulum, Fistula
• C/P , lab , radiology are the same
• Treatment according to cause
Genitourinary tuberculosis
• Chronic inflammatory granulomatous disease caused by mycobacterium

tuberculosis of human or bovine type
• Renal TB is 2ry or 3ry to 1ry focus in lung, bone, GIT or LNs
Fate of renal TB: healing & scarring (calcification), progress and spread
(casseation) and encapsulation
Diagnosis
• History of TB for pt or family

194
• Clinical picture
– Asymptomatic
– Frequency of micturition: due to Acidic urine, polyurea, irritation of
bladder, TB cystitis, 2ry infection, contracted bladder.
– Hematuria
– Dull aching pain in loin or colic
– TB prostate, Seminal vesicle or epididymis
– General symptoms
• Urine examination: Sterile pyuria, highly acidic urine, Identification of

organism (see chapter 23)
• Radiological finding:
– PUT: enlarged renal shadow Punctuate calcification

– US: size, stones, parenchyma and content of pelvis
– IVU:
* Moth-eaten appearance of calyces due to pap. ulcers

* Abscess connected with calyces
* Ureteral strictures with dilation
* Straightening of ureter from shortening and fibrosis
Treatment:
• Anti-TB drugs
• Surgery: in advanced unilateral disease

Chapter 25
Diseases of urinary bladder
Include: Congenital anomalies, Endometriosis, Inflammtory diseases as cys-

titis, Benign and Malignant tumors
CYSTITIS
*Definition: It is inflammation of the urinary bladder.

*Types:
A. Acute cystitis:
Causes
1. Bacterial infections: E.coli, Proteus and staph. aureus.

2. Radiation: as in pelvic irradiation for malignant tumors.
3. Drugs: as antimalignant drugs e.g. cyclophosphamide.
B. Chronic cystitis:
Chronic specific cystitis Chronic non-specific cystitis

Bilharziasis. Interstitial (Hunner’s cystitis).
Tuberculosis. Eosinophilic cystitis
BCG: used in the treatment of papillary Polypoid cystitis: Related to catheteriza-
transitional cell carcinoma grade I. tion.
Toxoplasmosis. Emphysematous cystitis.
Hemorrhagic cystitis
Malakoplakia.
A. Acute cystitis: see chapter 24
B. Chronic cystitis:
1- Chronic specific cystitis: as bilharziasis, tuberculosis.
195
196
2- Chronic non-specific cystitis:

*Interstitial cystitis (Hunner’s chronic non-specific cystitis): charac-
terized by ulceration and marked lamina propria edema affecting adult
females. Its cause is unknown but may be autoimmune.
*Eosinophilic cystitis: as in allergic disorders and parasitic infesta-
tions.
*Emphysematous cystitis: occurs due to gas forming bacteria and
characterized by the presence of gas-filled vesicles.
*Hemorrhagic cystitis: due to drugs or viral infection (as herpes sim-
plex and CMV).
*Polypoid cystitis: It resembles a neoplasm grossly. Its typical site
is the posterior wall of the bladder above the trigone. Grossly, it may
be bullous cystitis (rounded broad elevations), or papillary cystitis (thin
and villous).
*Malakoplakia: Chronic cystitis characterized by mucosal yellowish
plaques, nodules or polyps.
Microscopically: it is characterized by dense collections of macrophages
with abundant granular cytoplasm. Within the cytoplasm are round,
laminated concretions called Michaelis-Guttmann bodies that stain pos-
itively with PAS stain as well as calcium and iron stains. Malakoplakia
may be of immunologic origin in some cases.
Metaplastic changes of the urinary bladder:
• Glandular metaplasia: change of the transitional epithelium into

glandular epithelium as in bilharziasis.
• Squamous mataplasia (leukoplakia): change of the transitional ep-
ithelium into squamous epithelium as in bilharziasis and calculi.
• Mesonephroid (adenomatoid) metaplasia: change of the transi-
tional epithelium into mesonephrioid-like tubules due to infection, cal-
culi or prolonged catheterization.
Chapter 26
Urinary antiseptics, drugs modifying Urine pH
Urinary antiseptics
Definition: they are oral agents that its antibacterial activity is restricted to
urine with no systemic effects (their level in circulation is not sufficient for an-
tibacterial effects), so they are effective against lower urinary tract infections
Include: Nitrofurantoin-Methenamine-Fosfomycin
Nitrofurantoin
• Absorption is rapid and complete orally

• Metabolism and excretion are rapid so no plasma levels or sys-
temic actions
• Excreted in kidney by glomerular filtration and tubular secretion
• Mode of action: bacterial enzymatic reduction of nitrofurantoin to

intermediates which destruct bacterial DNA
• Spectrum: effective against E-coli and enterococci, BUT, Porteous,
pseudomonas, Enterobacter and klebsiella are resistant
• NO cross resistance between nitrofurantoin and other antimi-
crobials so it is a good alternative in case of cotrimoxazole and
quinolones resistant E-coli infections
• Acidic pH of urine is important to its antibacterial activity
III. Uses
197
198
1. lower urinary tract infections (not recommended in prostatitis or pyelonephri-

tis)
2. prevention of recurrent urinary tract infections
Dose: 50-100mg/6hours with meals and bedtime, 100mg/12h for 7
days for macrocrystalline preparations, course should not exceed 14
days
IV. Adverse effects
1. Nausea, vomiting and diarrhea

2. Brown urine discoloration
3. Polyneuropathy especially in renal impairment and chronic therapy
4. Hypersensitivity reactions: chills, fever, leukopenia, hepatocellular dam-
age
5. Hemolytic anemia is G6PD deficiency and in newborn
6. Acute pneumonitis, cough, dyspnea, chest pain. Pulmonary infiltra-
tion and fibrosis (chronic use)
V. Contraindications
1. Pregnant women at term, during, labor, delivery or imminent delivery

to avoid possible hemolytic anemia.
2. Patients with renal impairment to avoid systemic toxicity
Methenamine
• Absorbed orally, it is unstable in gastric secretion unless coated

• Excreted in urine
• Mode of action: it is a prodrug that generate formaldehyde at acidic

pH, formaldehyde is antibacterial
• Spectrum:
All bacteria are sensitive to free formaldehyde
Chapter 26. Urinary antiseptics 199
NO microorganism resistance
NB:
• urea splitting microorganisms as proteus raise urine pH and inhibit

release of formaldehyde
• acidification increase activity, so it is formulated with mandelic or hip-
puric acid or acidification of urine with acidifying agent e.g. ascorbic
acid
III. Uses:
• Used in chronic suppression of urinary tract infections caused by

E-coli, most gram negative, staph aureus and epidermises
• Not used in treatment of acute infections
1. GIT distress
2. Painful and frequent micturition, hematuria and albuminuria (at high
doses)
V. Contraindications:
1. Hepatic encephalopathy due to ammonia production

2. Renal failure is NOT contraindication of methenamine alone, but acids
formulated with methenamine may be harmful in these patients so
should be avoided
VI. Drug interactions: released formaldehyde binds to sulfonamides and

form insoluble compound so not given at the same time
Fosfomycin
It is phosphoric acid derivative
• Available as a powder formulation dissolved in water and adminis-

trated orally, bioavailability 40%, half-life 6-8h
200
• Attain high urinary concentration and low serum concentration after

oral administration
• Mode of action: it inhibits initial steps of bacterial cell wall synthesis

• Spectrum: E. coli, Proteus, Enterococcus, and Staphylococcus saphro-
phyticus. Variable activity against Klebsiella, Enterobacter, and Ser-
ratia spp. Pseudomonas and Acinetobacter are typically resistant
III. Uses:
1. Prevention and treatment of urinary tract infections

2. 3 g single dose for acute uncomplicated urinary tract infections
3. 3 g every 10 days for urinary tract infections prophylaxis
IV. Adverse effects: it is well tolerated but GIT distress, vaginitis, headache,
dizziness may occur
Drug that alter Urine pH
Table 26.1: Drug that alter Urine pH
Urine acidifiers Urine alkalizers

Vitamin C, mandelic and hippuric acid Na or K bicarbonate
Ammonium chloride: rarely used Na and K Citrate: metabolized via the
Krebs cycle and generate bicarbonate
which is excreted in urine
Na or K Acetate
Carbonic anhydrase inhibitors
Uses: Uses:
Acidification of urine: to enhance ex- Treatment of metabolic acidosis
cretion of weak basic drugs Alkalinize urine to enhance secretion
Potentiate urinary antiseptics as of weak acid drugs as salicylates
methenamine Na channels blocker toxicity (NaHco3)
Dissolve uric acid and help excretion
Used in cysteine stones
Prevent crystalluria of sulfonamides
Decrease dysuria (common symptom
of infections)
Contraindicated in liver and kidney dis-
ease
Chapter 27
Parasites affecting The Urinary system

A) Parasites with a direct effect on B) Parasites with an indirect effect
the urinary system: on the urinary system:
Urinary schistosomiasis. Malaria
Lymphatic Schistosomiasis
filariasis. Leishmaniasis
Enterobius vermicularis Trypanosomiasis
Strongyloides stercoralis Filariasis
Hydatid disease Toxoplasmosis
Amoebiasis Trichinosis
Trichomonas vaginalis. Arthropod toxins
Genitourinary myiasis
Trichomonas vaginalis
Disease: Trichomoniasis.
Geographical distribution: Cosmopolitan.
Morphology: It has a trophozoite form only:
• Oval or pear-shaped, about 15×8 with a great

variation in size.
• Has one large oval vesicular nucleus and a very

small anterolateral cytostome.
• Has 3–4 free anterior flagella plus a recurrent

flagellum that arises anteriorly and parallels the
body posteriorly to form the outer margin of the
undulating membrane that never extends beyond
the middle of the body.
• Has numerous granules along its slender ax-

ostyle. The axostyle extends beyond the poste-
rior end.
• Has a thick parabasal body.

201
202
Life cycle:
Habitat: -In females: vagina and rarely urethra

-In males: urethra, prostate, epididymis
and seminal vesicle
Definitive host: Man
Diagnostic stage: Trophozoite
Infective stage: Trophozoite
Mode of infection: 1) Sexual intercourse (venereal disease)
2) Direct contact with contaminated linens,
towels, toilet seats or underwear
3) Babies may be infected from mother dur-
ing birth
- When the trophozoites are placed in the vagina or the urethral orifice,
they multiply by longitudinal binary fission if the pH is suitable.
- The optimal pH for its growth is 4.9, so it cannot live in the normal acidity
of the vagina (pH 3.8–4.4) which is maintained by the action of Doderlein
bacillus on the glycogen present in the vaginal mucosa producing lactic
acid.
- Once infection is established, the parasite causes a shift towards alka-

linity which encourages further parasitic growth.
- The trophozoites are discharged in vaginal or prostatic secretions and

urine.
Clinical aspects:
*The pathogenicity is affected by:
1- The pH of the vagina (it dies in high acidic or high alkaline media).
2- Decrease in secretory IgA in the vagina.
3- Bacterial flora in the vagina. Infection is associated with decrease or dis-

appearance of D. bacillus.
*Mechanical and toxic irritations by trophozoites lead to the following:

In females: vaginitis, urethritis and occasionally cystitis.
The disease may be asymptomatic, or the patient may suffer from:
Chapter 27. Parasites affecting The Urinary system 203
- Profuse odorous vaginal discharge.
- Burning sensation and itching in the vagina.
- Cervical erosion is common
- Mild dysuria and frequency of micturation.
In males: Urethritis, prostatitis and rarely seminal vesiculitis.

The disease is almost always asymptomatic. However urethral discharge or
dysuria may occur.
In infants born to infected mothers: neonatal pneumonia and conjunctivi-
tis have been reported.
Diagnosis:
A. Clinical picture.
B. Direct laboratory:
1. Microscopic examination of fresh vaginal or urethral discharge, pro-

static secretions, or urine to detect motile trophozoites.
2. In vitro culture for 2–7 days is considered the gold standard for diagno-
sis, if microscopic examination is negative.
C. Indirect laboratory:
- Detection of the parasite antigens in the above mentioned specimens

using labeled monoclonal antibodies.
- Fluorescent antibody staining of these specimens.
Treatment:
- Local:
a) Acidifying vaginal douches with lactic acid to restore the normal

acidity of the vagina.
b) Metronidazole vaginal inserts: 500 mg/day for 10 days.
- Systemic: Metronidazole 250 mg orally t.d.s for 7–10 days. Both part-
ners should be treated at the same time to avoid reinfection.
204
Prevention and control:
1. Personal hygiene.
2. Health education.
3. Both partners should be treated at the same time.
Schistosoma haematobium
(Urinary schistosomiasis)
Geographical distribution: Egypt (Nile valley), Africa
& South America
Morphology:
Adult male:
• Size: 12 mm.
• Shape: Lateral margins folded ventrally to form

gynaecophoric canal.
• Tegument: covered with fine tuberculated.
• Suckers: Oral sucker and ventral larger one.

Figure 27.1: Adult S.
• Genital pore: Just posterior to the ventral sucker.
haematobium
• Alimentary canal: The two simple intestinal

caeca unite into a single caecum in the posterior
third of the body.
Adult female:
• Size: 20 mm.
• Shape: The body is cylindrical and longer than the male.
• Tegument: Smooth.
• Ovary: Ovoid in the posterior third of the body in front of union of the
intestinal caeca
The egg:
Size: 140 x 60 mum
Shape: Large terminal spine
Color: Translucent
Content: Miracidium
Miracidium: It is small, oval, elongated and

ciliated.
Sporocyst: A sac-like stage containing
germinal cells.
Cercaria: Furcocercus cercaria with pene-
tration glands and bifid tail.
Schistosomulum: It is the migratory larval form within the definitive host.

Morphologically, it is a tail-less cercaria.
Life cycle
Habitat: Vesical and pelvic venous plexus

Hosts: D.H.: Man
R.H.: ———
I.H.: Bulinus trancatus
Diagnostic stage: Mature egg
Infective stage: Furcocercous cercaria
Mode of infection: Skin penetration
Life span: Up to 20 years
206
Figure 27.2: Life cycle of Schistosoma
1. The female in gynaecophoric canal of the male ! pass against blood

stream to the smaller capillaries until the male could not pass any more
blocking the blood flow. The female leaves the male and being thinner
proceeds furthermore and starts laying eggs one by one with the spine
directed posteriorly, returning backwardly after each egg being laid.
2. By the action of a lytic enzyme secreted by the miracidium, recoil of the

venule and pressure of the spine on the wall of the vessel, eggs pass into
the perivascular tissue of the urinary bladder. About half the deposited
eggs penetrate the urinary bladder wall and reach the lumen to be dis-
charged in urine.
3. In fresh water, the miracidia hatch immediately ! penetrate the soft tis-
sue of the snail ! sporocysts ! daughter sporocysts! cercariae.
4. D.H. infection: Cercariae penetrate the skin actively helped by the pro-
teolytic secretion of their penetration glands! leave their tails out, now
called schistosomula ! venous circulation ! the right side of the heart !
lung ! systemic circulation! portal circulation! become adult.
5. Paired worms migrate to the vesical and pelvic plexus where eggs are
laid. Eggs appear in urine in about 5–8 weeks after infection.
Clinical aspect:
The manifestations are divided according to the stage of infection:
Stages Clinical aspect Manifestations

1. Cercarial dermatitis At the penetration sites of cer-
Early cariae ! itching & papular erup-
tion
2. Schistosomular migration Migration of schistosomula!
lungs: pneumonitis (fever,
cough and hemoptysis) and
! liver (tender hepatomegaly)
3. Acute schistosomiasis It occurs when worms mature
(Katayama syndrome) in the liver, migrate to the small
venules and begin to lay eggs.
There is fever, abdominal pain,
diarrhea, wheezing, urticaria,
marked eosinophilia, sometimes
lymph node enlargement and
hepatosplenomegaly. It is more
common in S. japonicum.
Late Chronic urinary schistosomi- Oviposition in the vesical
manifes- asis plexus! terminal hematuria,
tations dysuria, and frequency
1) Obstruction of the urinary tract ! hydroureter and hy-
dronephrosis
2) Urinary stones
Advanced
3) Recurrent bacterial urinary infections
complica-
4) Egg embolism ! Lung & CNS
tions
5) Bladder cancer
Diagnosis of urinary schistosomiasis:
I. Clinically: presentation of terminal hematuria in an endemic area is

suggestive.
II. Direct parasitological diagnosis:
• Repeated urine examinations and/or concentration procedures (such

as cellulose membrane filtration technique for quantification of infec-
tion in urine samples) are indicated.
208
• Cystoscopy: to take bladder snips or biopsy for diagnosis, and ex-

amination of urinary complications.
N.B. Closed schistosomiasis means absence of eggs in the excreta
due to extensive fibrosis despite the presence of active schistosomal
infection.
III. Immunodiagnosis:
a. Detection of antibodies in serum.
b. Detection of antigen in serum or urine.

N.B. These tests may be helpful when eggs could not be detected
(early in the incubation period or late in closed schistosomaisis and
for epidemiological studies).
IV. Molecular techniques:Using polymerase chain reaction (PCR). It is highly

sensitive and specific, but more expensive.
V. Other investigations
1. Blood picture: anemia, thrombocytopenia, and eosinophilia.
2. Imaging techniques
a. Pelvi-abdominal X-ray: detect genitourinary calcification or stones.

b. Intravenous pyelography (IVP) to see ureteric obstruction, and as-
sess renal function.
c. Ultrasonography: this is a non-invasive simple method. It can
demonstrate urinary tract stones or obstructions.
d. Computerized Tomography (CT) or Magnetic Resonance Imaging
(MRI) may be useful in evaluation of cerebral schistosomiasis and
in assessment of bladder
Treatment of schistosomiasis:
1. Specific medication (antihelminthic drugs):
• Praziquantel (PZQ): It is the drug of choice. It is taken orally in a dose

of 40 mg/kg body weight single oral dose.
• Artemisinin: This antimalarial drug shows strong schistosomicidal ef-

fect especially against the immature forms of the parasite. So it has a
role in the prophylaxis and treatment of schistosomiasis.
• Combination therapy of PZQ plus artemisinin may be recommended
since it is more effective than if each drug is given separately.
2. Follow-up of patients: Examinations of urine or stool for Schistosoma

eggs should be monthly done 3 months after treatment. The viability test
should be done to decide whether the patient is cured or not.
Prevention and control:

A successful control program should run along the following channels:
1) Mass treatment of patients.
2) Public health education: Explanation of the life cycle, the mode of infec-
tion and hazards of the disease in a simple way to the population. This
done in schools, mosques, churches, press, cinema and TV.
3) Sanitation:
a. Avoiding bathing or swimming in snail-infested waters.

b. Proper sewage disposal.
4) Snail eradication:
a. Environmental control:
i Clearance of canals from weeds and vegetations.
ii Drying of canals.
iii Construction of canals using concrete.
iv Putting palm leave-traps to collect and destroy snails.
b. Biological control:
i. Plantation of special trees toxic to snails as Balanites aegyptiaca.
ii. Using natural enemies as ducks, geese and mollusc-eating fish
such as Tilapia and Gambusia.
iii. Using competitor snails as Marisa and Helisoma.
c. Chemical control (molluscicides):
210
i. Copper sulphate (5 p.p.m.) is effective against adult snails only.

ii. Bayluscide (dichloro-nitrosalicylicanilid) 0.5 p.p.m., kills both adult
snails and their eggs.
5) Vaccine development: offers promise of control of this important health

problem.
Chapter 28
Tumors of urinary system
TUMORS OF THE KIDNEY
Benign tumors: Malignant tumors:

1. Renal papillary adenoma. A. Primary:
2. Transitional cell papilloma of
1. Renal cell carcinoma (hypernephroma).
the renal pelvis.
3. Others as oncocytoma, he- 2. Embryoma (Wilm‘s tumor).
mangioma, fibroma, lipoma, an-
giomyolipoma and leiomyoma. 3. Transitional cell carcinoma of the renal
pelvis.
B. Secondary: metastatic from carcinoma

of the lung and breast, or from osteosar-
coma and malignant melanoma.
RENAL CELL CARCINOMA (HYPERNEPHROMA)

*Definition: the commonest primary malignant tumor of the kidney
*Origin: it arises from the epithelium of the convoluted tubules.
*Incidence: usually common in males more than 40 years of age.
*Gross picture:
• The tumor forms a large rounded well circumscribed sharply demar-

cated mass usually at one pole of the kidney.
• Cut surface is yellowish (rich in lipids) with areas of hemorrhage and

necrosis giving the tumor golden yellow appearance.
1. Clear cell type: the most common form. It is formed of large rounded
cells with clear cytoplasm and central nuclei. The cells are arranged in
solid sheets, cords or tubules and separated by thin fibrous trabeculae.
211
212
2. Other types: less common such as chromophobe cell type, papillary type,
and sarcomatoid type.
Figure 28.1: Renal cell carcinoma
*Spread:
1. Direct spread to the renal pelvis and causes hematuria.
2. Lymphatic spread to the Para-aortic lymph nodes.
3. Blood spread occurs early to the lungs, liver, bones and other organs.
*Effects: Renal cell carcinoma may be associated with paraneoplastic syn-

dromes such as: hypercalcemia due to elaboration of parathyroid hormone,
erythrocytosis due to erythropoietin, hypertension due to increased rennin
and amyloidosis.
NEPHROBLASTOMA (WILM’S TUMOUR)

*Definition: one of the commonest malignant tumors of childhood (first 5
years of life).
*Origin: It is believed that it arises from pluripotent rudimentary blast cells.
*Gross picture:
• The tumor forms large well circumscribed swelling
• Fleshy or firm in consistency with grayish white cut surface.
• Areas of cystic changes, hemorrhage and necrosis are present.
- The tumor consists of three main components:
• Blastemal component: composed of rounded or spindle cells (blastema

cells) resembling sarcoma. These cells have a small amount of deeply
basophilic cytoplasm.
Chapter 28. Tumors of urinary system 213
• Epithelial component: epithelial cells having tendency for formation of

tubules and glomeruli.
• Mesenchymal component: Smooth muscle fibers and cartilage-like tis-

sue may be also found.
*Spread:
• Direct spared to near-by kidney tissue forming a huge mass.
• Blood spread to the lungs.
• Lymphatic spread to the regional lymph nodes.
TUMORS OF THE URINARY BLADDER
I. Primary tumors:
• Benign urothelial tumors:

A. Epithelial tumors:
1. Exophytic papilloma and inverted papilloma
2. Villous adenoma.
3. Condyloma accuminatum.
B. Mesenchymal tumors: Leiomyoma, fibroma, hemangioma and
neurofibroma,
• Malignant tumors:
A. Epithelial tumors:
1- Urothelial (transitional cell) carcinoma:
– Non-invasive papillary urothelial carcinoma, carcinoma in
situ, papillary carcinoma of low malignant potential, low grade
papillary and high grade papillary carcinomas).
– Invasive (infiltrating) urothelial carcinoma: (May be with squa-
mous differentiation, glandular, microcystic, giant cell, and
clear cell differentiations or undifferentiated).
2- Squamous carcinomas: Squamous cell carcinoma, Verrucous
carcinoma.
214
3- Adenocarcinomas: Intestinal, mesonephroid, clear cell and

signet ring cell types.
4- Small cell (neuro-endocrine) carcinoma and carcinoid tumor.
5- Mixed carcinoma. 6. Undifferentiated carcinoma.
B. Mesenchymal tumors: leiomyosarcoma and rhabdomyosarcoma,...
II. Metastatic tumors: Rare and usually arise from the colon, prostate and
female genital tract.
URINARY BLADDER CARCINOMA
*Age: usually more than 40 years.

*Gender: males are affected more than females (about 3:1).
*Incidence: bladder carcinoma is the seventh most common cancer world-
wide.
*Residence: in industrial areas, transitional cell carcinoma (T.C.C.) is more
common, while in rural areas, squamous cell carcinoma (S.C.C) is more com-
mon.
*Etiology of bladder carcinoma:
1. Chemical carcinogens: aniline dyes containing benzidine,

-nephthylamine
and phenacitine are more commonly involved in the development of T.C.C.
2. Cigarette smoking: it increases the risk to two to four times.
3. Schistosomiasis leads to squamous metaplasia and dysplasia then squa-

mous cell carcinoma. So, more commonly involved in the development of
S.C.C.
4. Abnormalities in chromosomes number 9 and 17 have been reported.
5. Heavy long–term exposure to immunosuppressive agents as cyclophos-

phamide
6. Exposure of the bladder to radiation.
7. Increased tryptophane metabolites in urine which occurs more commonly

with schistosomiasis.
8. Chronic irritation especially with diverticulae and metaplastic changes.

Chapter 28. Tumors of urinary system 215
*Clinical presentations of bladder carcinoma: painless total hematuria,

necroturia, frequent urination, dysuria (with the presence of bacterial infec-
tion).
*Pathology of bladder carcinoma:
Site: lateral walls (37%), posterior wall (18%), trigone (12%), bladder
neck (11%), ureteric orifices (10%), bladder dome (8%) and anterior
wall (4%).
Size: variable from small flat to large fungating mass.

1. Exophytic:
• Papillary with central connective tissue core as

in urothelial carcinoma and verrucous carci-
noma.
• Solid nodular without central core.
2. Endophytic: Ulcerative: More common in S.C.,

Flat and infiltrating.
3. Combined exophytic and endophytic.

1. Urothelial (Transitional cell) carcinoma (T.C.C): It represents about 95%

of bladder carcinoma. It is the commonest urothelial tumor.
• Two distinct precursor lesions to invasive urothelial carcinoma

are recognized. The most common is a noninvasive papillary tu-
mor. The other precursor is carcinoma in situ (CIS) which is defined
by the presence of cytologically malignant cells within a flat urothe-
lium.
• Noninvasive papillary urothelial neoplasms showing papilliform le-
sion consists of very thin fibrovascular core. Each papilla is covered by
malignant transitional epithelium (more than seven layers). Invasive
urothelial cancer associated with papillary urothelial cancer (usually
of high grade) or CIS may superficially invade the lamina propria or ex-
tend more deeply into underlying muscle. Almost all infiltrating urothe-
lial carcinomas are of high grade.
216
2. Squamous cell carcinoma (3-7% of bladder carcinoma): It may be

well, moderate or poorly differentiated squamous cell carcinoma accord-
ing to the percentage (%) of the degree of keratinisation and the degree
of nuclear pleomorphism or may be verrucous carcinoma.
Figure 28.2: Papillary transitional cell carci- Figure 28.3: Squamous cell carci-
noma noma
3. Adenocarcinoma: It is less common and is histologically identical to in-

testinal adenocarcinoma.
4. Neuroendocrinal tumors: Rare.
5. Undifferentiated carcinoma.
*Staging of bladder carcinoma:

0: tumor limited to mucosa (in situ).
A: tumor invades the lamina propria.
B1: tumor invades inner half of muscle layer.
B2: tumor invades outer half of muscle layer.
C: tumor invades the perivesical tissue.
D1: metastasis of pelvic lymph nodes.
D2: distant metastasis.
*Spread of bladder carcinoma:
1. Direct spread: To the prostate and pelvic organs.
2. Lymphatic spread: To the pelvic and paraaortic lymph nodes.
3. Blood spread: Distant metastasis.

Chapter 29
Obstructive uropathy
Definition: Functional or anatomic obstruction of urine flow at any level of

the urinary tract.
When obstruction causes Functional or anatomic renal damage, lt is called
the obstructive nephropathy
Classification
Acute or Chronic Upper tract or lower tract

Congenital or Acquired Mechanical or Functional
Unilateral or bilateral Intraluminal, Intramural or Extra luminal
Causes of Obstructive uropathy
Congenital Acquired
Meatal Stenosis Urethral stricture secondary to infection or injury
Stenosis Distal Urethra, BPH or prostate cancer
Posterior Urethral Valves, Vesical tumor involving the bladder neck or one or both
Ectopic Ureters,Ureteroceles, ureteral orifices
The Ureterovesical and Uretero- Local extension of cancer of the prostate or cervix into
pelvic Junctions the base of the bladder, occluding the ureters
Damage To Sacral Roots 2–4 In Compression of the ureters at the pelvic brim by
Spina Bifida metastatic nodes from prostate or cervical cancer
Myelomeningocele Ureteral stone
Retroperitoneal fibrosis or malignant tumor
Pregnancy
217
218
Figure 29.1: Differential diagnosis of lower urinary tract obstruction
Figure 29.2: Causes of unilateral ureteric ob- Figure 29.3: Causes of bilateral uri-
struction nary tract obstruction
Pathologic Changes of Obstruction (porcine model)
Gross Pathologic Changes
• 42 hours- Dilation of the pelvis and ureter and blunting of the papillary
tips.
• 7days- Increased pelviureteric dilation and weight. Parenchyma is ede-

matous
• 21-28 days- External dimensions of kidneys are similar but the cortex
and medullary tissue is diffusely thinned
• 6 weeks - Enlarged, cystic appearing
Microscopic Pathologic Findings
• 42 hours- Lymphatic dilation, interstitial edema, tubular and glomerular

preservation
Chapter 29. Obstructive uropathy 219
• 7 days- Collecting duct and tubular dilation, widening of Bowman’s space,

tubular basement membrane thickening, cell flattening
• 12 days- Papillary tip necrosis, regional tubular destruction, inflamma-

tory cell response
• 5-6 weeks- widespread glomeular collapse and tubular atrophy, intersti-

tial fibrosis, proliferation of connective tissue in the collecting system
Compensatory Renal Growth
• Enlargement of the contralateral kidney with unilateral hydronephrosis

or renal agenesis
• A reduction in compensatory growth occurs with age
• An increase in the number of nephrons or glomeruli does not occur,

despite enlargement
Renal Recovery after Obstruction
• Degree of obstruction, age of patient, and baseline renal function affect

chance of recovery
Two phases of recovery may occur: Tubular function recovery, GFR
recovery
• Duration has a significant influence
– Full recovery of GFR seen with relief of acute complete obstruction

– Longer periods of complete obstruction are associated with dimin-
ished return of GFR
Clinical findings
I Symptoms
– Lower And Midtract (Urethra And Bladder)
* Symptoms of urethral stricture, BPH, neurogenic bladder, and

tumor of the bladder involving the vesical neck.
* The principal symptoms are hesitancy in starting urination,

lessened force and size of the stream, and terminal dribbling
220
* Hematuria, which may be partial, initially, with stricture or total

with prostatic obstruction or vesical tumor.
* Cloudy urine (due to complicating infection), acute urinary re-
tention.
– Upper Tract (Ureter And Kidney)
* Symptoms of obstruction of the upper tract are typified by the

symptoms of ureteral stricture or ureteral or renal stone.
* The principal complaints are pain in the flank radiating along
the course of the ureter, gross total hematuria (from stone).
* Gastrointestinal symptoms, chills, fever, burning on urina-
tion, and cloudy urine with onset of infection, which is the com-
mon sequel to obstruction or vesicoureteral reflux.
* Nausea, vomiting, loss of weight and strength, and pallor
are due to uremia secondary to bilateral hydronephrosis.
I Signs
– Lower and midtract
* Palpation of the urethra- induration about a stricture.

* Rectal examination -Atony of the anal sphincter (damage to the
sacral nerve roots) or benign or malignant enlargement of the
prostate.
* Vesical distention may be found
* A flow rate under 10 mL/s is indicative of obstruction or weak
detrusor function
* Atonic neurogenic bladder (diminished detrusor power), or with
urethral stricture or prostatic obstruction (increased urethral re-
sistance) 3–5 mL/s
– Upper tract
* An enlarged kidney may be discovered by palpation or percus-

sion.
* Renal tenderness (+) if infection is present.
* A large pelvic mass (tumor, pregnancy) can displace and com-
press the ureters.
Chapter 29. Obstructive uropathy 221
* Children with advanced urinary tract obstruction (usually Due to

posterior urethral valves) may develop ascites.
Laboratory finding
• Microscopic hematuria may indicate renal or vesical infection, tumor,

or stone.
• Anemia secondary to chronic infection or in advanced bilateral hydronephro-

sis (stage of uremia).
• Leukocytosis —acute stage of infection.
• Bilateral hydronephrosis —urine flow through is slowed.
• An urea-creatinine ratio – above the normal 10:1
Management of Patients with Obstruction
Diagnostic Imaging
• Renal US
– Good initial screening test

– May have false negative in acute obstruction (35%)
– Hydronephrosis= anatomic diagnosis
-Can have caliectasis or pelviectasis in an unobstructed system
– Doppler- measures renal resistive index (RI), an assessment of ob-
struction
Figure 29.4: Grading of Hydronephrosis by ultrasound
• Excretory Urography: limited use in renal insufficiency
• Retrograde Pyelography
222
– Gives accurate details of ureteral and collecting system anatomy

– Good if renal insufficiency or other risks for contrast
– Loopogram- use for evaluation of patients with cutaneous diversions
• Antegrade Pyelography: Can do if RGP is not possible and other imag-

ing doesn’t offer enough details
• Nuclear Renography: Provides functional assessment without contrast
• CT
– Most accurate study to diagnose ureteral calculi

– More sensitive to identify cause of obstruction
– Helpful in surgical planning
– Preferred initial imaging study in those with suspected ureteral ob-
struction
• MRI
– Can identify hydro but unable to identify calculi and ureteral anatomy
of unobstructed systems
– Diuretic MRU can demonstrate obstruction
- Especially accurate with strictures or congential abnormalities
– Still several limitations in its use
Treatment: Eradication of infection, Relief of obstruction

Chapter 30
Hematuria
Blood in urine originating from: Ur tract (kidney – ureter – bladder – prostate)
Types
• Gross: seen by naked eye (with or without blood clots)
• Microscopic: discovered accidentally during routine microscopic urine

examination / by dipstick
Causes
• Tumors:
– Most worrisome diagnosis

– Commonly: bladder / kidney tumors (most common tumors of uri-
nary tract).
– May cause both gross or microscopic hematuria
– Usually painless
– Carcinoma-in-situ of the bladder presents with dysuria & hematuria.
• Infection & Stones: cause hematuria due to irritation & is usually ac-
companied by pain or dysuria & fever in cases of pyelonephritis.
223
224
• Glomerulo-nephritis: group of collagen / auto-immune disease that

causes inflammatory allergic response at the glomerular membrane (de-
position of the antigen/antibody complexes).
• Benign Prostatic Hyperplasia: a benign condition affects aging men.
• Bleeding tendency & coagulopathy Trauma: blunt – penetrating – sur-

gical trauma
• Polycystic kidneys: a genetic disease usually cause gross hematuria

– hypertension – renal failure
• Other conditions – usually microscopic:
– Vigorous exercise such as jogging

– Hypertension & congestive heart failure patients
Approach to Diagnosis
• Special Questions
– Painful – painless:
* Painless: Trauma – TB – Tumors (early non-invasive)

* Painful: Infections – advanced malignancy – stones
– Color:
* Dark red: usually from upper urinary tract (kidney)

* Bright red: usually from lower (bladder – prostate)
– Clots:
* Present or not
* Shape: Discoid / small pieces – Slender shape
– Relation to act:
* Total: any part from the UT

* Initial: anterior urethra pathology
* Terminal: prostate – bladder (Bladder neck / trigone)
• Clinical examination
– Vital signs
Chapter 30. Hematuria 225
– General examination
– Abdominal examination
– Examination of the external genitalia
– Digital rectal examination (PR exam)
Diagnostic methods
I. Laboratory
• Urine
– Sample and method of collection (see urine analysis in practi-
cal handout)
– Urine Microscopic Examination:
* RBCs Casts: diagnostic of glomerulo-nephritis

* Presence of crystals may suggest stone
* WBCs & bacteria (+ve culture): diagnostic of UTI
* WBCs & – ve culture = sterile pyuria
· Urinary tract tuberculosis
· UTI under antibiotic treatment
· Urinary stone, bladder tumor.
– Urine culture
• Blood
– Routine (general) blood tests:
* CBC – Liver functions – blood sugar

* Coagulation profile (bleeding & coagulation time)
– Serum creatinine:
* Most commonly used kidney function test

* Normal: 0.7 – 1.2 mg
* Disadvantage:
· Starts to rise when 75% of kidney function is lost
· Does not provide data on split kidney function
– Tumor markers:
•PSA: prostate specific antigen – routine after age of 50 (<4ng)
226
II. Imaging
• Imaging mainly answers the question Where is the lesion ?
• Imaging may also provide some functional data
• Common imaging modalities used for urologic investigations:
Plain X-Ray: can detect urinary stones and abnormal tissue calcification
Intra-Venous Urography IVU: diagnoses tumors, stones
Abdominal Ultrasound
• Abdominal US evaluates:
– Kidney:
* Detects renal mass (tumors): solid – cystic lesions

* Urinary tract dilatation – size of the kidney
* Kidney stones (all types of stones)
– Bladder & prostate – bladder must be fully distended with urine:
* Bladder tumors
* Prostate size & post-residual volume
• Others: TRUS (Trans-rectal ultrasound) – scrotal ultrasound
Computed Tomography
• CT is now the gold standard for imaging urinary tract.
• CT in Tumors: Clearly demonstrates primary tumor & draining lymph

nodes
• CT in urinary tract infection: Renal abscess
• Can detect all types and any size of stones in all planes
• Retrograde urethrogram:
– Visualized the urethra

– Performed when urethral stricture is suspected
Chapter 30. Hematuria 227
• VCUG Voiding Cysto-Urethro-Gram: Performed in children urinary

tract infection
• Renal scan
• Transrectal ultrasound: for evaluation of the prostate
Endoscopy
Cystourethroscopy
• Direct visual evaluation of lower urinary tract

(urethra – prostate - bladder)
• Instruments:
– Rigid: under regional anesthesia – OR – superior image quality

– Flexible: under local anesthesia – can be done at clinic – inferior
image quality
Indications
• Diagnostic:
–Hematuria: inspection of mucosa + biopsy of suspicious lesions
• Therapeutic:
– Trans-urethral prostatectomy
– Trans-urethral bladder tumor resection
– Stone fragmentation
– Incision of urethral strictures or posterior urethral valve
228
Chapter 31
Urinary incontinence
31.1 Urinary incontinence
Definition: It is involuntary leakage of urine

Risk factors:
• Sex: Females > male - Age: Old age - Overweight-
• Other factors: COPD , kidney disease and Diabetes mellitus
Differential diagnosis
1. Non urinary wetness: measure the creatinine level of the fluid
2. Non-urethral urinary incontinence: Fistula, Ureteral ectopia
Classification of incontinence
1. Stress urinary incontinence: involuntary leakage of urine on effort , ex-

ertion (cough , sneeze)
2. Urge urinary incontinence: involuntary leakage of urine preceded by

urgency.
3. Mixed urinary incontinence: involuntary leakage of urine on effort and

preceded by urgency
4. Overflow incontinence: leakage of urine + urine retention.
5. Continous incontinence.
6. Nocturnal enuresis: only during sleep.
229
230 31.1. Urinary incontinence
Assessment of a case of incontinence
1. History
2. Physical examination
3. Urodynamic
4. Imaging studies
5. Treatment
History
1. Identification of the type of incontinence.
2. onset, course and severity, duration , associated LUTS (lower urinary tract
symptoms).
3. Past medical history (medications , surgeries)
4. Gynaecological, obstetric history including POP (pelvic organ prolapse).
5. Neurologic history: ex, spinal cord injury or surgery.
Examination
1. Abdominal examination
2. Pelvic examination: External genitalia, Internal pelvic organs, POP, Stress

test
3. Neurologic Examination. Sensory examination, Reflexes
Urodynamic studies
1. Uroflowmetry
2. Cystometrogram
3. Voiding pressure
4. EMG (electromyogram)
5. UPP (urethral pressure profile)
6. Videourodynamics
Chapter 31. Urinary incontinence 231
Urodynamic studies assess the lower urinary tract function by measuring

physiologic parameters as pressure, flow, leak, volume, bladder descent.
These measurements help determining the underlying pathophysiology and
can help in making treatment decisions.
1-Uroflowmetry: recording urine flow rate in mL/sec.
2-cystometrogram: Filling the bladder while recording the pressure-volume

relationship
3-Voiding pressure; measuring pressure in the bladder with voiding.

4-Electromyogram of urethral sphincter: measures sphincters activity
Elecrodes either placed on perineal skin or needles are placed directly into
urethral sphincters
232 31.1. Urinary incontinence
5-Assessment of urethral function:
a. N.B. the normal urethra shouldn‘t leak with intra abdominal pressure.
b. The urethral pressure profile:

the continual recording of pressure through a hole in the side of a small
catheter as it is pulled from a point within the bladder, through the vesical
neck, and down the entire urethra; it gives indications of the functional
length of the urethra and the points of maximal urethral resistance.
6-Videourodynamics: combines cystography with urodynamics.
Imaging studies:
1. Voiding cystourethrogram (VCUG) PATIENT strains with full bladder „

leakage (if present)is recorded radiologicaly it also may be used to mea-
sure the degree of cystocele.
2. Magnetic resonance imaging (MRI) Used to measure the POP with out
radiation
Disadvantage: should be done at supine position so,it may underestimate
the degree of prolapse
Treatment: 1. Palliative 2. Pharmacological 3. Surgical

Palliative treatment
1. Behavioral modification: Teach patients some habits to improve symp-

toms like telling them not to delay voiding or decrease the caffeine intake
2. Pelvic floor therapy (KEGEL exercises)
3. Urethral inserts, pessary, catheters
Pharmacological treatment of Stress incontinence:
1. -adrenergic agonists: increase the tone of internal sphincter e.g. Pseu-

doephedrine
2. Estrogen in post menopausal women
3. Antimuscarinic agents to supress the detrusor overactivity

• Oxybutynine chloride (Ditropan)

• Tolterodine tetrate (DETROL)
Surgical treatment
Surgical treatment of stress incontinence:
Aims to make the bladder outlet resistant against increased intra abdominal
pressure.
A. Urethral bulking; collagen, teflon, silicon or autologous fat.
B. Colposuspentions (retropubic suspention procedures) support and re-

store bladder neck to its retropubic location.
C. Transvaginal bladder necksuspentions:
D. Pubo-vaginal sling: tapes below the bladder neck to support the urethra
to suprapubic rectus muscle
E. Artificial urinary sphincter: artificial inflated cuff around bladder neck

and proximal urethra and deflated by scrotal or labial pump
Surgical treatment of urge urinary incontinence:
• A-Augmentation cystoplasty:
bowl segments could be used for patients with overactive bladder refrac-
tory to medications
• B-Sacral neuro modulation:

placement of a surgical electrod permanently stimulating S3 afferent or
motor nerves this could be used for patients with over active bladder or
urine retention refractory to medications
Urinary diversion
for stress and urge incontinence with patients refractory to all above men-
tioned ways .
234 31.2. Drug and urinary incontinence
31.2 Drug and urinary incontinence
Urge urinary incontinence
Anticholinergic drugs are first line pharmacologic treatment effective in

suppressing premature detrusor contractions and relieve symptoms
Oxybutynin and tolterodine
• Immediate release with high rate of adverse effects as: dry mouth, con-
stipation, headache, tachycardia, cognitive impairment and urinary re-
tention so not preferred to use in complex drug regimen
• Extended release causes less dry mouth
• Sedation at initial phases of treatment, so, warn patient against driving

and working machines
• If patient report intolerable adverse effects or inadequate symptoms re-

live, switch to other agents
Mirabegron:
1. Beta 3 agonist
2. First line drug for overactive bladder, relax detrusor muscle, takes 4-8
weeks to optimal efficacy
3. Adverse effects: hypertension, nasopharyngitis, UTI and headache
Tricyclic antidepressants:
• No more efficacy than oxybutynin
• May cause serious adverse effects
• Reserved for patients having depression or neuropathic pain, mixed UI
Stress incontinence
Surgery is the first line therapy

Drug therapy:
Agents enhancing supportive structure underneath urethral mucosa
Estrogen
• Local vaginal estrogen only in case of local estrogen deficiency
• Mode of action of local estrogen:
– Enhance local microcirculation,

– Trophic to uroepithelium and collagenous structure around urethra,
– Enhance number and sensitivity of alpha receptor
• Oral estrogen is associated with adverse effects and risks and may in-
duce UI
Agents enhancing 5HT and NE dependent pathways of micturition
Duloxetine
• Selective 5HT-NE reuptake inhibitor
• Enhance urethral tone via affecting ascending and descending pathways

controlling urethral smooth muscle
• Disadvantages: intolerability, drug interactions and withdrawal manifes-

tation in case of sudden stoppage
Agents that stimulate urethra
Alpha agonists
•Not used due to long list of contraindications (hypertension, arrhythmia, my-

ocardial infarction, renal failure and narrow angle glaucoma) and adverse
effects as hypertension, headache, dry mouth, nausea and insomnia
236 31.2. Drug and urinary incontinence
Drugs that exacerbate urinary incontinence
Drug Effect
Diuretics Causes polyuria, urgency and frequency
Alpha antagonists Cause urethral relaxation so benefit men with ob-
struction
Cause worsening of stress incontinence in fe-
males
Alpha agonists Cause urethral contraction, so worsen obstruc-
tion in males
May be potential treatment in stress incontinence
Calcium channel decrease smooth muscle contractility of bladder,
blockers (dihy- so may cause urinary retention in males and
dropyridine) overflow incontinence
Opioid analgesics Impair bladder contractility (urine retention)
Sedative hypnotics Causes confusion and sedation so lead to func-
tional incontinence
Atropine and at- Causes impaired urinary bladder contraction
ropine like drugs (urine retention)
May treat urge urinary incontinence
Tricyclic antide- Combination of anticholinergic and alpha block-
pressants (TCA) ing lead to unpredictable effects on UI
ACEIs Cause cough and worsen stress incontinence
References & Further reading
[1] Richard S. Snell. Clinical Anatomy by Regions. Lippincott Williams & Wilkins, 9th
edition, 2012.
[2] Leslie P. Gartner and James L. Hiatt. Color Textbook of Histology, chapter 19. Urinary
System., page 411. W.B. Saunders Company. Philadelphia, 3rd edition, 2007.
[3] Anthony L. Mescher. Junqueira’s, Basic Histology, Text and Atlas., chapter 19. Urinary
system. McGraw-Hill Education, 13th edition, 2013.
[4] David L. Nelson, Michael M. Cox, and Albert L. Lehninger. Lehninger’s Principles of
Biochemistry. Macmillan, 5th edition, 2008.
[5] Donald Voet, Judith Voet, and Charlotte Pratt. Fundamentals of biochemistry : life at
the molecular level. Hoboken, NJ: Wiley, 3rd edition, 2008.
[6] Richard Goering, Hazel Dockrell, Mark Zuckerman, Derek Wakelin, Ivan Roitt, Cedric
Mims, and Peter L. Chiodini. Mims’ medical microbiology. Philadelphia, PA: Mosby
Elsevier., 2008.
[7] Geo. Brooks, Karen C. Carroll, Janet Butel, and Stephen Morse. Jawetz, Melnick &
Adelberg’s medical microbiology. New York : London: McGraw-Hill Medical., 26th edi-
tion, 2013.
[8] Kaplan Medical. USMLE Step 1 Lecture Notes. Kaplan Test Prep. Kaplan Publishing,
1st edition, 2019.
[9] Lynne Shore Garcia. Diagnostic Medical Parasitology. Wiley, 6th edition, 2016.
[10] Elizabeth Zeibig. Clinical Parasitology: A Practical Approach. Saunders, 2nd edition,
2013.
[11] Jonathan Epstein. Robbins and Cotran pathologic basis of disease, chapter Male gen-
ital system and lower urinary tract., pages 657–680. Elsevier Saunders, 9th edition,
2015.
[12] Charles E. Alpers and Agnes B. Fogo. Robbins and Cotran pathologic basis of disease,
chapter Diseases of the kidney and collecting, pages 517–547. Elsevier, 9th edition,
2015.
[13] Mohan H., Mohan P., Mohan T, and mohan S., editors. Text book of pathology. Jaybee
Brothers Medical publishers, 7th edition, 2015.
237
238 References & Further reading
[14] Bertram Katzung, editor. Basic and Clinical Pharmacology. McGraw-Hill Education /
Medical, 14th edition, 2017.
[15] Laurence Brunton, Bjorn Knollmann, and Randa Hilal-Dandan. Goodman and Gilman’s
The Pharmacological Basis of Therapeutics. McGraw-Hill Education / Medical, 13th
edition, 2017.
[16] Joseph DiPiro, Robert Talbert, Gary Yee, Gary Matzke, Barbara Wells, and L. Michael
Posey. Pharmacotherapy: A Pathophysiologic Approach. McGraw-Hill Education / Med-
ical, 10th edition, 2016.
[17] John E. Hall. Guyton and Hall Textbook of Medical Physiology. Saunders, 13th edition,
2015.
[18] K Sembulingam and Prema Sembulingam. Essentials of Medical Physiology. Jaybee

Brothers Medical publishers, 6th edition, 2012.
[19] Kim E. Barrett, Susan M. Barman, Scott Boitano, and Heddwen Brooks. Ganong’s Re-
view of Medical Physiology. LANGE Basic Science. McGraw-Hill Education / Medical,
24th edition, 2012.
[20] Parveen Kumar and Michael Clark, editors. Kumar and Clark’s Clinical Medicine. Else-
vier, 9th edition, 2017.
[21] Michael L. Bishop, Edward P. Fody, and Larry E. Schoeff. Clinical Chemistry: Tech-
niques, Principles, Correlations. Wolters Kluwer Health- Lippincott Williams and
Wilkins, 6th edition, 2010.
[22] Jennifer Stevens, Jethro A. Herberg, and Michael Levin. Textbook of Pediatric Nephrol-
ogy, chapter Infectious Diseases and the Kidney in Children, pages 1616–1620.
Springer Heidelberg New York Dordrecht London., 7th edition, 2016.
[23] Priya Pais and Ellis D. Avner. Nelson Textbook of Pediatrics, chapter Nephrotic Syn-
drome, pages 2521– 2530. Philadelphia, 21th edition, 2019.
[24] John Reynard, Simon F. Brewster, Suzanne Biers, and Naomi Laura Neal. Oxford
Handbook of Urology. Oxford university press, 4th edition, 2019.
[25] Michael Chen, Thomas Pope, and David Ott. Basic Radiology. LANGE Clinical
Medicine. McGraw-Hill Education / Medical, 2nd edition, 2010.
[26] Murray Longmore, Ian Wilkinson, Andrew Baldwin, and Elizabeth Wallin. Oxford Hand-
book of Clinical Medicine. Oxford Medical Handbooks. Oxford University Press, 9th
edition, 2014.

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1 Anatomy and development of Kidney and Ureter 1

2 Histology of Glomerulous and renal tubules 21

3 Functions of the kidney 33

5 Role of Kidney in Acid Base Balance 61

7 Glomerular diseases in children 81

8 Pathology of glomerular diseases 89

10 Diabetic nephropathy 103

11 Chronic Kidney disease 105

12 Laboratory assessment of renal functions 109

13 Drug induced kidney injury 115

14 Acute kidney injury 119

15 Pathology of different renal diseases 123

16 Anatomy and development of urinary bladder and urethra 127

17 Histology of excretory passages 143

18 Physiology of urinary bladder 147

19 Nucleotide Metabolism 151

20 Imaging of urinary system 159

21 Urinary tract symptoms 165

22 Urolithiasis (Urinary Calculi) 171

23 Microbiology of urinary tract infections 177

24 Urinary tract infections 189

25 Diseases of urinary bladder 195

26 Urinary antiseptics 197

27 Parasites affecting The Urinary system 201

28 Tumors of urinary system 211

29 Obstructive uropathy 217

31 Urinary incontinence 229

1.1 Renal system organs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1

2.1 Diagram showing nephron components . . . . . . . . . . . . . . . . . . . . 22

3.1 Metabolic interrelationships of tissues in kidney failure. . . . . . . . . . . . . 38

4.1 Tubular functions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 39

5.1 pH value in the body . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 62

7.1 Degrees of proteinuria in children . . . . . . . . . . . . . . . . . . . . . . . . 87

8.1 Focal glomerulonephritis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 92

17.1 Ureter . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 144

18.1 Cystometrogram . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 148

19.1 Nucleotides . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 151

20.1 Normal PUT . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 160

27.1 Adult S. haematobium . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 204

28.1 Renal cell carcinoma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 212

29.1 Differential diagnosis of lower urinary tract obstruction . . . . . . . . . . . . 218

4.1 Difference between water and osmotic diuresis: . . . . . . . . . . . . . . . . 60

23.1 IMVC formula . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 181

26.1 Drug that alter Urine pH . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 200

Anatomy and development of Kidney and Ureter

Figure 1.1: Renal system organs

Figure 1.2: Right and left kidneys

Figure 1.3: The positions of the kidneys in male and female

Longitudinal section Kidney

• It is composed of an outer cortex and inner medulla.

Figure 1.4: Longitudinal section in the kidney

Coverings of the kidney

The kidneys have the following coverings from inside to outside:

Figure 1.5: Coverings of the kidney

Relations to the kidney

Anterior relations of right and left kidneys

Figure 1.6: Anterior relations of right and left kidneys

Posterior relations of the right and left kidneys

Figure 1.7: Posterior relations of the right and left kidneys

Blood supply of the kidney

There is a network of blood vessels throughout the kidneys

• There are no segmental veins like the segmental arteries. Blood