Infections and Pathology of the Urinary Tract

Question 1

Introduction

Answer 1

Bacterial infections common in young and
middle-aged females
• Occurs in infant males and elderly men if there
is an underlying UT abnormality
• Aetiologic organisms is usually a gram neg
bacterium, often a faecal contaminant from the
perineum, such as E. coli or Klebsiella
• Basic sequence starts as a cystitis, with or
without vesico-ureteral reflux, followed by
ureteritis and acute pyelonephritis, and possibly
then chronic pyelonephritis

Question 2

Cystitis:

Introduction/Definition

Answer 2

Cystitis
• Inflammation of the urinary bladder,
mostly due to bacterial infection
• Commonly seen in girls and young women
owing to the shorter urethra, as
compared to males
• Cystitis in males is due to an underlying
urethral abnormality
• Congenital urethral valves in infants
• Prostate enlargement in older men
Cystitis
Clinical presentation
• 
Acute cystitis with ulceration
Acute cystitis
A

Question 3

Cystitis:

Predisposing Factors

Answer 3

• Predisposing conditions include:
➢Pregnancy
➢Intercourse with urethral trauma
➢Poor toilet hygiene
➢Diabetes mellitus
➢Instrumentation and catheterization

Question 4

Cystitis:

Clinical Picture

Answer 4

Dysuria
• Frequency
• Nocturia
• Urgency
• Sometimes supra-pubic pain and
tenderness
• Usually no fever

Question 5

Acute Pyelonephritis:

Definition

Answer 5

Defined as infection of the renal pelvis
and parenchyma
• Important cause of renal disease
• Also a commonly undiagnosed cause of
death in diabetic patients

Question 6

Acute Pyelonephritis:

Pathogenesis

Answer 6

Pathogenesis of acute
pyelonephritis
• Ascending infection: starts as an acute
cystitis with damage to the vesicoureteral valves, causing reflux of
infected urine that results in ureteritis
and subsequent pyelitis (inflammation of
the renal pelvis), followed by spread of
infection through collecting tubules into
renal parenchyma
Pathogenesis of acute
pyelonephritis
Pathogenesis of acute
pyelonephritis
• Haematogenous spread from another
infection through septicaemia or pyaemia
• Examples include:
➢Infective endocarditis
➢Pneumonia
➢Osteomyelitis
• Here the infection begins in the renal
parenchyma and then spreads later to the
renal pelvis
• Both kidneys are usually involved

Question 7

Acute Pyelonephritis:

Clinical Picture

Answer 7

Clinical presentation
• Symptoms of cystitis may be present,
i.e. dysuria, frequency, nocturia and
urgency
• Patients are usually febrile
• Flank pain with renal angle tenderness

Question 8

Acute Pyelonephritis:

Pathology-Macroscopy

Answer 8

Pathology of acute pyelonephritis
• Macroscopic appearance:
➢Kidneys are enlarged, red and oedematous
➢Small yellow subcapsular abscesses may be
present
➢Cut-section may show yellow lines of
suppuration stretching up from papillae
➢Pelvic mucosa is hyperaemic and
oedematous
➢Urine is turbid or frankly purulent
Kidney surface with multiple subcapsular abscesses
Abscess within renal parenchyma

Question 9

Acute Pyelonephritis:

Pathology-Microscopy

Answer 9

Pathology of acute pyelonephritis
• Microscopic appearance:
- Neutrophils present within the renal
tubules as well as the interstitium
(infective tubulo-interstitial nephritis)
- May show abscess formation
- Glomeruli are normal

Question 10

Acute Pyelonephritis:

Complications

Answer 10

Acute renal failure
• Recurrent episodes of acute infection with eventual
chronic pyelonephritis
• Papillary necrosis – decrease in medullary blood
flow especially common in diabetic patients or
where there is urinary tract obstruction
• Pyonephrosis whereby pus fills and distends the
entire renal pelvis, calyces and ureter (seen in total
urinary obstruction)
• Rupture of a subcapsular abscess with extension of
infection into the perinephric tissue
• Even septicaemia

Question 11

Papillary Necrosis

Answer 11

Infection in the context of obstruction
• Infection in the context of diabetes
mellitus
• Analgesic nephropathy (NSAID abuse -
phenacetin)
Prognosis of acute pyelonephritis
•

Question 12

Acute Pyelonephritis:

Prognosis

Answer 12

Prognosis is generally good with
antibiotic treatment
• Acute pyelonephritis may prove fatal if
untreated
• Some patients, particularly babies and
elderly individuals, do not necessarily
present with the classic symptoms of
pyelonephritis, so remember to examine
the urine with a dipstick

Question 13

Chronic Pyelonephritis:

Introduction/Definition

Answer 13

Chronic pyelonephritis is fairly common

Usually seen in adults

One of the most common causes of chronic renal failure

Question 14

Chronic Pyelonephritis:

Aetiology and Pathogenesis

Answer 14

• Usually develops as a complication of
repeated attacks of acute pyelonephritis
• Also occurs in chronic urinary tract
obstruction that predisposes to ascending
urinary infections:
➢Calculi (kidney stones)
➢Tumours
➢Prostate enlargement
➢Ureteral strictures
• Congenital vesico-ureteric reflux

Question 15

Chronic Pyelonephritis:

Vesico-ureter Reflux

Answer 15

Vesico-ureteric reflux is a congenital abnormality of the terminal portion of the ureter

Presents in early childhood

The high pressure in the renal pelvis causes intra-parenchymal reflux with parenchymal scarring

Question 16

Chronic Pyelonephritis:

Pathology-Macroscopic

Answer 16

• Macroscopic appearance
➢Unilateral or bilateral involvement
depending on the pathogenesis
➢Kidney is small
➢Kidney shows numerous large, irregular
cortical scars
➢The renal pelvis and calyces are deformed
and often dilated (hydronephrosis) with
accompanying pressure atrophy of renal
cortex

Question 17

Chronic Pyelonephritis:

Pathology-Microscopic

Answer 17

Chronic inflammatory cell infiltrate in the
kidney interstitium, i.e. lymphocytes and
plasma cells

➢Interstitial fibrosis

➢Tubules are atrophic

➢Some tubules are dilated and filled with hyaline casts, which resembles the thyroid gland (called thyroidization)

➢Glomeruli show secondary changes, such as
glomerular sclerosis and peri-glomerular fibrosis

Question 18

Chronic Pyelonephritis:

Complications

Answer 18

Chronic renal failure

Secondary hypertension

Question 19

Bilharzia:

Incidence

Answer 19

All ages

In South Africa, bilharzia is very
common in the provinces north of the
Vaal River, as well as in the northern
regions of Kwa Zulu Natal

Question 20

Bilharzia:

Pathogenesis

Answer 20

Bilharzia caused by the trematode (fluke) Schistosoma haematobium

Bilharzia seen where fresh water has become contaminated by Schistosoma

People bathing or swimming in such water are at risk

Lifecycle involves the fresh water snail and the human

Schistosoma ova (eggs) are excreted in the urine into the water

Ovum releases a motile ciliated miracidium that enters an aquatic snail host

After a period of development within the snail
host, the cercaria are released, and these penetrate the skin of people in the water

The cercaria, now called schistosomules,
migrate to the lungs where they mature into adult worms

Adult worms usually migrate to the portal vessels where they mate

The adult female fluke then migrates to the venous plexus around the bladder

The ova (eggs) are laid in the bladder wall

The eggs secrete enzymes that dissolve host
tissues in the vicinity, and so doing allows the
eggs to enter the bladder lumen, where they
can be excreted in the urine, and so perpetuate
the cycle

Live bilharzia eggs elicit an acute inflammatory
reaction

Once the eggs die and calcify, they elicit a
granulomatous response as well as fibrosis

Question 21

Bilharzia:

Clinical Presentation

Answer 21

The most important clinical feature in bilharzial cystitis is haematuria

Question 22

Bilharzia:

Pathology-Macroscopy

Answer 22

Mucosa of the bladder and ureters becomes thickened and granular, i.e. a ‘wet sand’ appearance macroscopically

Ureters may become stenotic because of
the fibrosis

Question 23

Bilharzia:

Pathology-Microscopy

Answer 23

Bilharzia ova present in mucosa, viable or
calcified

Acute inflammation with eosinophils

Granulomas with foreign body-type giant cells

Later fibrosis

Overlying transitional epithelium undergoes
squamous metaplasia

Question 24

Bilharzia:

Complications

Answer 24

• Squamous cell carcinoma of bladder
• Fibrosis of ureter(s) causes ureter
obstruction, which leads to hydronephrosis
and predisposes to ascending bacterial
infections of the urinary tract, such as
pyelonephritis
• In a heavy Schistosoma infestation, eggs
may enter the systemic venous circulation,
i.e. vesical venous plexus to inferior vena
cava, and so embolise to the lungs, causing
pulmonary hypertension

Question 25

Renal Tuberculosis

Answer 25

Uncommon Secondary to pulmonary tuberculosis Two types: 1.Miliary tuberculosis 2.Isolated organ tuberculosis, called tuberculous pyelonephritis, which may be uni- or bilateral, and shows extensive caseation and destruction of the kidney

Question 26

Glomerular Disease/Glomerulopathy: Definition/Introduction

Answer 26

The term glomerulopathy includes several diseases that affect the glomeruli (inflammatory and non-inflammatory) Glomerulonephritis refers to inflammatory disease / inflammation of the glomerulus. These diseases have different aetiologies, different morphologic appearances and varying prognoses The glomerulopathies may also clinically present in different ways Some glomerulopathies resolve and have a good prognosis, but other cases follow a chronic course, resulting in a chronic glomerulonephritis /-opathy with eventual chronic renal failure (such patients require dialysis and/or renal transplantation)

Question 27

Glomerular Disease/Glomerulopathy: Aetiology

Answer 27

1. Primary, i.e. the glomeruli are the primary target of the disease process 2. Secondary, i.e. glomerular damage occurs because of another underlying systemic disease (extra-renal organs also involved): - Autoimmune diseases, like SLE (inflammatory) - Diabetes mellitus (non-inflammatory) - Systemic hypertension (non-inflammatory)

Question 28

Glomerular Disease/Glomerulopathy: Clinical Presentation

Answer 28

Recurrent painless haematuria Asymptomatic proteinuria Nephritic syndrome: ➢ Haematuria ➢ Proteinuria ➢ Hypertension ``` Nephrotic syndrome: ➢ Heavy proteinuria (in adults >3,5 g/day and in children >2 g/m²/day) ➢ Hypoproteinaemia ➢ Severe oedema (often anasarca) ➢ Hypercholesterolaemia ``` Chronic renal failure Acute diffuse proliferative glomerulonephritis • Incidence: ➢ Fairly common ➢ All age groups, but mainly children • Aetiology: ➢ Usually follows on a streptococcal infection (often called post streptococcal glomerulonephritis) • Pathogenesis: ➢ Antibodies bind to the organism, complement is bound and immune complexes are formed, which are deposited on the subepithelial part of the glomerular basement membrane • Clinical picture: ➢ Nephritic syndrome

Question 29

Glomerular Disease/Glomerulopathy: Clinical Presentation

Answer 29

Recurrent painless haematuria Asymptomatic proteinuria Nephritic syndrome: ➢ Haematuria ➢ Proteinuria ➢ Hypertension ``` Nephrotic syndrome: ➢ Heavy proteinuria (in adults >3,5 g/day and in children >2 g/m²/day) ➢ Hypoproteinaemia ➢ Severe oedema (often anasarca) ➢ Hypercholesterolaemia ``` Chronic renal failure

Question 30

Acute Diffuse Proliferative Glomerulonephritis: Incidence

Answer 30

Fairly common All age groups, but mainly children

Question 31

Acute Diffuse Proliferative Glomerulonephritis: Aetiology

Answer 31

Usually follows on a streptococcal infection (often | called post streptococcal glomerulonephritis)

Question 32

Acute Diffuse Proliferative Glomerulonephritis: Pathogenesis

Answer 32

Antibodies bind to the organism, complement is bound and immune complexes are formed, which are deposited on the subepithelial part of the glomerular basement membrane

Question 33

Acute Diffuse Proliferative Glomerulonephritis: Clinical Picture

Answer 33

Nephritic syndrome

Question 34

Acute Diffuse Proliferative Glomerulonephritis: Pathology-Macroscopy

Answer 34

Kidneys slightly enlarged Pale appearance

Question 35

Acute Diffuse Proliferative Glomerulonephritis: Pathology-Microscopy

Answer 35

All glomeruli involved, i.e. diffuse The entire glomerulus is involved, i.e. global Glomeruli are hypercellular owing to increase in mesangial cells and swelling of endothelial cells Glomeruli have a lobular appearance Neutrophils in glomeruli Tubules contain casts and may show acute tubular necrosis

Question 36

Acute Diffuse Proliferative Glomerulonephritis: Pathology-Ultrastructural

Answer 36

Immune complexes are present between the podocytes (visceral epithelial cells) and the glomerular basement membrane, forming so-called “subepithelial humps”

Question 37

Acute Diffuse Proliferative Glomerulonephritis: Prognosis

Answer 37

In children, prognosis is good, with over 90% of patients recovering within weeks In adults, prognosis is reasonable, with approximately 60% of patients recovering Death may occur Hypertension in the acute phase More commonly, death results from progressive renal disease and chronic renal failure

Question 38

Membranous Glomerulopathy: Incidence

Answer 38

Less common than post streptococcal glomerulonephritis, but still fairly common All age groups, but usually adults

Question 39

Membranous Glomerulopathy: Aetiology

Answer 39

Primary (85% of cases) Secondary (15% of cases), which includes: ~ Infections, e.g. hepatitis B, syphilis, malaria ~ Drugs (penicillamine, gold, mercury, heroin) ~ Certain malignant tumours (lymphomas, melanomas, bronchus and breast CA)

Question 40

Membranous Glomerulopathy: Pathogenesis

Answer 40

Immune complexes are formed and deposited between the basement membrane and the epithelial cells The basement membrane then grows outwards so that the immune complexes are eventually incorporated into the basement membrane •

Question 41

Membranous Glomerulopathy: Clinical Picture

Answer 41

Initially nephrotic syndrome, but some patients | progress to chronic renal failure

Question 42

Membranous Glomerulopathy: Pathology-Microscopy

Answer 42

➢The glomerular basement membrane shows diffuse thickening, giving a rigid appearance to the glomerulus on light microscopy (i.e. open loops but with thickened walls) ➢No increase in cellularity ➢No inflammatory cells either ➢Silver stains accentuate the thickened basement membranes, showing characteristic “spikes”

Question 43

Membranous Glomerulopathy: Pathology-Ultrastructure

Answer 43

``` The electron microscopic picture varies according to the stage of the disease: ➢Stage I: Subepithelial immune complex deposits (these deposits are actually intramembranous) ➢Stage II: Deposits and BM “spikes” ➢Stage III: Deposits enclosed by BM ➢Stage IV: Deposits disappear, with a “moth-eaten” appearance to the basement membrane ```

Question 44

Membranous Glomerulopathy: Prognosis

Answer 44

In children, prognosis is reasonable In adults, prognosis is less favorable Prognosis remains unpredictable

Question 45

Minimal Change Disease: Incidence

Answer 45

Fairly common Mainly children aged 1 to 4 years of age

Question 46

Minimal Change Disease: Aetiology

Answer 46

Unknown

Question 47

Minimal Change Disease: Pathogenesis

Answer 47

There is damage to the glomerular basement membrane causing a selective proteinuria of low molecular weight protein, such as albumin No immune complex formation (no inflammation)

Question 48

Minimal Change Disease: Clinical Picture

Answer 48

Nephrotic syndrome

Question 49

Minimal Change Disease: Pathology-Microscopy

Answer 49

Normal

Question 50

Minimal Change Disease: Pathology-Ultrastructure

Answer 50

Shortening and fusion of the foot processes of the podocytes (this is nonspecific and probably results from the proteinuria) Prominent microvilli

Question 51

Minimal Change Disease: Prognosis

Answer 51

Generally good Patients usually respond dramatically to steroid therapy

Question 52

Rapidly Progressive Glomerulonephritis: Incidence Aetiology

Answer 52

Rare Aetiology: Commonly follows on post streptococcal glomerulonephritis but it can also complicate other types of glomerulonephritis (eg. SLE, vasculitides) Also known as CRESCENTIC GLOMERULONEPHRITIS

Question 53

Rapidly Progressive Glomerulonephritis: Pathogenesis

Answer 53

There is severe glomerular injury causing leakage of fibrin, which in turn stimulates the epithelial cells lining Bowman’s capsule to proliferate These cells form “crescents” which eventually compress the glomeruli

Question 54

Rapidly Progressive Glomerulonephritis: Pathology-Microscopy of crescentic glomerulonephritis

Answer 54

Usually an acute diffuse proliferative glomerulonephritis is present Formation of cellular crescents Cellular crescents eventually become fibrotic crescents

Question 55

Rapidly Progressive Glomerulonephritis: Prognosis

Answer 55

``` Prognosis is very poor • Crescentic glomerulonephritis is characterised by a rapid clinical course, hence its alternative name of rapidly progressive glomerulonephritis • Patients die of chronic renal failure within months ```

Question 56

Diabetes Mellitus: Incidence

Answer 56

Diabetes mellitus is a frequent cause of renal disease, particularly in type I diabetes (IDDM)

Question 57

Diabetes Mellitus: Pathogenesis

Answer 57

Microangiopathy

Question 58

Diabetes Mellitus: Clinical Presentation

Answer 58

Initially nephrotic syndrome Later hypertension and chronic renal failure

Question 59

Renal Pathology of Diabetes Mellitus

Answer 59

Diffuse glomerulosclerosis: ➢Diffuse increase in the amount of the mesangial matrix and thickened basement membrane Nodular glomerulosclerosis: ➢Nodular lesions of mesangial matrix present in some of the glomeruli Insudative lesions (comprise of plasma proteins and lipid): ➢Hyaline arteriolosclerosis, i.e. hyaline thickening of the small arteries and arterioles ➢“Capsular drop” within the basement membrane of Bowman’s capsule ➢“Fibrin cap” around the periphery of the glomerular capillary loops

Question 60

Diabetes Mellitus: Complications

Answer 60

Increased incidence of urinary tract infections More susceptible to papillary necrosis in acute pyelonephritis

Question 61

Focal Segmental Glomerulosclerosis: Incidence

Answer 61

Important cause of nephrotic syndrome 10 % of nephrotic syndrome in children Primary or secondary to other disease causing focal segmental scarring of the glomerulus: ➢Diabetes, HIV, heroin abuse, reflux

Question 62

Focal Segmental Glomerulosclerosis: Pathogenesis

Answer 62

Focal (some of the glomeruli) segmental (only | part of the glomerulus) is scarred (sclerotic)

Question 63

Acute Tubular Necrosis: Aetiology

Answer 63

Important cause of renal failure Toxic injury (drugs or toxins) or Ischaemic injury (usually secondary to haemodynamic causes eg. shock)

Question 64

Acute Tubular Necrosis: Clinical Picture

Answer 64

Oliguric phase followed by diuretic phase Regeneration of the tubules permits clinical recovery

Question 65

Acute Tubular Necrosis: Pathology-Macroscopic

Answer 65

Pale cortex Swollen medulla

Question 66

Acute Tubular Necrosis: Pathology-Microscopic

Answer 66

Tubular epithelial cell injury (no glomerular involvement) : - No proteinuria - Only abn in electrolyte and fluid homeostasis Sloughing to form cellular and granular casts Vacuolisation of cells Flattening of cells