GLOMERULAR DISEASES
PRESENTER:DR. ARIAGA
CONSULTANT PATHOLOGIST
SCOPE
•
•
•
•
•
Basic anatomy of the kidney.
Basic physiology of the kidney.
Classification of glomerular diseases
Clinical presentation
Examples of glomerular diseases
Anatomy of the kidney-Location
• Paired organs found along the posterior
muscular wall of the abdominal cavity.
• Retroperitoneal and partially protected by the
11th and 12th ribs
• Right kidney is slightly lower that the left due
to liver
• Surrounded by renal capsule ,adipose tissue
and renal fascia
Anatomy of the kidney-Structure
Anatomy of the kidney-Nephron
• Functional unit of the kidney
• Each kidney contains around 1 million
individual nephrons.
• Made of 2 main parts:
• Renal corpuscle which is responsible for
filtering the blood. Its formed by the
capillaries of the glomerulus and the
glomerular capsule (also known as Bowman’s
capsule).
Anatomy of the kidney-Nephron
• Renal tubule is responsible for tubular
reabsorption and tubular secretion.
• Its made up of the proximal convoluted
tubule, Loop of Henle, distal convoluted
tubule and the collecting duct.
• The renal tubule carries urine from the
glomerular capsule to the renal pelvis.
Anatomy of the kidney-Nephron
Physiology of renal function
• Kidneys make up 1 % of body mass.
• Receive about 25% of cardiac output.
Main functions of the kidney
Removes metabolic wastes from the body
especially those containing nitrogen
Regulation of water & électrolyte balance
Regulation of acid - base balance
Regulation of arterial blood pressure
Production of erythropoietin & activation of
vitamin D
Basic categories of Renal diseases
• The study of kidney diseases is facilitated by
dividing them into those that affect the four
basic morphologic components: glomeruli,
tubules, interstitium, and blood
Glomerular diseases
• A group of diseases characterized by similar
clinical manifestations ：Proteinuria,
hematuria, edema, hypertension
• Can be primary glomerulopathies or
secondary glomerular diseases.
Primary glomerular diseases
• Rapidly progressive (crescentic)
glomerulonephritis
• Membranous nephropathy
• Minimal-change disease
• Focal segmental glomerulosclerosis
• Membranoproliferative glomerulonephritis
• Dense deposit disease
• IgA nephropathy
Systemic diseases with glomerular
involvement
•
•
•
•
•
•
•
•
Systemic lupus erythematosus
Diabetes mellitus
Amyloidosis
Goodpasture syndrome
Microscopic polyarteritis/polyangiitis
Wegener granulomatosis
Henoch-Schönlein purpura
Bacterial endocarditis
Structure of the Glomerulus
• Glomerulus consists of an anastomosing
network of capillaries lined by fenestrated
endothelium invested by two layers of
epithelial cells ,visceral epithelial cells
(podocytes) are incorporated into the capillary
wall and parietal epithelium, situated on the
Bowman capsule.
Structure of glomerulus
Structure of glomerulus
• The glomerulus has fenestrated endothelial
cells that are impermeable to proteins of the
size of albumin (70 kilodaltons [kD] molecular
weight) or larger, permeability is also charge
dependent(the more cationic,the more
permeable). Glomerulus has anionic
components
Pathogenesis of Glomerular Injury
• Immune mediated mechanisms underlie most
forms of primary glomerulopathy and many of
the secondary glomerular disorders
• Two forms of antibody-associated injury have
been established:
1. Injury by antibodies reacting in situ within the
glomerulus, either binding to insoluble fixed
(intrinsic) glomerular antigens or extrinsic
molecules planted within the glomerulus
2. Injury resulting from deposition of circulating
antigen-antibody complexes in the glomerulus.
Antibody mediated GN-In-situ
Immune complex
Location: GBM sub-epithelial
•Circulating autoantibodies with intrinsic autoantigens
Antibody mediated GN
- In-situ Immune complex
(trapped Ag)
Location: GBM sub-epithelial
Extrinsic antigens planted within the glomerulus
Glomerulonephritis from deposition
circulating immune complexes
• Glomerular injury is caused by the trapping of
circulating antigen-antibody complexes within
glomeruli
• The antibodies have no immunologic
specificity for glomerular constituents
• The antigens that trigger the formation of
circulating immune complexes may be of
endogenous origin( SLE or in IgA nephropathy)
or they may be exogenous, as may occur
• The antigen may be exogenous e.g tumors,
infections-bacterial products (streptococcal
proteins), the surface antigen of hepatitis B
virus, hepatitis C virus antigens,antigens of
T.pallidum, P.falciparum.
Mechanisms of Glomerular Injury
• The antigen-antibody complexes formed or
deposited in the glomeruli may elicit a local
inflammatory reaction that produces injury
1. Cell-Mediated Immunity-sensitized T cells cause
glomerular injury and are involved in the
progression of some glomerulonephritides
2. Activation of Alternative Complement Pathway
3. Antibodies may also be directly cytotoxic to cells
in the glomerulus.
Pathogenesis
In situ immune
complex
Circulating
immune complex
Activation of T
lymphocytes
Acitvation of complements
cytokines
C5b-9
C5a,C3a
Epithelial, mesangial,
Endothelial cells
polynuclear
leucocyte, platelets
Mesangial
cells
Macrophage
oxidative stress, protease, matrix accumulations
Glomerular Disease
Mediators of glomerular Injury
Cells
o Neutrophils and monocytes
 Infiltrate the glomerulus due to activation of
complement via chemotactic agents and Fcmediated adherence and activation.
 Neutrophils release proteases which cause
GBM degradation; oxygen-derived free
radicals, which cause cell damage
o Macrophages and T lymphocytes,
o Platelets may aggregate in the glomerulus during
immune-mediated injury, release of eicosanoids
that cause vascular injury and proliferation of
glomerular cells.
o Resident glomerular cells, particularly mesangial
cells, produce inflammatory mediators, including
reactive oxygen species (ROS),cytokines, growth
factors, eicosanoids,NO
Soluble Mediators
o Complement activation leads to the
generation of chemotactic products that
induce leukocyte influx, the formation of the
C5b-C9 causes cell lysis but, stimulates
mesangial cells to produce oxidants,
proteases, and other mediators.
o Cytokines, particularly IL-1 and TNF, induce
leukocyte adhesion
o Chemokines such as monocyte chemoattractant
protein 1 promote monocyte and lymphocyte
influx. Platelet-derived growth factor (PDGF) is
involved in mesangial cell proliferation,fibroblast
growth factor cause ECM deposition and
hyalinization leading to glomerulosclerosis.
o The coagulation system is also a mediator of
glomerular damage.
Epithelial Cell Injury
o Podocyte injury is common to many forms of
both primary and secondary glomerular
diseases
o morphologic changes in the podocytes are
effacement of foot processes, vacuolization,
and retraction and detachment of cells from
the GBM
Glomerulus injury pathological
response
• One or more of four basic tissue reactions
occur after injury
1. Hypercellularity- proliferation of mesangial or
endothelial cells,Infiltration of leukocyte
2. Basement membrane thickening.
3. Hyalinosis and Sclerosis is characterized by
deposition of extracellular collagenous matrix
Nephritic Syndrome
• Presents with hematuria, red cell casts in the
urine, azotemia, oliguria, and mild to
moderate hypertension.
• Proteinuria and edema are common, but
these are not as severe as in encountered in
the nephrotic syndrome,
• Occurs in:
Acute Proliferative (Poststreptococcal,
Postinfectious) Glomerulonephritis
• Characterized histologically by diffuse
proliferation of glomerular cells associated
with influx of leukocytes.
• These lesions are typically caused by immune
complexes.
• The inciting antigen may be exogenous or
endogenous.
Poststreptococcal Glomerulonephritis
• It usually appears 1 to 4 weeks after a
streptococcal infection of the pharynx or skin
(impetigo). Skin
• Poststreptococcal glomerulonephritis occurs
most frequently in children 6 to 10 years of age
• Etiology and Pathogenesis: Caused by immune
complexes containing streptococcal antigens and
specific antibodies, which are formed in situ.
• Streptococcal pyogenic exotoxin B (SpeB) is
the principal antigen which activates
complement directly
• Morphology: Enlarged, hypercellular
glomeruli
• The proliferation and leukocyte
infiltration is global and diffuse
• Swelling of endothelial cells leads to
obliterates the capillary lumen
• By immunofluorescence microscopy, there
are focal granular deposits of IgG,C3, and
sometimes IgM in the mesangium.
• Clinical Course: In children malaise, fever,
nausea, oliguria, and hematuria1 to 2 weeks
after recovery from a sore throat.
• Red cell casts in the urine, mild proteinuria
(usually less than 1 gm/day), periorbital
edema, and mild to moderate hypertension.
• In adults, hypertension or edema, frequently
with elevation of BUN.
• Lab: elevations of antistreptococcal antibody
titers and a decline in the serum
concentration of C3
Nephrotic syndrome
• Nephrotic syndrome is caused by a derangement
in glomerular capillary walls resulting in increased
permeability to plasma proteins. The
manifestations of the syndrome include:
– Massive proteinuria, with the daily loss of 3.5 gm or
more of protein (less in children)
– Hypoalbuminemia, with plasma albumin levels less
than 3 gm/dL
– Generalized edema
– Hyperlipidemia and lipiduria
• Nephrotic syndrome can be
• Primary, being a disease specific to the
kidneys,
• Secondary, being a renal manifestation of a
systemic general illness
Primary causes
• Minimal-change nephropathy(70-90% children
and 10-15%inadult)
• Focal glomerulosclerosis (15%inadult)
• Membranous nephropathy (30%inadult)
• Mesangial proliferative glomerulonephritis .
• Rapidly progressive glomerulonephritis
Secondary causes
•
•
•
•
Diabetes mellitus
Lupus erythematosus
Amyloidosis and paraproteinemias
Viral infections (eg, hepatitis B, hepatitis C,
HIV )
• Preeclampsia
• Pathophysiology of proteinuria-damage to the
endothelial surface, the glomerular basement
membrane, or the podocytes. It is due to both
the proteinuria and due to the increase renal
catabolism (in tubules).
Pathogenesis of edema
Metabolic consequences of proteinuria
Metabolic consequences of the nephrotic syndrome include
the following:
⦁
⦁
⦁
Infection
Hyperlipidemia and atherosclerosis
Hypovolemia
Proposed explanations of Infection in NS
Proposed explanations include the following:
⦁ Urinary immunoglobulin losses
⦁
Edema fluid acting as a culture medium
⦁
Protein deficiency
⦁
Decreased bactericidal activity of the leukocytes
⦁
Immunosuppressive therapy
⦁
Urinary loss of a complement factor (properdin factor B)
that opsonizes certain bacteria
Hypperlipedemia
⦁
Due to increase hepatic lipoprotein synthesis that is triggered
by reduced oncotic .
⦁
Defective lipid catabolism has also important role.
⦁
⦁
LDL and cholesterol are increased in majority of patients
whereas VLDL and triglyceride tends to rise in patients with
severe disease.
It increases the relative risk for MI
Hypercoagulability
⦁
Multifactorial in origin
⦁
Increase urinary loss of antithrombin III
⦁
Hyperfibronogenemia due to increase hepatic synthesis.
⦁
Alteration in endothelial function
Symptoms and signs
⦁
Prolonged NS may result in nutritional
deficiencies, including protein malnutrition
⦁
,myopathy,
⦁
Spontaneous peritonitis and opportunistic
infections
⦁
Coagulation disorders, with decreased
fibrinolytic activity
Episodic hypovolemia, are a serious
thrombotic risk ( renal vein thrombosis).
⦁Edema
⦁
Pathogenesis of edema
Membranous Nephropathy
• Characterized by diffuse thickening of the
glomerular capillary wall due to the accumulation
of deposits containing Ig
• Causes:
 Drugs (penicillamine, captopril, gold, nonsteroidal
antiinflammatory drugs (NSAIDs).
 Infections (chronic hepatitis B, hepatitis C,
syphilis,schistosomiasis, malaria)
• Pathogenesis; immune complex-mediated
disease. The antigens may be endogenous or
exogenous.
• By light microscopy the glomeruli have diffuse
thickening of the glomerular capillary wall
Minimal-Change Disease
• Characterized by diffuse effacement of foot
processes of visceral epithelial cells
• Most frequent cause of nephrotic syndrome in
children
• Peak incidence is between 2 and 6 years of
age
• C/F Proteinuria
HIV-Associated Nephropathy
• HIV infection can directly or
indirectly(drugs,infections) cause renal injury
• Morphologic features of HIV-associated
nephropathy include collapsing variant of FSGSsclerosis of some, but not all, glomeruli and in the
affected glomeruli, only a portion of the capillary
tuft is involved
• C/F; nephrotic syndrome ,Hypertension,
microscopic hematuria, and some degree of
azotemia
Focal segmental glomerulosclerosis
Tubular and Interstitial Diseases
• Present as:
1. Primary tubular diseases: Include tubular
injury by ischaemic or toxic agents i.e. acute
tubular necrosis.
2. Tubulointerstitial diseases: Include
inflammatory involvement of the tubules and
the interstitium i.e. pyelonephritis (acute and
chronic)
Acute Tubular Injury/Necrosis
• Acute tubular injury (ATI) is a clinicopathologic
entity characterized clinically by acute renal
failure and morphologic evidence of tubular
injury, in the form of necrosis of tubular
epithelial cells.
• ATI accounts for some 50% of cases of acute
kidney injury in hospitalized patients.
• ATI is a reversible process.
Causes of acute tubular injury
 Ischemia, due to decreased or interrupted blood
flow as seen in polyangiitis, malignant
hypertension, and systemic conditions associated
with thrombosis(e.g., hemolytic uremic syndrome
[HUS], thrombotic thrombocytopenic purpura
[TTP], and DIC
 Direct toxic injury to the tubules by
endogenous/exogenous agents e.g myoglobin,
hb, monoclonal light chains, bile/bilirubin,
drugs,radiocontrast dyes, heavy metals, organic
solvents)
Causes of acute tubular injury
 Urinary obstruction as seen in prostatic
hypertrophy, or blood clots (so-called
postrenal acute renal failure)
Pathogenesis
• The critical events in both ischemic and
nephrotoxic AKI are tubular injury and
disturbances in blood flow
Pathogenesis
Tubule cell injury
• Tubular epithelial cells are particularly sensitive
to ischemia and are also vulnerable to toxins
• Factors predisposing the tubules to toxic injury
include:
Increased surface area for tubular reabsorption,
Active transport systems for ions and organic acids
 A high rate of metabolism and oxygen consumption
that is required to perform these transport and
reabsorption functions.
Pathogenesis
Tubule cell injury
• Ischemia causes numerous structural and functional
alterations in epithelial cells.
• The structural changes include:
– reversible injury (such as cellular swelling, loss of brush border
and polarity due to redistribution of membrane proteins (e.g.,
the enzyme Na,K+-ATPase) from the basolateral to the luminal
surface of tubular cells resulting abnormal ion transport across
the cells and increased sodium delivery to distal tubules which
incites vasoconstriction via tubuloglomerular feedback. Ischemic
tubular cells express cytokines and adhesion molecules, thus
recruiting leukocytes that appear to participate in the
subsequent injury. Injured cells detach from the basement
membranes and cause luminal obstruction, increased
intratubular pressure, and decreased GFR.
– Irreversible/lethal injury (necrosis and apoptosis).
Pathogenesis
Tubule cell injury
• The biochemical changes include:
Depletion of ATP;
Accumulation of intracellular calcium
Activation of proteases (e.g., calpain)
Cytoskeletal disruption;
Activation of phospholipases, which damage
membranes;
Generation of reactive oxygen species; and
Activation of caspases, which induce apoptotic cell
death.
Pathogenesis
disturbances in blood flow
• Ischemic renal injury is also characterized by
hemodynamic alterations that cause reduced
GFR.
• Hemodynamic alterations:
– vasoconstriction
Pathogenesis
disturbances in blood flow
• The vasoconstrictor pathways include:
– The renin-angiotensin system, stimulated by
increased distal sodium delivery (via
tubuloglomerular feedback) and
– Endothelial injury, leading to increased release of
the vasoconstrictor endothelin and decreased
production of the vasodilators nitric oxide and
prostacyclin (prostaglandin I2).
Pathogenesis
• Once the precipitating cause is removed, there
is recovery of function of the tubules. This is
because of patchiness of tubular necrosis and
maintenance of the integrity of the basement
membrane along many segments that allows
repair of the injured foci.
Pathogenesis
Morphology
• ATI is characterized by focal tubular epithelial
necrosis at multiple points along the nephron,
with large skip areas in between accompanied
by rupture of basement membranes
(tubulorrhexis), interstitial edema and
occlusion of tubular lumens by casts.
Acute tubular injury morphology
Clinical Course
1. The initiation phase-lasts about 36 hours, presents
with decline in urine output with a rise in BUN.
2. Maintenance phase is characterized by sustained
decreases in urine output to between 40 and 400
mL/day (oliguria), salt and water overload, rising BUN
concentrations, hyperkalemia, metabolic acidosis
3. Recovery phase is ushered in by a steady increase in
urine volume that may reach up to 3 L/day. The
tubules are still damaged, so large amounts of water,
sodium, and potassium are lost in the flood of urine.
TUBULOINTERSTITIAL DISEASES
• Renal diseases that involve inflammatory
injuries of the tubules and interstitium that
are often insidious in onset and are principally
manifest by azotemia
Causes of
Tubulointerstitial
Nephritis
• Infections
– Acute bacterial pyelonephritis
– Chronic pyelonephritis (including reflux
nephropathy)
– Other infections (e.g., viruses, parasites)
• Toxins
–
–
–
–
–
Drugs
Acute-hypersensitivity interstitial nephritis
Analgesics
Heavy metals
Lead, cadmium
Causes of tubulointerstitial nephritis
• Metabolic Diseases
–
–
–
–
–
Urate nephropathy
Nephrocalcinosis (hypercalcemic nephropathy)
Acute phosphate nephropathy
Hypokalemic nephropathy
Oxalate nephropathy
• Physical Factors
– Chronic urinary tract
obstruction
• Neoplasms
– Multiple
• Immunologic
myeloma (light-chain
Reactions
– Transplant rejection
– Sarcoidosis
• Vascular Diseases
cast nephropathy)
Pyelonephritis
• Def: Inflammation affecting the tubules,
interstitium, and renal pelvis.
• Two forms: Acute pyelonephritis and chronic
pyelonephritis
• Pyelonephritis is a complication of urinary
tract infections that affect the bladder
(cystitis), the kidneys or both.
Acute pyelonephritis
• Is suppurative inflammation of the kidney and
the renal pelvis
• Etiology:
– Bacteria infections, commonly; Escherichia coli,
other includes; Proteus, Klebsiella, Enterobacter,
and Pseudomonas causing recurrent infections
– Sometimes viral (e.g., polyomavirus) infection
• Route of Entry:
– Hematogenous infection: seeding of the kidneys by
bacteria in septicemia or in infective endocarditis e.g
staphylococcus. Hematogenous route is less common.
More likely to occur in the presence of ureteral
obstruction, and in debilitated patients, in patients
receiving immunosuppressive therapy.
– Ascending infection: more common, bacteria from
lower UT as in cystitis, prostatitis, urethritis ascends to
kidney
• Hematogenous
spread:
 Blood borne
spread to kidneys.
 Occurs in
bacteraemia
mostly S.aureus
1/10/2024
MMUST.
78
Pathogenesis
• The first step in ascending infection is the
colonization of the distal urethra by coliform
bacteria.
• Bacterial adherence to urethral mucosal
epithelial using adhesive molecules (adhesins)
on the P-fimbriae (pili) of bacteria that
interact with receptors on the surface of
urothelial cells.
Pathogenesis
• From the urethra to the bladder, organisms gain
entrance during urethral catheterization or other
instrumentation.
• In the absence of instrumentation, urinary
infections are much more common in females
cause of the shorter urethra in females,as well as
the absence of antibacterial properties found in
prostatic fluid and urethral trauma during sexual
intercourse, or a combination of these factors.
• Ascending Infection:
 most common route.
 organisms ascend through urethra
into bladder.
organism
Colonize in
perineal and
periurethral areas
Ascend to
bladder,
kidneys
UTI
1/10/2024
MMUST.
81
Pathogenesis
• The mechanisms by which microbes move from the bladder
to the kidneys
 Urinary tract obstruction and stasis of urine.
• Ordinarily, organisms introduced into the bladder are
cleared by continual voiding and by antibacterial
mechanisms.
• In outflow obstruction or bladder dysfunction resulting in
incomplete emptying and residual urine, bacteria
introduced into the bladder can multiply unhindered.
• Accordingly, UTI is frequent among patients with lower
urinary tract obstruction, such as may occur with BPH,
tumors, or calculi, or with neurogenic bladder dysfunction
caused by diabetes or spinal cord injury
Pathogenesis
 Vesicoureteral reflux.
• Incompetence of the vesicoureteral valve allows
bacteria to ascend the ureter into the renal pelvis.
• The normal ureteral insertion into the bladder is a oneway valve that prevents retrograde flow of urine when
the intravesical pressure rises, as in micturition
• An incompetent vesicoureteral orifice allows the reflux
of bladder urine into the ureters (vesicoureteral reflux)
• Causes of reflux: congenital absence or shortening of
the intravesical portion of the ureter In addition, it may
be acquired by bladder infection or in persistent
bladder atony caused by spinal cord injury.
Pathogenesis
 Intrarenal reflux. Vesicoureteral reflux also
affords a ready mechanism by which the
infected bladder urine can be propelled up to
the renal pelvis and deep into the renal
parenchyma through open ducts at the tips of
the papillae (intrarenal reflux).
Macroscopy:
• One or both kidneys may be involved, may be normal
or enlarged and swollen
• Renal surface and cortex shows multiple, discrete,
yellow-white abscesses measuring several mm in
diameter
Microscopy:
• Early; suppurative necrosis limited to interstitial tissue,
but later; abscesses rupture into tubules, give rise to
white cell casts in the urine
• Glomeruli not affected
Macroscopy:
Microscopy
Clinical features and lab findings
• Fever and malaise.
• Dysuria, frequency, and urgency.
• Urinalysis- leukocytes (pyuria) derived from
the inflammatory infiltrate,
• Quantitative urine culture.
Complications of acute pyelonephritis
1. Renal Papillary Necrosis; An infrequent form of
pyelonephritis seen in; diabetics, UT obstruction,
analgesic abuse, sickle cell anemia
• Morphology: Sharply defined gray-white to yellow
necrosis of apical two thirds of the renal pyramids,
Microscopy; one or all papillary tips show coagulative
necrosis surrounded by neutrophilic infiltrate
2. Pyonephrosis: when pus fills renal pelvis, calyces, and
ureter in cases of obstruction
3. Perinephric abscess: collection of pus in the
perinephric tissue
Chronic Pyelonephritis
• Chronic pyelonephritis is a disorder in which
chronic tubulointerstitial inflammation and
scarring involve the calyces and pelvis
• Chronic pyelonephritis can be divided into two
forms:
 Reflux nephropathy. This is by far the
• More common form
• Occurs early in childhood as a result of
superimposition of a urinary infection on
congenital vesicoureteral reflux
• Reflux may be unilateral or bilateral; thus, the
continuous renal damage may cause scarring and
atrophy of one kidney or involve both, leading to
renal insufficiency.
Chronic obstructive pyelonephritis.
• Obstruction predisposes kidney to recurrent
infections, inflammation and scarring
• Bilateral occurs with calculi and unilateral
obstructive lesions of the ureter
Macroscopy
• One or both kidneys may be involved, either
diffusely or in patches
• Hallmark is scarring of pelvis or calyces, or
both, leading to papillary blunting, dilated
calyces and marked calyceal deformities
• Uneven scarring differentiate it from more
symmetrically contracted kidneys associated
with "benign nephrosclerosis" and chronic GN
Macroscopy
Microscopy
• Mixed inflammatory infiltrate involving
calyceal mucosa, wall and tubules
• Interstitial fibrosis and tubular atrophy some
dilated tubules contain pink to blue, glassy,
PAS-positive casts that suggest thyroidization
• Thickened hyalinised vascular walls
• Glomeruli may be normal, or shows
periglomerular fibrosis or hyalinization
Microscopy
Urinary Tract Obstruction
(Obstructive Uropathy)
• The structural or functional disorder leading
to impaired urinary flow.
• The obstruction may be in the upper or lower
urinary tracts and will have corresponding
signs and symptoms based on the site, degree
of obstruction and duration.
• The obstruction at the anatomical locations
can be due to intraluminal, intramural or
extramural causes affecting the renal system
unilaterally or bilaterally; partially or
completely; insidiously or suddenly.
• Obstruction results in three important
Sequelae of hydronephrosis, hydroureter and
hypertrophy of the bladder
Epidemiology in the young
• Generally due to congenital anomalies of
the urinary tract:
–PUVs
–VURs
Epidemiology in the older age
• Equal in under 20s
• M>F in 20-60 due to pregnancy and Gynae
pathologies
• M>F in over 60 due to prostate disorders.
Can be classified
•
•
•
•
Acute or chronic – duration
Congenital or acquired
Unilateral or bilateral
Upper tract obstruction and lower tract
obstruction – site of obstruction
• Mechanical or functional
– Intraluminal
– Intramural or
– Extra luminal
Causes
Mechanical
1.Common anatomical sites: the PUJ, the
crossing of the ureter at the pelvic brim and the
UVJ. These sites have a tendency to be involved
either by kinks or intraluminal blocks.
2.Congenital anomalies like ureteroceles,
ectopic ureters, megaureters and PUVs
Mechanical causes
3. Inflammations : post surgical, infective(TB,
Schistosomiasis) or idiopathic.
4. Intraluminal blocks: clots, stones, papillary
slough or fungal balls.
5. Neoplasms : intrinsic and extrinsic.
Particularly gynaecological (uterine, cervical and
ovarian malignancies) and GI e.g. colorectal.
Functional causes
• Seen in line with the neural and myogenic
anomalies that impair the contractile or
propulsive capacity of the urinary tract.
1. Neurogenic conditions like stroke, parkinsonism,
SCI, Diabetes Mellitus, MS
2. Medications anticholinergics and antihistamines.
3. Myogenic conditions like myasthenia gravis and
altered muscular functions due to chronic
obstruction.
Causes of obstruction
A. Intraluminal
• Calculi
• Tumours (e.g. cancer of the kidney and
bladder)
• Sloughed renal papillae
• Blood clots
• Foreign body
B. Intramural
• Pelvic-ureteric junction (PUJ) obstruction
• Vesicoureteric obstruction
• Urethral stricture
• Urethral valves
• Inflammation (e.g. phimosis, cystitis)
• Neuromuscular dysfunction
C. Extramural
• Pregnant uterus
• Retroperitoneal fibrosis
• Tumours (e.g. carcinoma of the cervix, rectum,
colon, caecum)
• Prostatic enlargement, prostatic carcinoma
and protatitis
• Trauma.*
Pathophysiology
• Obstruction causes back flow of the glomerular
filtrate into the renal interstitium and perirenal
spaces, from where it ultimately returns to the
lymphatic and venous systems.
• The affected calyces and pelvis become dilated.
• The high pressure in the pelvis is transmitted
back through the collecting ducts into the cortex,
causing renal atrophy, compresses the renal
vasculature of the medulla, causing a diminution
in inner medullary blood flow.
Morphology
• If the obstruction is sudden and complete:
mild dilation of the pelvis and calyces,
sometimes atrophy of the renal
parenchyma.
• The kidney may be slightly to massively
enlarged, depending on the degree and the
duration of the obstruction.
• In chronic cases: cortical tubular atrophy with
marked diffuse interstitial fibrosis.
Hydronephrosis
Clinical features.
• Pain attributed to distention of the collecting system
or renal capsule
• Inability to concentrate urine, reflected by polyuria and
nocturia.
• Distal tubular acidosis,
• Renal salt wasting, secondary renal calculi, and chronic
tubulointerstitial nephritis with scarring and atrophy of
the papilla and medulla.
• Hypertension is common.
• Complete bilateral obstruction : oliguria or anuria and
is incompatible with survival unless