Diseases of urinary system Zhang Hongying

How to learn systemic pathology (pathology of urinary system) ? basic science (anatomy, histology, physiology, immunology … ) physiology, immunology … ) general pathology general pathology systemic pathology systemic pathology clinic practice clinic practice *correlations between structural and functional changes (clinicopathologic correlations)

Functions of the kidneys Eliminating metabolic waste products Eliminating metabolic waste products Regulating fluid and electrolyte balance Regulating fluid and electrolyte balance Influencing acid-base balance Influencing acid-base balance Secreting hormones (prostaglandins, erythropoietin, 1,25-dihydroxycholecalciferol, renin) Secreting hormones (prostaglandins, erythropoietin, 1,25-dihydroxycholecalciferol, renin)

The nephron The main functional unit of the kidney

Normal glomerulus

Outline Glomerulonephritis Glomerulonephritis Tubulointerstitial nephritis Tubulointerstitial nephritis Diseases of the lower urinary tract Diseases of the lower urinary tract Tumors of urinary system Tumors of urinary system

Etiology of glomerular diseases Primary(majority):disease process appears to start within the glomerulus Primary(majority):disease process appears to start within the glomerulus Secondary:disease process is secondary to systemic disease (SLE, vascular diseases, diabetes mellitus) Secondary:disease process is secondary to systemic disease (SLE, vascular diseases, diabetes mellitus) Hereditary:congenital diseases ( Fabry ’ s disease) Hereditary:congenital diseases ( Fabry ’ s disease)

Primary glomerulonephritis kidney is the only or predominant organ kidney is the only or predominant organ

Mechanism of glomerular injury Circulating immune complex nephritis Circulating immune complex nephritis immune complex nephritis in situ immune complex nephritis in situ Cell-mediated immunity Cell-mediated immunity Other mechanisms Other mechanisms

Granular pattern Immunofluorescence microscopy

Linear pattern Immunofluorescence microscopy

Mechanism of glomerular injury Circulating immune complex nephritis Circulating immune complex nephritis immune complex nephritis in situ immune complex nephritis in situ Cell-mediated immunity Cell-mediated immunity Other mechanisms Other mechanisms

Steps in diagnoses of glomerular lesions Clinical presentation Clinical presentation Renal biopsy Renal biopsy

Clinical manifestations Hematuria (red blood cells in urine) Hematuria (red blood cells in urine) Proteinuria (protein lost in urine) Proteinuria (protein lost in urine) Oliguria or anuria (no urine flow) Oliguria or anuria (no urine flow) Edema Edema Hypertension Hypertension Urinary casts (cell casts, granular casts, hyaline casts) Urinary casts (cell casts, granular casts, hyaline casts) Azotemia (waste products accumulation) Azotemia (waste products accumulation) Uremia (with autotoxication symptom) Uremia (with autotoxication symptom)

Clinical presentations Acute nephritic syndrome: acute onset, blood pressure ， hematuria, proteinuria, edema, azotemia Acute nephritic syndrome: acute onset, blood pressure ， hematuria, proteinuria, edema, azotemia Rapidly progressive nephritic syndrome: abrupt or insidious onset of hematuria, proteinuria, anemia and rapidly progressing renal failure Rapidly progressive nephritic syndrome: abrupt or insidious onset of hematuria, proteinuria, anemia and rapidly progressing renal failure Glomerulonephritis

Clinical presentations Nephrotic syndrome: heavy proteinuria, hypoalbuminemia, sever edema, hyperlipidemia and lipiduria Nephrotic syndrome: heavy proteinuria, hypoalbuminemia, sever edema, hyperlipidemia and lipiduria Chronic nephritic syndrome: slowly developing renal failure accompanied by proteinuria, hematuria hypertension and uremia Chronic nephritic syndrome: slowly developing renal failure accompanied by proteinuria, hematuria hypertension and uremia

Key facts renal failure Two renal syndromes of total renal failure ( acute and chronic renal failure) Two renal syndromes of total renal failure ( acute and chronic renal failure) Two main syndromes of partial renal failure (nephritic syndrome and nephrotic syndrome) Two main syndromes of partial renal failure (nephritic syndrome and nephrotic syndrome) Chronic renal failure is irreversible, as it is caused by permanent destruction of nephrons Chronic renal failure is irreversible, as it is caused by permanent destruction of nephrons Acute renal failure sometimes recovers when the damaging stimulus resolves Acute renal failure sometimes recovers when the damaging stimulus resolves

The renal biopsy Histological examination Histological examination Immunofluorescence examination Immunofluorescence examination Electron microscopic examination Electron microscopic examination

The renal biopsy Histological examination Histological examination Immunofluorescence examination Immunofluorescence examination Electron microscopic examination Electron microscopic examination

Primary glomerulonephritis Acute diffuse proliferative glomerulonephritis Acute diffuse proliferative glomerulonephritis Crescentic glomerulonephritis Crescentic glomerulonephritis Membranous glomerulonephritis Membranous glomerulonephritis Lipoid nephrosis Lipoid nephrosis Focal segmental glomerulosclerosis Focal segmental glomerulosclerosis Membranoproliferative glomerulonephritis Membranoproliferative glomerulonephritis IgA nephropathy IgA nephropathy Chronic glomerulonephritis Chronic glomerulonephritis

Diffuse proliferative glomerulonephritis Diffuse, global, acute inflammation of glomeruli is caused by the deposition of immune complexes in glomeruli, stimulated by a preceding infection Diffuse, global, acute inflammation of glomeruli is caused by the deposition of immune complexes in glomeruli, stimulated by a preceding infection Children are more commonly affected Children are more commonly affected

Etiology Poststreptococcal (most common): onset is 1-2 weeks after a primary infection with  - hemolytic streptococci of group A Poststreptococcal (most common): onset is 1-2 weeks after a primary infection with  - hemolytic streptococci of group A Non-streptococcal(less common): a range of bacterial, viral and protozoal infections Non-streptococcal(less common): a range of bacterial, viral and protozoal infections

Morphology Gross examination Swollen with scattered petechia

Histologic features Endothelial cells proliferation Endothelial cells proliferation Mesangial cells proliferation Mesangial cells proliferation Neutrophils infiltration Neutrophils infiltration

Normal glomerulus

Post-streptococcal glomerulonephritis

Immunofluorescence Granular deposits

Subepithelial “lumps” immune complexes deposition Electron microscopy

Clinical features Systemic symptoms Systemic symptoms Acute nephritic syndrome Acute nephritic syndrome Acute onset Oliguria Edema Hypertension Hematuria Azotemia Injures of the capillary wall GFR decrease Fluid retention Fluid retention, renin increase waste products increase

KEY FACTS: Diffuse proliferative glomerulonephritis Caused by immune complexes in glomerulus, often after streptococcal infection Caused by immune complexes in glomerulus, often after streptococcal infection Causes nephritic syndrome, with proliferation of endothelium and mesangium and recruitment of neutrophilis Causes nephritic syndrome, with proliferation of endothelium and mesangium and recruitment of neutrophilis Most cases recover, but a minority may rapidly progress to renal failure or slowly develop chronic renal failure Most cases recover, but a minority may rapidly progress to renal failure or slowly develop chronic renal failure

Main types of glomerulonephritis Acute proliferative(poststreptococcal, postinfectious)glomerulonephritis Acute proliferative(poststreptococcal, postinfectious)glomerulonephritis Rapidly progressive (cresentic) glomerulonephritis Rapidly progressive (cresentic) glomerulonephritis Chronic glomerulonephritis Chronic glomerulonephritis

Rapidly progressive glomerulonephrits (RPGN; crescentic glomerulonephritis) RPGN is a manifestation of severe glomerular injury characterized by the formation of crescent- shaped masses within the Bowman ’ s space RPGN is a manifestation of severe glomerular injury characterized by the formation of crescent- shaped masses within the Bowman ’ s space RPGN occurs in a small percentage of patients with poststreptococcal glomerulonephritis, but can also be associated with many other forms of glomerular damage RPGN occurs in a small percentage of patients with poststreptococcal glomerulonephritis, but can also be associated with many other forms of glomerular damage

Pathogenesis Type I RPGN (12%): anti-GBM antibodies ( special type: Goodpasture syndrome) Type I RPGN (12%): anti-GBM antibodies ( special type: Goodpasture syndrome) Type II RPGN (44%): immune complex-mediated disorder Type II RPGN (44%): immune complex-mediated disorder Type III RPGN (44%): pauci-immune complexes Type III RPGN (44%): pauci-immune complexes

Crescentic glomerulonephritis

Histological features The characteristic is the presense of crescents in most of the glomeruli (>50%) The characteristic is the presense of crescents in most of the glomeruli (>50%) The crescents lining Bowman ’ s capsule are composed of a mixture of epithelial cells and macrophages proliferating The crescents lining Bowman ’ s capsule are composed of a mixture of epithelial cells and macrophages proliferating

Basement membrane destruction Cresentic glomerulonephritis

Crescentic glomerulonephritisCrescent

Cresentic glomerulonephritis

Goodpasture syndrome

Clinical features RPGN is characterized by rapid and progressive loss of renal function associated with sever oliguria even anuria RPGN is characterized by rapid and progressive loss of renal function associated with sever oliguria even anuria Prognosis is poor Prognosis is poor

Main patterns of glomerulonephritis Acute proliferative(poststreptococcal, postinfectious)glomerulonephritis Acute proliferative(poststreptococcal, postinfectious)glomerulonephritis Rapidly progressive (cresentic) glomerulonephritis Rapidly progressive (cresentic) glomerulonephritis Chronic glomerulonephritis Chronic glomerulonephritis

Chronic glomerulonephritis end stage kidney end stage kidney It may be caused by many diseases It may be caused by many diseases

Morphology Macroscopically, affected kidneys are small and there is graularity of external surface (symmetrically contracted) Macroscopically, affected kidneys are small and there is graularity of external surface (symmetrically contracted) Microscopically, there is fibrosis, hyalinization of glomeruli, tubular atrophy and interstitial fibrosis Microscopically, there is fibrosis, hyalinization of glomeruli, tubular atrophy and interstitial fibrosis

Chronic glomerulonephritis

Chronic renal failure

End stage kidney

Clinical features Chronic glomerulonephritis develops insidiously Chronic glomerulonephritis develops insidiously Chronic glomerulonephritis is characterized by chronic nephritic syndrome Chronic glomerulonephritis is characterized by chronic nephritic syndrome Hypertension Proteinuria Anemia Azotemia Uremia Edema

Uremic fibrinous pericarditis

Required readingSuggested reading

Case study A 13-year-old girl who is brought by her parents because she had become lethargic and her face appeared swollen, particularly around her eyes. On enquiry, she had recently recovered from a flu-like illness. As part of routine examination her urine is tested with a dip-stick and is found that to contain both protein and blood. A 13-year-old girl who is brought by her parents because she had become lethargic and her face appeared swollen, particularly around her eyes. On enquiry, she had recently recovered from a flu-like illness. As part of routine examination her urine is tested with a dip-stick and is found that to contain both protein and blood.

Case study She is also noted to have a mildly raised blood pressure. The patient is referred to hospital where she is found to have urea and creatinine together with a reduced urine output. Renal biopsy is performed. She is also noted to have a mildly raised blood pressure. The patient is referred to hospital where she is found to have urea and creatinine together with a reduced urine output. Renal biopsy is performed.

Histology The histology report reveals hypercellularity of glomeruli with neutrophils in capillary lumina. Granular deposition of IgG, C1q and C3 are seen in the glomerular basement membrane and mesangium. Electron microscopy confirms the presence of electron dense deposits in the basement membrane, predominantly in a subepithelial location. The histology report reveals hypercellularity of glomeruli with neutrophils in capillary lumina. Granular deposition of IgG, C1q and C3 are seen in the glomerular basement membrane and mesangium. Electron microscopy confirms the presence of electron dense deposits in the basement membrane, predominantly in a subepithelial location.

Diseases of urinary system Glomerulonephritis Glomerulonephritis Tubulointerstitial nephritis Tubulointerstitial nephritis Diseases of the lower urinary tract Diseases of the lower urinary tract Tumors of urinary system Tumors of urinary system

Tubulointerstitial nephritis Tubulointerstitial nephritis refers to a group of inflammatory diseases of the kidneys that primarily involve the interstitum and tubules Tubulointerstitial nephritis refers to a group of inflammatory diseases of the kidneys that primarily involve the interstitum and tubules

Tubulointerstitial nephritis Pyelonephritis Pyelonephritis Acute tubular necrosis Acute tubular necrosis Interstitial nephritis Interstitial nephritis

Pyelonephritis Affecting tubules Affecting tubules Affecting interstitum Affecting interstitum Affecting renal pelvis Affecting renal pelvis One of the most common diseases of the kidney One of the most common diseases of the kidney

Pyelonephritis Acute pyelonephritis Acute pyelonephritis Chronic pyelonephritis Chronic pyelonephritis

Acute pyelonephritis Incidence parallels that of obstructive uropathy Incidence parallels that of obstructive uropathy Caused by bacterial infection Caused by bacterial infection Common suppurative inflammation of the kidney and the renal pelvis Common suppurative inflammation of the kidney and the renal pelvis

Acute pyelonephritis Childhood Childhood Pregnancy Pregnancy Elderly Elderly Infancy: males>females Puberty to middle age: females>males Post-40 years: males>females Three age peaks Gender differences

Routes of bacterial infection Ascending infection from the lower urinary tract(most common): enteric gram-negative rods ( Escherichia coli) Ascending infection from the lower urinary tract(most common): enteric gram-negative rods ( Escherichia coli) Bloodstream spread in bacteremic or septicemic states: staphylococci Bloodstream spread in bacteremic or septicemic states: staphylococci

Route of infection

Gross feature Suppurative inflammation Suppurative inflammation Cortical abscesses Cortical abscesses Medullary abscesses Medullary abscesses

Acute pyelonephritis

Histological feature Infiltration of tubules by neutrophils Infiltration of tubules by neutrophils Abscess formation Abscess formation Interestitial edema Interestitial edema

Acute pyelonephritis

Clinical feature Sudden onset Sudden onset Pain in the back Pain in the back Evidence of systemic infection( chills, fever, malaise) Evidence of systemic infection( chills, fever, malaise) Indications of bladder and urethral irritation( dysuria, urgency, frequency of micturition) Indications of bladder and urethral irritation( dysuria, urgency, frequency of micturition)

Urinary findings Pyuria ( white blood cells and pus cells in urine) Pyuria ( white blood cells and pus cells in urine) Bacteriuria (bacteria in urine) Bacteriuria (bacteria in urine)

Complications and sequelae Resolution Resolution Healing with scarring Healing with scarring Chronicity Chronicity Pyonephrosis Pyonephrosis Renal papillary necrosis Renal papillary necrosis Perinephric abscess Perinephric abscess Death in uremia Death in uremia

Papillary necrosis

Pyelonephritis Acute pyelonephritis Acute pyelonephritis Chronic pyelonephritis Chronic pyelonephritis

Chronic pyelonephritis Chronic pyelonephritis is defined as a morphologic entity in which prodominantly interstitial inflammation and scarring of the renal parenchyma is associated with grossly visible scarring and deformity of the pelvicalyceal system Chronic pyelonephritis is defined as a morphologic entity in which prodominantly interstitial inflammation and scarring of the renal parenchyma is associated with grossly visible scarring and deformity of the pelvicalyceal system

Chronic pyelonephritis Obstructive chronic pyelonephritis Obstructive chronic pyelonephritis Reflux-associated chronic pyelonephritis (vesicoureteral reflux) Reflux-associated chronic pyelonephritis (vesicoureteral reflux)

Gross feature Kidneys are not equally damaged Kidneys are not equally damaged Irregular areas of scarring Irregular areas of scarring Marked calyceal deformities Marked calyceal deformities

Gross feature not equally damaged Irregular areas of scarring Marked calyceal deformities Chronic pyelonephritis

Histological feature Chronic inflammatory cells infiltration, occasionally neutrophils Chronic inflammatory cells infiltration, occasionally neutrophils Uneven interstitial fibrosis Uneven interstitial fibrosis Dilation or contraction of tubules Dilation or contraction of tubules Glomeruli show periglomerular fibrosis Glomeruli show periglomerular fibrosis

Chronic pyelonephritis

“Thyroidization”Dilation of tubules

Clinical feature Gradual onset of renal insufficiency Gradual onset of renal insufficiency Tubular dysfunction (polyuria) Tubular dysfunction (polyuria) Urinary tract infection Urinary tract infection Uremia Uremia

Diagnosis Intravenous pyelogram Intravenous pyelogram Urine culture Urine culture

Requirement List the complications of acute pyelonephritis List the complications of acute pyelonephritis Name the two types of pathogenesis for chronic pyelonephritis Name the two types of pathogenesis for chronic pyelonephritis

Outline Glomerulonephritis Glomerulonephritis Tubulointerstitial nephritis Tubulointerstitial nephritis Diseases of the lower urinary tract Diseases of the lower urinary tract Tumors of urinary system Tumors of urinary system

Infection Obstruction Stone formation Tumor formation Developmental abnormalities Diseases of the lower urinary tract

Urinary outflow obstruction Renal stones Renal stones Hydronephrosis Hydronephrosis

Renal stones Urolithiasis is calculus formation at any level in the urinary collecting system Urolithiasis is calculus formation at any level in the urinary collecting system most common sites: pelvicalyceal system and bladder. most common sites: pelvicalyceal system and bladder.

Main predisposing factors Increased concentration of solute in urine Increased concentration of solute in urine Reduced solubility of solute in urine Reduced solubility of solute in urine

Etiology Acquired Acquired Inherited Inherited

Renal calculus

Renal staghorn calculus S

Staghorn calculus Hydronephrosis Abscess

Fluoroscopy Ureteral calculus

Clinical feature Without symptoms Without symptoms Renal colic with nausea, vomiting and hematuria Renal colic with nausea, vomiting and hematuria Dual ache in the loins Dual ache in the loins Recurrent urinary tract infection Recurrent urinary tract infection

Urinary outflow obstruction Renal stones Renal stones Hydronephrosis Hydronephrosis

Hydronephrosis Hydronephrosis refers to dilation of the renal pelvis and calyces, with accompanying atrophy of the parenchyma, caused by obstruction to the outflow of urine Hydronephrosis refers to dilation of the renal pelvis and calyces, with accompanying atrophy of the parenchyma, caused by obstruction to the outflow of urine

Renal pelvis Pelviureteric junction Ureter Bladder Urethra Hydronephrosis Obstruction of the levels

Morphology Unilateral :caused by obstruction at the level of the ureter, pelviureteric junction or renal pelvis Unilateral :caused by obstruction at the level of the ureter, pelviureteric junction or renal pelvis Bilateral: caused by obstruction of the level of the bladder or urethra Bilateral: caused by obstruction of the level of the bladder or urethra

Hydronephrosis

Normal urinary tract Intravenous pyelogram (IVP)

Hydronephrosis Intravenous pyelogram (IVP)

Hydronephrosis ( cut surface)

Clinical feature Clinical features depend on the cause and site of the lesion Clinical features depend on the cause and site of the lesion

Effects of hydronephrosis Obstruction is removed: renal function returns to normal Obstruction is removed: renal function returns to normal Persistence of obstruction: atrophy of renal tubules with glomerular hyalinization and fibrosis Persistence of obstruction: atrophy of renal tubules with glomerular hyalinization and fibrosis

Outline Glomerulonephritis Glomerulonephritis Tubulointerstitial nephritis Tubulointerstitial nephritis Diseases of the lower urinary tract Diseases of the lower urinary tract Tumors of urinary system Tumors of urinary system

Tumors of urinary system Tumors of the kidney Tumors of the kidney Tumors of the bladder Tumors of the bladder Tumors of the ureter Tumors of the ureter Tumors of the urethra Tumors of the urethra

Angiomyolipoma

MRI

Angiomyolipoma

Renal cell carcinoma

Renal cell carcinoma invade into the renal vein

MRIRenal cell carcinoma

Renal cell carcinoma (clear cell type)

Key facts renal cell carcinoma Male: female incidence is 3:1 Male: female incidence is 3:1 Incidence is greatest in those over 50 years, and increases with age Incidence is greatest in those over 50 years, and increases with age Common presenting symptoms include painless hematuria, loin pain, loin mass Common presenting symptoms include painless hematuria, loin pain, loin mass Occasional presenting symptoms include bone metastasis,brain metastasis, polycythemia Occasional presenting symptoms include bone metastasis,brain metastasis, polycythemia

Key facts renal cell carcinoma Local spread through renal capsule into perinephritic fat Local spread through renal capsule into perinephritic fat Lymphatic spread to para-aortic and other nodes Lymphatic spread to para-aortic and other nodes Blood stream spread to lungs, bone, brain, liver Blood stream spread to lungs, bone, brain, liver Prognosis depends on stage at presentation Prognosis depends on stage at presentation

Wilm’s tumor (Nephroblastoma) Common malignant tumors of childhood Abdominal enlargement Genetic defects on chromosome 11

Wilm’s tumor

Metastatic carcinoma of the kidney

Questions List five kinds of diseases of unilateral enlargement of the kidney. List five kinds of diseases of unilateral enlargement of the kidney. What are the causes of urinary tract obstruction? What are the causes of urinary tract obstruction?

Tumors of the lower urinary tract Most tumors of the lower urinary tract arise from transitional-cell epithelium Most tumors of the lower urinary tract arise from transitional-cell epithelium

Transitional cell carcinoma of the bladder

Intravenous pyelogram (IVP) Carcinoma of the bladder

Carcinoma of renal pelvis

Transitional cell carcinoma

Case study A 57-year-old draughtsman who presents to his family practitioner complaining of a dragging sensation in his left loin. On questioning, he admits to having had intermittent painless hematuria for three weeks. Following referral to a urological surgeon, investigation reveals a large mass replacing the left kidney. He undergoes a left nephrectomy from which he makes a good recovery. A 57-year-old draughtsman who presents to his family practitioner complaining of a dragging sensation in his left loin. On questioning, he admits to having had intermittent painless hematuria for three weeks. Following referral to a urological surgeon, investigation reveals a large mass replacing the left kidney. He undergoes a left nephrectomy from which he makes a good recovery.

Questions What is the most likely diagnosis? What is the most likely diagnosis? The most likely diagnosis is renal cell carcinoma

Questions What is the most common histological pattern of this lesion and what causes this appearance? What is the most common histological pattern of this lesion and what causes this appearance? Carcinomas of the kidney are adenocarcinomas. The most common histological pattern is of lipid and glycogen within the cytoplasm of neoplastic cells

Questions What factors in the histopathologists report would have a particular bearing on the prognosis for this patient? What factors in the histopathologists report would have a particular bearing on the prognosis for this patient? If carcinoma is present within blood vessels (particularly the renal veins) at the hilum, then there is a greater likelihood that metastasis spread will ensue. If tumor is confined within the renal capsule there is a 70% 10-year survival