Please enable JavaScript.
Coggle requires JavaScript to display documents.
Urogenital Pathology (Glomerular Diseases (Specific Glomerular Diseases…
Urogenital Pathology
Glomerular Diseases
1. Nephrotic Syndrome
- Characteristics:
- Heavy proteinuria
- More than 3.5gm of protein loss/24 hrs
- Frothy urine
- May be selective or non-selective in nature
- Hypoalbuminemia
- Anasarca
- Marked periorbital & pedal edema, facial & abdominal swelling
- Hyperlipidemia
- Due to compensatory increase in synthesis of lipoproteins by liver
- Lipiduria
- Due to hyperlipiduria + leakage of lipoproteins into urine
- Others
- Loss of immunoglobulins - increased susceptibility to Staphylococcal and Pneumococcal infections
- Loss of anticoagulants and antiplasmins
- Causes:
- Primary Glomerular diseases
- Minimal change disease
- Membranous glomerulopathy
- FSGS
- Membranoproliferative glomerulonephritis
- Systemic Disease
- DM
- Amyloidosis
- SLE
- Drugs (NSAID, penicillamine, street heroin)
- Infection (HBV, HCV, malaria, syphillis, HIV)
- Malignancies (multiples myeloma, lymphoma)
- Heterozygous Alport disease
- Clincal Features:
- Age is important in differential diagnosis of cause of nephrotic syndrome
- Childhood nephrotic syndrome is almost always sensitive to steroid Tx (minimal change disease)
- Renal biopsy performed when child does not respond to steroid Tx
2. Nephritic Syndrome
- Characteristics:
- Oliguria
- Azotemia (elevation of serum creatinine and blood urea nitrogen levels)
- Gross hematuria
- Edema (usu not as prominent as in nephrotics)
- HTN (due to fluid retention)
- Proteinuria
- Causes:
- Primary glomerular diseases:
- Post-streptococcal glomerulonephritis
- IgA nephropathy
- Systemic disease:
- Goodpasture syndrome
- SLE
- Systemic vasculitis (eg. polyarteritis nodosa)
- Infective endocarditis
- Henoch-Schonlein purpurn
- Clinical Features:
- 3 possible outcomes:
- Complete resolution with no residual damage
- Rapid progression to rapidly progressive glomerulonephritis causing acute renal failure
- Slow progression to chronic renal failure (chronic glomerulonephritis)
- LM often shows focal segmental proliferative glomerulonephritis (hence differential diagnosis depends on the immunofluorescence pattern)
3. Rapidly Progressive Glomerulonephritis
- Characteristics:
- Rapid development of anuria/severe oliguria with a rise in serum creatinine over 3 months or less
- LM exhibits crescents in >50% of glomeruli
- Causes:
- Type 1 (anti-glomerular basement membrane Abs)
- Type 2 (immune complex)
- Post-streptococcal glomerulonephritis
- SLE
- Henoch-Schonlein purpura
- Type 3 (pauci-immune)
- ANCA-associated
- Systemic vasculitis (Wegener granulomatosis, microscopic polyangiitis)
- Clinical Features:
- Share common aetiologies with nephritic syndrome
- Results in acute renal failure
- Exclude other causes of acute renal failure:
- Prerenal causes: shock, renal hypoperfusion
- Renal causes: Acute tubular necrosis, tubulointerstitial nephritis
- Postrenal causes: Urinary tract obstruction
4. Microscopic Hematuria
- Characteristics:
- Hematuria not visible to the naked eye (detectable only by urinanalysis)
- Some degree of proteinuria (below nephrotic range)
- No change in urine volume
- No HTN
- No azotemia
- Causes:
- Usually milder forms of proliferative GNs
- IgA nephropathy
- Thin basement membrane syndrome
- Clinical Features:
- Always exclude lower urinary tract causes of hematuria in differential diagnosis (Trauma, tumour, infections, stones)
5. Chronic Renal Failure
- Stage 1: Diminished renal reserve
- GFR = 50% of normal
- Normal serum creatinine and blood urea nitrogen
- Asymptomatic
- Stage 2: Renal Insufficiency
- GFR = 20-50% of normal
- Azotemia appears
- Anemia, HTN, polyuria, nocturia
- Stage 3: Chronic renal failure
- GFR < 20-25% of normal
- Overt uremia (azotemia + GI, neurological and cardiovascular complications)
- Edema, metabolic acidosis, hyperkalemia
- Stage 4: End-stage renal diseases
- Characteristics:
- Change in urine volume:
- Initial polyuria as tubules cannot concentrate glomerular filtrate
- Terminal oliguria when little functioning nephrons are left
- Consequences of decreased filtration
- HTN and edema
- Uremia
- Metabolic derangements (hyperkalemia, metabolic acidosis)
- Decreased endocrine functions of kidney:
- Anemia (decreased EPO production)
- Secondary hyperparathyroidism (due to decreased vit D activation by renal tubules leading to hypocalcemia)
- Causes of chronic renal failure:
- Chronic glomerulonephritis
- Tubulointerstitial diseases
- Chronic pyelonephritis
Pathogenesis of Glomerular Injury
- Antibody-Mediated Mechanisms
- In-situ formation of immune complexes
- Against native antigen - Goodpasture disease
- Against planted antigen that localises in glomerulus - HBV, HCV, Streptococcus, syphillis, malaria
- Circulating immune complex deposition in glomerulus eg. Lupus nephritis
- Anti-Neutrophil Cytoplasmic Antibodies (ANCA) - interacts with neutrophils within glomeruli
- Other pathogenic factors:
- Activation of alternative complement pathway (no Abs required)
- Seen in membranoproliferative glomerulonephritis type II
- Platelet
- Aggregate in glomeruli during immune-mediated injury, can subsequently release eicosanoids and growth factors which promotes inflammation and cellular proliferation
- Coagulation system
- Leakage of fibrin through damaged GBM into Bowman's space induces proliferation of the parietal layer of Bowman's capsule (forms crescents)
- Cytokines
- Angiotensin
- Podocyte-released cytokines
-
-
Renal, Bladder Neoplasms
1. Angiomyolipoma
- Most common benign tumour of the kidney
- Epidemiology and associations:
- Belongs to the family of PEComas (tumours containing perivascular epithelioid cells) which includes:
- Lymphangioleiomyomatosis
- Clear cell sugar tumour of the lung, pancreas, uterus
- Cardiac rhabdomyomas
- Occurs at all ages, but usually resected after age 40 or older
- Most commonly found in kidneys, but can also occur in: Liver, Lungs, Retroperitoneum
- Pathogenesis:
- Sporadic
- Familial - asc with tuberous sclerosis
- Loss of function mutations of TSC1 or TSC2 tumour suppressor genes
- Characterised by cerebral cortical lesions (producing epilepsy and mental retardation), skin abnormalities and unusual benign tumours (eg. cardiac tumours)
- Gross:
- Unencapsulated
- Variegated cut surface with yellow fatty areas
- Histology:
- Mixture of myoid spindle cells , epithelioid cells, adipocytes and blood vessels (often thick walled)
- Myoid cells show immunostaining for HMB-45
- Clinical features:
- Can be accurately diagnosed on CT scan due to its large fat content (appears radiolucent)
- May rupture and bleed
2. Renal Cell Carcinoma
- Malignant tumour arising from the renal tubular epithelium
- Epidemiology:
- Accounts for 85% of malignant renal tumours in adults
- Accounts for 1% of all visceral cancers
- Mostly occurs in the 6th and 7th decades of life
- Male:female = 2:1
- Most common types of RCC:
- 1. Clear cell RCC (70-80%)
- Arises from proximal tubules
- Gross:
- Solitary, unilateral, with a circumscribed appearance
- Yellowish cut surfaces with foci of necrosis and haemorrhage
- Invasion of renal vein not uncommon
- Tendency to metastasise widely, may be late
- Histology:
- Polygonal cells with clear cytoplasm
- Delicate branching vasculature
- Invasion of renal vein and its branches may be seen
- 2. Papillary RCC (10-15%)
- Arises from distal tubules
- 3. Chromophobe RCC (5%)
- Arises from the intercalated cells of collecting tubules
- Clinical Features:
- Painless haematuria
- Mass in flank
- Fever due to necrosis
- Costovertebral pain
- Paraneoplastic syndromes (polycythaemia, HTN, hypercalcemia, Cushing syndrome, amyloidosis etc)
3. Urothelial Carcinoma
- Arises from the urothelium (transitional cell epithelium) lining the renal calyces, pelvis, ureter and bladder
- Patients are at risk of synchronous or subsequent urothelial tumours anywhere in the urothelial tract, as well as recurrent tumours
- Types:
- Papillary urothelial carcinoma (non-invasive)
- Invasive urothelial carcinoma - may arise from previously non-invasive papillary UC or from UC in-situ (flat, high grade dysplasia)
- Morphology:
- Identical to urothelial carcinoma of the bladder
- Exophytic mass
- Usu asc with urothelial carcinoma of the ureter and bladder
- Clinical features:
- Usually discovered early
- Fragmentation causes noticeable haematuria
- Blockage of urinary outflow gives rise to hydronephrosis and flank pain
4. Wilms Tumour (Nephroblastoma)
- Paediatric renal tumour
- Epidemiology:
- Usually diagnosed between ages 2-5
- Asc with congenital malformation syndromes:
- WAGR sundrome, Denys-Drash syndrome, Beckwith-Wiedemann syndrome
- Gross:
- Well circumscribed greyish soft mass
- Begins in renal cortex and replaces entire kidney
- Histology:
- Sheets of small blue cells (blastemal component)
- Abortive tubular and glomeruloid structures (epithelial component)
- Spindle-shaped cells (stromal component)
- Heterogenous elements such as striated/smooth muscle and cartilage may be found
- Clinical features:
- Large abdominal mass
- Fever due to necrosis and haemorrhage
- Haematogenous and lymphatic spread to lungs, liver, brain and lymph nodes
- Treatment:
- Combination nephrectomy and chemotherapy
- Generally good prognosis even for tumours which have spread beyond the kidney
Bladder Neoplasms
- Occupational risk factors:
- 2-napthylamine
- 4-aminobiphenyl
- Benzidene
- Non-occupational risk factors:
- Cigarette smoking
- Schistosomiasis (causes squamous metaplasia)
- Cyclophosphamide (induces hemorrhagic cystitis)
- Phenacetin (analgesic)
- Types:
- Benign
- Papilloma
- Inverted papilloma
- Nephrogenic adenoma
- Malignant
- Papillary urothelial carcinoma (non-invasive)
- Invasive urothelial carcinoma
- Squamous cell carcinoma - common in middle east due to frequent bladder infections (eg. schistosomiasis)
- Adenocarcinoma
Congenital Abnormalities
1. Renal Agenesis
- Due to:
- Lack of metanephric primordial
- Failure of ureteric bud formation
- Failure of contact of ureteric bud and metanephros
- Bilateral renal agenesis:
- Incompatible with life, rare
- Male:female = 25.1:1
- Stillborn
- Unilateral renal agenesis:
- Male: female = 2:1
- Opp kidney usu enlarged due to compensatory hypertrophy
- Some eventually develop progressive glomerulosclerosis in the remaining kidney due to adaptive changes in hypertrophied nephrons
2. Renal Hypoplasia
- Small kidney with reduced no. of lobules and calyces (less than 5, normal > 10)
- Histologically: Primitive glomeruli and tubules in dense fibrous or fatty interstitium
- Usu unilateral. If bilateral, results in renal failure in early childhood
- Renal hypoplasia with oligomeganephronia (kidney small with hypertrophied glomeruli)
3. Ectopic Kidney
- Abnormal positions of the kidney:
- Just above the pelvic brim
- Within the pelvis
- Kinking or tortuosity of ureters, leading to urinary tract obstruction
4. Horseshoe kidney
- Fusion of lower (90%) or upper (10%) poles
- 1 in 500 to 1 in 1000 incidence
- Complications - Urolithiasis
-
Prostate, Penis, Testes
Prostate
Benign Prostate Hypertrophy/Nodular Hyperplasia
- Extremely common condition in men over age 50
- Pathogenesis:
- Conversion of testosterone in prostate stromal cells into DHT by 5-alpha reductase (type 2)
- DHT binds to androgen receptors in the epithelial and stromal cells --> induces the production of growth factors that increase growth rate, decrease death rate of these cells
- Leads to progressive hyperplasia of the stromal and epithelial cells, forming nodules
- Prostatic smooth muscle tone (mediated via alpha-1 adrenergic receptors) worsens the lower urinary tract obstruction
- Most prominent in transitional zone - region surrounding prostatic urethra
- Complications:
- Urinary tract obstruction due to compression of prostatic urethra, leading to:
- Bladder distention and hypertrophy (yields a distended bladder with a trabeculated wall)
- Bladder hypotonia, diverticulum
- Hydronephrosis and hydroureter
- UTI
- Urolithiasis
- Chronic kidney disease
- Treatment: Transurethral resection of the prostate (TURP)
Prostatic Carcinoma
- Usually occurring in men over 50 years old
- Risk of contracting it increases with age
- Types:
- Acinar adenocarcinoma (more common)
- Ductal adenocarcinoma
- Clincal Features:
- Usually occurs in the peripheral zone of the prostate - cannot be resected by TURP
- Metastatic disease is uniformly fatal (Bones are a common site)
- Prognostic Factors:
- TMN Staging
- Gleason grading:
- Grade 1:
- Well-differentiated tumour
- Glands are uniform and round in appearance, packed into well circumscribed nodules
- Grade 5:
- No glandular differentiation
- Tumour cells infiltrate stroma in cords, sheets and nests
- Most tumours contain more than 1 pattern
- First and second most frequent patterns are assigned a score each and added tgt
- Well-differentiated (2-4), Intermediate (5-6), Moderate to poorly differentiated (7), High grade tumour (8-10)
- Tests:
- Serum Prostate Specific Antigen (PSA) level testing
- Often done in patents with enlarged prostate/LUTS
- But does not always correlate with presence/absence of prostatic carcinoma, unless significantly elevated
- Inherent false -ve and +ve
- Prostate core biopsy done to test for presence of prostatic carcinoma (inherent false -ve rate due to sampling)
Penis Neoplasms
Condyloma Acuminatum
- Benign sexually-transmitted tumour of the penis
- Asc with HPV types 6 and 11
- Gross: Lesion found on coronal sulcus, on the inner surface of the prepuce
- Histology: Clear vacuolation of squamous cells
Penis Squamous Cell Carcinoma
- Geographic variations in prevalence
- Circumcision is protective
- Asc HPV types 16 and 18
- Clinical course:
- Slowly growing
- Locally invasive
- Metastasis to inguinal/iliac lymph nodes --> grim prognosis
Testes
Orchitis and Epididymitis
- Inflammation of the testes/epididymitis
- Tuberculosis
- Begins in the epididymis, spreads to rest of testes
- Typical caveating granulomas
- Mumps
- Primarily cause inflammation and swelling of the parotid glands
- Complication in post-pubertal males include orchitis and acute pancreatitis
- Gonorrhea
- Typically cause orchitis as an extension from infection of the urethra, which first affects the epididymis
- Produces frank abscesses
- Syphilis
- Usually affects testes without affecting epididymis
- May produce gummas
Filariasis
- Chronic helminthic infection of lymphatics resulting in impairment of lymphatic drainage --> lymphedema of affected tissues
- Clinical features:
- Chronic filariasis gives rise to persistent lymphedema of the scrotum, penis and vulva and limbs
- Results in subcutaneous fibrosis and epithelial hyperkeratosis
- Elephantiasis (limbs)
- Scrotal enlargement
Testicular Neoplasm
- Vast majority are germ cell tumours (95%) which are mainly seen in young men. Lymphomas are seen in older men
- Predisposing factors:
- Cryptorchidism (undescended testes)
- Genetic factors
- Testicular dysgenesis syndrome
- Cryptorchidism + hypospadias + poor sperm quality
- Clincal features and tumour markers:
- Painless enlargement of testis
- Raised serum alpha-fetoprotein
- Raised serum human chorionic gonadotrophin (HcG) beta subunit
Seminomatous germ cell tumours
- Remain localised for a long time
- Very radiosensitive
- Spread by lymphatics to para-aortic nodes
- Examples:
- Seminoma (commonest germ cell tumour, peak in 4th decade)
Non-seminomatous germ cell tumours (NSGCT)
- Metastasise relatively earlier
- Radioresistant
- Spreads via hematogenous route
- Examples:
- Yolk sac tumour
- Aka infantile embryonal carcinoma or endodermal sinus tumour
- Most common testicular tumour in infants
- Good prognosis
- Usu occurs in mixed tumours when in adults
- Choriocarcinoma
- Teratoma
- Contains a variety of mature and/or immature tissue types, most often from more than one germ layer
- Common in females (benign), always malignant in males
- May exist in combination with other germ cell tumours (mixed germ cell tumour)
- Embryonic carcinoma
- More aggressive than seminomas
- Peak between ages 20-30
Mixed tumours:
- Seminoma + any NSGCT (one or more types)
- Teratoma + embryonal carcinoma
- Seminoma + embryonal carcinoma
- Teratoma + choriocarcinoma
- Other combinations
Vascular Diseases
Benign Nephrosclerosis
- Renal pathology asc with sclerosis of renal arterioles and small arteries, due to longstanding or poorly controlled diabetes
- Morphology:
- Arteries: atherosclerosis
- Arterioles: hyaline arteriolosclerosis
- Patchy ischemic atrophy (interstitial fibrosis, glomerular changes, tubular atrophy)
- Pathological effects and complications:
- Proteinuria (may be nephrotic range)
- Mild reduction in GFR
Accelerated Nephrosclerosis
- Renal pathology due to malignant hypertension
- Initiating stimuli results in increased renal vascular permeability and increased release of PDGF
- Causes fibrinoid necrosis and hyper plastic arteriolosclerosis
- Changes in arterioles narrow lumen of afferent arteriole
- Decrease GFR and salt delivery to distal tubules - triggers renin production - in turn constricts renal vessels (Vicious cycle)
- Morphology:
- Hyperplastic arteriolosclerosis (onion-skin appearance)
- Fibrinoid necrosis
- Pathological Effects and Complications:
- Renal failure (after initial proteinuria and hematuria)
- Associated lesions in malignant HTN:
- Papilledema
- Retinal hemorrhages
- Encephalopathy
-