Renal pathology Flashcards
Nephrotic vs Nephritic
Nephrotic
- Heavy proteinuria (>3.5 gm/day)
- Edema
- Lipiduria & Hyperlipidemia (Oval fat bodies, free fat droplets)
- Low serum proteins (albumin)
- few cell elements
- fatty casts
Nephritic
- Proteinuria (<3.5 gm/day)
- Azotemia
- Hematuria
- red cells casts
- Granular casts
- variable proteinuria
- Oliguria
Nephrotic syndrome
Dx
- heavy proteinuria (>3.5gm/day) Hypoalbuminemia
- Cholesterol casts -> Maltese cross shape
- Edema
- Hypogammaglobulinemia -> infections
- Hypercoagulable state due to loss of anti-thrombin III
- Hyperlipidemia & lipiduria
- Normal complement levels
- incr Glomerular permeability capillaries to protein
Diseases include
- immunoglonulin deposition: membranous nephropathy
- no immunoglobulin deposition: minimal change, Focal segmental glomerulosclerosis (FSGS), diabetic nephropathy, amyloidosis
Minimal change disease
Most common disorder in children
- 15% in adults
- Idiopathic usually
- assoc w Hodgkin lymphoma, or renal cell carcinoma
- due to cytokine releasing causing foot process damage
Etiopath:
- The primary target is the glomerular epithelial cells (podocyte)
- Injury results in increased glomerular permeability & subsequent massive proteinuria
- No immune-complex deposition,
- Non –inflammatory injury to visceral epithelial cells by T cell-derived cytokines
Sx: Normal BP, Edema (periorbital, pedal)
Dx Labs:
- Serum: low albumin, normal Creatinine
- Urine: Selective proteinuria (subepithelial lesion), bland urine sediment
- LM: nl
- ***EM: Fusion of foot processes & effacement detachment of BM
C&C
- no tendency to progress into CRF/ESRD
FSGS
- Focal: some glomeruli are affected but not others
- Segmental: affecting only a segment of each glomerulus
- Glomerulo: of glomeruli
- Sclerosis: pink scarring on H&E
- 10-15% of idiopathic nephrotic syndrome in children
- Higher in adults (African American & Hispanics)
- Often idiopathic,
- Secondary to: causes of renal mass reduction
- - HIV,
- Morbid obesity,
- Chronic reflux nephropathy
- - Heroin use,
- Malignancies (lymphoma)
- - Sickle cell
Sx
- Present with insidious onset of asymptomatic proteinuria Progression to nephrotic syndrome with massive proteinuria & microscopic hematuria (both subepithelial and subendothelial lesions)
- Many are hypertensive & have renal insufficiency
- Degree of proteinuria is an important prognostic indicator
- Most patients will have persistent proteinuria & progressive decline in renal function
- ESRD by 5-20 years
Dx
- LM: FSGS
- *IF: negative/ or non specific granular deposits of IgM &C3
- * EM: patchy fusion of the foot processes & effacement
Secondary FSGS
Anything causing a reduction in renal mass will result in compensatory hyperfiltration in remaining glomeruli leading injury pattern {FSGS}
*Renal ablation nephropathy (partial nephrectomy)
** Glomerulonephritis
** Congenital unilateral renal agenesis or aplasia
Membranous nephropathy
- Present with nephrotic syndrome, microscopic hematuria (50%), HTN, renal insufficiency (late), renal vein thrombosis
- 20 years follow up: 25% of patients have spontaneous remission, 50% persistent proteinuria and stable or only loss of renal function, 25% develop ESRD
- Poor prognosis: male, > 50 age, >10 gm proteinuria
Etiopath:
- IC Deposits in sub-epithelial zone (Heymann Nephritis animal model)
- Complement activation
- Activation of mesangial cells releasing proteases and degradative enzymes
Sx: Massive proteinuria -> hypercoagulable state due to loss to anti-thrombin-3
Assoc Disorders & Ag
- **Idiopathic
- **Endogenous Antigens { DNA “SLE”/ tumors}
- **Exogenous antigens:
- Hepatitis B
- Syphilis
- Malaria
- Captopril
- Mercury
- Gold
- Penicillamine
Dx
- LM: diffuse thickening of the glomerular basement membrane with little increase of cellularity
- IF: Fine granular deposits of IgG, C3 along the basement membrane – subepithelial
- EM: subepithelial immune complex deposits and proliferation & growth of new GBM resulting in“spikes & domes” formation
Diabetic nephropathy
- important cause of end-stage renal failure (ESRF)
Morphology
- Ischemia: causes tubular atrophy, interstitial fibrosis
- Hyaline arteriolosclerosis
- ****Kimmelstiel-Wilson nodules {nodular glomerulosclerosis} nodules contain lipids & fibrin **-> Fibrin Cap & capsular drop ( plasma proteins )
- basement membrane thickening and mesangial expansion
- diffuse glomerulosclerosis
Etiopath
- Kidney disease is a result of adverse effects of systemic hyperglycemia
- Earliest lesions: expansion of mesangial matrix & thickening of GBM
- Initially hyperglycemia leads to hyperfiltration ( increased GFR) & increased glomerular hydrostatic pressure
- Later lesions: diffuse global glomerulosclerosis with:
- Diffuse increase in mesangial matrix & diffuse thickening of GBM
- After 7-13 years of disease: microalbuminuria (30-300mg/24h) appears- incipient nephropathy (reversible renal failure)
- After 10-20 years: macroalbuminuria (>300mg/24h) - overt/established nephropathy
- Afterward there is persistent & progressive proteinuria, HTN, highly variable decline in GFR 1-24 ml/min/year ( median 12 ml/min/year)
Amyloidosis in kidney
Etiopath
Renal involvement can be seen with either AL or AA amyloid
Difference bw AL (majority of amyloid) vs AA: kappa or lambda
LM: nodular, amorphous hyaline material in the mesangium & capillary loops, with resultant narrowing or closing of capillary lumens; Similar morphology in diabetic neph (DDx)
Congo Red Stain positive with polarizable apple green birefringence
EM: subendothelial & mesangial fibrils
Sx
Proteinuria, edema, most common renal presentation, nephrotic syndrome
Renal insufficiency is present in 50% at time of Diag.
Electrolyte abnormalities (Fanconi’s syndrome)
Systemic disease: Include:
Heart: CM/ CHF, arrhythmias, heart block
GI: hepatomegaly, malabsorption, bleeding
Neuro: ischemic stroke, neuropathy, orthostatic hypotension
Skin: easy bruising, purpura
AA secondary amyloidosis
Rheumatoid arthritis
Behçet syndrome: recurrent aphthous ulcers, genital ulcers, and uveitis
Crohn’s disease
Osteomyelitis
Tuberculosis
Renal cell carcinoma
Hodgkin’s disease
Nephritic disorders
Normal complement levels:
- IgA nephropathy/ Henoch-Schönlein Purpura
- Alport’s syndrome (hereditary nephritis)
- SLE ( class I, II, V)
- Benign hematuria
Low complement levels:
- Post-streptococcal glomerulonephritis
- Membranoproliferative glomerulonephritis
- SLE ( class III, IV)
- Bacterial endocarditis/ infected ventriculoatrial shunt Cryoglobulinemia
variable complement:
- **Rapidly progressive glomerulonephritis
Dx
- Salt retention w periorbital edema HPT
- Azotemia
- Hematuria
- red cells casts
- Granular casts
- variable proteinuria
- Oliguria
IgA nephropathy Mesangioproliferative glomerulonephritis aka Berger’s disease
- Most common type of Glomerulonephritis
- May present at any age ( peak 2nd/3rd) decades
Morphology
- LM: Segmental areas of increased mesangial matrix & hypercellularity
- IF: Mesangial and subendothelial deposits of IgA & C3 (+/- IgG, IgM)
- EM: Mesangial and Subendothelial deposits
Etiopath
- Greatest incidence in Asians & Caucasians; Rare in blacks
- Production of IgA IC ( predominately polymeric IgA1 subclass, which is mainly derived from the mucosal immune system)
- Supported by clinical observation that hematuria worsens during URI or GI infections
- Unknown why? But predilection for mesangium
- Most likely deposition of IgA on mesangial matrix -> complement activation
- Incr endothelin, less NO
Sx
- Episodes of gross hematuria (associated with viral respiratory illness or GI illness)
- Persistent microscopic hematuria between these episodes
- HPT
- Azotemia
- Proteinuria (<3.5gm/day)
- Normal C3/C4
C&C
- Generally a prolonged benign course, BUT:
- 20% patients will progress to ESRD
- Most cases of IgA nephropathy are clinically restricted to kidney
- Or associated with arthritis, vasculitis, non- thrombocytopenic purpura -> Henoch-Schönlein- Purpura) {HSP}
Assoc disorders
- Hepatic cirrhosis
- Gluten enteropathy
- HIV infection
- Minimal change disease
- Others: membranous, Wegener’s, Ankylosing spondylitis, small cell Ca
Post-strep Glomerulonephritis (PSGN)
Clinical
- GN manifests usually 10 days following pharyngitis & 3 weeks following impetigo
- More common in children (6-10year age)
- Usually abrupt onset of nephritic syndrome with:
- Proteinuria >2gm/day
- Complement levels always low
LM:
- Hypercellular glomeruli (neutrophils + monocytes) * Proliferation of mesangial, endothelial, epithelial cells.
- Process is diffuse (entire lobules of all glomeruli)
- Closure of capillary loops due to: proliferation & swelling of endothelial cells & leukocytes infiltration
IF: granular deposits of IgG & C3 in the mesangium & along capillary walls
EM showing subepithelial humps (deposits); (subendothelial usually cleared away w/in first 2 months)
Etiopath
- Initially: IC subendothelial deposits and clearance
- Later: characteristic subepithelial “HUMPS” responsible for epithelial cell damage & proteinuria. IC deposits cleared slowly (separated from circulation by GBM) limiting their clearance
Dx
- History,
- clinical presentation,
- elevated titers of anti-streptolysin O Ab or anti-DNAase B in association with low complement
Sx
- hematuria (cola-colored urine)
- oliguria
- HPT
- periorbital edema
- usually seen in children
Membranoproliferative Glomerulonephritis (MPGN)
- Glomerular disease characterized by:
- thickening of basement membrane, mesangial proliferation, infiltration of inflammatory cells
- Can be primary (idiopathic) or secondary (underlying systemic disorder)
- Same histological findings
3 major types
Type I: subendothelial deposits; C3 & IgG;
- Idiopathic rare; Secondary forms are more common; Hep B & C
- more often assoc w Tram tracks
- Classical complement pathway
Type II: deposition of dense material along GBM (unknown composition; maybe C3 nephritic factor); 4 presentations
- 1-Hematuria or proteinuria discovered on urinalysis
- 2-Acute nephritic syndrome with hematuria, HTN and edema
- 3-Recurrent episodes of gross hematuria
- 4-Insidious onset of edema and nephrotic syndrome
- Most progress to ESRD within 10-15years
- Alternative complement pathway involving C3 convertase stablized by Ab
Type III: subendothelial, mesangial, subepithelial deposits; C3 & IgG
Morphology
- PAS stain showing splitting of GBM (tram-track appearance) due to mesangial cells
- Silver stain showing gaps (arrow) & tram-track appearance
- EM: ribbon-like extension of immune complexes; type 1 deposition -> subendothelial
- Type I (bottom left): subendothelial deposits (lamina rera interna)
- Only Type II: C3 decr due to C3 Nephritic factor = Ig (lamina densa deposits) -> Dense deposit disease
-
Dx: C3 Nephritic factor = Ig, nl C4 but C3 decr
- LM cannot differentiate bw type I to III
- C&C: poor prognosis
Rapidly progressive GN (RPGN)
associated severe oliguria & if untreated death from renal failure within weeks to months
** Renal biopsy & serologic analysis are indicated for diagnosis:
** sub classified in to 3 types ( I, II, III)
- Type I: Goodpasture’s syndrome,
- Type II: SLE, PSGN, IgA, Henoch-Schonlein Purpura, Diffuse Proliferative Glomerulonephritis
- Type III: Wegner’s (no IF, hemoptysis, hematuria, sinusitis), PAN, Churg-Strauss
Morphology
- LM: characterized by a proliferative GN with prominent “crescent” formation in 30-70% of glomeruli and +/- segmental necrosis
- Crescent composed of fibrin and macrophages
Sx
- severe glomerular injury:
- Proteinuria (non-nephrotic), hematuria, red blood cell casts, hypertension, edema, variable degree of oliguria
Lupus nephritis
- Fullhouse disease: +ve for multiple immunofluorescence (IgG, IgA, IgM, C3, and C1q) -> SLE
- Based on histology:
- I- minimal mesangial
- LM: nl
- IF & EM: mesangial immune deposits
- II- mesangial proliferative
- mesangial immune deposits resulting in expandion & hypercellularity
- clinical: mild disease; microscopic hematuria, proteinuria, nephrotic syndrome/ renal insufficiency rare.
- III- focal segmental proliferative
- <50% glomeruli affected on LM
- subendothelial & mesangial IC deposits; complement activation, influx of inflammatory cells
- Clinical: hematuria, nephrotic syndrome, hypertension, renal failure
- IV- diffuse proliferative
- >50% glomeruli affected on LM
- Marked deposition of IC in subendothelial & mesangium
- Crescents & necrotizing lesions
- Clinical: most common & most severe form; hematuria, proteinuria, nephrotic syndrome, renal failure, low complements, high anti-DNA levels
- V- membranous
- Subepithelial immune complex deposits
- Diffuse thickening of GBM
- Clinical: same as idiopathic membranous: nephrotic syndrome, “bland” urine sediment, mild renal insufficiency, normal C3/C4, negative anti-DNA
* IC deposits in blood vessels
- VI- advanced sclerosing lupus nephritis
- Global sclerosis of >90% of glomeruli
Advanced interstitial fibrosis & tubular atrophy
Represents healing of prior inflammatory injury, advanced stages of chronic Class III, IV, V lupus nephritis
Benign hypertensive nephrosclerosis
Benign as patients are asymptomatic Usually normal or slight reduced GFR Clinical paradox:
HTN ( 25% in patients with ESRD) Risk factors for ESRD:
- Blacks ( 8- fold)
- Higher blood pressure
- Second underlying CKD (diabetes)
Morphology
Vascular: medial & intimal thickening
* Hyaline arteriolosclerosis ( due to extravasation of plasma proteins through injured endothelium)
\*Glomerular: Global sclerosis (ischemic injury)...leading to nephron loss
FSGS( adaptive injury), compensatory hyperfiltration due to nephron loss
\* Tubules & interstitium: Tubular atrophy Interstitial fibrosis (ischemic mediated)
Etiopath
- HTN -> large & small arteries medial & intimal thickening -> luminal narrowing -> ischemic injury to glomerulus, tubules, interstitium
Sx
long standing history of hypertension
Slowly progressive elevation in serum Creatinine
Mild proteinuria (<1 g/day) No microscopic hematuria, Bland urine sediment with mild proteinuria
C&C
- LVH ( left ventricular hypertrophy)
- Retinopathy
- Stroke
ARF (Pathoma)
Prerenal azotemia:
- due to decr blood flow to kidney; common cause of ARF
- decr. GFR and oliguria
- Rebasorption of fluid and BUN ensues (serum BUN: Cr>15)
- Tubular fx remains intact (FENa <1%; urine osm>500 osm/kg)
Postrenal azotemia:
- obstruction downstream of kidney
- decr GFR and oliguria
- Early stage: incr tubular pressure forces BUN into blood (serum BUN: Cr>15); Tubular fx remains intact (FENa
- Long-standing obstruction: decr reabsorption of BUN (serum BUN: Cr<15; FENa>2% and urine osm<500 osm/kg)
ATN
- most common cause of ARF
- 2 major causes:
- ischemic: preceded by pre-renal azotemia; PT and medullary segment of ThAL susceptible
- nephrotoxic: PT susceptible
- Acute Interstitial Nephritis: drug-induced Hypersensitivity Reaction (HSR) -> Eos; Ex. NSAIDS, PCN, and diuretics
- necrotic cells plug tubule leading to *acute decline in GFR,
- *oliguria/anuria,
- *serum BUN & Creatinine increased
- Metabolic acidosis ( low HC03 )
- Hyperkalemia
- Hyperphosphatemia
- Anemia ( decrease erythropoietin from renal peritubular interstitial cells)
Clinical course
3 predictable phases:
**Initiation phase (36 Hrs):
Acute decrease in GFR to very low levels Rapid increase in serum creatinine & BUN
- ***Maintenance phase:**
- plateau of serum creatinine & BUN
- Lasts for days to 3 weeks (oliguria)
- Uremic symptoms, fluid overload, metabolic acidosis, hyperkalemia requiring dialysis
**Recovery phase:
Tubular function is restored Increasing GFR
Increase urine volume
Gradual decrease in creatinine & BUN
**Dx **
- Hypotension
- Low urine output ( oliguria / anuria )
- Uremic signs ( pericardial friction rub; confusion)
- Vasodilatory (septic shock): systemic infection
- Hemorrhagic shock: gastrointestinal bleeding
- Hypovolemic shock: vomiting, diarrhea
- Muddy brown granular casts
- Epithelial cells casts
- Free epithelial cells
- Proteinuria (mild)
- Microscopic hematuria (mild)
- No pyuria
- ** urine may be “normal” in less severe disease
ESRD
- most common causes are diabetes, HPT, and glomerular disease
Uremia sx:
- nausea
- anorexia
- pericarditis
- PLT dysfunciton
- encephalopathy w asterixis
- urea crystal depositions
- salt and H2O retention -> HPT
- hyperkalemia w metabolic acidosis
- anemia (EPO made up renal peritubular interstitial cells)
Complications
- hypocalcemia
- renal osteodystrophy (osteitis firbos cystica, osteomalacia, and osteoporosis
Malignant Hypertension
>180/120mmHg/(diastolic >130mmHg)
Develops in patients with pre-existing essential hypertension, secondary hypertension { pheochromocytoma, primary hyperaldosteronism)
Most common in young black males
Morphology
Gross: “flea-bitten appearance” -> Small, pinpoint petechial hemorrhages.
Microscopic:
Fibrinoid necrosis of arterioles -> homogenous, granular eosinophilic appearance
“Onion-skin appearance” -> proliferation of intimal cells -> hyperplastic arteriolosclerosis
Etiopath
Severe HTN -> breakthrough transmission of high pressure -> arterioles & capillaries -> endothelial wall injury -> release of fibrinogen, platelet deposition, plasma proteins -> fibrinoid necrosis & intravascular thrombosis
C&C: hypertensive crisis
Thrombotic Microangiopathies
Hemolytic uremic syndrome (HUS)
Thrombotic thrombocytopenic purpura (TTP)
- Disorders characterized by abnormal platelet aggregation leading to thrombosis in arterioles & capillaries throughout the body
- Thrombosis in small vessels results in mechanical injury to circulating RBCs with
- resultant“ microangiopathic hemolytic anemia”
- Clinically: microvascular thrombi lead to ischemic injury to target organs: kidney, brain, heart
- Rare: affects 1-4 people in every 1 million
SX
- Microangiopathic hemolytic anemia
- ( schistocytes in peripheral blood smear)
- Thrombocytopenia
- Purpuric rash
- Acute renal failure (mild to moderate proteinuria, hematuria)
- Neurological abnormalities: headache, confusion, seizure, stroke
- Fever
HUS:
- HUS/TTP: Clinical:
- Classically seen in children (one week after episode of bloody diarrhea caused by enterohemorrhagic E. coli ( 0157:H7)
- More severe renal failure, less pronounced CNS involvement
- Associated with other infections: viral, Shigella, Salmonella
- Drug induced: Quinine (tonic water), Gemcitabine, Cyclosporine, Ticlopidine, Oral contraceptives
TTP:
- CNS involvement more pronounced , renal failure less severe
- Often associated with SLE, HIV, hematological malignancy
RAS
Etiology
- 75-90% due to occlusion by atheromatousplaque
- 10-25% fibromuscular dysplasia
- Others: Takayasu’s arteritis, aortic/renal artery dissection
- Onset of HTN age<30 or >55
- Sudden onset of uncontrolled HTN in previously well controlled patient
- Accelerated/malignant hypertension
- Intermittent pulmonary edema with normal LV function
Ischemic nephropathy
- Diffuse ischemic atrophy in kidney of affected RA stenosis
- Crowded glomeruli
- Atrophic tubules
- Interstitial fibrosis
- No significant arteriolosclerosis in kidney of affected RA stenosis:
- Arterioles “protected” from transmission of high pressure due to stenotic renal artery
- Hypertensive arteriosclerosis in contralateral kidney due to increased systemic pressure.
Sx
- Flank or epigastric bruit
- ARF
Dx: Renal arteriogram is GS
Types of cell casts
- all cylindrical due to formation in renal tubules; if injury post-renal such as kidney stone -> cells (hematuria)
- Hyaline cast: cylindrical casts accumulate in CD
- Tamm-Horsefall proteins -> mucuoid protein made in Tubules -> tubule injury
- Some myoglobin
- Seen in dehydration; not always pathological
- Granular cast: cigar-shaped
- Epithelial cells and Ig light chains
- ATN (epithelial shedding)
- Nephritis
- Waxy cast: broad-large w sharp edges due to oliguria
- Low urine flow > chronic renal failure
- Red cell casts: a type of hematuria
- always pathological -> nephritis: Wegner’s, SLE, PSGN, Goodpasture
- Never in kidney stones
- WBC casts:
- Acute pylonephritis
- Acute interstitial nephritis
- Urine sediments: showing hematuria & pyuria (WBC)
- Oval fat bodies: bubbly appearance
- Nephrotic syndromes -> due to high levels apolipoproteins -> epithelial cells absorb lipds -> tubule shedding of lipid-ladened epithelial
Alport syndrome
- Nephritic syndrome (hematuria, proteinuria, renal failure)
- Males 5 to 20 yo
Etiology:
- X-linked Mutation in col4A4 for type IV collagen
- absence of globular region of alpha 3 chain of type IV collagen. (AD, AR and X-linked)
- defective GBM synthesis
Morphology
– LM: Thinning, splitting and fragmentation of GBM; foam cells in glomeruli and tubules
–IF: Negative
–EM: Basket weave splitting of lamina densa
Clinically:
• Microscopic haematura
Sx
- isolated hematuria
- Nerve deafness (esp. to high frequencies),
- Eye disorders (cataracts and dislocated lens)
- Disorders of skin
- Disorders of platelets
Acute pyelonephritis
- Gross: collection of abscess (whitish)
- Microscopic: focal inflammation & necrosis
Sx
- Fever (high)
- Dysuria
- Flank pain
- Nausea, vomiting
- Costovertebral angle tenderness
Dx
- Elevated BUN, Creatinine (volume depletion)
- Elevated WBC
- Pyuria, bacteruria,
- WBC casts
Etiopath:
- Intense interstitial edema -> compress renal arterioles ->Decr GFR
- Predisposing factors: decr urine flow -> UTI, endocarditis, diabetes, BPH, renal stones, catheters
C&C
- Papillary necrosis
- Pyonephrosis
- Perinephric abscess
Obstructive Uropathy (OU)
- Obstruction at any level of urinary tract from urethra to renal pelvis
- Obstruction above the bladder can be unilateral or bilateral
- Common causes:
- BPH
- Bladder cancer
- Kidney stone
- Retroperitoneal adenopathy
- Papillary necrosis (sloughed papillae)
UO w Hydronephrosis
- Dilatation of renal pelvis & calyces
- As a result of continued glomerular filtration, but unable to be excreted due to obstruction..
- Diffuses back in to renal interstitium
- High pressure in pelvis is transmitted through collecting tubules into renal cortex causing renal atrophy
- Renal function fully recovered if relieved fast
- Irreversible damage & renal failure if obstruction not relieved by 2-3 weeks
Autosomal dominant polycystic kidney disease (ADPKD)
Etiology
- Characterized by development of multiple fluid filled cysts…leading to increased kidney size
- Common: occurs in1-400 to 1000 lives births
- Often clinically silent
- Less than 50% of cases will be diagnosed during the patient’ lifetime
- Accounts for 4-6% of ESRD
Pathogenesis of renal failure
- Abnormal Chromosome 16p13.3 (APKD1 gene) -> Majority cases
- Abnormal Chromosome 4q21 (APKD2 gene)
- **Milder phenotype:
- •Later onset of cysts •Fewer & smaller cysts •Slower progression
- •Later age of ESRD
- Possible mechanisms for cyst formation in PKD
- mutations in polycystin 1,2 or fibrocystin
- defects in cell-cell and cell-matrix interactions
- altered tubular epithelial growth and differentiation leading to changes promoting cyst formation
- abnormal ECM
- cell proliferation
- fluid secretion
- Cystic growth leads to:
- 1- Compression & destruction of normal adjacent parenchyma
- 2- Glomeruli are overperfused
BUT: - Small number of nephrons <5% involved
- No evidence of FSGS
Sx: Renal manifestations
- HPT due to Cysts lead to compression of renal vessels–> renin, aldosterone
- Hematuria due to Rupture of cysts in collecting system
- Flank pain due to Stretching of renal capsule
- Nephrolithiasis due to >50% uric stones, calcium oxalate
- Renal failure
Sx: Extra-renal manifestations
- Hepatic cysts: 80% over age 30, usually asx & mild, liver fx intact
- Cerebral aneurysms
- Pancreatic cysts
- Cardiac valve disease (MVP, AR) Colonic diverticular disease Abdominal wall & inguinal hernia
Image below
- Left: Hepatic cysts
- Right: Berry aneurysm
- Cysts any where in kidne
Dx
- Renal Biopsy: Arteriolar sclerosis or Interstitial fibrosis
Childhood Polycystic kidney: AR PCKD
- Enlarged, cystic kidneys at birth
- newborns may present w Potter sequence (Pathoma)
- Cysts arising from collecting ducts
- Assoc w Congenital Hepatic fibrosis -> liver fx intact but can present w portal HPT
- Typical outcome: variable {death in infancy or childhood}
Renal cell carcinoma (RCCa)
- Gross: solitary large yellow mass on upper pole due to tumour
- Microscopic:
- High vascularization
- Polygonal cells with very clear cytoplasms
- Malignant tumor of renal tubular epithelial cells
- Majority sporadic/ unilateral/ single
- Clear cell carcinoma:
Etiopath
- males more than females
- Tobacco, obesity, HPT
- Renal vein invasion -> poor prognosis
- Sporadic or hereditary: both involving VHL gene
- Autosomal dominant RCCa
- Von-Hippel-Lindau (VHL) disease: Von Hippel Lindau syndrome (renal, CNS, retina)
- incr IGF-1 and
- incr HIF which in turn VEGF & PDGF
- Hereditary papillary RCCa: ( multiple, bilateral, younger age group)
- Von-Hippel-Lindau (VHL) disease: Von Hippel Lindau syndrome (renal, CNS, retina)
Clinical
- Incidence peaks in six decade of life
- M:F 2:1
- SX: hematuria/flank pain/ palpable mass <10% of patients
- *Hematuria is most common sign *Frequently asymptomatic (incidental) on
- abdominal imaging/ work up for hematuria
Assoc. w Paraneoplastic syndrome
Dx
- Renal ultrasound
- CT scan
- IV pyelograph
- biopsy
- Urine cytology useless
Horseshoe kidney
–Fusion of kidney during developing
–Usually asx -> maybe obstructions, UTI, and renal stones
Nephrolithiasis compositions & causes
See table below (Pathoma)
- AMP stone -> stag horn caliculus in adults
- Uric acid -> seen in Pt w leukemia and myeloproliferative
- Cysteine -> stag horn caliculus in children
Urothelial carcinoma
- Jagged edges obstructing bladder lumen
Etiology
- 50 to 80 yo males
- Risk factor:
- Smoking- greatest risk factor (2X)
- Drugs: Analgesic abuse (phenacetin)
- Cyclophosphamide
- Chemicals in workplace: (Naphthylamine, rubber products)
Pathogenesis
- assoc w p53, Rb,p16 gene mutations
- Squamous cell carcinoma: Schistosoma haematobium; worse prognosis
- Classification
- Flat type
- Papilllary type
Sx:
- painless hematuria
- Dysuria (20%)
- Urgency & frequency
- Flank pain
- Metastatic disease (up to 20% )
Rx: TUR, chemo, radio, surgery,
Flat vs Papillary type
Papillary type
- 75% of all bladder tumor
- * Exophytic tumor
- * Low grade tumor
- * Superficial invasion
- * Multiple recurrence
- * Multifocal ( urinary tract)
- **Tumor progression ( 5-10%)
- * high grade
Flat carcinoma: invasive carcinoma
- * Deeply invasive at diagnosis
- * Infrequently papillary (10%)
- * Usually high grade tumor ( poorly differentiated)
- * Metastases to: regional nodes/ liver/lung/bone
- * Poor prognosis
BPH
Gross image:
–Prostate larger than 4 cm
–Slit like urethra
–Bumpy (vs smooth in adenocarcinoma)
Microscopic:
- large glands producing serine proteases, stroma thickening,
- 2 layers lining glands (outer cuboidal or innner transitional): suggesting nl or hyperplasia
- Peri-urethral or transitional zone -> BPH
Signs & Symptoms: Only 10% are symptomatic
- **Urethral compression:
- Difficultystarting&stoppingurination
- Frequency/Dribbling
- Nocturia,Dysuria
- **Urine retention: due in part to inability to completely empty the bladder leading to infections, obstruction -> dribbling
Etiopath:
- Etiopath: proposed to involve increased DHT-R and estrogen
C&C:
- non-neoplastic & Not premalignant
- diverticulum inside bladder
- UTI due to stasis
- Bladder stones
- Obstructive uropathy
Rx:
- TURP-transurethral resection
- 5- alpha reductase inhibitors - Fenastiride
Prostatitc adenocarcinoma
Microscopic:
- Single layer surround glands -> Less stroma to parenchyma
Etiopath:
- 7th or 8th decade
- Race: African, Caribbean African American are at higher risk (low in Asians)
- High fat diet
- Family hx increases risk
- Hereditary prostate cancer gene: 1 or HPC1 -> RNASEL gene
Sx
- Often asymptomatic – 50% (early stage)
- Hematuria
- Bone pain - usually back pain (late stage/ metastasis)
- Weight loss
- Nodular hyperplasia like:
- Dysuria, weak interrupted urine flow
Dx:
- PSA velocity: rate of incr. > 0.75ng/ml/year suggestive of adenocarcinoma
- PSA density (PSA levels: prostate vol. ratio)
- DRE: Posterior-lateral (periphery) zone enlargement -> adenocarcinoma
- Transurethral Ultrasound & possible biopsies
- Bound to various protease inhibitors like: Alpha 1 anti-chymotrypsin & alpha 2- macroglobulin
- Both free & total PSA are measured
- PSA > 10 ng/ml -> HIGH
Cryptorchidism
- More common on right side
- Unilateral in majority but 25% cases – B/L
Microscopic
- More intestitium and Leydig cell in bw
- Thickening of BM
- Seminiferous tubules: atrophy and less cells, more eosinophilic
- Sparing of Leydig and Sertoli cells
- Spermatogonia destruction
Etiopath
•Failure of Gubernaculum
•Hormonal dysfunction
•Other congenital abnl ex. Hypospadias
•Incr cancer risk even in descended testes
C&C:
- Intra-abdominal germ cell tumour (3 to 5x)
- Infertility
- Orchidopecsy before 5 yo to prevent cancer risk
- Orchidopecsy before 2 yo to prevent infertility
Seminoma
Microscopic
- Sheets of Fried egg appearance cells w clear cytoplasm w prominent cytoplasm (similar to dysgerminoma ovaries & medullary carcinoma of breast)
- Lymphocytic infiltrates in interstitium
Etiopath:
•Males 30 to 50 yo
•Germinal cell tumour
•Isochr12p
•Risks: Testicular dysgenesis & Klinefelter disease, cryptoorchdism
Sx
- Unilateral testicular mass
- Feeling of heaviness in the scrotum Dull ache in the groin or abdomen Hydrocele
- Testicular pain
- Breast enlargement
- Metastatic disease in lymph nodes
Investigations: beta-HCG
C&C: good prognosis with radiotherapy
•Risk of metastasis to para-aortic LN via lymphatic spread
Non-seminona
- Embryonal carcinoma (3% pure)/ more in mixed
- Teratoma (children ( B) / adult (M)
- Yolk sac tumor (serum AFP) (children/adult)
- Choriocarcinoma (serum B-HCG)- rare
-
Mixed germ cell tumor (60%) {seminoma& non seminoma}
- **Peak 3rd decade
- **Ill defined hemorrhagic mass, cystic, solid
- Rx: surgery + chemo
- C&C: both hematogenous & lymphatic spread
Penile carcinoma in situ (CIS)
- all associated w HPV 16 & 18 infections
Bowen’s disease: Old people
- Solitary
- Shaft
- Plaque (scaly)
- Associated visceral malignancies;
- Progress to invasive
Erythroplasia of Queyrat
- Solitary or multiple
- Glans & perpuce
- Red patch, shiny plaque
- Progress to invasive SCca (Penile Squamous Cell Carcinoma)
Bowenoid papulosis: middle age
- multiple
- Shaft (glans/foreskin)
- Papular
- doesn’t progress to invasive SCca
Penile Squamous Cell Carcinoma
- Protective effect of circumcision
-
Etiopath:
- Carcinogens in smegma HPV 16,18
- Cigarette smoking Bowen’s disease ( CIS)
- Maximum incidence between the ages of 40-70 years
- C&C: slow growing locally invasive tumors
