Renal- revision Flashcards
Alport syndrome is an X-linked dominant disease caused by mutations in genes encoding ———-?
a5 type IV collagen
Morphology
(Electron Microscopy):
* Irregular foci of thickening and thinning and splitting of GBM–> “Basket-weave” appearance
Features of?
Alport Syndrome
Alport Syndrome
EM: Irregular thickening and thinning and splitting of the GBM –> ————— appearance
“Basket weave”
CF of Alprot syndrome
1) Eye disorders (e.g. Lens dislocation, Posterior
Cataracts, Corneal dystrophy)
2) Slowly progressing Proteinuria
3) Gross or microscopic Haematuria
4) Nerve Deafness
* Can’t see, Can’t pee, Can’t hear a bee
menomic : Can’t see, Can’t pee, Can’t hear
what CM do these stand for+ which disorder is this?
1) Gross or microscopic Haematuria
2) Slowly progressing Proteinuria
3) Nerve Deafness
4) Eye disorders (e.g. Lens dislocation, Posterior
Cataracts, Corneal dystrophy)
Alport Syndrome
causes of Rapidly progressive Glomerulonephritis
Goodpasture syn., post-infectious GN, SLE
What distinctive microscopic feature identifies Rapidly progressiVe Glomerulonephritis
“Crescents”
aka Rapidly progressive (Crescentic) GN
CM of Rapidly progressive GN
1) Rapid and progressive loss of renal function
2) Severe Oliguria
3) Signs of Nephritic Syndrome
what stain is used to demeonstrate Renal BM?
jones’ Methenamine Silver stain (JMS)
* Same as PAS
Microscopic features:
- Areas of necrosis with rupture of capillary loops
- “Wire loop” lesion of Lupus Nephritis
- Epithelial Crescent
- IF: Fibrinogen Ab
Feautres of?
Rapidly progressive (Crescentic) GM
Macroscopic Features:
* Enlarged and pale kidneys
* Petechial, cortical located haemorrhages
Microscopic Findings:
* Formation of “Crescents”, by the proliferation parietal cells and the infiltration of monocytic inflammatory cells
* IF: Strong staining of linear IgG and C3 deposits, along the GBM
* EM: Focal disruptions of the GBM
* Treatment: Plasmapheresis
Features of?
Anti-glomerular BM Antibody-mediated Crescentic GN
*type I class of Rapidly progressive GN
On IF of Anti-Glomerular BM Antibody-mediated Crescentic GN , Strong staining of linear ——- and ———– deposits, along the GBM are found
Strong staining of linear IgG
and C3 deposits, along the GBM
Immune Complex-Mediated progressive GN (Type II)
Microscopic Findings:
* Segmental necrosis and GBM breaks –> ”———–“ and
* Diffuse proliferation and leukocyte exudation (Post Infectious Glomerulonephritis, SLE)
* Mesangial proliferation (IgA Nephropathy, HenochSchönlein Purpura)
* IF: Characteristic granular (“—————”) pattern of immune complex disease
*Segmental necrosis and GBM breaks –> “Crescents”
*IF: (“lumpy bumpy”) pattern of immune complex disease
Microscopic Findings:
* Segmental necrosis and GBM breaks -> “Crescents” and
* Diffuse proliferation and leukocyte exudation
* Mesangial proliferation
* Immunofluorescence: Characteristic granular (“lumpy bumpy”)
Features of?
Immune Complex-Mediated progressive GN (Type II)
Most common type of Lupus Nephritis
Diffuse Lupus Nephritis (Class IV)
* (35-60% of patients) and most
serious form
Micro features of Diffuse Lupus Nephritis (Class —):
* Extensive —————– immune complexes –>
Circumferential thickening of the capillary wall
(“—————”)
* Involvement of >–%of glomeruli
(Class IV)
* Extensive sub-endothelial immune complexes -> Circumferential thickening of the capillary wall
(“wire loops”)
* Involvement of >50% of glomeruli
CF of Diffuse Lupus Nephritis (Class IV)
1) Haematuria,
2) moderate to severe Proteinuria,
3) Hypertension and
4) Renal Insufficiency
Microscopic Findings:
* Segmental necrosis and GBM breaks –> “Crescents”
* Lack of anti-GBM Abs or Immune Complexes (IF & EM)
features of?
Pauci-immune Crescentic GN
Lab findins of Pauci-immune GN?
ANCA in serum
———-: Disorder in which chronic tubulo- interstitial inflammation and renal scarring are associated with pathologic involvement of the pelvi-calyceal system
Chronic Pyelonephritis
Macroscopic Features:
* Irregular scarring; Coarse, discrete, cortico-medullary scars
* Dilated, blunted, or deformed calyces
* Flattened papillae
Microscopic Findings:
* Uneven interstitial fibrosis
* Mixed inflammatory cell infiltrates
* Dilatation of tubules, with atrophy of the lining
epithelium
* Presence of intraluminal colloid (PAS[+]) casts –> Resemblance to Thyroid tissue [“Thyroidization”]
* Hyaline Arteriolosclerosis (Hypertension)
* Focal Segmental Glomerulosclerosis
features of?
Chronic Pyleonephritis
* Chronic Pyelonephritis
Macroscopic Features:
* —————; Coarse, discrete, cortico-medullary scars
* Dilated, blunted, or deformed ——-
* Flattened ————–
Microscopic Findings:
* Uneven interstitial fibrosis
* Mixed inflammatory cell infiltrates
* Dilatation of tubules, with atrophy of the lining
epithelium
* Presence of ——————- –> Resemblance to Thyroid tissue [”————–”]
* Hyaline Arteriolosclerosis (Hypertension)
* Focal Segmental Glomerulosclerosis
Macroscopic Features:
* Irregular scarring; Coarse, discrete, cortico-medullary scars
* Dilated, blunted, or deformed calyces
* Flattened papillae
Microscopic Findings:
* Uneven interstitial fibrosis
* Mixed inflammatory cell infiltrates
* Dilatation of tubules, with atrophy of the lining
epithelium
* Presence of intraluminal colloid (PAS[+]) casts –> Resemblance to Thyroid tissue [“Thyroidization”]
* Hyaline Arteriolosclerosis (Hypertension)
* Focal Segmental Glomerulosclerosis
CF of Chronic Obstructive Pyelonephritis
- Insidious Onset or
- Manifest as Acute Recurrent Pyelonephritis, with:
- Back pain
- Fever
- Frequent Pyuria (puss in pee)
causes of MALIGNANT HYPERTENSION?
Appearance either de novo or with a sudden onset in patients with pre-existing mild hypertension
* de novo –> ‘from the beginning’
Macroscopic features:
- Multiple small, pin-point petechial haemorrhages (on the kidneys)
- Flea-bitten Kidney
Microscopic features:
- Hyperplastic Arteriolosclerosis (Onion skin lesions)
- Fibrinoid Necrosis of Afferent Arteriole
Malignant HTN
Epi of Minimal-Change disease
* Type of Nephrotic Syndrome
Most common cause of Nephrotic
Syndrome in children (1-7 years)
CF of Minimal change disease
* Type of Nephrotic syndrome
1) Insidious (slow) onset of Nephrotic Syndrome
2) Albumin selective proteinuria
CF of Membranous Nephropathy
- Insidious onset of Nephrotic Syndrome (most cases)
- Non-selective proteinuria
- Haematuria and mild hypertension (15-35% of cases)
Progression and Prognosis of Membranous Nephropathy
- Persistent proteinuria (>60% of cases)
- Progressive disease leading to Renal Failure, after 2 to 20 years (40% of cases)
- Partial or complete remission (disappearnace) of proteinuria (10-30% of cases)
Microscopic Findings (Electron & Fluorescence Microscy):
* Discrete sub-endothelial electron-dense deposits (EM)
* Irregular granular deposition of C3 (IF)
* Presence of IgG and early complement components (IF)
Features of ?
MPGN- Type I
**
Microscopic Findings:
-
LM:Glomeruli enlarged and Hypercellular
(in a diffuse pattern : Leukocytic infiltration [neutrophils and monocytes, Proliferation of endothelial and mesangial cells, Crescent formation (severe cases)] - EM: Subepithelial IC “humps”
- IF: Scattered granular appearance “lumpy hump” due to IgG, IgM, and C3 deposits within GBM walls and mesangium
Features of?
Acute Post-streptococal Glomerulonephritis
CF of Acute Post-Infectious Streptococcal GN
Abrupt onset of:
* Malaise
* Slight Fever
* Nausea
* Oliguria and Haematuria (smoky or cola-coloured urine)
* HTN
* Peripheral and periorbital oedema
* Mild Proteinuria
**
MPGN-1 vs Dense Deposit disease
Microscopic features:
Light microscopy:
* “Double-contour” or “Tram-track” appearance of the glomerular capillary wall.
* “Splitting” of GBM
IF: IgG and early complement components.
EM: Discrete sub-endothelial electron-dense deposits.
features of?
Membrano-Proliferative GN type 1
Cause Post-Streptococcal GN
* type of Nephritic Syndrome
~ 2-4 weeks after infection w/ certain “Nephritogeninc” strains of group Α,β-heam. Streptoc.
(infection of pharynx or skin)
* most common in children
Lab findings of ACUTE POST-INFECTIOUS
(POST-STREPTOCOCCAL) GN
- +ve strep titers (Elevated anti-Streptolysin O Ab-titers)
- ↓ complement levels (C3) due to consumption (during the active phase)
Clinical Manifestations of Nephritic vs Nephrotic Syndrome.
Note : there is proteinuria and oedema in Nephritic however it’s mild
patho of MALIGNANT HYPERTENSION:
* Long-standing hypertension –> Injury to the arteriolar walls –> i. ——-,———-,———–> Fibrinoid necrosis of vessels —> (————) -> Increased narrowing of the arteriolar lumen –> Marked —— changes of the kidneys
* Renal ischaemia –> Further, Renin secretion (“———-”) -> Elevated ——— levels –> Salt retention -> Aggravation of blood pressure
- Long-standing hypertension –> Injury to the arteriolar walls –> i. increased permeabilty, endothelial injury and platelet deposition–> Fibrinoid necrosis of vessels —> (Hyperplastic Arteriolosclerosis) -> Increased narrowing of the arteriolar lumen –> Marked ischaemic changes of the kidneys
- Renal ischaemia –> Further, Renin secretion (“vicious cycle”) -> Elevated Aldosterone levels –> Salt retention -> Aggravation of blood pressure
Light microscopy
* Normal appearance of the glomeruli
* Protein droplets and lipids within the PCT -proximal convoluted tubules
Electron microscopy (Masson’s trichrome dye)
* Flattening of podocytes’ cytoplasm -> effacement (d.t cytokine damage)
* Epithelial cell vacuolisation
* Microvillus formation
* Focal detachments
Features of?
Minimal change disease
Macroscopic Features:
* Involvement of some of the glomeruli (focal); initially only the juxta-medullary glomeruli -> With disease progress, all cortical levels
Microscopic Findings:
* segmental glomerular lesions
* Increased mesangial matrix
* Obliterated capillary lumina
* Deposition of hyaline (hyalinosis)
* Foamy (lipid-laden) macrophages
* IF: Non-specific trapping of IgM and complement (C1,C3)
* EM: Effacement of podocytes’ foot processes; similar to Minimal Change Disease
Features of?
FOCAL SEGMENTAL GLOMERULOSCLEROSIS (FSGS)
* ass. w/ HIV
Patho of Membranous Nephropathy:
diffuse thickening of the —– and —- caused by subepithelial immune deposits -> Activation of the Complement –> ———— –> Damage of the mesangial cells and ——- –> Loss of slit filter integrity -> ——-
diffuse thickening of the glomerular capillary wall and GBM caused by subepithelial immune deposits -> Activation of the Complement –> C5b-C9 Membrane Attack Complex (MAC) –> Damage of the mesangial cells and podocytes –> Loss of slit filter integrity -> Proteinuria
**
Microscopic Findings:
Light microscopy: Uniform, diffuse thickening of the glomerular capillary wall and BM
IF: Granular deposits of IgG and complement (C5b-C9 -MAC) along the GBM
Electron microscopy:
* Characteristic “spike and dome” appearnace of sub-epithelial deposits
* Irregular dense deposits of immune complexes , deposition between the BM and the overlying epithelial cells
* Effacement of podocytes’ foot processes
MEMBRANOUS NEPHROPATHY
CM of Prune Belly Syndrome
Classical triad:
1. Urinary Tract anomalies
2. Deficient abdominal musculature (wrinkled/Prune-like Appearnace of the abdomin wall)
3. Bilateral Cryptorchidism
other CF:
1) Club foot (Talipes Equinovarus
2) Pulmonary hypoplasia
3) Imperforate Anus
4) Arthrogryposis (joint stiffness at birth)
CF of Autosomal Dominant (Adult) Polycystic kideny disease
1) Flank pain
2) Heavy dragging sensation
3) Palpation of an Abdominal Mass
4) Intermittent Gross Haematuria
5) Berry Aneurysms, with high incidence of Subarachnoid Haemorrhage (10-30% of patients)
Macroscopic Features:
* Enlarged organs, with a smooth external surface
* Cut surface: Numerous small Cysts in the Cortex and
Medulla –> Sponge-like appearance
Microscopic Findings:
* Dilated, elongated cystic spaces, vertical to the cortical surface
* Uniform lining of cuboidal cells
* Cysts in the Liver
Features of?
AR (Childhood) Polycystic Kidney disease
Macroscopic features:
* Staghorn Calculi in the renal pelvis
* marked hydronephrosis
Microscopic features:
* mix of calcium oxalate w/ calcium phosphate stones (in the calcyces)
features of?
Renal stones - Uroluthiasis
Staghorn calculi : large renal stones in the renal pelvis
Macroscopic Features:
* Tan colour
* Central Stellate Scar
Microscopic Findings:
* Numerous mitochondria, within neoplastic cells –> Finely granular eosinophilic cytoplasm
* Hypocellular Hyalinised Stroma
* small, round nuceli
features of?
Oncocytoma
Macroscopic Features:
* Usually, solitary and large, sphaerical masses (3-15cm)
* Cut surface: Yellow to orange to gray-white
* Dilated renal Calcyes
* Central tumour Necrosis and Haemorrhage
* Invasion of Calyces and Pelvis, as well as of the Renal Vein, Inferior Vena Cava and even the Right Heart-side
Microscopic Findings:
* Vacuolated, Clear cells (due to intra-cytoplasmic glycogen and lipid) - classic sign
* Small, round nuclei
Solid cytological picture:
* Cells with pink granular cytoplasm (as tubular epithelium)
features of?
Renal Clear cell carcinoma
Epi of CHromophobe Renal Carcinomas
5% of all Renal Cell Carcinoma
Macroscopic Features:
* Tan-brown colour
Microscopic findings:
* Clear, flocculent (Fine reticular) cytoplasm
* Prominent distinct, thick cell membranes
* Peri-nuclear “halos” of clear cytoplasm
features of?
Chromophobe Renal Carcinomas
CF of Chromophobe Renal carcinomas
Classic Triad:
1) Haematuria (>50% of cases)
2) Dull Flank Pain
3) Palpable Abdominal Mass
Macroscopic Features:
* Most common, large, solitary, well-circumscribed mass
Cut surface:
* Soft, homogeneous Tumour, with tan to gray colour
* Foci of Cystic degeneration, Haemorrhage and Necrosis
Microscopic Findings:
* Classic triphasic combination of blastemal, stromal and epithelial cell types
- Blastemal component: Sheets of small blue cells
- Stromal component: Fibrocytic or Myxoid cells
- Epithelial component: Abortive Tubules or Glomeruli
features of?
WILMS tumour
Macroscopic Features:
* Very large Kidneys
* Cut surface: Mass of Cysts (up to 3-4 cm), with no
intervening parenchyma
* Content: Clear, turbid or haemorrhagic fluid
Microscopic Findings:
* Variable lining epithelia of the cystic spaces
* Occasionally, presence of glomerular tufts within the cysts
features of?
AD (Adult) Polycystic Kidney disease
Adults w/ AD Polycystic Kidney disease have a high incidence of developing?
Subarachnoid
Haemorrhage (10-30% of patients)
complications of AD (Adult) Polycystic kideny disease
- Hypertension (75% of cases)
- Urinary infection
Cf of AR (Childhood) polycystic kideny disease
- Death of young infants, from Hepatic or Renal Failure
- Patients, who survive infancy -> Development of Liver
Cirrhosis
Macroscopic Features:
* Marked Kidney enlargement
* Prominent distention of the Pelvi-Calyceal System
* Compression and Atrophy of the Renal Parenchyma
* Obliteration of the Papillae & Flattening of the Pyramids
Microscopic Findings:
* Tubular dilation
* Atrophy and Fibrosis of the tubular lining
* Atrophy and Loss of Glomeruli
* Coagulative Necrosis of the Renal Papillae
* Superimposed Pyelonephritis
features of?
Hydronephrosis
CF of Hydronephrosis in cases of Complete, Bilateral Obstruction
Anuria
CF of Hydronephrosis in cases of Incomplete, Bilateral Obstruction
Polyuria
Complications of Oncocytoma
Spontaneous Haemorrhage
location of Renal Cell Carcinoma
renal Cortex
Epi of Renal Cell Carcinoma
80-85% of all primary Renal Malignant Tumours
M>F
Macroscopic Features:
* Multifocal and bilateral occurrence; Early-stage Tumours
* Cut surface: Weak orange-yellow colour; Necrosis,
Haemorrhage and Cystic degeneration
Microscopic Findings:
* Formation of Papillae with fibrovascular cores
* Foamy macrophages
features of?
Papillary Renal cell carcioma
WILMS tumour is aka?
Nephroblastoma
WILMS tumour causes
- Patients with the ———- Syndrome (1/3 of cases -> Wilms Tumour); Loss of genetic material of WT1 gene
- Patients with ———- Syndrome (90% -> Wilms Tumour); Dominant negative inactivating mutation in WT1 gene
- Patients with the WAGR Syndrome (1/3 of cases -> Wilms Tumour); Loss of genetic material of WT1 gene
- Patients with Denys-Drash Syndrome (90% -> Wilms Tumour); Dominant negative inactivating mutation in WT1 gene
CF of WAGR Syndrome
1) Wilms Tumour
2) Aniridia (partial or complete absence of the iris)
3) Genito-Urinary anomalies
4) Mental Retardation
CF of Denys-Drash Syndrome
1) Wilms Tumour
2) Intersex disorders (Gonadal dysgenesis)
3) Congenital Nephropathy
CF of WILMS tumour
- Commonly: Palpable abdominal mass, extending across the midline and down into the pelvis
- Less often: Fever, Abdominal Pain, and Haematuria
