Renal I (b) - Nephritic Syndrome Flashcards
IG-A Nephropathy is aka?
Berger Disease
IG-A Nephropathy is one of the most common causes of micro/macoscopic ————
Haematuria
There is an increased frequency of developing IG-A Nephropathy in px w/ ———- ?
Coeliac disease
IG-A Nephropathy (Berger disease)
Pathogenesis:
Respiratory or GI tract infections (in genetically susceptible individuals) –> ————- –> Deposition of ——— and ———— in the ————– –> Activation of the alternative complement pathway –> Initiation of glomerular injury
Respiratory or GI tract infection (in genetically susceptible individuals) –> Increased IgA synthesis —> Deposition of IgA and IgA-containing immune complexes in the Mesangium –> Activation of the alternative complement pathway –> Initiation of glomerular injury
Morphology:
* Normal glomeruli
* Mesangial widening and segmental inflammation of some glowmruli (Focal proliferative GN)
LM: Mesengial proliferation
IF: Mesangial IgA deposits, often w/ C3
Features of?
IG-A Nephropathy (Berger disease)
Microscopic Findings:
* Mesangial cell proliferation
* Segmental endo-capillary proliferation
* Segmental glomerulosclerosis and adhesion
* Focal accumulation of hyaline
* Focal presence of glomerular crescents
* Tubular atrophy with interstitial fibrosis
* Mesangial hypercellularity
* mesangial IgA depositis on IF
features of?
IG-A Nephropathy (Berger disease)
CF of Berger disease (IG-A Nephropathy)
1) Macro-Haematuria after respiratory/GI tract infection (>50%)
2) Micro-haematuria +/- proteinurea (30-40%)
3) 5-10 % –> Typical Nephritic Syndrome
25-50% of cases of Berger’s disease –> Development of ————–
Chronic Renal Failure
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
Calssification of Rapidly progressive GN
1) Type I (Anti-GBM Antibody)
2) Type II (Immune Complex)
3) Type III (Pauci-Immune)
CM of Rapidly progressive GM
1) Rapid and progressive loss of renal function
2) Severe Oliguria
3) Signs of Nephritic Syndrome
In Rapidly progressive GM the presence of < 80% of “Crescents” –> [Better/poor] prognosis
Better
what organs are involved in Goodpasture syndrome ?
Kidney and Lungs
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
Lab finding of Anti-Glomerular BM Antibody-mediated Crescentic GN
Serum anti-GBM Antibodies
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)
pathogenesis of Lupus Nephritis:
Deposition of ————- within the glomeruli -> Inflammatory response –> Proliferation of the ————–, ————— and/or ———–, but also ———— of the glomeruli, in severe cases
Deposition of DNA-anti-DNA complexes within the glomeruli –> Inflammatory response ->Proliferation of the endothelial, mesangial and/or epithelial cells, but also necrosis of the glomeruli, in severe cases
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
* Lupus Nephritis
———- Lupus Nephritis (Class –):
- Immune complexes in the mesangium
Minimal Mesangial Lupus Nephritis (Class I):
* Immune complexes in the mesangium
* Lupus Nephritis
—————- Lupus Nephritis (Class —):
* Immune complexes in the mesangium
* Mild to moderate increase in the mesangial matrix
and cellularity
Mesangial Proliferative Lupus Nephritis (Class II):
————- Lupus Nephritis (Class —):
- Complete sclerosis of greater than 90% of glomeruli
Advanced Sclerosing Lupus Nephritis (Class VI):
CF of Advanced Sclerosing Lupus Nephritis (Class VI)?
End-stage Renal Disease
———— Lupus Nephritis (Class —):
* Diffuse thickening of the glomerular capillary wall, due to deposition of sub-epithelial immune complexes
Membranous Lupus Nephritis (Class V):
Membranous Lupus Nephritis (Class —-):
* Diffuse thickening of the —————,
due to deposition of ————- immune
complexes
Membranous Lupus Nephritis (Class V):
* Diffuse thickening of the glomerular capillary wall, due to deposition of sub-epithelial immune complexes
Focal Lupus Nephritis (Class —-):
* Lesions in < –% of the glomeruli
* Segmental or global distribution, within each glomerulus
* Active lesions: Swelling and proliferation of
———- and ———– cells, neutrophilic infiltrates, —————, capillary thrombi
Focal Lupus Nephritis (Class III):
* Lesions in < 50% of the glomeruli
* Segmental or global distribution, within each glomerulus
* Active lesions: Swelling and proliferation of
endothelial and mesangial cells, neutrophilic infiltrates, fibrinoid deposits, capillary thrombi
———–Lupus Nephritis (Class —):
* Lesions in < 50% of the glomeruli
* Segmental or global distribution, within each
glomerulus
* Active lesions: Swelling and proliferation of
endothelial and mesangial cells, neutrophilic
infiltrates, fibrinoid deposits, capillary thrombi
Focal Lupus Nephritis (Class III):
CF of Focal Lupus Nephritis (Class III)
From mild microscopic Haematuria and Proteinuria to —> erythrocyte casts and Acute, Severe Renal Insufficiency
causes of pauci-immune Crescentic glomerulonephritis
Systemin Vasculitis
1) Microscopic Polyangiitis
2) Wegnes Granulomatosis
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
Inflammatory reactions of the tubules and interstitium –> ————
Tubulo-Interstitial Nephritis
Ischaemic or toxic tubular injury –> ———–
Acute Tubular Injury
Causes of Tubulo-Interstitial Nephritis
- Pyelonephritis
- Toxins (e.g. Drugs, Analgesics, Heavy Metals, etc.)
- Metabolic diseases (e.g. Hypokalaemic-, Oxalate-, Acute Phosphate-Nephropathy, etc. )
- Chronic Urinary Tract Obstruction
- Neoplasms (e.g. Multiple Myeloma)
Causes of Acute Pyelonephritis
* Ischaemic or toxic tubular injury
Enteric gram (-) rods (e.g. E. coli, Proteus,
Klebsiella, etc.)
Macroscopic Features:
* Discrete, pale, raised abscesses on the surface
Microscopic Findings:
* Intra-parenchymal liquefactive necrosis, with abscess development
* Prominent, intra-tubular, neutrophil cell infiltrates
* Extension into the collecting ducts, resulting in
the formation of the white cell casts in the urine
featurs of?
Acute Pyelonephritis
Acute Pyelonephritis
Macroscopic Features:
* Discrete, ——–, raised ————- on the surface
Microscopic Findings:
* —————— liquefactive necrosis, with abscess development
* Prominent, intra-tubular, ————–
* Extension into the collecting ducts, resulting in
the formation of the —————- in the urine
Micro:
* Discrete, pale, raised abscesses on the surface
Macro:
* Intra-parenchymal liquefactive necrosis, with abscess development
* Prominent, intra-tubular, neutrophil cell infiltrates
* Extension into the collecting ducts, resulting in
the formation of the white cell casts in the urine
CF of Acute Pyelonephritis
1) Pain at the costo-vertebral angle
2) Generalised Signs and Symptoms of infection:
- Chills
- Fever
- Malaise
3) Dysuria, Frequency and Urgency
4) Turgid urine (Pyuria)
Predisposing factors of Acute Pyelonephritis
1) Benign Prostatic Hyperplasia and Uterine Prolapse (Ouflow obstruction)
2) DM
3) Vesico-Ureteral Reflux (Incompetence of VesicoUreteral Orifice); i. Congenital defect, ii. Acquired
(Spinal Cord Injury, Neurogenic Bladder Dysfunction
[DM])
Patho of Acute Pyelonephritis
-Bacterial spread to the kidney by:
1) —————-
2) —————–
Bacterial spread to the kidney by:
1) Ascending infection : Mucosal adhesion of the bacteria –> Colonisation of the distal Urethra –> Movement against urine flow –> Extension to the Urinary Bladder and Kidneys
2) Haematogenous dissemniation : In the course of Septicaemia or Infective Endocarditis
Complication of Acute Pyelonephritis
1) Papillary necrosis
2) Pyonephrosis
3) Peri-Nephric Abscess
* p.45 (explanation)
———: Total or almost complete obstruction and accumulation of pus in pelvis, calyces and ureter
Pyeonephrosis
———-: Disorder in which chronic tubulo- interstitial inflammation and renal scarring are associated with pathologic involvement of the pelvi-calyceal system
Chronic Pyelonephritis
causes of Chronic Pyelonephritis
2 forms:
1) Chronic obstructive Pyelonephritis
2) Chronic Reflux-associated 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)
Cf of Chronic Reflux Nephropathy
1) Hypertension, in children
2) Loss of tubular function –> Polyuria and Nocturia
What is observed on imaging in a px w/ Chronic Pyelonephritis
- Asymmetrically contracted Kidney
- Blunting and deformity of the Calyceal system (Caliectasis)
Cause of Drug-induced Interstitial Nephritis
1) Synthetic Penicillins (e.g. Methicillin, Ampicillin, etc.)
2) NSAIDs
3) Diuretics (e.g. Thiazides)
CF of Drug-Induced Interstitial Nephritis
About 15 days, after exposure to the Drug, with:
1) Fever
2) Eosinophilia
3) Haematuria
4) Minimal or no Proteinuria
5) Leukocyturia (indication of UTI)
6) Serum Creatinine elevated or Acute Kidney Injury
with Oliguria (50% of cases)
cause of Chronic Obstructive Pyelonephritis
- Bilateral (Congenital Anomalies of the Urethra)
- Unilateral (e.g. Calculi)
Causes of Reflux Nephropathy
* Chronic Reflux-associated Pyelonephritis
UTIs (on Congenital vesico-ureteral Reflux and Intra-renal reflux)
* Mostly children
Patho of Reflux Nephropathy:
* Superimposition of an ———- on Congenital Vesico-Ureteral Reflux and intra-renal reflux -> Renal damage –> ——— and ————–>
Chronic Renal Insufficiency (in cases of ——— involvement)
Superimposition of an urinary tract infection
on Congenital Vesico-Ureteral Reflux and
intra-renal reflux –> Renal damage –>Scarring and Atrophy –> Chronic Renal Insufficiency (in cases of bilateral involvement)
Patho of Drug induced Intertitial Nephritis :
* Covalent binding of drug (acts as hapten) to cytoplasmic or extra-cellular component of tubular cells –> Acquisition of immunogenicity –> ——- and ———— to tubular cells or their basement membranes**
IgE and cell mediated immune reaction
causes of Acute tubular injury
1) Acute Kidney Injury (Oliguria; Urine Output: <400mL/day)
2) Severe Glomerular disease
3) Diffuse Renal Vascular Diseases (Thrombotic Microangiopathies, Microscopic Polyangiitis)
4) Acute Drug-induced Allergic Interstitial Nephritis
5) Ischaemic Acute Tubular Injury –> Generalised or localised reduction in blood flow; Marked Hypotension and Shock
6) Nephrotoxic Acute Tubular injury: Various Poisons (e.g.Heavy Metals, Organic Solvents, some Antibiotics etc.)
CF of Acute tubular Injury
1) Oliguria (cases of Acute Kidney Injury), Anuria or even non-oliguric (milder) cases
2) Decreased GFR
3) Electrolyte abnormalities
4) Acidosis
5) Signs and Symptoms of Uraemia and Fluid Overload
Ischaemic Acute Tubular Injury:
Morphology
* Mainly affected segments: Straight portion of the
————— and —————–
* —————- and sloughing of brush borders
* Detachment of tubular cells from BM
* Vacuolisation of cells
* —————— casts (mainly ———— protein or Uromodulin) in the distal tubules and collecting
ducts
* —————- of the interstitium
* Mild, mixed inflammatory cell infiltrates
Ischaemic Acute Tubular Injury:
* Mainly affected segments: Straight portion of the
proximal tubule and ascending thick limb
* Blebbing and sloughing of brush borders
* Detachment of tubular cells from BM
* Vacuolisation of cells
* Proteinaceous casts (mainly Tamm-Horsfall protein or Uromodulin) in the distal tubules and collecting ducts
* Generalised oedema of the interstitium
* Mild, mixed inflammatory cell infiltrates
