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NON-NEOPLASTIC PATHOLOGY of the KIDNEY 2 - Coggle Diagram
NON-NEOPLASTIC PATHOLOGY
of the KIDNEY 2
GLOMERULOPATHIES ASSOCIATED TO SYSTEMIC DISEASES
SLE
renal involvement in 2/3 patients; variable injury depending on the immunological status of the patient --> renal biopsy for diagnosis, to evaluate disease progression and to modulate the therapy
pathogenesis
circulating and in situ formed ICOX, affinity of the cationic DNA-histone complex with components of the BM and of the mesangium
WHO classification
class I: MINIMAL MESANGIAL LN
normal at light microscopy
mesangial immune deposits at IF/EM
class II: MESANGIAL PROLIFERATIVE LN
purely mesangial hypercellularity or mesangial matrix expansion with mesangial immune deposits (LM)
mesangial immune deposits; few immune deposits in eubepithelial or subendothelial deposits possible (IF/EM)
class III: FOCAL LN
active or inactive focal, segmentsl or global glomerulephritis, involving <50% of all globeruli (LM)
subendothelial and mesangial immune deposits (IF/EM)
class IV: DIFFUSE LN
active or inactive diffuse, segmental or global GN involving >50% of all glomeruli; subdivided into diffuse segmental class and diffuse global (LM)
subendothelial immune deposits (IF/EM)
class V: MEMBRANOUS LN
diffuse thickening of glimerular BM, without inflammatory infiltrate (LM)
subepithelial and intramembranous immune deposits (IF/EM)
class VI: ADVANCED SCLEROSIS LN
advanced glomerular sclerosis involving >90%of glomeruli, interstitial fibrosis and tubular atrophy (LM)
few, if any immune deposits (IF/EM)
micro
in III and IV variants, also tubulointerstitial involvement with edema and infiltration of monocytes and granulocytes and granular deposits at IF on the tubular BM
involvement of vessels with variable degree: hyaline arteriosclerosis, deposition of ICOX with necrosis, thrombotic microangiopathy or vasculitis
IF
different qualitative and quantitative changes, ICOX deposition of IgG, IgM and C'. negative in class I, large mesangial and B, subendothelial deposits in classes III and IV or subepithelial in classes II and V
EM
evaluation of the site and extenrion of deposits, peculiar "fingerprint features", more frequently in class IV
clinical findings and evolution
classes I and II microhematuria and/or proteinuria; classes III and IV progressively ingravescent hematuria and proteinuria, up to renal failure; class V nephrotic syndrome
DIABETES
most frequent cause of renal failure in western countries; 30% in type I diabetes. Involvement of glomeruli (necorsis of the papilla, nephritis and pyelonephritis) and (frequently dominant) of blood vessels (sclerosis of medium-sized arteries and of the afferent and efferent glomerular arterioles)
pathogenesis of the glomerulopathy
hemodynamic factors (increased volume and filtration surface of the glomerulus) + metabolic factors (protein glycosylation with thickening of the BM and increased mesangial stroma)
micro
similar in type I and II DM; thickening of the BM, diffuse glomerulosclerosis (increased mesangium) or nodular glomerulosclerosis (Kimmelstiel-Wilson disease), ovoidal nodular deposition of acellular/hyaline matrix in the mesangium
IF
linear positivity for IgG in B,, Bowman capsule and tubuli (entrapement)
EM
diffuse thickening of BM and, in the presence of proteinuria, fusion of foot processes of podocytes
evolution
severity is linked to the duration of the disease and control of glycemia; progressive increase of proteinuria and hypertension (sign of vascular damage)
ENDOCARDITIS
rapidly progressive GN
AMYLOIDOSIS (acquired or hereditary)
7% of nephrotic syndromes in Italy
type AA (after chronic inflammatory diseases) or AL (light chains, lymphoproliferative disorders)
amyloid deposition in glomeruli, tubuli and blood vessels
MYELOMA
amyloidosis AL, immunotactoid GN and others + tubulopathy (obstructive, necrosis + cast formation)
SCHONLEIN HENOCH PURPURA
clinical features
purpura at the limbs (leukocytoclastic vasculitis) + abdominal pain (mimicking appendicytis) + arthralgia
the kidney is involved in 30% of cases with features of IgA nephropathy with more proliferative features; childhood most frequently have an indolent course, more aggressive in the adults
ALPORT SYNDROME
nephritis + deafness + ocular alterations
2 hereditary forms
X-linked --> mutations in Xp gene coding for collagen IV A5, a component of the basal membrane --> altered structure and functions
autosomic dominant and recessive, mutations in COL4A3 and COL4A4 genes on Chr2
pathology
macro
no alterations or reduced volume
micro
segmental mesangial proliferation with sclerosis, lipoid cells in tubuli and glomeruli, interstitial fibrosis
IF/IHC
negative for collagen components
EM
irregular thickening of the BM with retiform features
evolution
always hematuria, with or without proteinuria; X-linked form is the most severe with renal failure before the age of 40
TUBULOINTERSTITIAL DISEASES
proximal tubuli absorb 2/3 of Na and H2O, glucosa, K, P, proteins = microvilli
interstitium: fenestrated capillaries and fibroblasts
WITH PREDOMINANT TUBULAR INVOLVEMENT
ACUTE TUBULAR NECROSIS
clinical pathological entity (reversible) with destruction of tubular cells and decreased renal function
most frequent cause of acute renal failure (85%)
--> <400 ml of urines/24h
ischemic or toxic or combined injuries
clinical features
early phase (36h) with slight decrease of urine output and increased azotemia
steady state with oliguria 40-400 ml/day
recovery phase with increase of urines volume up to 3l/day
causes
ischemic shock
incompatible transfusion (hemoglobinuria)
toxic from drugs (gentamicin)
toxic agents (Hg)
solvents (CCl4)
bile
infectious agents
pathogenesis
tubular injury + glomerular vasoconstriction (glomerular-tubular feedback)
macroscopy
larger, edematous kidney; pale cortex (vasoconstriction and necrosis) and congested medulla
microscopy
focal necrosis (variable extension depending on the cause), BM rupture (limiting the restitutio ad integrum), occlusive damage by casts formation (pigmented in the case of hemoglobinuria and myoglobinuria)
OSMOTIC NEPHROSIS and HYPOKALEMIC NEPHROPATHY
TUBULOINTERSTITIAL NEPHRITIS
infections
PYELONEPHRITIS
inflammation of tubuli + interstitium + renal pelvis
causes
usually, E. Coli or Proteus
hematogenous spread
ascending
ascending
anomalies of the renal papillae, which will look flatter
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anomalies of the vescico-urethral junction
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forms
ACUTE
increasedrenal volum, exudative process + micro-abscesses + necrosis of the papilla + extrarenal involvement
males in the early years of age (malformations or functional defects) or elderly (prostatic hypertrophy), females in the reproductive age (cystitis)
CHRONIC
obstructive and not obstructive
important cause of uremia
asymmetry
superficial scars, caliceal dilation
micro
"THYROIDIZATION"
with chronic interstitial inflammation; xantho-granulomatous form with foamy macrophages, monolateral in middle-aged women, caused by Proteus infection
non-infectious
INDUCED BY TOXINS and DRUGS
mechanisms
interstitial immune reaction
direct tubular injury
mild cumulative chronic injury
drugs
synthetic penicillin, rifampicin, phenylbutazone, cimetidin
clinical features
usually 15 days after drug exposure: fever, skin rash, eosinophilia and renal dysfunction (hematuria, proteinuria, pyuria)
macro
increased volume with interstitial edema
micro
lymphocytic infiltration, monocytes and eosinophils, neutrophils and occasionally granulomas + necorsis and tubular reactive changes
immune-related pathogenesis
IgE, but also type IV
analgesics
chronic renal disease due to prolonged use of analgesics with:
necrosis of the papilla (early event)
chronic interstitial nephritis
macro
papillary necrosis or detachment, calcification (different stages)
DD with diabetes
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micro
papillary necrosis and chronic pyelonephritis; reduced cortical parenchymal thickness; scars with chronic inflammation; fibrosis and calcifications at the site of detachment or necrosis
toxins
urates
acute
increased uric acid levels (i.e. after therapy of leukemias and lymphomas) --> tuular deposition of crystals --> obstruction --> acute renal failure
chronic
birefringent needle-like crystals in distal tubuli or in the interstitium (granulomatous reaction)
nephrolithiasis
hypercalcemia
HPT, myeloma, vitamin D abuse, Milk-Alkali syndrome, bone metastases
Ca++ calculi in the kidney + intracellular tubular metabolic alteration due to increased Ca++ and calcifications of the BM --> obstructive atrophy
other rare forms
radiation-induced
balcan endemic nephropathy
aristolochic acid-induced nephropathy (wild ginger, used in Chinese herbal medicine)
TUMORS
hypercalcemia, increased uric acid levels, uretral obstruction, drug-induced nephropathy
myeloma associated to renal injury in 50% of cases; Bence-Jones proteinuria --> light chains are toxic for the tubular epithelium and/or injury linked to their complexation when in acid environment with urinary glycoproteins (Tamm-Horsfall) --> crystals with obstruction
macro
superficial scars
micro
tubular cast formation + giant cells
RENAL VASCULAR DISEASES
NEPHROSCLEROSIS (hypertensive)
hyaline arteriolosclerosis, in pts with "benign" hypertension
obliteration of the lumen + increased arteriolar thickness + duplication of the lamina elastica (in medium-sized arteries)
malignant nephrosclerosis (associated with malignant hypertension)
de novo or evolution of a benign hypertension
clinical features
diastolic blood pressure >130, encephalopathy, renal failure
micro
fibrinoid necrosis + parietal inflammation = necrotizing arteriolitis
hyperplastic changes of the tunica media: onion skin-like thockening + necrosis of the glomeruli
infarcts due to a terminal circulation --> ischemic, pale scar with "V" appearance or necrotic areas if recent
renal arteries stenosis (1-5% of cases of hypertension) from atherosclerosit plaque or fibromuscular dysplasia --> decreased renal volume, fibrosis, tubular atrophy
PATHOLOGY OF RENAL TRANSPLANTATION
adequacy of donor patient/organ
rejection (antibody-mediated or T cell-mediated)
drug toxicities
viral infections
systemic diseases (diabetes, hypertension)
recurrent glomerulopathies
de novo glomerulonephritis
evaluation of the kidney
based on a classification
different scores on the basis of what i see
parameters
interstitial inflammation
tubulitis
intimal arteritis
glomerulitis
peritubular capillaritis
C4d
interstitial fibrosis
tubular atrophy
vascular fibrous intimal thickening
GBM double contours
mesangial martix expansion
arteriolar hyalinosis
hyaline arteriolar thickening
total inflammation
inflammation in the area of IFTA
features of inflammation
plasma cells in the interstitum surrounding tubular structures (INACTIVE INFLAMMATION)
lymphocytes in the interstitium and within tubular cells
(ACTIVE INFLAMMATION)
lymphocytes involving blood vessels
T cells in the glomeruli
hyalinization of the BM of tubules
alteration of blood vessels with proliferative changes in the intima
--> inflammation should be quantified in every location !
different types of rejections
HYPERACUTE
pre-formed circulating antibodies; in a few minutes, endothelial swelling, granulocytes, thombosis
ACCELERATED
newly formed antibodies, in a few days, injury similar to the hyperacute form
ACUTE
cellular respons, withon one year, tubulointerstitial with T cell infiltrates and variable proportion of the features in Banff score
CHRONIC
causes are not completely known, after the first year, glomerular and vascular lesions
drug toxicity
more relevant in the kidney
acute injury: vascular and glomerular lesions + tubular lesions with vacuolization; clinical presentaation similar to the acute rejection
chronic injury: arteriolar hyalinosis + tubular atrophy and fibrosis due to a reduced perfusion; slowly progressive
polyomavirus BK
injury similar to acute rejection + IHC or molecular biology to detect the virus
asymptomatic infection in immunocompetent subjects, through the airways and then in the kidney (latent infection)