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PA - Lower Urinary Tract & Male Genital Tract, PA - Ren (Glomeruli,…
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PA - Ren (Glomeruli, Tubules & Interstitium, Vascular)
Overview
- Renal component: glomeruli, tubules, interstitium, vascular
- Renal function:
- Excretion of the waste products of metabolism
- Regulation of body water and salt
- Maintenance of acid balance
- Secretion of hormones and prostaglandin
Glomerular Disease
Clinical Manifestations in Glomerular Disease (2):
- Nephrotic syndrome: proteinuria (>3.5 g daily in adult), hypoalbuminemia (<3 g/dL plasma albumin level), generalized edema, hyperlipidemia and lipiduria
- Nephritic syndrome: hematuria (red cells and red cell casts in urine), proteinuria with or without edema, Azotemia (elevation of blood nitrogen & creatinin levels (reflect decrease of GFR) → uremia (azotemia give rise to clinical manifestations and systemic biochemical abnormalities), htn
Notes: kelainan pada glomerulus dapat menyebabkan nephrotic ataupun nephritic synd → bisa muncul salah satu/bersamaan
- Nephrotic syndrome: dominan pada edemanya
- Nephritic syndrome: dominan hematurianya
Glomerular Intro:
- Glomerular: jar.kapiler yang tertanam pada 2 lapis epitel
- Podocytes: membungkus kapiler
- Glomerular consist of an anastomosing network of capillaries invested by two layers of epithelium
- Visceral epithelium composed of podocytes
- Parietal epithelium encircles Bowman space (urinary space)
- Glomerular basement membran consist of collagen (mostly type IV, laminin, polyanionic proteoglycans, fibronectin, and several other glycoproteins.
- Mesangial cells lie in mesangial matrix between the capillaries that support the glomerular tuft.
Patogenesis:Immune mechanism underlie most type of primary glomerular disease and many of the secondary glomerular diseases, with this two mechanism:
- Circulating immune complexes: deposition of circulating antigen-antibody complexes in the glomerular capilary wall or mesangium
- Glomerulonephritis caused by Immune complexes formed in situ: antibodies reacting in situ within the glomerulus, either with fixed (intrinsic) glomerular antigens or with extrinsic molecules that are planted in the glomerulus
- Glomerular disease caused by complement activation
Non-immune mechanism:
- Podocyte injury
- Nephron Loss
Patogenesis of "glomerulonephritis caused by circulating immune complexes":
Ag (endogen, exogen, unknown) → karena ada ag → ada complex (Ag-Ab complexes) → mengaktivasi sistem komplemen → rekrut leukosit → injury
- Ikatan ag ab di pemb,darah terdeposisi di ginjal
Patogenesis of "glomerulonephritis caused by immune complexes formed in situ":
- Deposition of antibodies specific for fixed (intrinsic) or planted (from outside) antigens in the glomerulus
- Antigens expressed by podocytes have been implicated in membranous nephropathy
- Planted antigens include nucleosomal complexes, mainly derived from breakdown of apoptotic cells, in patients with SLE; bacterial products; and large agregated protein which tend deposit in mesangium.
Patogenesis of "glomerular diseases caused by complement activation":
- Less frequent
- Unregulated activation of the alternative complement pathway, which may be trigerred by acquired autoantibodies against complement components or inherited abnormalities of complements regulatory proteins.
Bedanya kalau sama yang circulating itu ada banyak ikatan Ag-AB, kalau ini gangguan pada protein regulator
Patogenesis of "podocyte injury":
- Can be induced by antibodies to podocyte antigens, by toxin, certain cytokines (tidak ada mekanisme autoimun yg memengaruhi)
- Podocytes injury produces morphologic changes:
- Effacement of foot processes, vacuolization, retraction, dettachment cells from the GBM
Patogenesis of "nephron loss":
- Nephron: 1 unit glomerular + renal tubule
- Destroy sufficient nephron can reduce GFR to 30-50%
Summary of primary glomerular disease
- Light microscopy: to see structural morph
- Fluorescence microscopy: ikatan imun terpulas dengan fluoroscent nampak pola dengan mikroskop (glow in the dark)
- Electron microscopy: higher mag to see ultrastructural morph
Primary Glomerulopathies/ Primary Glomerular Disease (explanation) → 9 disease:
- Minimal Change Disease
Defintiion: relatively benign disorder, is the most frequent cause of the nephrotic syndrome in children and is characterized by glomeruli that have a normal appearance by light microscopy
- Patogenesis Some circulating molecules (unknown) injure podocytes and cause proteinuria with effacement of foot processes
- Klinis: nephrotic syndrome
- Morphology:
- Light microscope: normal
- Fluorescent microscope: (-)
- Electron microscope: diffuse effacement of the foot processes
- Focal Segmental Glomerulosclerosis
Definition: FSGS is characterized by sclerosis of some (but not all) glomeruli that involves only a part of each affected glomerulus. May be primary (idiopathic) or secondary to one of the following conditions: HIV, heroin abuse, inherited
- Patogenesis: podocytes injury
- Klinis: nephrotic synd., hematuria & htn
- Morphology:
- Light microscope: PAS staining: increased mesangial matrix, obliterated capillary lumina, deposition of hyaline
- :star: Bedanya sama MCD pada gambaran light microscopy
- Fluorescent microscope: Non spesific trapping IgM in the area of hyalinosis
- Electron microscope: effacement of the foot processes
- Membranous Nephropathy
Definition: membranous nephropathy is characterized by subepithelial Ig-containing deposits along the GBM. Occurs secondary to other conditions: (infections (chronic hepatitis B, syphilis, schistosomiasis), malignant neoplasm (lung ca, colon ca, melanoma), autoimmune disease (SLE), exposure to inorganic salts (gold, mercury), drugs (penicilamine, captopril, NSAID)
- Patogenesis: antibodies reacting insitu to endogenous or planted glomerular antigen
- Klinis: nephrotic synd., usually failed to corticosteroid therapy
- Morphology:
- Light microscope: diffuse thickening of capillary wall
- Fluorescent microscope: granular deposit
- Electron microscope: spikelike protrusion of deposit in subepithelial
Dari 3 penyakit diatas:
- Gejala ketiga kelainan ini hampir sama, tapi pada membranous nephropathy biasanya tidak respon dengan terapi corticosteroid, dan didapatkan kelainan padapmx light micros yaitu pada glomerulus didapatkan diffuse thickening dinding kapiler
- Didapatkan kaitannya dengan mekanisme imun, karena tanda dari membranous nephropathy didapatkan deposit di sepanjang subepithelial GBM mengandung Ig
- Membranoproliferative Glomerulonephritis
Definition: MPGN is manifested histologically by alteration in the GBM and mesangium and by proliferation of glomerular cells.
- Patogenesis: caused by deposition of circulating immune complexes or by in situ immune complex formation with a planted antigen
- Klinis: nephrotic syndrome, begin with acute nephritis or mild proteinuria (nephrotic diawali nephritis synd. akut)
- Morfologi:
- Light microscope: glomeruli are large with proliferation of mesangial and endothelial cells with leukocytes infiltration (pembesaran glomerulus, proliferasi sel mesangial dan sel endotel, dengan infiltrasi leukosit)
- Fluorescent microscope: C3 is deposite in a irregular granular pattern (C3 granular)
- Electron microscope: discrete subendothelial deposits (deposit subendothelial menyebar (nyeplok2))
- C3 Glomerulopathy
Definition: the term C3 glomerulopathy encompasses 2 conditions: dense deposit disease (formerly: MPGN type II) and C3 glomerulonephrities.
- Patogenesis: complement dysregulation (acquired/hereditary)
- Klinis: nephrotic /nephritic snyd.
- Morphology:
- Light microscope: = MPGN I
- Fluorescent microscope: dense deposit of C3 along the mesangial, capilaries wall and tubular basement membran
- Electron microscope: waxy deposit or ribbonlike deposit in mesangial, subendothelial, tubular basement membran
Dari 2 penyakit diatas:
- Kelainan yang sama dengan MPGN I, dulu dinamakan MPGN type II
- Light micros: = MPGN I
- Tapi deposit dari C3 tebal dan luas bukan hanya di subendothelial
- PG dikarenakan disregulasi komplemen
- Acute Post-Infectious (Post-Streptococcal) Glomerulonephrities
Definition: acute postinfectious GN is caused by glomerular deposition of immune complexes resulting in proliferation and damage to glomerular cells and infiltration of leukocytes, especially neutrophils.
- Pada pasien dengan post strepto infection, Ikatan imun menyebabkan aktivasi sistem komplemen dan merusak glomerulus
- Patogenesis: immune complex disease which tissue injury is primarily caused by complement activation by the classical pathway
- Klinis: nephritic synd., 1-4 week after recover from streptococcal infection from pharynx or skin
- Morphology:
- Light microscope: glomerular hypercellularity caused by infiltration of leukocytes and glomerular cells
- Fluorescent microscope: granular deposits of IgG
- Electron microscope: subepithelial hump deposits
- IgA Nephropathy
Definition:IgA nephropathy is one of the common cause hematuria and is the most common glomerular disease revealed by renal biopsy worldwide. The hallmark of the disease is the deposition of IgA in the mesangium.
- Patogenesis: the abnormal of IgA1
- Klinis: children and young adults, hematuria can develop to acute nephritic syndrome
- Morphology:
- Light microscope: maybe normal or mesangial proliferation (Non spesific morphology)
- Fluorescent microscope: mesangial deposition of IgA
- Electron microscope: eletron dense deposit in mesangium
Dari penyakit MCD & IgA, resume:
- Sama dengan MCD pada anak2, tapi beda gejala ini dengan hematuria,
- Penyebab tersering hematuria
- Light microscope: normal, ga spesifik
- Fluor : deposisi IgA
- Rapidly Progressive Glomerulonephritis
Definition: RPGN is characterized by the presence of crescents and in most cases appears to be immunologically mediated
- Patogenesis: associated with a number of disease: anti-GBM antibody mediated (Godpasture disease), immune complex-mediated, pauci-immune type (ANCA)
- Klinis: nephritic syndrome
- Morphology:
- Light microscope: crescent formation formed both by proliferation of epithelial cells and by migration of monocytes
- Fluorescent microscope: linear staining of IgG and C3 along the GBM
- Electron microscope: rupture of GBM
Prinsip Fluorescence Microscopy:
- Lokasi terbentuknya immune complex akan mempengaruhi morfologi yg akan ditunjukan pada microscope fluorescence
- Terbentuk immune complex di subepithelial, mesangial, subendothelial, podosit (semua ini berongga) → gambaran granular fluorescence
- Antibodi thd GMB (lokasi immune complex di GMB: strukturnya rata, spt pita) → gambaran linear fluorescence
- Granular: patternnya kasar, characteristic of circulating and in situ immune complex deposition
- Linear: patternnya halus, rata, characteristic of classic anti-GBM antibody glomerulonephritis
- Anti-Glomerular Basement Membran (Antibody-mediated glomerulonephritis)
- Results from the glomerular deposition of autoantibodies direted against protein components of the GBM
- Cresentic GN (Goodpasture disease)
Tubulo-Interstitial Nephritis
(refer to a group of inflammatory kidney disease that primarily involve the intertitium and tubules)
- Acute Pyelonephritis
- Common suppurative inflammation of the kidney
- Caused by gram negative bacteria (E.Coli, Proteus, Klebsiella, Pseudomonas, Enterobacter)
- More in female
- Clinical feature: pain in costovertebral angle, systemic evidence of infection (chills, fever, nausea, malaise), local symptoms (dysuria, frequency, urgency), pyuria
- Morphology: yellowish abcesses, intratubular neutrophils
- Chronic Pyelonephritis
- Usually associated with urinary obstruction or reflux
- Signs of kidney disease noticed on routine lab test or radiology imaging (kidney assimetrically contracted)
- Morphology: inflammatory infiltrates, dilation tubules contain pink to blue colloid casts (thyroidization), fibrosis
- Drug Induced Tubulointerstitial Nephritis
- As an adverse reaction to any one of an increasing number of drug
- Hypersensitivity reaction
- Latent reaction (>15 days) after drugs exposure
- Fever, eosinophilia, rash, hematuria, rising serum creatinin
- Morfologi: Interstitial space edema and infiltration of eosinophils
- Acute Tubular Injury/ Necrosis
- Clinicopathologically entity characterized by damage to tubular epithelial cells and an acute decline in renal function
- Etiologi: iskemik, nephrotoxic
- Clinical features: initially by medical, surgical, or obstetric event, oligouria, decreased of GFR, and electrolyte abnormalities, acidosis, uremia, fluid overload
- Morfologi: vacuolization of cells, sloughing of brush border, detachment of tubular cells, proteinaceous casts, tubular atrophy and interstitial fibrosis
Kidney Diseases
- Chronic Kidney Disease
Definition: chronic kidney disease is a broad term that describes the final common pathway of progressive nephron loss resulting from any type of kidney disease
- Progressive renal damage destroys more nephron
- Clinical feature: proteinuria, htn, azotemia
- Morphology:
- Macros: symetrically contracted kidney, scars
- Micros: interstitial fibrosis, atrophy tubules, lymphocytic infiltrates
- Simple Cyst - Cystic Kidney Disease
- Single/multiple,1-5 cm diameter, no clinical significance
- Morphology:
- Macros: Filed with clear fluid, layered with grey glistening smooth membrane at cortex
- Micros: Single layered cuboidal/flattened epithelium
- Policystic Kidney Disease (Autosomal Dominant - adult)
- Autosomal dominant (adult) polycystic kidney disease
- Multiple expanding cysts destroy parenchyma
- Doesn’t produce symptoms until it quite large
- Morphology:
- Macros: filed with clear fluid, maybe turbid or hemorrhagic
- Micros: may arise at any level of nephrons
- Policystic Kidney Disease (Autosomal Recessive - childhood)
- Perinatal, neonatal, infant, juvenile
- Mutation of PKHD1 gene coding for membran receptor called fibrocystin
- May die quickly from hepatic or renal failure
- Morphology:
- Macros: Numerous small cyst in cortex and medulla give bilateral kidney a spongelike appeareance
- Micros: uniform lining of cuboidal cells
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Neoplasm of the Kidney
Benign Tumor
- Oncocytoma
- Benign neoplasm that arise from the intercalated cells of intercalated cells of collecting duct.
- Represent about 10% of renal neoplasm
- Associated with loss of chromosome 1 and Y
- Asymptomatic-hematuria, flank pain, palpable abdominal mass
- Morphology:
- Macros: well demarcated, yelowish mass
- Micros: solid-nested pattern, granular eosinophilic cytoplasm, nuclei round and regular
Malignant Tumor
- Renal Cell Ca
- Derived from renal tubular epithelium
- 60-70 years old, men > women
- Risk: smokers, htn, obese, cadmium exposure
- Clinical: hematuria, flank pain, palpable mass
- Metastase: lungs & bones
- Clear Cell Ca
- Most common (>65%)
- Associated with VHL disease, loss of a segment on chromosome 3p (autosomal dominant inherited disease, characterized by hemangioblastoma of the cerebellum and retina)
- Morphology:
- Macros: yellow tan
- Micros: clear cell cytoplasms
- Papillary Renal Cell Ca
- 10-15% of all renal cancers
- Hereditary MET proto-oncogene located on chromosome 7q
- Morphology:
- Macros: bilateral and multiple, necrosis and hemorrhage
- Micros: growth in papillary pattern with fibrovascular stalk
- Chromophobe Renal Ca
- Representing 5% of all renal cell carcinomas
- Morphology:
- Macros: tan-brown
- Micros: eosinophilic cytoplasms, distinct cell membrans, nuclei surrounded by halos of clear cytoplasm
- Pediatric Neoplasm - Wilm's Tumor (Nephroblastoma)
- 2-5 years old
- Derived from the mesoderm, contain of variety of tissue component
- Abnormalities of WT1 gene located on chromosome 11p13
- Morphology:
- Macros: large and solid tumor, bilateral or multicentric, on cut section: soft, homogenous, tan to grey, foci of hemorrhage, necrosis, and cystic degeneration
- Micros: triphasic combination of blastemal, epithelial and stromal