ACP-L23 & L24 Medical Renal Diseases PDF

67 UROGENITAL SYSTEM ACP-L23 & L24 Medical renal diseases Glomerulopathy Glomerular disease, a more appropriate umbrella term c.f. glomerulonephritis (GN: inflammation must be present) Anatomy of glomerulus 1 2...

67 UROGENITAL SYSTEM ACP-L23 & L24 Medical renal diseases Glomerulopathy Glomerular disease, a more appropriate umbrella term c.f. glomerulonephritis (GN: inflammation must be present) Anatomy of glomerulus 1 2 5 3 4 Physiology Pathology Endothelial cell With fenestration (6 50). Glomerular basement Type IV collagen, with heparan sulfate Thickened in: membrane (GBM) producing negative charge ve - Membranous nephropathy Main filtration barrier: filter large MW DM: ↑ type IV collagen synthesis molecules of negative charge, e.g. albumin -highlight Carbohydrates GBM , Visceral epithelial cells Produce GBM Minimal change disease: fusion of (VEC) Podocytes as final filtration barrier podocytes Ie podocytes Mesangial cells Support glomerular capillaries IgA nephropathy: IC deposition → release inflammatory mediators -mesangial expansion Parietal epithelial cell Lining cells of Bowman capsule Crescentic GN: proliferate and compress on glomerular tuft Terminology of glomerular diseases : tissue structure + cell details % of abnormal glomeruli Focal: < 50% ~ hypercellularity v crescents (RPGN) vtubular changes Diffuse: > 50% Affected part of the involved glomerulus Segmental: only a segment affected Global: whole glomerulus affected Studies on renal biopsy specimens Technique Examples Role Light microscope H&E, PAS, PASM Classify type of glomerular disease Immunofluorescence · Anti-IgA Ab Identify protein deposition, e.g. for detecting IgA (IgA nephropathy) Linear IF: anti-GBM disease, e.g. Goodpasture syndrome (Ab Anti-GBM Ab T alone not detectable by EM) auto-antibodies not detectable which also attack GBM (4IgG) · , Granular IF: IC type GN g. lupus nephritis IgA nephropathy e. , Electron microscope Lead citrate Detect submicroscopic defects, e.g. podocyte fusion (nephrotic syndrome) Detect site of IC deposition, e.g. subendothelial, subepithelial, intramembranous  68 Anti-GBM: linear pattern Immune-complex: granular pattern Mechanisms of injury of damagea Mechanism clauses glomerular Details Example ① Immune complex (MC) Type III HSR: IC circulate and deposit in glomeruli Most nephritic → activate C' → C5a → neutrophil attracted → syndrome glomerulonephritis (GBM) glomerular damage (inflammation) pulmonaryhemoph are , involve & Antibodies against GBM antigens T cell production of cytokines Type II HSR Affect GBM (lose negative charge) & podocytes from blood to urine Goodpasture syndrome Minimal change disease ↳ of (damaged and fused) leakage protein · heavy proteinuria , edema , hypoalbumines nephrotic syndrome => Clinical manifestation Often chronic and progressive leading to ESRD lend-stage renal disease) Aetiology: often unknown Tx: often no specific Tx, supportive Tx to slow disease progression Biopsy: for Dx, Px and Tx Classification Primary GN vs Secondary GN vs Hereditary GN Primary GN: membranous nephropathy, minimal change nephropathy, crescentic GN, IgA nephropathy ② Secondary GN: lupus nephritis, diabetic glomerulosclerosis, amyloidosis, post-streptococcal GN ③Hereditary GN: Alport’s syndrome, thin membrane disease, Fabry’s disease Nephritic syndrome vs nephrotic syndrome [CPY-L27] Q Nephritic syndrome ② Nephrotic syndrome * no haematuria Definition Glomerular injury due to Glomerular injury due to cytokines but neutrophils * inflammation &GFR not neutrophils ↓ serum albumin nitrogenous waste product General clinical and HT: fluid retention in azotaemia blood in HT: RAAS activation ∵ ECF ↑ WateHO retention blood volume lab findings Periorbital puffiness +/- pitting Pitting oedema: hypoalbuminaemia fluid escape from blood to tissue oedema: salt retention in loose skin Proteinuria: >150mg/day but Proteinuria: >3.5g/day - lipiduria appearance mostly glomerular damage → Fatty casts with Maltese crosses and tubular damage oval fat bodies renal = Crenaltubularepithelial cell) significant proteinraise  69 Specific SSx Pathogenesis Pathology Treatment Outcome Nephritic syndrome Post-streptococcal In children Following Group A streptococci infection, Diffuse proliferative pattern Spontaneously Good ↑cell no GN bacterial Ag is trapped in glomerulus (VIC complex) resolve (95%) F Crescentic GN^ Rapid I Anti-GBM: Goodpasture syndrome* - linear IF. Crescents: ≥2 layers of cells in Very poor Px endocarditis - -T subacute bacterial Bowman space Iproliferationof injiefibroblast parietaepitheliales, T progression to. IC disease: lupus nephritis, SBE - granular IF 2 immeositAsmaessevasculitis Shil cytoplasm little XIC(min 39Pauci-immune: microscopic polyarteritis, use stem - · AKI -RPGN bodies Leucocyte infiltration Wegener's granulomatosis - IF -ve; ANCA +ve clause) Necrotising lesion deposit # :X immue - IgA nephropathy MC GN IgA-containing IC: mucosal synthesis + IgA IC-autoAB + abnormal Focal proliferative pattern Anti-hypertensive Slow progression of IgA antibodies the mesangial ↑ cell no of distinct location (e g clearance of IgA region of thedeposition. mesangial cells) abnormal in (Berger disease) Synpharyngitic Steroid for to sclerosis and ·. glomeruli inflammation + - haematuria ( URI) + proteinuria ESRD Nephrotic syndrome Minimal change MC cause in Unknown; ?T-cell cytokines cause GBM to lose LM: appear normal Steroid Good disease children negative charge → selective proteinuria EM: Fused podocytes Normal RFT (albumin not globulin) albumin only not creatinine/area , Albuminuria Membranous MC cause in adult Primary: anti-phospholipase A2 receptor LM: thick GBM, "spike and cell Steroid: may slow 1/3 resolved visceral epithelial nephropathy (PLA2R) Ab autoimmune disease dome" pattern beneath VEC progression 1/3 persistent Secondary: (subepithelial deposits) 1/3 progressive Malignancy IF: granular pattern Drug: penicillamine, gold, ACEInhibitors EM: diffuse subepithelial Infection: HBV, HCV, syphilis electron-dense deposits (EDD) Secondary GN Lupus nephritis Multisystem IC disease Variable Immunosuppression: Most progress to in SLE (systemic lupus erythematosus) (kidneys affected → serological test: ANA, ENA, dsDNA, etc steroid + ESRD anti-nuclear AB extractable in 90% of SLE) nuclear antigens cyclophosphamide Butterfly rash, etc blood glucose Inon-enzymatic glycation /scarring 4protein glycation →creating + hardening Diabetic Nephrotic type Glomerulosclerosis: ① mesangial expansion Glomerulosclerosis: ACEI: selective nephropathy Microalbuminuria advanced glycation end product (AGE) → ② Thickening of GBM ③podocyte injury Kimmelstiel-Wilson disease dilation of EA, for moderate ↑ in albumin in urine (30-300 mg/day) increase permeability to proteins (mesangial nodular sclerosis, microalbuminuria Arteriolosclerosis: AGE affecting mainly IF –ve)(no involvement autoimmune in efferent arterioles ↓ inflammation oxidative Stress LDL Arteriolosclerosis: benignSmall damagi , , hyaline pattern [L8] ^Any cause of GN can cause crescentic GN (except minimal change disease) leakage of protein & lipid deposit on Vessels ↳ narrowing the lumen *Goodpasture syndrome: Pathogenesis: Anti-BM Ab against glomeruli and pulmonary capillaries (GBM Ag: NC1 of COL4α3) Manifestations: begin with haemoptysis, end with AKI Treatment: plasma exchange, steroid, cyclophosphamide inflammation of surrounding interstitial tissue + renal tubules 70 Tubulo-interstitial nephritis (TIN) SSx Causes & pathogenesis Pathology Tx Outcome causing inflammation Acute MC cause of TIN Bacterial (MC E. coli) & immunerespondincomplying > A UT - Enlarged kidney, with Ciprofloxacin, Reversible lesion flank / perris / pyelonephritis Fever, loin pain, RF: obstruction, indwelling urinary catheter, DM - abscess nitrofurantoin Recovery or relapse dysuria Pathogenesis: Polymorphs in Repair VUR Complications: ascending infection asseurinary tactbdral wrine flow backwards from bladder to wreters inflammation compress the renal blood vessels -> Pischemia - Ascending: vesicoureteral reflux (VUR) - interstitium and papillary necrosis abnormal intravescial portion of ureter tubules (coagulative necrosis allows urine reflux into ureter during of pyramid), micturition [MIC-L30]allowing bacteria from bladder ascend kidneys to perinephric abscess bypassing protective mechanism localized collection of pus in perinephric space Haematogenous spread: suspect if S aureus b common inflammation of kida found in urine immunocompromised/systemic infection * : millary granm-milmalgranulomasSpreadthroughoutthebodykidney Tuberculosis Haematogenous spread from primary focus Miliary, cavitary * nephritis granulomatoa b Granuloma Drug-induced Abrupt onset Drug: penicillin, sulphonamide, thiazide Eosinophilia Drug withdrawal dri metabolitetrige ae cosinophils : WBC in allergic reactions/HSR to interstitial nephritis fever, oliguria, HSR: type I/IV inflammation of kidney interstitium AKI > - > - acc in reval interstitium +issue damage + inflammation detayed Type , > - : Xantibodies Vi cells ((D4+, CD8 ) rash, latent + eosinophilia aspirin Analgesic Combined chronic use of ASA + paracetamol Papillary necrosis 10X + Vasoconstriction of toxic metabolite ASA: inhibit PGE2 → ATII unopposed + · acc nephropathy. , bblood flow (dose-dependent) Paracetamol: oxidative injury (toxic metabolite) Acute tubular AKI Ischemic: hypovolaemia caused by shock, MI, etc* Renal tubular cell Reversible lesion: necrosis (ATN) Nephrotoxic: aminoglycosides (MC) necrosis → cast tubular basement death of tubular epithelial cells oxidative stress + acc in proximal tubules , membrane intact Recovery depends on severity Obstructive Asymptomatic Q Intraluminal: renal stone Curolithiasis) Dilated ureter and nephropathy Acute flank renal by colic ②Mural changes acute pain caused wall of urinary tract acute obstruction g minary bladder stone : in the e.. tumors in renal pelvis g. e. AKI oligaria , ⑤Extramural: BPH benign prostatic hyperplasia bladder : Pserum creatinine level , fluid overload ( : ischemic tubular obstruction (BOO) - outlet vacuole Tubular cells injury in renal (damaged organelles) , Radiation nephritis ①Abnormal Curinary) Therapeutic or accidental Low dose: vacuolation, sediments proteinura staSediment (UBC etc) focal atrophy localized -↓ area cell : no. cell size urinary injury/ active + acte tubular ② Impaired RFT glomerular involvement High dose: tubules cells from renal T shedding of epithelial ↑BUNtcreatinine desquamation, = necrosis, regenerative Cellular · immunity atypia regenerating atypical cellular features maglinary risk4 > - (kidney transplantation · humoral immunity Immunologic Impaired RFT Cellular & humoral immunity Swollen kidney inflammation one Immunosuppressant Reversible lesions, but transplant rejection Tellmediated rejection antibody-mediated rejection Tubulitis inflammationofrenal tubulesacutecellularrejection o is chronic insult progressivefibrosisSeveral infiltrate interstitium > - inflammation tissue *Regarded as prerenal injury in AKI [CPY-L23]  71 Vascular diseases [L8] Disease Cause & pathology Atherosclerosis Large arterial wall thickening, loss of elasticity Hypertensive nephrosclerosis Benign HT complication of Chronic hypertension protein lipid → hyaline arteriolosclerosis of renal arterioles , → tubular atrophy, glomerular sclerosis (focal Segmental → small kidneys with finely granular surface thrombotic end-organ damage (severe) hemolytic acute uremia symptoms thrombocytopenic purpuratUs : by caused 0157 : H7 (triad of Symptoms). pathogenic E Coli. Thrombotic microangiopathy Malignant HT, HUS/TTP, etc = thrombus in Micro-vessels/microcirculation ↓ Shiga toxin : damageof microthrombi/autoimmua ↳Microthrombi obstruct blood flow , causes ischemia in various organs → endothelial cell degeneration, thrombosis ANCA vasculitis (autoimmune disease) ANCA-stimulated neutrophil infiltration of vessel wall=> endothelial cell degeneration antibodies renalcortex infarct ( ? anti-metrophil cytoplasmic → cortical infarcts, fibrinoid necrosis, inflammatory cells V leakage of serum protein coagulation factors Cystic diseases , 4) deposition of fibrin-like protein in small vessels wall Disease Pathogenesis Simple cyst MC adult renal cyst generally benign Intratubular obstruction → defect in tubular BM matrix altered cell growth → defective fluid secretion > fluid-filled sacs -. Cystic renal dysplasia MC children renal cyst Abnormal development of kidney with abnormal structures, e.g. cartilage Non-functional, a/wdisease obstruction function structure & polycystic Kidney 1 cilia of renal epithelial cells (of Locilia (sensory organelles Adult polycystic kidney AD mutation in PKD1 gene (chr 16) for polycystin → ciliopathy → aberrant disease (ADPKD) signalling pathway → abnormal cell proliferation & ion secretion Cysts in: kidney, liver, pancreas, etc Juvenile polycystic AR mutation in PKHD1 gene (chr 6) for fibrocystin (regulate polycystin-2 kidney disease (ARPKD) expression) Et B Stillbirth or rapid progression to ESRD Dialysis/ acquired cystic Occur in 50% of patients on long-term dialysis disease Tubular obstruction by interstitial fibrosis, oxalate crystals, etc Increased risk of RCC of extracellular matrix acc deposit renal tubules in ↑tubular toxicity