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Week 23 Glomerulonephritis

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Week 23 Glomerulonephritis Powered By Docstoc
					                                  Wk 23 GLOMERULAR DISEASE
DDx Causes of Glomerular Disease
S+S      All Glom Dis               Due to Glom dam => ↓GFR/ Proteinuria/ Haematuria (Dysmorphic RBC)
                                    Sue to Na & H2O rentention + ↑↑Renin secretion => HT/ Oedema
         IgA N                      Recurrent frank haematuria 1~2 days post URTI
         Post Infective GN          Nephritic syndrome 1~3 wks post infection (strep)
         Goodpasture’s              Haemoptysis with rapidly progressive GN
         SLE                        Skin & Jt involvement/ Vasculitis/ Multisystem prob
         IE                         Cardiac valve lesion

Clinical Features of Nephrotic Syndrome
Oedema                      ↓Albumin => ↓Intravascular vol => Renal Hypoperfusion => (+) RAS
Proteinuria + ↓Albumin      IgG & Immune proteins loss in urine => ↑Inf risk/ Malnutrition
Hypercoagulopathy           Thromboregulatory protein (AT III, Protein S & C) lost + Fibrionogen synth
Hyperlipidemia              Urine loss of liporegulatory subs => ↑LDL & VLDL


                 Nephrotic Syndrome                                       Nephritic Syndrome
 ↑Glom BM perm to protein => ↑↑ Proteinuria (Pink)          Glom Inflam + Necrosis (Blue - Hypercellularity)
 Matrix (BM/ Mesangial cell)                              Cellular prolif => Mesangial, endothelial cells
 Fibrosis (Sclerosis/ Fibrosis)                           Exudation => Neuts, Monocytes, Lymphocytes
 Protein (Hyalinosis/ Amyloid/ Immune deposit)            Crescent formation => Accum of prolif cells in BC
Proteinuria + Oed + ↓Blood albumin + ↑Cholesterol                    Haematuria + Oedema + HT
(Ascites + Normal JVP + Peri-orbital, face, arm oedema)             Proteinuria + Oliguria + Uraemia
     All GN (esp MCD/ Membranous/ FSGN)                   Post Streptococcal resp Inf
     Diabetic nephropathy                                 Systemic vasculitis
     Amyloid nephropathy                                  Goodpasture’s (Anti GBM)
     Myeloma nephropathy                                  Cryoglobulinaemia
General Ix                                                Dx Ix
 Urine Micro (Dysmorphic RBC & cast => Glom)              ASOT/ Throat swab => Post Strep GN
 ↑24 hr protein or Dipstick (Proteinuria/ DM)             ANA/ dsDNA/ ↓C3+4 => SLE
 Renal US (normal)                                        ANCA => Wegnener’s Granulomatosis
 Urinary cytology & cystoscopy (Ca Screen if > 50)        Anti-GBM AB => Goodpastures
 ↑Bl Urea + Cr/ ↓Bl Albumin/ ↓Cr clearance                HBV, HCV, HIV, Blood culture
 CXR (pulm oedema)                                        Cryoglobulines (Cryoglobulinemia)
 Renal Biopsy (Light/ IF/ EM)
Mx
 Fluid balance/ BP monitoring/ Salt & H2O restrict/ Diuretics
 Antibiotics (post strep inf) / High dose steroid & Cyclophosphamide (MCD)
 Nephrotic => Prophylaxis for DVT + ACEi (↓Eff A vasocon => ↓Glom press => ↓Proteinuria)
Cx                                                        Cx
 DVT (anticoag)/ Renal V thrombosis/ PE                   HT encephalopathy/ Pulm Oed/ Severe Uraemia
 ↑IHD (HT + ↑Lipid)/ Sepsis/ Oliguria


Complicated UTI
              Structural Problem                                    Functional Prob
 Child => VU reflux/ Renal Duplication/ PUV        Neuropathic bladder => Reflux/ Catheterisation
 Adult => Renal Calcus/ Cystic abn/ Big Prostate   Chronic retention => Age/ DM/ Bladder Inj
 Surg => Correct CAKUT                             ↑Emptying by catheterization
                                                    ↓Bladder overactivity by anticholinergic drug
   Recurrent child UTI => MCU + DMSA renography (Ax renal scar)
                                          Glomerular Pathologies

Proliferative Glomerulopathy
IgA Nephropathy         Most common cause of haematuria, affecting children & young adult
(Berger)                ↑Bl Polymeric IgA=> trap in mesangium=> (+)Complement => Glom dam
                        Haematuria/ Proteinuria/ Nephrotic/ Nephritic/ CRF/ RPGN
Henoch-Schonlein        Gross haematuria 1~2 days post RESP/ GIT Inf + Loin P
Purpura                 Assoc Celiac dis/ CD/ Sjogren’s/ Liver dis
                        IF => Mesangial expansion + IgA Deposition
                        Renal f(x) intact in most cases but 40% progress to RF
                        Bad px signs = Old/ Heavy proteinuria/ HT/ Extensive Glomerulosclerosis
                        1/3 pts develop ESRD, may recur post renal X’plant
                        (cf Henoch-Schonlein => Systemic c Purura, Abdo P, Arthritis)
Diffuse Prolif GN       1~4 wks post recovery from strep Inf of pharynx (also HBV/ HCV)
                        Most often affects childen 6~10 but also adults
Strep/ IE               Prolif of Epithelial/ Endothelial/ Mesangial cells
SLE                     Malaise, fever, oliguria, haematuria
                        Red cell casts in urine, mild proteinuria, periorbital oedema, low C3
                        Rx with antibiotics & supportive Mx => 95% recovery fully
                        Better prognosis in children/ Adult may lead to ESRF 10~20 yrs
Rapid Progressive       GBM rupture => Fibrinogen & inflame cell enters => Crescents
GN                      Rapid loss of renal f(x), severe Oliguria + Azotemia, death fr RF (wks ~mth)
                        Haematuria with red cell cast in urine/ Proteinuria/ Variable HT & Oedema
Vasulitis               I => Anti GBM dis => Linear Ig deposit eg Goodpasture => Haemoptysis (Xfusion)
Goodpasture’s           II => Immune complex mediated => Granular Ig deposits (SLE, IgA N)
SLE                     III => ANCA in bl => Wegener Granulomatosis (Adults/ Elderly)
                        Rx = Early intensive plasma exchange + Steroid + Cytotoxic agents +/- Xplant
MPGN I & II             Glom cell prolif + BM thickening + WBC infiltrate, Mesangial expansion into cap
                        Older children or young adults
HCV                     Px initially as nephritic, later nephrotic syndr
Cryoglobulinemia        I => Subendothelial deposits, Immune complex mediated
SLE                     II => Intramemb dense deposits,
                        May be 2 to HCV, HBV, SLE, HIV
                        Poor & progressive prognosis, not responsive to steroid, ESRF in 10~15 yr

Disease of the Glomerular BM
MCD                      Benign nephrotic syndr (80% of children nephrotic syndr, 20% of adult)
(Lipoid Nephrosis)       Disorder of T cell f(x)
                         Normal Glom in light microscopy, Effacement of foot process under EM
NSAID                    Peak 2~3 yrs, sudden onset, reversible, normal renal f(x)
                         S+S of nephrotic => Puffy face, Wt gain, Ascites, Selective proteinuria (albumin)
                         Excellent prognosis, steroid responsive
Membranous               Most common cause of nephrotic in adults (30~40%), rare in children
Nephropathy              Slowly progressive dis, peak 30~50 yo
                         AB reaction to endogenous Glom Ag => Subepithelial Immune complex deposit
Malign                   Light microscopy => Diffuse thickening of GBM
SLE                      Non selective Proteinuria/ Microhaematuria/ HT
HBV                      2 Cause (15%)=> Penicillamine/ Gold/ Ca/ SLE/ Inf/ HBV & HBV/ Tu Ag
Gold/ Penacillamine      1/3 Remission, 1/3 Unchanged, 1/3 CRF
                         Not respond to steroid Rx, progress to ESRF in 10~15 yrs
FSGN                     15% of nephrotic syndr in Adult
                         “Focal” & “Segmental” sclerosis + Inj to visceral epithe cell (no immune complex)
HIV                      Haematuria & HT, non selective proteinuria
                         2 => Due to HIV/ IgA N/ Heroin => Rx the cause
                         Unresponsive to steroid, 50% progress to ESRF in 5~10 yrs
Proteinuria
Causes         Functional (Benign)  Acute illness/ Ex/ Orthostatic proteinuria
               Overload (Outflow)  ↑Plasma level => Bence Jones protein in Myeloma
               Glomerular             Filtration leak => GN/ DM
               Tubular                ↓Tubular reabsorptn of LMW protein => 2- microglobulin (ATN)
Types          Selective              Outflow or Tubular (↑GFR or ↓reabsorption of small protein)
               Non Selective          Glomerular prob (Dam of GBM)
Mechanisms      Haemodynamic changes to Glom cap (Fever, CCF)
                Loss of charge selectivity => Affects Albumin, not (+) charged protein
                Loss of Glom cap wall integrity/ Dam to podocytes
Oedema          ↓Oncotic pres (protein loss) + Na retention (resistance to ANP)
                Rx = Loop diuretics + Thiazide + Albumin infusion + low salt diet

Haematuria
Glom                   IgA                    Men 20~30, episode of pharyngitis + myalgia
Deformed RBC           Neprhopathy            Followed within 1 day by frank haematuria lasting 2~6 days
Casts + Proteinuria                           Renal f(x) may be impaired
  ANA, ASOT etc        Benign Familial        Repeated haematuria with normal renal f(x)
    Renal Biopsy       Haematuria             fHx/ Renal biopsy usu not necessary
Non Glom               RCC                    “Triad” + Fever + ↑Ca + Erythrocytosis => Dx by US kidney
Normal RBC             TCC                    +/- Ureteric obstruction
         US            Prostatic Ca           Palp in DRE/ PSA/ Diffic passing urine/ Poor stream/ Urgency
     Cystoscopy        Stone                  Renal colic (Unilat flank P)/ Restless/ N+V/ Sweating
       +/- IVU         UTI                    Frequency/ Dysuria/ Tenderness over bladder/ Fever/ Pyuria
                       Coagulopathy           Signs of generalized bleeding eg bruising
                       Trauma                 pHx UG surg/ Catheter/ Renal biopsy
Red Urine c/o Blood    Dye                    Beetroot/ Drugs (Rifampicin)
                       ↑ free Hb              Haemolysis
                       ↑ free Mb              Rhabdomyolysis
Clinical Approach      Hx                     Flank P/ Dysuria/ Urethral dc/ Wt loss/ Fever/ Nocturia/ MC
                                              Recent throat Inf/ Ex/ Hx stones/ Medication/ fHx/ Travel
                       O/E                    Skin for coagulopathy & vasculitis
                                              Costovertebral angle tenderness/ Abdo mass
                                              Urethral dc/ Suprapubic tenderness/ DRE
                       Ix                     Urinalysis & Differentiate Glom/ Non Glom/ No RBC
                                              Urine Culture & Cytology => Inf/ Malign
                                              If Non Glom => US/ IVP/ CT => Stone/ Cysts/ Mass
                                              If Glom => ESR/ ANA/ Complement/ ASOT/ Cryoglobulin
                                              Invasive Renal Biopsy (Glom)/ Cystoscopy (non Glom)

Renal Ix
Structural       Plain Xray             Calcification + Calculi
                 US                     Renal size/ Mass vs Cysts/ Pelvis Dilatation (obstruction)
                                        Doppler (Renal A perfusion/ Renal V thrombosis)
                 CT                     Detail characteristics of mass + Tu stage
                                        Retroperitoneal Mass/ Renal V & A/ Radiolucent calculi
                 IVU/ IVP               Renal & UT outline for Scars/ Mass/ Dilatation/ Stones
                                        IV Iodine => Allergic reaction
                                        C/I => Impaired GFR/ UTI/ Vol Depletion/ Allergy/ DM
Functional       MCU                    Urethra & Bladder emptying for Reflux & Bladder dysf(x)
                                        Catherisation + Constrast into bladder => Void => UV reflux
                                        Cx => Catheter Inf/ Invasive/ Painful/ Radiation to gonads
Microscopic      Renal Biopsy           Nephritic/ Nephrotic/ Unexplained renal failure/ Haematuria
                                        C/I => Unco-op pt/ 1 kidney/ Coagulopathy/ Uncontrolled HT/ Obese
                                        Cx => Haematuria/ Flank P/ Inf
Urolithiasis
Pathophysiology           Change in Renal BF + GFR + Ureteric motility
S+S                       Asympt/ Recurrent Inf/ Renal impairment/ Haematuria
                          Renal colic (Loin to Groin)/ N+V/ Dysuria/ Renal tenderness
                          Exclude GIT dis/ Diarrhoea/ Use of antacid & diuretics
                          fHx & Diet (Fluid/ Protein/ Na/ Ca/ Oxalate/ Purine/ Vit D intake)
Ix                        Exclude UTI & Ax renal F(x) => Urinalysis/ Serum Ca, PO4, Urate, Cr, Urea
                          Confirm Dx => Plain abdo Xray (Ca stones)/ Helical CT scan or IVP
                          Recurrent stone formation => 24 hr collection (detect cystinuria to prevent renal fail)
Types of Stones       Ca             Ca oxalate, CaPO4 => Visible on Xray
                      (80%)          RF = ↑Urine Ca (↑PTH, Ca, Immobility, Vit D)/ ↑Oxalate/ ↓Citrate/ ↓Vol
                                     ↑Oxalate due to ↑Protein & CHO diet
                                     Prevent ↑Oxalate by ↑H2O, ↓protein, ↑fibre, KMg Citrate
                      Urate          Not visible on Xray
                      (10%)          RF = ↑Urine urate/ ↓pH/ ↓Vol/ Gout
                                     Rx = ↓Purine intake/ Allopurinol/ Urinary alkalinisation
                      Cystin         Weakly visible on Xray, assoc Cystinuria
                      e (2%)         Rx = ↑Diurnal Fluid intake/ Urinary alkalinisation/ Thiol donors
When to Rx                Pt factor => (P + Nausea) > 2wks
                          Renal factor => Renal impairment/ Infection
                          < 6 mm Spontaneous passage
Fever + Renal Colic       Obstruction + Inf = Uro Emergency => Obstructive urosepsis 72 hrs → renal dam
                          Fever < 38/ ↑WCC/ Ileus & Bowel sympts
Staghorn Calculus         Obstruction in pyeloureteric j(x) & infundibulum => Results in ESRF & Sepsis
Rx                    Conservative            Narcotic Analgesic + ↑Fluid intake
                                              FU if ↑P, signif nausea, fever => Rx if no progress in 2 wks
                      Surgery                 Shock wave lithotripsy (ESWL) => v effective if < 1.5cm
                      (Lithotomy)             Ureteroscopy/ Percutaneous/ Open (rare)

PBL Case: IgA Nephropathy => Ch GN => CRF
Ix Results ARF or CRF            ↑Cr, Urea, K, Metabolic Acidosis
            CRF                  Anaemia/ B disease/ ↓Ca/ ↑PO4/ ↑PTH
            ↓HCO3                Due to Metabolic Acidosis
            ↓Ca                  ↓1,25(OH)2 D3
            ↑PO4                 B/d from B to buffer acid
            ↑PTH                 ↓Ca triggers 2º HyperPTH
            ↑Ca + ↑PTH           3 HyperPTH => Ch hypersecretion of PTH
Drugs       Ramipril             ACEi => Prevent ATII vasocon on eff A => ↓Glom pres => ↓Proteinuria
            Amlodipine           Ca Channel blocker => ↓HT
            Caltrate             Ca Carbonate => Prevent OP due to ↓Ca + Rx acidosis (carbonate + H)
            Calcitriol           1,25(OH)2 Vit D3/ Also slows development of 2 HyperPTH
            Folate/ Vit B/ FGF   To ↑RBC synthesis/ Also Folate ↓Cysteine => ↓CVS dis due to renal fail
            Coloxyl + Senna      Coloxyl absorbs H2O, Senna stim bowel => Rx constipation due to ↑Ca
            Temazepam            Sedatives for sleep (cf Diazepam also has anxiolytic effect)
            Dilosyn              Antihistamine => CRF → CaPO4 deposit in skin → Itch
            Atorvastatin         HMG CoA reductase inhibitor
            Omeprazole           ↑Ca stim Gastrin release => ↑PUD
            NaHCO3               Rx Metabolic acidosis
            Aranesp              EPO => Rx Anaemia due to CRF
Monitor     Cardiac Dis          BP/ ECG/ Echo/ Lipid (Ch HT → Fibrosis → Diastolic Dysf(x) → LVF)
            Ren Osteodystrophy  ALP, Ca & PO4, Vit D, PTH/ B mineral density
            PVD/ Stroke/ AAA     Bruits
            P Neuropathy         Numbness & Burning in stocking distribution/ Monofilament & Vib
            B Marrow Suppress  Folate/ Vit B12/ FBC
            GIT                  Endoscopy => ↑Gastric acid => Reflux => Barrett’s Oes => Oes Ca
Hypertension
Risks of HT     Stroke/ Atherosclerosis/ Renal impairment/ CVS dis
At Risk Grp    CVS        Stroke/ MI/ CHF/ PVD/ Dissecting aneurysm
               Renal      Diabetic nephropathy/ GN/ HT’ve renovascular dis
2    Causes   Endo      1 Aldosteronism           Unilat Adenoma => Surg
(10%)                                               Bilat Hyperplasia => Amiloride/ Spironolactone
                                                    Aldosterone: Renin Ratio
                         Phaeochromacytoma          24 hr Urine Catecholamine
                         Cushing’s                  G/C effect on Mineralcorticoid
                                                    Urine cortisol & dexamethasone suppression test
               Renal     Renal A Stenosis           ↓Renal BF => (+) RAS
                                                    Bruits/ US with small kidney/ Angiography
                         Renal Induced HT           RF => ↓GFR => Can’t secret Na + H2O
                                                    ECF expand => ↑BP => Abn kidney insensitive to ANP
                                                    (+) RAS => ↑Na/ K ATPase => Na retention => ↑↑BP
                         ADPK                       Renal US
               CVS       Coarctation of Aorta       ↓Renal perfusion => (+) RAS
                                                    Pulse weaker in legs
               Others  OCP/ Alcohol/ Pre-eclampsia/ Oral steroid
Evaluation     1.    Confirm Dx => ↑BP on 3 separate occasions or 24 hr ambulatory BP monitoring
Aim            2.    ID 2 Rx’able cause/ CVS RF/ CI to Rx
               3.    Ax damage => Retinopathy/ Stroke/ LVH/ Aortic Aneurysm/ Nephropathy/ PVD
Hx              Onset/ Duration/ Course/ Medication/ pMHx/ Assoc Sympts/ Lifestyle/ fHx
O/E            GH                    BMI/ Evidence of underlying dis/ Skin
               CVS                   LVH/ LVF (coarctation => rib notching on CXR)/ Loud A2
               Pulse                 BP/ Radiofermoral delay/ Carotid & Fem pulse & bruits/ PVS
               ABDO                  Renal Mass (ADPK)/ Bruits (AAA/ Renal A Stenosis)
               Others                Neuro & Fundoscopy
Ix                  U+E => ↑Urea & Cr (Renal dysfunction)/ ↓K (1 Aldosteronism/ Diuretics)
                    Fasting glucose & lipid (↑DM & Atherosclerosis)
                    Dipstick urinalysis => Bl/ Protein/ Glucose (Kidney Damage)
                    ECG (+/- Echo) => LVH/ CAD

Chronic Kidney Disease
Definition      GFR < 60ml/ min/ 1.73m2 for > 3 month OR
                Evidence of kidney dam (Micro or Macroalbuminuria, Haematuria, Patho abn, Radio abn)
                Kidney failure = When GFR < 15 => 98% needs dialysis
eGFR           Unreliable when…  Rapidly changing kidney f(x)/ eGFT > 60/ Dialysis dependent
(MDRD)                                Exceptional dietary intake/ Asian/ Abo/ Children
                                      Dis of skeletal ms/ Paraplegia/ Amputees/ Extreme body size
RF              HT/ DM/ Smoking/ Abo/ >50
Screening       BP/ eGFT/ Urinary analysis for albuminuria
CKD Rx          Tight BP control => ACE & ARB / Ca Blocker => ↓CVS & Renal risk
                EPO/ Statins
                Stop smoking/ Wt reduction/ Restrict protein diet
                Rx Acidosis with NaHCO3 (Malnutrition/ Renal Osteodystrophy/ CVS Arrhythmia)
                     Referral                                           Cx (stage 3 CKD)
 eGFR < 30                                           HT/ Anaemia/ CVS dis
 Rapidly declining kidney f(x) (> 15% in 3 m)        2 HyperPTH/ Renal Osteodystrophy
 Proteinuria > 16, Glom Haematuria                   OSA/ Restless leg/ Malnutrition
 Kidney impairment + Difficult to control HT
 DM + Kidney impairment or proteinuria

				
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