Location and Structure

Details of a Glomerulus - The Membrane for Filtration

Detail of the Capillary Wall

Capillary Wall- Filter-

ProximalTubule

AfferentArteriole

EfferentArteriole

CapillaryLoops

Bowman’sCapsule

Inside ofthe Capillary - Blood Side -

Outside ofthe Capillary- Urine Side -

Healthy Kidney Renal ReplacementPhysical BasisDiseased Kidney

A picture of a normal human glomerulusagainst which to compare the various diseases.

Tufts of capillaries

Afferent arteriole

Thinbasement membranes

Bowman’s Space

Tufts of capillaries

Nuclei ofglomerular cells

Pathological features of glomerulonephritis

Descriptive Terms

Patterns of Damage - 1

All glomeruli normal

= No glomerulonephritis

All glomeruli abnormal

= diffuse glomerulonephritis

Some glomeruli abnormal

= focal glomerulonephritis

(often secondary to

systemic disease)

One Glomerulus compared with another

Glomerular InjuryDiffuse vs. Focal

X

X X

X

X

XX

X

X

X

X

X

Diffuse Disease Focal Disease

Pathological features of glomerulonephritis

Descriptive Terms

Patterns of Damage - 2

Normal

= No glomerulonephritis

Damage to part

of glomerulus only

= segmentalglomerulonephritis

Damage to all parts

of glomerulus only

= globalglomerulonephritis

Within a single glomerulus

Glomerular InjuryGlobal vs. Segmental

XX

XX

XXXX

XX

XX

XXGlobal Disease

Segmental Disease

Nephritic Nephritic SyndromeSyndrome

Definisi:It is a clinical pattern characterized by sudden onset of :

1. Edema (sodium and fluid retention)2. Hypertension3. Urinary changes :

a. Mild proteinuriab. Variable degree of haematuria (macroscopic or

microscopic, RBCs cast)c. Olygouriad. Mild azotemia

Etiology :Etiology :1. Immune complex disease :

– primary• Idiopathic membranoproliferative MPGN• Mesangioproliferative GN• Berger’s disease (Ig A nephropathy)• Membranoproliferative GN

– Secondary• Infection : Post streptococcal-Infective endocarditis• Collagenic : SLE• Allergic : Henoch Schonlein Syndrome• Drug : Sulpha

2. Anti glomerular basement membrane Abs : Good pasture syndrome

3. Pauci Immune : PAN-TTP-DIC

If the inflammatory process is severe, GN may lead to a greater than 50% loss of nephron function over the course of weeks to months such a process is called Rapidly Progressive GN and maybe associated with crescent in > 50% of the glomeruli. This of GN may occur in post infectious, IgA nephropathy, SLE and others

Clinical Picture of Nephritic Syndrome :

Symptoms :1. anorexia, nausea & vomiting dt mucosal edema2. Red urine dt haematuria3. Head ache, epistaxis dt hypertension

Sign :1. Edema : dt salt & H2O retentionacute onset, appear in the eye lid in the morning & disappear in the afternoon to appear in the ankle in ambulated patient

Firm, pitting dt hypoproteinemiaRarely generalized & not associated with serious effusion2. Hypertension : salt & water retention3. Urine changes : oligouriahaematuria (cola colour, smoky or reddish brown urine), micro and macroscopicProteinuria < 2 g/day

Clinical Picture of Complication:

• CP of Complication1. Circulatory congestion :Congested pulsating neck veinPulmonary edema (dyspnoe or orthopnea) dt hypervolemiaNormal circulation time or heart failure (gallop & circulation time)

2. Hypertensive encephalopathy :dt loss of autoregulation of cerebral blood flow leads to brain edemaC/P : Head ache + vomiting + blurring of vision + focal sign

3. Non Resolution :Rapid progressive GN → ARFChronic GN → CRFAsymptomatic proteinuria → which may reach the nephrotic range (≥ 3.5 g/day →nephrotic phase of nephritic syndrome

Clinical Picture of the Etiology

• CP of the Etiology1. Clinical manifestation of Post-Streptococcal GN (PSGN) :a. Patients presenting with Acute Nephritic Syndrome, often have evidence of a recent infection of the pharynx or skin with group A B-haemolytic Streptococci especially type 12b. Age : Children and adolescencec. This may occur sporadically or in epidemicsd. It commonly appears after pharyngitis or impetigo within 1-3 weeks after infection (1-2 weeks in pharyngitis & 2-4 weeks in impetigo)

2. Clinical manifestation of IgA Nephropathya. IgA Neph (Berger’s disease) is a primary renal diseases of IgA deposition in the glomerular mesangium → proliferative GNb. It is a common seen in children and young adultsc. Recurrent macroscopic haematuria is the most frequent clinical presentation

Clinical Picture :•

d. It is frequently associated with : - URTI (follow by haematuria 1-2 days after onset

or URTI) - Gastrointestinal symptoms or flu like illnesse. Rarely, it presents with microscopic haematuria,

proteinuria & progressive RFf. Rapidly Progressive RF is unusual. It may results

from ATN as consequence of macroscopic haematuria or superimposed crescentic nephritis

g. Recurrent IgA deposisition is common after transplantation

IgA Nephropathy

IgA

Clinical manifestation of Henoch Schonlein Purpura (HSP)

a. Haematuriab. Arthritisc. Abdominal painc. Purpura

Henoch Schonlein Purpura

Often a multi-systemic Illness• Wegeners Granulomatosis

Sinusitis Lung haemorrhageSkin rashArthritisTesticular involvementmononeuritisAny organ

Wegener’s Granulomatosis

Cavitating Nodules

Wegener’s Granulomatosis

Haemorrage

Wegener’s Granulomatosis

Wegener’s Granulomatosis • c ANCA associated disease• Microscopic polyarteritis p ANCA assoc

disease• Untreated 80% mortality• Cyclophosphamide and Pred +/- plasma

exchange• Treated 80% cured, 10% resistant disease,

10% die from side effects of the drugs

ArthritisSkin rashHair lossAnaemia, thrombocytopenia, leucopeniaPleuritis, pericarditisEye inflammationMouth ulcers

Systemic Lupus Erythematosis

Lupus Nephritis• Auto-immune disease• 7:1 female to male • Classical treatment

Cyclophosphamide and prednisolone. • Good recent evidence for

Mycophenolate mofetil• Hardly ever cured usually just get it

under control

Lupus Rash

Lupus Nephritis

Diffuse proliferative GN (grade IV) Wire loops

Lupus Nephritis• Grade I Normal• Grade II mesangial proliferative GN• Grade III focal proliferative GN• Grade IV Diffuse Proliferative GN• Grade V Membranous GN• Grade VI diffuse scarring

Goodpastures

IgG and C3

Goodpastures

• Autoantibody directed against the basement membrane of the Glomerulus and Alveolus

• Pulmonary Haemorrhage and Crescenteric acute renal failure

• Plasma exchange, steroids and cyclophosphamide

• Rare to recover renal function. Can usually save their lives

Investigations :A. Urine analysis :• Physical

• Microscopic or gross haematuria (smoky)• Turbid (proteinuria)• Oligouria• specific gravity

• Biochemical : proteinuria < 3 g/day• Microscopic :

• Dismorphic (deformed) RBCs (Glomerular origin)• Hyaline & tubular epithelial casts• RBCs cast (Diagnostic)• Granular casts

Investigations :B. Blood Chemistry :• Anaemia• Creatinine is usually normal• BUN maybe increased disproportionately• Serum albumin is often (dilutional + urinary

loss) Na →dilutional due to volume overload• Hypercholesterolemic acidosis with mild K

C. Renal Imaging : US : Mild swelling of kidneys or Normal

Investigations : (con’t)D. Renal Biopsy :• Indicated if there is atypical presentation or there is

severe azotemia or anuria or persistenly low C3 or persistent proteinuria > 6 months

• Light microscopy :– Show diffuse proliferative GN (mesangial cell proliferation,

infiltration with PMN, monocyte in capillary lumina, mesangium). Severe disease may show crescent in urinary space.

• Electron microscopy :– Show large dense sub epithelial deposits or humps

• Immunofluorescence (IF) :– Show IgG and C3 in a granular pattern in the mesangium and

along the capillary basement membrane

Investigations : (con’t)D. Serological test :

• In PSGN1. serum complement (CH50, C3). C3 returns to normal level

within 6-8 weeks of the disease. Persistently low C3 suggest MPGN, lupus or endocarditis

2. Anti Streptolysin O titers (ASOT) unless antibiotic treatment was

taken. It starts to rise 10 – 14 days after pharyngeal infection,

peaks at 3-4 weeks then declines maybe till 6 months3. Throat or skin culture for Group A Stretococcus

• In Ig A nephropathy :1. Serum Ig A level is increased up to 50% of patients2. Serum complement level are usually normal

• > 3g proteinuria• Oedema• Low serum

Albumin• Hypercholesterol• bacterial infections• increased clotting

• Blood and proteinuria• Red cell casts• Hypertension• Raised creatinine• Often systemic illness

Nephrotic Nephritic

Treatment :Treatment :

• Treatment of the disease :General treatment

• Complete bed rest, till edema, haematuria & hypertension subside

• Diet : High CHO dietSalt & H2O restriction (in

marked oliguria and edema)Protein restriction (in case of

renal failure)K restriction (in case of

Hyperkalemia)

• Treatment of the disease :

Symptomatic treatment

• Diuretic (Furosemide) for edema• Nifedipine, furosemide or ACE-I for hypertension• In the vast majority of patient < 1 g/day, no specific

treatment is provided• In patient with significant proteinuria > 1 g/day, ACE-

I or ARB should be used to reduce proteinuria. The target BP is < 130/80 mmHg

• Patients with progressive disease with deteriorating kidney functions → aggressive treatment including steroid, plasmaparesis or cytotoxic drugs

• Renal transplantation is an option for patients with ESRD

• Treatment of the disease :

Treatment of the cause :A. Post Streptococcal GNPenicillin 1 million Unit/ 6 hours IV for 1 week

B. Good Pasture Syndrome :- Plasmapharesis- Pulse Corticosteroid therapy1 g methyl prednisolonemaintenance : 2 mg/kg/ every other day- Mini-pulse corticosteroid therapy : 250 mg prednisolone/day for 3

days (less toxic)

C. SLE- Pulse corticosteroid therapy- Cyclophosphamide pulse therapy- Plasmapharesis

Treatment of the Treatment of the complication:complication:

• Heart failure :• Salt restriction• Diuretic• Small dose digitalis• Peritoneal dialysis

• Renal Failure :• Dialysis

• Hypertensive encephalopathy :• Mannitol for brain edema• Diazepam for convultion

Prognosis:Prognosis:

• Prognosis in children is very favourable• Adult are more prone to crescentic

formation and chronic Renal Insufficiency• Less than 5% of adults will develop a

RPGN and smaller percentage will progress to ESRD

• Patients with proteinuria < 1 g/24 h usually have good prognosis