4) Acute Glomerulonephritis and rapid progressive glomerulonephritis

Question 1

what are the classification for acute glomerulonephritis ?

Answer 1

acute post infection glomerulonephritis :

• post strep GN +
• GN of infective endocarditis
• shunt nephritis

acute glomerulonephritis with systemic disorders :

> SLE (lupus nephritis in another topic)

> henoch scholein purpura (systemic form of IgA nephropathy) +

> microscopic polyangitis and other vasculitis disorders +

> wegner granulomatosis +

> Good pasture’s syndrome + ( anti glomerular basement membrane antibody mediated glomerulonephritis AntiGBM)

Question 2

what is the classification rapidly progressive glomerulonephritis ?

Answer 2

type 1 : anti glomerular basement membrane antibody - good pasture syndrome

type 2 - immune complex mediates glomerulonephritis :

membranoprolifertive neuropathy
henoch scholen purpura
lupus nephritis
post strep GN

Type III: glomerulonephritis associated with vasculitis (pauci GN)

ANCA associated crescentic glomerulonephritis = wegner

= microscopic polyangitis

= eosinophilic granulomatosis / shrug strauss syndrome

Question 3

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Answer 3

rapidly progressive glomerulonephritis

membranoproliferative glomerulonephritis

post infectious glomerulonephritis

Question 4

post strep GN most commonly seen in

Answer 4

children of 3–12 years and patients > 60 years of age

Question 5

post strep GN are high risk in ?

Answer 5

patients with diabetes, malignancies, and alcohol dependency.

Question 6

what is the etiology post strep GN ?

Answer 6

Occurs approximately 10–30 days following an acute infection:

most common cause :group A beta-hemolytic streptococci
inflaming the the mouth and tonsillitis, pharyngitis

Soft tissue infections : erysipelas : group A Streptococcus

non bullous impetigo : S. aureus or Group A streptococci

bullous : S. aureus

Osteomyelitis : Staphylococcus aureus

Question 7

immune complex mediated acute GN occurs in ?

Answer 7

infective endocarditis

Question 8

what is the pathophysiology of post strep GN ?

Answer 8

immune complexes containing the streptococcal antigen deposit within the subepithleila part of glomerular basement membrane

nephrotogenic aswell - molecular mimicry also likely

complement activation → destruction of the glomeruli → immune complex-mediated glomerulonephritis and nephritic syndrome

Question 9

what are the clinical features of post strep GN ?

Answer 9

50% asymptomatic

Nephritic syndrome :

Hematuria

Hypertension: can lead to headaches

generalised Edema;
may be associated with dyspnea
neurologic symptoms (e.g., seizures)

Oliguria

azotemia related symptoms - fatigue , axterixis (flapping tremor) , decreased alertness and confusion

===================

Influenza-like symptoms - fever

Flank pain

Question 10

how can we diagnose post strep GN?

Answer 10

Laboratory tests:

Normocytic, normochromic anemia

Possibly elevated BUN and creatinine (often transient)

↑ Antistreptolysin-O titer (ASO) (particularly following streptococcal infection of the pharynx)

↑ Anti-DNase B antibody (ADB) titer (particularly following streptococcal infection of the soft tissue)

↓ C3 complement

Urinalysis: nephritic sediment (e.g., hematuria and RBC casts, mild proteinuria)

===========
Ultrasound: enlarged kidneys

============
Renal biopsy (not performed in most cases)
Indication: suspected rapidly progressive glomerulonephritis

Light microscopy:
Glomeruli are globally and diffusely enlarge
diffuse hypercellularity due to mesangial and endothelial cell increase
infiltration of monocytes and polymorphonuclear cells.
all of this block the capillary

Immunofluorescent for every post infection : granular
garland pattern, the starry sky pattern, and the mesangial pattern

The starry sky pattern is an irregular, finely granular pattern with small C3 deposits on glomerular basement membrane This pattern is often seen in the early phase of the

The starry sky pattern may turn into the mesangial pattern, which is characterized by granular deposition of C3 with or without immunoglobulin G. - closely related to resolving

sometimes deposits are large and densely packed and aggregate into a garlandlike pattern. These correspond to the humps on the subepithelial side of the glomerular capillary wall seen with electron microscopy
These types of deposits may persist for months and may be associated with the persistence of proteinuria and the development of glomerulosclerosis

Electron microscopy:
“humps” = subepithelial immune complexes (between epithelial cells and the glomerular basement membrane)

Question 11

what is the treatment of post strep GN ?

Answer 11

In most cases the disease is self-limiting

treatmnet for nephritic syndrome :
low sodium diet
water restriction

if porteinirea or hypertension : acei or arb

if edema and pulmonary edema - loop diuretics

persisting streptococcal infection :penicillin G benzathine

If severe going into rapidly progressive : glucocorticoids,cyclophosphahemodialysis

Question 12

what are the complications of post strep GN ?

Answer 12

Acute renal failure

Rapidly progressive glomerulonephritis

Nephrotic syndrome later in the course of the disease

Question 13

what does microscopic polyangitis affect ?

Answer 13

small vessels

such as arterioles , venules and capillaries

Question 14

what are the clinical features of microscopic polyangitis ?

Answer 14

NEPHRITIC SYNDROME symptoms
but hypertension

palpable purpura
raynaud phenomena

neuropathy - numbness and tingling

myalgia an arthralgia

epistaxis
erosin and perforation of nasal septum - saddle nose deformity

scleritis , uveitis

recurrent otitis media

Question 15

what is microscopic polyangitis glomerulonephritis called ?

Answer 15

pauci immune glomerulonephritis = not associated with immune complex , antibodies or complements

Question 16

what is the diagnosis of microscopic polyangitis ?

Answer 16

x ray
alveolar haemorrhages = come as opacities

========
nephritic sediment
mild porteinurea

========
biopsy of the organ it affects
(kidneys and organs)

= NO GRANULOMAS different to wegners granulomatosis

= but there is FIBRINOID NECROSIS of neutrophils

immunoflurecsnce
NO IMMUNOGLOBULIN OR COMPLEMENT DEPOSITION

=========
nromocytic normochromic anemia

azotemia

MPO / pANCA positive
= different to polyarteritis nodosa (large vessel affecting)

Question 17

what is the treatment of microscopic polyangitis ?

Answer 17

immunosuppression with corticosteroids - prednisone with cyclophosphamide / azathioprim
or rituximab
Plasmapheresis may also be indicated in the acute setting to remove ANCA antibodies.

Question 18

what type of vessels do henoch scholen affect ?

Answer 18

arterioles , venules and capillaries

Question 19

what causes henoch purpura ?

Answer 19

preceding viral infection most commonly and upper respiratory tract one - group A strep

Gi infections also possible

Question 20

what is the pathophysiology of henoch purpura ?

Answer 20

exposure to antigen
STIMULATION TO iGa

depostion of these iga in vascular walls and mesangium - activation of components - inflammation and damage

Question 21

what are the clinical manifestation of hooch purpura ?

Answer 21

skin
symmetric distribution erythramatous macule colaescing into palpable purpura - esp in lower extremities and buttocks

jonts - arthritis and arthralgia

GI - colicky abdominal pain
bloody stools

kidneys - signs and symptoms of nephritic syndrome
there is nephrtic syndrome 
edema 
hypertension possibly and its symptoms 
there is heamturea

Question 22

what is the diagnosis for henoch purpura ?

Answer 22

cbc 
increas platelt count 
increase wbc 
normocytic normochornic
bun andcreatinin transient elevation

serum antibodies and complement
IgA increase
IgA complex
decrease in complement

increase in creatinine or BUN

urinalysis - of nephritic syndrome

======
biopsy
for severe renal involvement or persistent nephritic syndrome

skin - leukocytoclastic vasculitis with iga and C3 immune complex depostion is the hallmark

kidney
LM - diffuse mesangial proliferation because iga are dumped here
endocapillary proliferations

IF
mesangial IgA deposition
C3 complement and firbin

Question 23

what is the treatmnet for henoch scholen purpura ?

Answer 23

milld
no treatment
nsaids and pain management and adequate hydration

severe
Iv methylprednisolone pulse therapy with cyclophosphamide and azathioprim
plasmapheresis of refractive

renal transplant if ESRD

dialysis for AKI

antihypertensive drugs
reduce salt intake and water intake

Question 24

what is a serious complication of henoch scholen?

Answer 24

turns into rapid progressive glomerulonephritis with crescent formation

GI - intussusception or infraction

Question 25

granulomatosisi with polyangitis or others known as wegners etiology ?

Answer 25

idiopathic = occurs more often after a upper respiratory tract infection

Question 26

what are the clinical features for wegners granulomatosis ?

Answer 26

ENT chronic rhinitis- saddle nose chronic otitis / mastoiditis lower respiratory tract - potentially life threatening : cough , dyspnea , hemoptysis renal - potentially life threatening pauci immune glomerulonephritis which goes into rapidly progressive crescentic glomerulonephritis with possible pulmonary renal syndrome with nephritic syndrome skin papules , vessies , ulcers purpura of lower extremities ocular conjunctivitis , episcleritis , retinal vasculitis corneal ulcers cardiac - potentially life threatening pericarditis , myocarditis

Question 27

what are the diagnostics for granulomatosis with polyangitis

Answer 27

blood creatinn and BUN high PR3 - ANCA / C-anca normocytic normochromic anemia chest x ray - multiple bilateral cavitating nodular lesions urinalyisis nephritic sdiment and typical nephritic syndrome biopsy = NECESSARY TO CONFIM BIOPSY necrotic granulomatous vasculitis of small and medium sized

Question 28

WHAT IS THE TREATMNET FOR WEGNER disease ?

Answer 28

if mild glucocrticoids plus methotrexate / cyclophosphamide / rituximab moderate to severe glucocorticoids with cyclophosphomide . rituximab glucocrticoids tapered as soon as they respond remission maintenace - azathioprine , rituximab and methotrexate = should be considered for a year due to the high relapse

Question 29

what is the cause for good pasture syndrome ?

Answer 29

exposure to organic solvents - chloroform - tobacco - influenza a

Question 30

what is the pathophysiology of good pasture syndrome ?

Answer 30

abnormal plasma cell production of anti - GBM - against collagen type 4 anti -GBM attack the alveoli and glomeruli basement membrane attach to the epitope and activate the complement cascade

Question 31

what are the clinical manifestations of good pasture syndrome

Answer 31

lungs antedate the kidney symptoms hemoptysis cough dyspnea nephritic syndrome symptoms

Question 32

what is the diagnosis of good pasture's disease ?

Answer 32

renal biopsy immunofluorescence prescence of anti GBM antibodies specifically showing a strong linear ribbon-like appearance also can have c-ANCA = antedates x ray - alveolar haemorrhages

Question 33

what is the treatmnet for goodpasturedisease ?

Answer 33

plasmapheresis immunosuppressants = cyclophosphamide , prednisone , rituximab - prevent new anti-GBM antibodies azathioprine for maintenance

Question 34

what is the pathophysioogy of membranoproliferative disorders of type 1

Answer 34

type 1 - most common circulating immune complexes - caused by hep b or hep c over time they build in the glomerulus and activate CLASSICAL complement pathway or inapporpriate activation of complement pathway by the alternate complement pathway - C3 is converted to c3a and c3b by enzyme c3 converts this can be due to = > mutation >autoanitbodies against protein that regulate the process > c3 convertase only exist for a short time = inapropriate activation of IGg that bind to C3 converatse - making c3 converatse more stable that special type of IgG is called nephritic factor HERE NO IMMUNE COMPLEXES the immune complexes or the complement end up in the sub endothelium of the basement membrane - recruiting inflammatory cells - damaging the capillary wall and thickneing of the basement membrane triggers mesangial cells - to proliferate and reach through the thick basment membrane = mesangial interposition causing the basemnet membrane to split around the basement membrane = DUPILICATION OF BASEMENT MEMBRANE OR TRAM TRACK

Question 35

what is the pathophysioogy of membranoproliferative disorders type 2

Answer 35

in type 2 membranoproliferative GN there is no IMMUNE COMPLEXES - but complement deposits dense deposits DISEASE or C3GN activation of the alternate complement pathway IgG auto - nephritic factor involved c3GN - not intramembranous DDD is more aggressive than C3GN c3 levels are usually lo

Question 36

what is the pathophysiology of membranoproliferative GN of type 3

Answer 36

VERY RARE like type 1 involves immune complexes and and complements deposited in the subendothelial space ANDsubepithelial sapce too

Question 37

why should membranoproliferative GN not be confused with membranous gn ?

Answer 37

both have basement membrane thickening however mebranoproliferative Gn there is also mesangium thickening

Question 38

what are the clinical features specific for membranoproliferative GN type 2

Answer 38

develop drusen - deposts within the bruch's membrane and beneath the retinal epithelium = lipodystrophy =over time vision deteriorates , macular detachment

Question 39

what is membranoproliferative GN associated with ?

Answer 39

type 1 immune complex mediated : hep C / B associated nephropathy hcvasociated cyroglobulinemia monoclonal gammopathies chronic bacterial - endocarditis autoimmune SLE

Question 40

what is the diagnosis for membranoproliferative disorders

Answer 40

CAN HAVE BOTH NEPHROTIc AND NEPHRITIC SYNDROME - most common renal biopsy LM - MPGN is derived from two histological changes 1_ glomerular basmenet membane thicening 2_increase mesangial and endocapillary proliferation giving lobular appearance f the glomerular tuft type 1 - silver staining we can see tram tracking immunoflorescence findings type 1 = igG and C3 type 2 = C3 alone NO immunoglobulin type 3 = IgG and C3 EM = type 1 subendothelila and mesangial immune deposits and tram track appearance type 2 - DDD dense ribbon like appearance of the subendothelilal space of the basement membrane and mesangium INTRAMEMBRANOUS depositions c3GN = not dense deposition and not intamembranous light depositions in mesangium , sub endothelium type 3 = sub endothelia and mesangial and subepithelial

Question 41

how can we know if MPGN is induced by secondary causes?

Answer 41

hep C granular depositionof IgM and C3 and BOTH kappa and lambda light chains IgG may or may not be present and C1q is typically negative similar pattern for viruses monoclonal gammapathies - monotype kappa or lambda light chains autoimmune - full house pattern EM - cyropercipitates in mesangium shows fingerprint pattern

Question 42

how do we know if MPGN is triggered by autoimmune disease ?

Answer 42

full house patten of Ig deposotion - IgG and Igm , iGa , c1q , c3 , kappa andlambda light chains

Question 43

how do we know if MPGN is triggered by monoclonogammpoathy

Answer 43

one monoclonal antibodies sound with C1q , C3 and light chain restricts

Question 44

what is the mangement of MPGN?

Answer 44

immune complex mediated MPGN - should be evaluated for following disorders such as hep b or c serology chronic bacterial infections in blood cultures test for fungi test for parasitic infections autoimmune disease screening monoclonal gammopathy : serum protein electrophoresis , multiple myeloma , low grade b cell lymphoma ===== compliment mediated MPGN measure c3 , c4 genetic analysisi of mutation normal C3 levels do not rule out COMPLIMENT MEDIATED MPGN ========= give treatment to the underlying disease then treatment for only 3 conditions remain idiopathic immune complex mediated MPGN C3GN DDD ======= IICM MPGN normal GFR and non nephrotic range proteinurea = ACEI, regular follow up GFR LOW /NEphrotic range proteinurea / severe histological changes - CRESCENTS / progressive even with ACEI prednisolone and ACEI add cyclophosphamide if no response no response to cyclo = stop it and go rituximab ========== c3GN / DDD idiopathic autoantibodies to complement protein C3nef positive= glucocorticoids and rituximab combination therapy with corticosteroids and cyclophosphamide.  Methylprednisolone 3 day pusle treatment 10-15 mg/kg, after which the patient received a conventional dose of prednisone plasma exchange with albumin genetic mutation in the complement pathway - benefit from treatment stopping mac from forming = eculizumab factor h deficiency = plasma exchange WITH albumin if ESRD = renal transplant ======== if nephrotic syndrome Anti-aggregant therapy includes Dypiridamol along with Aspirin.  At severe nephrotic syndrome it is appropriate to administer Heparin

Question 45

what is RPGN ?

Answer 45

characterized by rapid destruction of the renal glomeruli that often leads to end-stage renal disease

Question 46

what is Eosinophilic granulomatosis with polyangiitis

Answer 46

characterized by necrotizing granulomatous vasculitis with eosinophilia, commonly involves the lungs and the skin but can also affect the renal, cardiovascular, gastrointestinal, and peripheral nervous systems

Question 47

what is the Etiology of eosinophilic granulomatosis with polyangiitis

Answer 47

unknownmaybe montelucast triggere

Question 48

what are the clinical features ofeosinophilic granulomatosis with polyangiitis

Answer 48

Severe allergic asthma attacks (chief complaint) Allergic rhinitis/sinusitis Skin nodules, palpable purpura nephritic syndrome CNS: impaired mental status, mononeuritis multiplex (loss of motor and sensory function, with wrist or foot drop) Pericarditis symptoms Gastrointestinal involvement: bleeding , perforation

Question 49

diagnosis of eosinophilic granulomatosis with polyangiitis

Answer 49

nephritic syndrome Peripheral blood : eosinophilia ↑ IgE level Circulating MPO /pANCA Biopsy (confirmatory test) Tissue eosinophilia Necrotizing vasculitis, and necrotizing granuloma

Question 50

treatment for Churg-Strauss syndrome ?

Answer 50

immunosuppression with glucocorticoids; possible in combination with cyclophosphamide

Question 51

diagnosis of RPGN ?

Answer 51

nephritic syndrome biopsy : crescent moon - epithelial cell proliferation that displaces the glomerulus

Question 52

always suspect RPGN and initiate testing immediatelywhen ?

Answer 52

serum creatinine rises rapidly due to renal damage