Nephrology: Glomerular Disease, Nephritis Flashcards
Which is more severe: Nephrotic or Nephrititc ?
Nephritic, more apt to you into renal failure (Have more hematuria than proteinuria whereas the Nephrotics are opposite )
Define Nephritic Syndrome
PHAROH (With Pyuria and Edema)
Proteinuria Hematuria Azotemia Red blood cell casts Oliguria Hypertension
Pyuria
Edema
Define Nephrotic Syndrome
Proteinuria of > 3.5 g/day Hypoalbuminemia Hyperlipidema (Fat Casts and Fat Ovals) Edema Often See Hypercoagubility
Define Asymptomatic Hematuria
Microhematuria with the same characteristics as in the Nephritic Syndrome, but patient lacks the other features
Define intermittent gross hematuria
Macrohematuria with the same characteristics as in the Nephritic Syndrome, but patient lacks the other features
Define Asymptomatic Proteinuria
Proteinuria without the additional features of the nephrotic syndrome
Define Rapidly Progressing glomerulo nephritis
Relentless loss of renal function within weeks or months (creatinine doubles in < 3 months), may have either of the features 1 - 5
Define Pulmonary-Renal Vasculitic Syndrome
As the name suggests, there is vasculitis with involvement of the lungs and the kidney. Usually presents with hematuria or the nephritic syndrome.
Chronic Renal failure
Patient presents with advanced renal failure. Often, the cause can no longer be determined with certainty
Primary Glomerulonephritis means…
That the disease is only present in the kidney and not due to diffuse pathology
Secondary glomerulonephritis refers to …
there is a systemic disease that involves several organs, among them the kidney, and the kidney disease is a glomerulonephritis
What are the four main Primary Glomerulonephritis’ ?
Minimal Change Disease
FSGS
IgA Nephropathy
Membranous nephropathy
List the Major Secondary Glomerulonephritis’
Postinfectious Glomerulonephritis
Membranoproliferative Glomerulonephritis with Hepatitis C
Renal Involvement in Systemic Vasculitis
Anti-GBM disease and Goodpasture’s Syndrome
Lupus Nephritis
Diabetic Nephropathy
Amyloidosis
Henoch-Schönlein Purpura
HIV associated nephropathy
Do minimal change disease, Membranous neuropathy and FSGS present as Nephrotic or Nephritic ? (Primary GN’s)
Nephrotic !
The only Primary GN that show as Nephritic is IgA Nehropathy (shows hematuria)
Membranous Neuropathy is often associated with what other disease state ?
Malignancy
A child presents with a NEPHROTIC syndrome. What do they most likely have ?
Minimal Change Disease
An african american presents with a NEPHROTIC syndrome. What is it likely to be ? ?
FSGS !
40 yo caucasian presents with a NEPHROTIC disease. What is it likely to be ?
Membranous Glomerulopathy
A half asian, half hispanic person presents with a NEPHROTIC disease that actually shows hematuria. What is it it likely to be ?
IgA Nephropathy
What is usually required to diagnose a specific type of primary glomerulonephritis ?
Biopsy !
Histopathology of minimal change disease
looks normal on light microscope
May see binding of the foot processes of podocytes (STARRED ON PPT)
Histopathology of FSGS
LOOK AT SLIDE 41 (STARRED)
Focal: Only in some portion of kidney
Segmental : Involve only a portion of the glomerulus
Glomerulosclerosis: Scarring of glomerulus
Histopathology of Membranous GN
LOOK AT SLIDE 43 (STARRED)
Thick basement membrane with sub-epithelial immune deposits.
PLA2R is target antigen
Membrane looks thick and rigid
SPIKES are seen with Jones Silver Stain * (Slide 45 is STARRED)
Immunofluorescence is GRANULAR (STARRED Slide 46) due to Immune complex deposition ! (Granular is Lumpy Bumpy)
Histopathology of IgA Nephropathy
MESANGIAL IgA deposits. (Immune complexes ?)
Clinical will show “dark urine” due to microhematuria. Often in Asians and Hispanics
Post- Infectious GN is a Secondary GN which commonly occurs after infection with which two pathogens ?
Strep (Group A, Beta Hemolytic –> Pyogenes, Mprotein)
Staph
Does Post Streptococcal GN (PS GN) present at Nephrotic or Nephritic ?
Nephritic ! May have gross hematuria (PHAROH PE)
How can you tell the difference between PS GN and IgA Nephropathy strictly by taking a history ?
PS GN occurs 10 days after a URI (21 after skin)
Resolves after 6 weeks typically
IgA occurs 5 days after URI
Persistent or recurrent hemturia for years
both can show gross hematuria..
What occurs to complement as PS GN progresses ? (Very Important to Know)
It starts out very low in the acute phase but increases steadily as the disease progresses
Immunofluorescence of PS GN will show what kind of pattern ?
Granular
Due to deposition of IgG-Antigen complexes and complement
Electron microscopy will show what findings in PS GN ?
lArge sub endothelial deposits (due to antigen complex deposition)
What four Secondary GN will give you low complement levels ?
PSGN
Membranoproliferative GN
Cryoglubulinemia
Lupus
in Light microscopy, how is PSGN describe ?
Diffuse, proliferative GN
How do you treat PS GN ?
Anti-biotice
Supportive (electrolyte and fluids)
What infectious agent is associated with Membranoproliferative GN ?
HEPATITIS C
Most Membranoproliferative GN is caused by hep c infection now . Was once though to be idiopathic
Membranoproliferative GN with Hep C is also associated with what other blood abnormality ?
Cryoglobulinemia
What is a cryoglobulin ?
Plasma proteins that precipitate in the cold, include Ig and complement components.
Describe Type I Cryoglobulinemia
Due to IgM or IgM fragments (light chain). Due to plasma cell dyscrasia (Multiple myeloma, Waldenstroms)
Describe Type II Cryoglobulinemia
Due to monoclonal IgM directed at IgG
Describe Type III Cryoglobulinemia
Due to polyclonal IgM directed at IgG
Cryoglobulinemia is usually associated with Hep C and also is positive for which auto-immune indicator ?
Rheumatoid Factor
What gross skin finding might you see in a patient with Cryoglobulinemia ?
Palpable purpura
May also see arthralgias and weakness
Vasculitis is also seen
What type of ‘cast’ will you see in the urine with cryoglobulinemia ?
RBC Casts
Membranoproliferative GN associated with HepC and cryoglobulinemia will present as Nephritic or Nephrotic ?
Actually it can present as both (Look for asymptomatic proteinuria and hematuria)
On light microscopy of Membranoproliferative GN (Hep C and Cryoglobulinemia) will show what indicative pattern ?
SPLIT MEMBRANE (Tram Tracking)
AMy also see ‘Closed loop’ glomeruli
Cryoglobulins may precipitate in the capillary loops making it look like thrombi
Vasculitis in the kidney is often associated with which sized vessels ?
SMALL!
Vasculitis in the kidney is often associated with which auto-immune marker ?
ANCA (Anti-Neutrophil Cytoplasmic Antibody)
What is the overall action of ANCA’s ?
Activates the cells they target.
In this case, it is neutrophils.
May lead to activation of Integrins and ICAM’s allowing for increased WBC extravasion.
C-ANCA
Cytoplasmic distribution.
Targets Proteinase 3 (PR3)
P-ANCA
Perinuclear distribution. Targets Myeloperoxidase (MPO)
What are the 3 major ANCA positive Small Vasculitis’ ?
Wegners Granulomatosis
Microscopic polyangitis
Churg-Strauss
How can you differentiate Microscopic polyangitis from Wegners and Churg Strauss ?
Microscopic polyangitis does not form granulomas like the other two
What is the major differential between Wegners and Churg Strauss ?
In Churg Strauss, asthma and eosinophilia are often present
They are not seen in Wegners
Why are the ANCA+ Small Vessel Vasculiti’ important to nephrologists ?
May be accompanied by Crescentic GN and Pauci- Immune GN
What does Pauci Immune refer to ?
ANCA involvement but not present on Immunfluroscopy (and serology ?)
Is Wegners Nephrotic or Nephritic ?
Nephritic
Describe the clinical Presentation of Wegners
Chronic sinusitis Nasal or mucosal ulcerations Purulent/bloody nasal discharge ANCA + Non-caseating granuloma
ABSENCE OF ASTHMA AND EOSINOPHILIA
Describe the clinical presentation of Microscopic Polyangitis
Similar to Wegners
Sinusitis
Nasal/Mucosal ulceration
bloody/purulent nasal discharge
ANCA +
NO GRANULOMA SEEN ON BIOPSY ( wegners shows granulomas)
Describe Isoloated Pauci-Immune GN
Nephritic
ANCA +
LIMITED TO THE KIDNEY (No lung or systemic involvement like in Wegners, Polyangitis and Churg Strauss)
Describe the Clinical Presentation of Churg Strauss
Allergic Rhinitis (Not sinusitis, that is for Wegners)
ASTHMA and long courses of inhaled corticosteroids
Rash: Palpable purpura or nodules ( cryoglobulinemia often show this )
PERIPHERAL NEUROPATHY
GASTROENTERITIS
EOSINOPHILIA
Nephritic, ANCA +
Pulmonary infiltrates on X-ray (lung involvement)
What is the difference between Anti-GBM disease and Goodpastures disease ?
In Anti-GBM disease, the antibodies are specific for the kidney GBM
In Goodpastures they cross react with basement membrane of the lung (and possibly other tissues)
What is a common non-renal symptom of Goodpastures disease ?
Lung hemorrhage
How would you describe the renal disease caused by Anti-GBM and Goodpastures disease ?
Nephritic
Rapidly progressing
Crescentic
Necrotizing GN
What immunofluorescence pattern does Goodpasture exhibit ?
LINEAR !
Type II hypersensitivity (direct binding of Ab’ to Collagen type IV)
Treatment for Anti-GBM and Goodpasture Disease
Corticosteroids
Immunosupressants
Cyclophosphamide
Plasmapheresis
Lupus nephritis usually affects which kind of patients ?
Young Women
On light microscopy Lupus Nephritis mimics which glomerular disease ?
ALL OF THEM !
What are common signs and symptoms of Lupus ?
Fever, fatigue, weight loss Photosensitive rash (often seen in butterfly pattern on face) Arthralgias Reynaud Alopecia Phlebitis
Self antibodies in SLE are directed against which cellular structures /
Nucleus
ANTI-NUCLEAR-ANTIBODIES (ANA)
Staining for ANA can look diffuse or perinuclear (Like the different forms of ANCA)
Define Class II Lupus Nephritis
Asymptomatic Proteinuria and Hematuria
Mesangial proliferation due to mesangial deposits.
Define Class III Lupus Nephritis
Nephritic
Prominent sub endothelial deposits
Endocapillary Proliferation
Define Class IV Lupus Nephritis
Nephritic
Large Confluent Subenodthelial deposits (Wire Loop)
Define Class V Lupus nephritis
NephrOtic
Subepithelial Deposits
What is the most common cause of end stage renal disease in the US ?
Diabetic Nephropathy
How long does Diabetic Nephropathy tend to take post diagnosis with Type I diabetes ?
The majority of patients who develop diabetic nephropathy will present before 20 years of dealing with diabetes (if they make it past 20 years then the chance for developing is very low)
30% of patients with Type I will develop diabetic nephritis.
What are the major risk factors for diabetic nephritis ?
Duration of disease
HTN
poorly controlled diabetes
The first screening measure for determining diabetic nephropathy is …
Calculating GFR (do so via the Cocroft-Gault assay)
The second screeinng for diabetic nephropathy is to test for microalbuminuria. To do this you measure a urine sample for albumin and creatinine then compare the ratio of albumin:creatine. Discuss the cut-offs for normal, Microalbuminuria and albuminuria.
Normal: Less than 30 mg/g
Microalbuminuria : 30 -300 mg/g
Albuminuria: Greater than 300 mg/g
What ‘nodules’ are seen on microscopy of Diabetic Nephropathy ?
Kimmelstiel-Wilson nodules
Besides management of hyperglycemia, what preventive measures can be taken to limit progression of Diabetic Nephropathy ?
ACE and ARB’s !
Primary amyloidosis occurs due to pathologic deposition of what ?
Light Chain !
AL = Primary amyloidosis.
Primary Amyloidosis is seen with what concurrent disease ?
Multiple myeloma
Secondary amyloidosis is caused by deposition of which substance ?
Amyloid (abnormal protein)
Is amyloidosis Nephrotic or Nephritic ?
Nephrotic
What stain is used to stain amyloid ?
Congo Red
What does stained amyloid look like under polarized light ?
GREEN APPLE BIREFRINGENCE
What most commonly dictates prognosis for amyloidosis ?
Cardiac involvement
Henoch-Shonelein Purpura is caused by what ?
IgA deposits in the vasculature (Don’t confuse with IgA nephropathy, a primary nephrotic syndrome.
What is the major determiner between IgA nephropathy and Henoch-Schonlein ?
HS is systemic disease and shows purport, whereas IgA is typically contained to the kidney
What does HIV associated GN typically resemble on light microscopy ?
FSGS (Collapsing subtype)
Iin HIV associated GN, what might be seen within endothelial cells of the kidney ?
Reticular inclusion bodies
