15 - Glomerular Disease Pathology II Flashcards
What is the first approach to diagnosing your patient with renal disease?
Classify the patients clinical symptoms using clinical and laboratory parameters into one of the clinical renal syndromes
Describe nephritic syndrome
EMPHASIZED
- HTN*** (due to salt retention)
- Oliguria (due to decreased GFR from inflamed glomeruli)
- Proteinuria (more than 150 mg/24 hrs BUT less than 3.5 g/24 hrs)
- Hematuria*** (with dysmorphic RBCs)
- RBC casts***
Know the starred things
Describe nephrotic syndrome
EMPHASIZED
- Proteinuria*** (with more than 3.5 g/24 hrs **)
- Generalized pitting edema* and ascites (due to hypoalbuminemia*)
- Hypercoagulable state
- Hypercholesterol
- Hypogammaglobinemia
- Fatty casts ***
Know the starred things
Describe the cause of nephritic syndrome
- Due to breaks in the glomerular capillary loops
- Erythrocytes spill out into urinary space
Describe the cause of nephrotic syndrome
- Due to glomerular capillary filtration defects
- Protein molecules spill out into the urinary space
What is effacement?
- Shortening and/or thinning of the epithelial cell foot processes
- This causes protein defects (nephrotic syndrome)
- This process can no longer stay attached to the basement membrane, so they will detach and the basement membrane will be leaky
- Protein can be reabsorbed
???
What is the cause of acute renal failure?
- Due to tubular injury in most cases
Describe the progression of renal disease
- Acute renal failure, nephrotic syndrome and nephritic syndrome can all occur
- If not treated or if it does not respond to treatment, all can progress to CHRONIC RENAL FAILURE (scarred or fibrosed kidneys)
- There will be a slow rise in creatinine over months to years
What are the gross features of CRF?
- Kidneys are small
- Cortex thinned
- Increase pelvic fat
What are the microscopic features of CRF?
- Glomerular sclerosis
- Interstitial fibrosis
- Tubular atrophy
KNOW SLIDE 39 (image of these pathologies)
What are the causes of nephrotic syndrome?
Primary causes
- Minimal change disease
- Focal segmental glomerulosclerosis
- Membranous nephropathy
Secondary causes
- Diabetic nephropathy
What are other systemic disorders that can cause nephrotic syndrome?
- Diabetes
- Amyloidosis
- SLE
- Drugs (gold, penicillamine, heroin)
- Infections (malaria, syphilis, Hep B, Hep C, HIV)
- Malignancies (carcinoma, melanoma)
Describe minimal change glomerulopathy
AKA minimal change disease or lipoid nephrosis
- **MOST COMMON CAUSE OF NEPHROTIC SYNDROME IN CHILDREN **
- Age 2-6 years old
- Normal glomeruli on LM and IF imaging ***
- Effacement of foot processes will be visible on EM ***
- Lipid tubular cells
- Usually responds to steroids
What do you NEED to remember about minimal disease?
- NOTHING will be seen on LM or IF
- EFFACEMENT of FOOT PROCESSES on EM
What is the KEY LESION in minimal change disease?
- Diffuse epithelial foot process effacement ****
What will you see in the tubular cells in minimal change disease?
- Lipids in tubular cells
- AKA “lipoid nephrosis”
- Tubular cells contain lipid, hence the name “lipoid nephrosis”
Describe focal segmental glomerulosclerosis (FSGS)
Proteinuria is a defining feature of FSGS
Incidence = 7 /million; increasing over recent years
Cardinal feature is progressive glomerular scarring
Early in the disease course, glomerulosclerosis is focal and segmental. With progression, more diffuse and global glomerulosclerosis develops.
What are the causes of focal segmental glomerulosclerosis (FSGS)?
EMPHASIZED***
- Heroin
- HIV
Primary
- Idiopathic disease (80%)
Secondary
- Virus-induced: HIV, CMV, EBV, Parvovirus B19
- Drug-induced: Heroin, anabolic steroies
- Family/genetic: mutations in podocyte genes
- Adaptive (hemodynamic adaptations): systemic hypertension, surgical renal ablation, aging kidney, sickle cell anemia, BMI (obesity; bodybuilding)
Describe the disease characteristics of focal segmental glomerulosclerosis (FSGS)?
- Nephrotic syndrome (or nephrotic-range proteinuria)
- Hypertension (common)
- Common in African Americans
- Variable degree of decreased renal function
- Microscopic hematuria
Describe the biopsy resutls of focal segmental glomerulosclerosis (FSGS)
- LM: Segmental sclerosis *** (this means only a SEGMENT of the glomerular capillary tuft is involved - “hyalinosis”
- IF: Mild IgM and C3 or negative
- EM: diffuse epithelial cell injury (foot process effacement)
Describe the clinical course of focal segmental glomerulosclerosis (FSGS)
- Response to steroids is variable
- Thus, differs from minimal change disease in prognosis
What are the causes of membranous glomerulopahty?
- Idiopathic (85%)
- 60% will develop “waxing and waning” proteinuria
- 15% go on to “classic nephrotic syndrome
What was EMPHASIZED about membranous glomerulopathy?
Deposition of Ag-Ab complexes
What will you see on renal biopsy of membranous glomerulopathy?
* KNOW THIS*
- LM: thickened capillary walls; “spikes” on silver stain
- IF: granular IgG and C3 along the GBM
- EM: subEPITHELIAL deposits
** KNOW subepithelial and NOT subendothelial ***
What type of antibody can be detected via IF in membranous glomerulopathy?
IgG *****
No other type
Describe Membranoproliferative glomerulonephritis (MPGN)?
DO NOT CONFUSE WITH MEMBRANOUS GLOMERULOPATHY
Usually nephrotic syndrome with a nephritic component (hematuria)
Describe the disease process of MPGN
- slowly progressive course
- steroids and immunosuppressive agents NOT effective
- 50% progress to chronic renal failure within 10 yrs
Describe the etiology of MPGN
Can be idiopathic or 2º to chronic immune diseases
What is the basic pathology of MPGN
Mesangial hypercellularity
PLUS
Capillary wall remodeling (with the formation of double contours)
What do we see in type 1 and type 2 MPGN?
Type 1 MPGN
- SubENDOthelial deposits
Type 2 MPGN
- Intramembranous deposits
**Predominant mesangial involvement ** KNOW THIS
Describe the pathology of MPGN
- thickening of the GBM (membrano) and proliferative mesangial cells
- reduplication (“splitting”) of the GBM (“tram tracks”)
What are the two types of MPGN?
- Type I (subendothelial deposits)
- Type II (intramembranous deposits)
Describe MPGN type 1
Cause: Primary (idiopathic) or secondary to chronic immune complex disorders (SLE, Hep B, Hep C, cryoglobulinemia, endocarditis, CLL/lymphoma)
Not important
Describe the biopsy findings of MPGN type 1
Pathology
- LM: “tram tracks” (on silver stain) ** KNOW TRAIN TRACKS*
- IF: granular C3 (and often with IgG)
- EM: subendothelial and mesangial deposits (mesangial interpositioning between endothelial cells and GBM)
This is SUBENDOTHELIAL, NOT subepithelial ***
Describe MPGN type 2
- 70% have C3 nephritic factor (C3NeF; an autoantibody which stabilizes C3 convertase, protecting it from enzymatic degradation)
- therefore, persistent C3 activation and consumption, causing hypocomplementemia
- *****low serum C3 !!!
Describe the pathology seen in renal biopsy of MPGN type 2
Pathology
- LM: “tram track” (on silver stain)
- IF: C3 only
- EM: Intramembrane deposit, lamina densa - electron dense material (“dense deposit”)
What are the features of nephritic syndrome?
- Patient complains of dark colored urine
- Microscopic analysis of the urine will show erythrocytes in urine
- The patient may also have renal failure (increase in serum creatinine and blood urea nitrogen/BUN_ in which case this is called ACUTE nephritic syndrome
What are the two conditions that cause acute nephritic syndromes?
- Diffuse proliferative glomerulonephritis
- Crescentic glomerulonephritis
Both of the above are NOT diseases per se, but descriptive pathological changes. There are each associated with specific diseases.
What are the causes of diffuse proliferative GN?
Acute post-strep GN
What are the causes of crescentic GN?
1 - Goodpasture’s disease
2 - Lupus nephritis
3 - ANCA-associated diseases
Describe acute glomerulonephritis
Hematuria, azotemia, oliguria, in children after a latent period of 1-3 weeks following a strep infection
Old term: POST-STREPTOCOCCAL
New term: POST-INFECTIOUS
Can be from Staph, Pneumococcus, Meningococcus, viruses (Hep B & C, mumps, HIV, varicella, EBV), and parasites (malaria, toxo)
95% full recovery
Describe acute post-streptococcal GN
- Affects children
- History of respiratory infection 2 weeks prior
- Only certain “nephitogenic” strains of beta hemolytic streptococci cause this
- Acute nephritic syndrome
- Renal failure (usually moderate)
- Hypertension
- **LOW complement 3 levels (C3) **
- ASO titer serially elevated
Just remember that the C3 levels in the serum are low because they are all accumulating in the kidney
Describe the pathological findings on renal biopsy of post-strep GN
- LM: diffuse proliferative GN with neutrophils (KNOW NEUTROPHILS ***)
IF: scattered granular (“starry sky”) IgG, IgM, and C3 along GBM and in the mesangium
EM: subepithelial “humps” IgG, IgM, C3 along GBM FOCALLY (KNOW subEPIthelial ***)
Descrie diffuse proliferative glomerulonephritis
- Endocapillary proliferation
- Note glomerulus suffused with inflammatory cells occluding capillary loops
Describe acute post-strep GN on pathology slides
- Enlarged, hypercelluar glomeruli with endothelial and mesangial cell proliferation
- IgG and C3 irregularly distributed along the basement membrane (“starry sky”) and in the mesangium***
What do you need to remember about post-infectious glomerulonephritis?
Post-infectious glomerulonephritis: subepithelial “humps” as well as mesangial and subendothelial deposits.
What is crescentic glomerulonephritis?
- Crescentic glomerulonephritis is a form of glomerular disease in which glomerular crescents are formed
- Crescents cause severe glomerular injury
- Severe renal failure and death can result if untreated
What will you see on slides of crescentic glomerulonephritis?
- Cellular crescentic proliferation of cells lining the Bowman’s space
- Compressed capillary loops
What fills the “cresentic” shape?
- Anti-GBM Ab
- ICs
- Anti-PMN Ab
What are the components of the crescents in crescentic GN?
- Plasma constituents into Bowman’s space, including coagulation factors and inflammatory mediators
- Fibrin forms and there is then proliferation of epithelial cells from the parietal wall of Bowman’s capsule, as well as influx of monocytes/ macrophages, resulting in crescent formation.
What will you see in type 1 (Goodpasture disease)?
- Linear “cigarette smoke” appearance
- Capillary loops outlined by linear anti-basement membrane antibodies
What will you see in type 2 (lupus)?
- Lumpy bumpy granular appearance
- Capillary loops are outlined by granular immune complex deposits
Describe anti-GBM disease (Goodpasture disease)
It is an anti-glomerular basement membrane antibody disease
- It is an autoimmune disease characterized by abnormal production of antibodies directed against Collagen IV (which constitutes the basement membrane of the glomerulus, lung, etc.)
- This results in vasculitis, especially in the lung and kidney, causing the pulmonary-renal syndrome
- Causes crescentif GN in the kidney
- Serum anti-GBM antibody level will be elevated
- Needs to be treated with high dose of steroids, cytotoxic agents and PLASMAPHERESIS***
What causes crescentic glomerulonephritis due to immune complex disease?
- Lupus nephritis
- IgA nephropathy/Henoch-Schonlein purpura
Describe pauci-immune crescentic GN (ANCA associated GN)
- A group of vasculitic disorders especially affecting small vessels (i.e. small arteries, capillaries, arterioles, veins, etc.)
- Can cause the pulmonary-renal syndrome
- Often associated with Anti-Neutrophil Cytoplasmic Antibody (ANCA)
- Immune deposits in glomeruli are either absent or minimal
- A classic example is Wegener’s granulomatosis
What was EMPHASIZED about rapidly progressive glomerulonephritis (RPGN)?
- It is a CLINICAL definition, NOT a specific pathologic one
- It is MOST associated with crescentic GN ***
What do you NEED to review and focus on for the exam questions?
Review
- Cartoons of histology
- Focus on LM, IF, and EM *****
- Pay attention to the process of the podocytes
- Know where the immune complex or antibody is (subepithelial or subendothelial *****)
