Glomerular Diseases Flashcards
Renal disease is divided into diseases of?
- glomeruli
- tubules
- interstitium
- vessels
Glomerular diseases are caused mainly by?
immunologically mediated
Tubular and interstitial disorders are often due to?
toxins or infections
How do glomerular and tubular diseases affect each other?
- glomerular disease impairs the tubular blood supply and increases tubular toxins
- tubular disease causes increased intraglomerular pressure
Describe how vascular disorders affect glomerular function?
decreases the amount of filtrate
What is Azotemia?
Increased serum BUN (blood urea nitrogen) and creatinine, due to reduced glomerular filtration rate
- causes are pre-renal, renal and post-renal
What is uremia?
Azotemia plus clinical signs/symptoms
- gastroenteritis, peripheral neuropathy,
fibrinous pericarditis
What is acute renal failure?
Abrupt anuria or oliguria with rapidly progressive azotemia identified by increase in BUN or ammonia
- urine output < 400 ml/24 hr
What are the causes of acute renal failure?
- Vascular obstruction (polyarteritis nodosa, malignant hypertension, hemolytic-uremic syndrome)
- Rapidly progressive glomerulonephritis
- Acute tubular necrosis
- Acute tubulointerstitial nephritis
- Pyelonephritis with papillary necrosis
- DIC
- Urinary obstruction
What is chronic renal failure?
Azotemia progressing to uremia over a period of years
What are the stages of chronic renal failure?
- diminished renal reserve (GFR 50% normal) with normal BUN/Cr,
- renal insufficiency - azotemia, anemia, hypertension, polyuria, nocturia,
- renal failure: GFR < 20% normal, kidneys cannot regulate volume or solutes and patients develop edema, metabolic acidosis and hypocalcemia,
- end stage renal disease: GFR <5% normal, represents the end stage of various renal diseases
What is nephrotic syndrome?
Proteinuria > 3.5 g/day
- hypoalbuminemia (serum level <3 g/dl)
- hyperlipidemia
- lipiduria
- severe edema (anasarca)
What is the pathophysiology of nephrotic syndrome?
- Increased permeability to plasma proteins cause massive proteinuria, hypoalbuminemia and generalized edema (pitting, periorbital & dependent edema)
- Hyperlipidemia due to increased lipoprotein synthesis and decreased catabolism
- Lipiduria due to leakage of lipoproteins with albumin
What is nephritic syndrome?
Grossly visible hematuria, hypertension, variable proteinuria, azotemia, oliguria, edema, RBC casts
Name categories under Primary Diseases?
- Diseases associated with Nephrotic syndrome
2. Diseases associated with Nephritic syndrome
Name the diseases associated with nephrotic syndrome?
- Minimal change disease
- Focal segmental glomerulonephritis
- Membraneous glomerulonephritis
- Systemic disease (SLE, diabetes,
amyloidosis)
Name the disease associated with Nephritic syndrome?
- Acute diffuse proliferative glomerulonephritis (post-streptococcal or not)
- Rapidly progressive (crescentic) glomerulonephritis
- Membranoproliferative glomerulonephritis
Name secondary renal diseases?
Systemic lupus erythematosus (SLE), diabetes, amyloidosis, polyarteritis nodosa, Goodpasture syndrome, Wegener granulomatosis, Henoch-Schonlein purpura, bacterial endocarditis
Name hereditary glomerular diseases?
Alport syndrome, thin membrane disease, Fabry disease
What are the microscopic manifestations of kidney disease?
- hypercellularity
- basement membrane thickening
- hyalinization and sclerosis of glomeruli
Describe hypercellularity?
- cellular proliferation
- white blood cells (acute and chronic),
- crescents (white blood cells and epithelial cells)
Describe basement membrane thickening?
- highlighted by PAS stain and electron microscopy;
2. EM also shows electron-dense deposits (usually immune complexes) in or adjacent to basement membrane
What is hyalinization and sclerosis of glomeruli?
end result of glomerular damage Changes can be: - diffuse (all glomeruli) or focal; - global (entire glomerulus) - segmental (part of glomerulus) or mesangial
Describe the pathogenesis of glomerular injury?
Usually immune mediated via antibody deposition , or cell mediated injury
- Antibodies deposited are either to insitu
antigens or circulating immune complexes
Insitu antigens are?
- Intrinsic (part of the basement membrane)
- Planted antigens - deposited in basement membrane
- may be exogenous (drugs, infectious
agents) or endogenous (DNA,
immunoglobulin, immune complexes)
- may be exogenous (drugs, infectious
Circulating immune complexes are?
- endogenous (DNA, tumors)
- exogenous (infectious products)
- deposits are usually mesangial or
subendothelial, resolve by macrophage
phagocytosis
- deposits are usually mesangial or
Minimal change disease is also known as?
lipoid necrosis, nil disease, foot process disease
What is minimal change disease?
disorder where there is damage to the glomeruli
- the damage can not be seen under a regular microscope but only an electron microscope
Describe the epidemiology of minimal change disease?
Causes 80% of cases of nephrotic syndrome in children (usually ages 2-6) and 20% in adults
What are the causes of minimal change disease?
Associated with respiratory infections, immunizations, allergies, NSAID usage, acute interstitial nephritis, Hodgkin lymphoma
Describe the clinical presentation of minimal change disease?
nephrotic syndrome, selective for albumin, often with severe edema or proteinuria, but with minimal microscopic glomerular alterations and usually no hypertension, no hematuria, no azotemia
Describe the micro morphology of minimal change diseases?
- normal glomeruli
2. tubules have lipid droplets due to reabsorption of lipoproteins that leak from glomeruli (“lipoid nephrosis”)
What is seen under immunofluorescence of minimal change disease?
negative
What is seen under the electron microscope of minimal change disease?
Extensive foot process fusion; microvillous transformation of epithelial cells
Describe the treatment of minimal change disease?
90% of children respond to steriods initially (foot processes return to normal), some children become steroid dependent/resistant, but this usually resolves at puberty
- Older adults with hypertension and severe proteinuria have a higher risk of reversible renal failure
What is focal segmental glomerulosclerosis?
A histologic pattern of glomerulosclerosis (some glomeruli, part of capillary tuft) associated with heavy proteinuria
What is the clinical settings for FSGS?
HIV, IgA nephropathy, hypertension, sickle cell disease, morbid obesity, obstruction, reflux, congenital or idiopathic
Describe the epidemiology of FSGS?
Children have better prognosis than adults
What are the causes of FSGS?
May be a continuum with minimal change disease
Describe the micro morphology of FSGS?
- Segmental sclerosis, hyaline deposits and foam cells or lipoid droplets in focal glomeruli
- focal tubular atrophy with interstitial fibrosis, hyaline thickening of afferent arterioles
What is seen in the immunofluorescence of FSGS?
IgM and C3 in sclerotic segments
Describe the prevalence of HIV associated nephropathy?
10+%
- up to half or more renal biopsies show it
When is HIV associated nephropathy seen?
before AIDS
What causes HIV associated nephropathy?
anti-HIV Abs
What is the microscopic morphology seen in HIV associated nephropathy?
typical lesion is focal segmental glomerulosclerosis (FSGS)
– accompanied by characteristic collapse of capillaries
Describe the clinical presentation of HIV Associated nephropathy?
usually proteinuria, maybe severe enough to cause nephrotic syndrome
Describe the prognosis of HIV associated nephropathy?
worse in adults
- patients with HIV can have a variety of other renal problems
What is membranous glomerulonephritis?
when the small blood vessels in the glomeruli which filter wastes in the blood become damaged and thickened
- Most common cause of nephrotic syndrome in adults due to in situ immune complexes in GBM
What are the causes of membranous glomerulonephritis?
85% are idiopathic autoimmune disease
Secondary cases of membranous glomerulonephritis are associated with?
- cancer ( lung, colon, melanoma)
- hepatitis B/C, malaria
- schistosomiasis
- drugs
- SLE
- diabetes
- thyroiditis
- it causes 40% of cases in adults, 5% in
children
What is seen microscopically in membranous glomerulonephritis?
- uniform diffuse capillary wall thickening without hypercellularity and without mesangial sclerosis - narrow capillary lumina
- glomerular spikes
- Proximal convoluted tubules contain hyaline droplets, reflecting protein re-absorption
What is seen in the immunofluoresence of membranous glomerulonephritis?
granular diffuse peripheral deposits
- IgG and C3
Describe the clinical course of membranous glomerulonephritis?
insidious onset of nephrotic syndrome
- must rule out secondary causes
What is post-streptococcal glomerulonephritis?
Deposition of immune complexes from antibodies against organisms
- Aka post-infectious or acute glomerulonephritis
Post-streptococcal glomerulonephritis is associated with what conditions?
- nephritogenic strains of Streptococcus pyogenes (beta hemolytic Strep group A)
- endemic malaria, toxoplasmosis, hepatitis B/C, HIV, varicella, spirochetes
Describe post-streptococcal glomerulonephritis in children age 6-10?
- abrupt onset of hematuria, oliguria, fever, malaise and nausea 1-4 weeks after strep infection of pharynx or skin (impetigo)
- RBC casts, proteinuria, periorbital edema, hypertension
- 95% recover and 1% develop RPGN - poor prognosis
Describe PSG in sdults?
- May have atypical presentation with sudden hypertension, edema, elevated BUN;
- 60% recover, others develop rapidly progressive glomerulonephritis
What is seen in laboratory tests for PSG?
- anti-streptococcal antibody titers
2. low C3 (due to consumption)
What is seen microscopically in PSG?
glomeruli - globally and diffusely enlarged and hypercellular due to neutrophils and macrophages
What is seen in immunofluoresence of PSG?
- lumpy-bumpy (granular) deposition of IgG
2. IgM and C3 in peripheral glomerular loops
What is seen under the electron microscope of PSG?
Subepithelial humps (immune complex deposits)
What is membranoproliferative glomerulonephritis?
- Alterations in basement membrane and proliferation of mesangial cells
- Presents with nephritic and nephrotic syndrome and hypertension
- intermittent remissions
- Aka lobular or mesangio-capillary glomerulonephritis
Describe the epidemiology of membranoproliferative glomerulonephritis?
5% of cases of GN affecting children and young adults
What is seen microscopically in membranoproliferative glomerulonephritis?
- irregular thickening of glomerular basement membrane by interposition of mesangial cells between endothelium and basement membrane
- causing tram track/double contour appearance
- large glomeruli, lobules are accentuated; neutrophils often present
What is seen under an electron microscope for membranoproliferative glomerulonephritis?
dense deposits in endothelium and mesangium cause large glomeruli with lobular accentuation
What is rapidly progressive (crescentic) glomerulonephritis?
Crescents are end result of damage to glomerular basement membrane or Bowman’s capsule
- due to deposition of fibrin and inflammatory cells
- Crescents affect 50% of glomerular circumference, 70% of glomeruli
What causes Rapidly progressive (crescentic) glomerulonephritis?
Rapid, usually irreversible loss of renal function associated with severe oliguria, unresponsive to steroids
- Symptoms of nephritic syndrome, nephrotic syndrome and renal failure
What is the gross anatomy of crescent glomerulonephritis?
enlarged, pale kidneys with cortical petechial hemorrhages
Describe the micro anatomy of crescent glomerulonephritis?
Crescents in glomeruli are proliferation of parietal epithelium of Bowman capsule with macrophages, neutrophils, lymphocytes, fibrin, collagen
What is seen under an electron microscope of crescent glomerulonephritis?
wrinkling and focal disruptions in glomerular basement membrane
What is IgA nephropathy?
Describe the epidemiology of IgA nephropathy?
- Most common glomerular disease worldwide
2. Common in children and young adults, who present with hematuria after respiratory infection
Describe the characteristics of IgAnephropathy?
- Slowly progressive: 25%-50% have renal
failure at 20 years - high serum IgA
Name the secondary diseases IgA nephropathy is associated with?
- gluten enteropathy
2. liver disease
State the poor prognostic features of IgA nephropathy?
prominent arteriolar hyalinization, older age, heavy proteinuria, hypertension
Describe the micro anatomy of IgA nephropathy?
normal or hypercellular glomeruli
What is seen under the immunofluorescence of IgA nephropathy?
IgA and C3 in mesangium
What is seen under the electron microscope of IgA nephropathy?
electron-dense deposits in mesangium
What is diabetic nephropathy?
kidney damage that results from having diabetes
- End stage renal disease in 30% of type I
What causes diabetic nephropathy?
glomerular disease, arteriolar sclerosis, pyelonephritis & papillary necrosis
- causes 20% of deaths in those younger than age 40
Describe characteristics of diabetic nephropathy?
- Proteinuria occurs in 50%
- Early increased GFR and microalbuminemia are predictive of future diabetic nephropathy
- Tight diabetic control reduced renal disease
Describe the microscopic anatomy of diabetic nephropathy?
- Basement membrane thickening and increased mesangial matrix, in ALL patients.
- Diffuse glomerulosclerosis - increase in mesangial matrix, basement membrane thickening and obliteration of capillary loops
- Nodular lesions – aka Kimmelstiel-Wilson nodules; - ovoid, spherical, laminated hyaline masses in peripheral of glomerulus - eventually obliterate glomerular tuft
- Hyalinization of afferent arterioles (hyaline arteriolosclerosis) - specific for diabetes
Describe the microscopic anatomy of diabetic nephropathy?
- Basement membrane thickening and increased mesangial matrix, in ALL patients.
- Diffuse glomerulosclerosis - increase in mesangial matrix, basement membrane thickening and obliteration of capillary loops
- Nodular lesions – aka Kimmelstiel-Wilson nodules; - ovoid, spherical, laminated hyaline masses in peripheral of glomerulus - eventually obliterate glomerular tuft
- Hyalinization of afferent arterioles (hyaline arteriolosclerosis) - specific for diabetes
What is chronic glomerulonephritis?
end stage disease due to progression of various types of glomerulonephritis,
- occasionally there is no prior history of kidney disease
- Paradoxically, nephrotic syndrome decreases as glomeruli disappear
Name the kidney diseases that lead to chronic glomerulonephritis?
- rapidly progressive (90%)
- focal segmental glomerulosclerosis (50-80%)
- membranous GN (50%),
- membranoproliferative (50%)
- IgA nephropathy (30-50%) (slow)
- Poststreptococcal
- others
Describe the gross anatomy of chronic glomerulonephritis?
symmetrically small kidneys with thin granular cortex and increased peripelvic fat
Describe the micro anatomy of chronic glomerulonephritis?
glomerulosclerosis, arterial and arteriolar sclerosis, tubular atrophy & interstitial fibrosis (thyroidisation of tubules), lymphocytes
