Path: Histopath Flashcards
Triad in nephrotic syndrome
oedema
proteinuria (>3g/24h)
hypoalbuminaemia (<30g/L)
What are features seen in nephrotic syndrome aside from the triad?
hyperlipidaemia
thrombotic disease
buzzwords for nephrotic syndrome in SBAs
swelling (classically periorbital in children)
frothy urine (occurs due to proteinuria)
Primary causes of nephrotic syndrome
Minimal change disease
membranous glomerular disease
focal segmental glomerulosclerosis
secondary causes of nephrotic syndrome
Diabetes mellitus
Amyloidosis
SLE
Diagnosis of nephrotic syndrome
urine dip (proteinuria; no haematuria)
urine PCR (>300 mg/mmol)
serum albumin - low
total cholesterol - high
immunoglobulins - low
renal biopsy - diagnostic investigation of choice in adults (avoided in children)
What is minimal change disease?
a cause of nephrotic syndrome
most common cause of nephrotic syndrome in children
no changes are seen on light microscopy; on electron microscopy loss of podocyte foot processes is seen.
responds well to steroids
no immune deposits
associated with eczema and asthma
recent allergic reaction is a possible trigger
How is minimal change disease managed?
1st line: steroids (90% respond)
2nd line: cyclosporine (calcineurin inhibitor)
epidemiology of minimal change disease
children (75%)
second peak in elderly
histological changes in minimal change disease
no changes on light microscopy
loss of podocyte foot processes on EM
no immune complex deposition (immunofluorescence)
Prognosis of minimal change disease
good prognosis
5% ESRF
triggers for minimal change disease
Often idiopathic
Secondary causes (rare)
- Immune stimulus (e.g., infection, immunization, allergic reaction)
- Tumors (e.g., Hodgkin lymphoma)
- Certain drugs (e.g., NSAIDs)
In what demographic is FSGS most common?
most common in afro-caribbean/afro-american/hispanic
Common in adults (30%)
What can be seen on histology in FSGS?
LM:
- focal and segmental glomerular consolidation and scarring
- hyalinosis (hyaline deposits)
EM:
- loss of podocyte foot processes
FSGS
focal segmental glomerulosclerosis
What part of the nephron can be affected by disease processes?
- glomeruli
- tubules & interstitium
- blood vessels
response rate to steroids in FSGS?
50%
prognosis of FSGS
50% have ESRF in 10 years
Management of FSGS
- steroids
- plus immunosuppressants if needed (e.g. calcineurin inhibitors second line - cyclosporine, tacrolimus)
ACEi or ARB to control BP
-> ESRF if left untreated
Causes of FSGS
mostly primary idiopathic
can be secondary to:
- obesity
- HIV
- drugs (lithium, heroin)
- lymphoma
Do you see immune deposits in FSGS?
no
What cause of primary nephrotic syndrome has immune deposits?
membranous glomerular disease
-> immune complex deposits along entire GBM
membranous glomerular disease - does it respond to steroids?
poor response
What histological findings are seen in membranous glomerular disease?
LM: diffuse glomerular BM thickening
EM: loss of podocyte foot processes; sub epithelial deposits = ‘spikey’
In what pattern are immune deposits seen in membranous glomerular disease?
immune complex deposits along entire GBM
Prognosis if membranous glomerular disease
40% ESRF after 2-20 years
Management of membranous glomerular disease
ACEi or ARB to control BP
steroids (often poor response)
other immunosuppressants e.g. cyclophosphamide in severe disease
Causes of membranous glomerular disease
Primary: anti-phospholipase A2 antibodies (present in `75%)
Secondary: SLE, infection(HBV, HCV, malaria, syphilis), drugs (NSAIDs, penicillamine, gold), malignancy (lung, prostate)
Differentials for asymptomatic haematuria
thin basement membrane disease (benign familial haematuria)
IgA nephropathy (Berger’s disease)
Alport Syndrome (would be seen in children?)
Differentials for asymptomatic haematuria
thin basement membrane disease (benign familial haematuria)
IgA nephropathy (Berger’s disease)
Alport Syndrome (would be seen in children?)
How can you differentiate thin basement membrane disease and IgA nephropathy?
difficult!!!
IgA: more likely to cause frank haematuria; more common in asian population; more likely to cause changes in renal function (raised Cr)
what anitbody is seen in myasthenia gravis?
Anti-ACh-receptor antibody
What antibodies are seen in pernicious anaemia?
anti-parietal cell antibodies (90%)
anti-IF antibodies (intrinsic factor) - (50%)
antibodies in limited cutaneous scleroderma?
anti-centromere
Histological findings in nephrotic syndrome secondary to diabetes mellitus
diffuse glomerular basement membrane thickening
mesangial matrix nodules (aka Kimmelstiel Wilson nodules)
When do you see Kimmelstiel Wilson nodules
diabetic kidney disease
-> pathognomonic
Ddx in diffuse glomerular basement membrane thickening and nephrotic syndrome
membranous glomerular disease
diabetic kidney disease
in DM KD you also see: kimmelstiel Wilson nodules (mesangial matrix nodules, hyaline deposits)
What are Kimmelstiel-Wilson nodules?
seen in Diabetic nephropathy on microscopy of renal tissue
mesangial thickening due to nodular, hyaline deposits within the glomerulus.
how does diabetic nephropathy first present ?
microalbuminuria
demographic for diabetic nephropathy
classically found in asians
Histology of nephrotic syndrome caused by amyloidosis
apple green birefringence with Congo-red stain
AA vs AL amyloidosis
AA: acute phase protein - associated with chronic inflammation e.g. RA, chronic infections (TB)
AL: light chains - most commonly due to multiple myeloma
What is the most common presentation of amyloidosis?
nephrotic syndrome
(=secondary cause of NS due to amyloid deposits)
What is amyloidosis?
a multisystem d/o
caused by deposition of misfiled amyloid proteins as amyloid fibrils in tissues
this disrupts the normal function of these tissues
Features of amyloidosis
Caused by amyloid deposits in different parts of the body
Kidneys: nephrotic syndrome
Heart: restrictive cardiomyopathy, conduction defects, heart failure, cardiomegaly
Liver/spleen: hepato/splenomegaly
Macroglossia in 10%
neuropathies incl. carpal tunnel syndrome
Histopath in amyloidosis
apple green birefringence with Congo red stain under polarised light
remember: Amy ate a green apple with her Congo red hair
What is ATN?
damage to tubular epithelial cells
What is the commonest intrinsic/renal cause of AKI?
ATN
Commonest causes of CKD in the UK
- Diabetes (20%)
- glomerulonephritis (15%)
- HTN and vascular disease (15%)
- reflux nephropathy (chronic pyelonephritis) (10%)
- Polycystic kidney disease (9%)
What part of the nephron is affected in ATN?
tubules
icshemic: The straight segment of the proximal tubule and the straight segment of the distal tubule (i.e., the thick ascending limb) are particularly susceptible to ischemic damage
toxic: The convoluted segment of the proximal tubule is particularly susceptible to damage from toxins.
What are the causes of ATN?
ishaemia
toxins
Pathophysiology of ATN
damage to tubular cells → necrotic proximal tubular cells (casts) fall into the tubular lumen → debris obstructs tubules → reduced flow and increased haemodynamic pressure in nephron → reduced pressure gradient across BM → decreased GFR and acute renal failure
tubular glomerular feedback reduces the BS to kidneys further.
Which nephrotoxins can cause ATN?
NSAIDs
aminoglycosides
cisplatin
radiographic contrast agents
myoglobin (secondary to rhabdomyolysis)
haemoglobinuria
amphotericin
lead
ethylene glycol
Blood findings in ATN?
azotemia
hyperkalemia
metabolic acidosis
urine sodium in ATN?
high
> 40 mmol/L
urine osmolality in ATN
<350 mOsm/kg
What is the most common type of amyloidosis?
primary (AL) amyloidosis
What are the different types of amyloidosis?
- primary (AL)
- secondary (AA)
- haemodialysis associated (Abeta2M)
- familial amyloidosis
What organs can be affected by amyloidosis most commonly and what is the result?
- Kidneys (nephrotic syndrome is the commonest presentation)
- heart (restrictive cardiomyopathy, conductive defects, heart failure, cardiomegaly)
- liver/spleen (hepato/splenomegaly)
- tongue (macroglossia in 10%)
- neuropathies (incl. carpal tunnel syndrome)
-> remember 5
Kidneys are most commonly affected (nephrotic syndrome), amyloidosis is a restrictive (CM) disease, due to the plaques it is hard to conduct and the heart fails and becomes big, the car goes through tunnels and people with amyloidosis have to talk about it a lot so they get a big tongue.
How do you manage amyloidosis?
chemotherapy with melphalan and corticosteroids
also depends on the type and is managed by specialists
What is the pathological hallmark of sarcoidosis?
granulomas (non-caseating)
How can sarcoidosis affect the heart?
It can affect the…
- epicardium -> pericarditis
- myocardium -> heart failure
- endocardium -> valvular lesions
can cause dysrhythmias, conduction defects
What is the underlying pathology in amyloidosis?
it is a multisystem disorder caused by extracellular aggregation and deposition of amyloid in various organs.
these are misfolded proteins.
name 2 types of amyloid proteins seen in amyloidosis
beta pleated sheet structure
resistant to enzyme degradation
What is amyloid?
insoluble protein/protein fragments
localised vs systemic amyloidosis
localised affects a single organ
What is the commonest form of amyloidosis?
light chain (AL) amyloidosis
What is deposited in AL amyloidosis?
Ig light chains
most associated with MM, but some may not have MM
What are bence jones proteins and when are they seen>
seen in MM / AL amyloidosis / Waldenstroem’s macroglobulinaemia
monoclonal Ig light chain found in the urine
What causes AA amyloidosis?
buildup of serum amuloid A (acute phase protein)
-> therefore this form of amyloidosis is seen in chronic infections/inflammation
What diseases is AA amyloidosis associated with/
AA - secondary Amyloidosis associated with chronic inflammation/infection and deposit of A-SAA (acute phase serum amyloid A)
AID - RA, ankylosing spondylitis, IBD
infections - TB, osteomyelitis, IVDU (skin infections)
Non-immune - renal cell carcinoma, Hodgkin’s
Pathophysiology of haemodialysis associated amyloidosis
in haemodialysis you get accumulation of beta 2 microglobulin (becuase it cannot cross the dialysis membrane)
usually occurs in someone with longstanding CRF, esp if on peritoneal dialysis
associated with articular depositions and carpal tunnel syndrome
Familial amyloidosis
ATTR
mutated transthyretin deposition (it is a protein made in the liver)
in the MedEd guide they mention something about AR (FMF) being the commonest one.
how do you diagnose amyloidosis?
tissue biopsy -> congo red stain under polarised light should show apple green birefringence.
Management of FMF
colchicine (inhibits granulocyte function; prevents acute episodes and progression to AA amyloidosis)
What vessles are in the portal triad?
hepatic portal vein
hepatic artery
bile duct
Which liver enzyme may be raised post MI?
aspartate aminotransferase (AST)
Name of criteria for dx of infective endocarditis
modified Duke criteria
Troisier sign
palpable LN in the L supraclavicular fossa
palpable LN in the L supraclavicular fossa - name of this sign
Troisier
