Glomerular disease 1 Flashcards
what tests do we do when get a kidney biopsy?
3 tests :
Immunofluorescence microscopy : i add antibodies for whatever protein i suspect in is in the biopsy ( for example if i suspect theres igG i add igG antibody )
Light microscopy ( LM ) : view the kidney in 4 diff stains
Electron microscopy ( EM ) : highlight features of glomerulus
why PCT cells are very eosinophilic and big?
most of absorption happen here so we need strong cells
what are the stains we use light microscopy ?
4 stains
H&E ( hemotaxylin and eosin ) stain
PAS stain ( Periodic acid-schiff )
Masson trichrome stain
Silver stain
describe H and E stain?
Hematoxylin and eosin stains
classic stain
we see inside the glomerulus :
Red circles = RBCS cuz we are in the lumen of capillaries so we see RBCS
between the capillaries lumens of the glomerulus ( tuft of capillaries ) we see pinkish area with large purple nuclei —> these are mesangium cells and its normal between the capillaries 2-3 MAX cells and shouldnt exceed that
we also see THIN capillary walls ( should be thin for filtration )
describe PAS stain?
periodic acid shiff stain
We use to to detect 2 things :
Thickness of capillary wall
Mesangium proliferation
so if u suspect thickness of capillary or proliferation of mesangium it can be seen with PAS stain
describe masson trichrome stain?
used to detect fibrous tissue ( also used in liver fibrosis )
so we use it if we suspect FIBROSIS IN GLOMERULUS
it gives blue color
BUT normally we have some fibrous tissue ( Mesangium )
but if u see a lot of blue obliterating = glomerulus fibrosis
describe silver stain?
uses to assess the thickness of wall of capillary
thickness of basement membrane or thickness glomerular wall ( both are the same )
what are 3 features of glomerular disease ?
Hyper-cellularity
Thickness of basement membrane
Hyalinosis and sclerosis
describe hyper-cellularity ?
We have 4 cells in the glomerulus :
Endothelial, mesangial, podocyte and parietal
so hyper cellularity will include those
Increased number of cells in the glomerulus
1- proliferation of mesengial or endothelial cells ( CAPILLARY LUMEN STILL PATENT )
2- Leukocyte infiltration ( neutrophils, monocytes, lymphcytes invade the capillary lumen )
3- Proliferation of parietal epithelial cells
4- Proliferation and hypertrophy of PODOCYTES
when do we call it endocapillary proliferation ?
when we have 1 + 2
Proliferation of mesangial and endothelial cells
+
Leukocyte infiltration ( neutrophils, monocytes, lymphocytes )
in this case the lumen will be closed and absent in the microscope
cuz mseangial cells and endothelial cells are big now + neutrophils infiltration
what happens when parietal epithelial cell proliferate?
Basement membrane rupture
then fibrin starts leaking through it
FORMS CRESCENT
what happens when podocyte proliferate and hypertrophy ?
podocytes sit on top of the capillary
Proliferation and hypertrophy of the podocyte = COLLAPSE OF THE CAPILLARY LOOP
What causes thickening of basement membrane (2nd feature of glomerular disease )
Deposition of immune complexes (Antigen+ antibody ) –> could be under it , on it , in it
Thickening of Basement membrane proper (itself )
Formation of additional layers of basement membrane
we use PAS, sliver stains to see it via light microscopy
describe hyalinosis and sclerosis in glomerulus ?
Hyalinosis : any change that gives a glassy reddish appearance which can indicate protein deposition
Sclerosis : Hardening but in kidney means FIBROSIS , also indicate proteins
both give us reddish eosinophilic look due to accumulation of homogenous eosinophilic substances
how do differentiate between hyalinosis and sclerosis ?
since both give us reddish eosinophilic appearance we use mason trichrome stain
if its sclerosis it will give us blue color under trichrome stain
whats the result of hyalonisis and sclerosis ?
can lead to :
Obliteration of capillary lumen glomerular tuft
why do always care about patency of capillary lumen?
cuz if its gone = no more blood = no more filtration = no more kidney function
what are the further subdivision of the pathological changes ( hyper-cellularity , Thickening, hyanolisis/sclerosis )?
Diffuse —> involve more than 50% of the glomeruli
Focal —> Involves less than 50% of glomeruli (opposite to diffuse)
Global —> involve all parts of the glomeruli
Segmental —> involve only a part of the glomeruli
Mesangial —> Affecting predominantly the mesangial region
what is membranous change?
pathological change where the glomerular wall is thickened
what is membranoproliferative change?
Pathological change where the glomerular wall is thickened
+
Endocapillary filtration
what is the cause of both nephrotic and nephritic issues?
immune problems
what are the types of immune problems seen?
antibody mediated injury
Cell mediated immune injury
Activation of alternative complement pathway
what are the types of antibody mediated injury?
In-situ immune complex deposition ( immune complex forms and deposit in the glomeruli )
Circulating immune complex deposition ( immune complex was circulating in the blood then got deposited in glomeruli )
what are types of in situ immune complex deposition?
Fixed intrinsic tissue antigen ( antigen is part of normal glomeruli )
Planted antigens (antigen was introduced to the glomeruli then it rested there and formed complex )
what are the examples of in-situ fixed intrinsic tissue antigen ?
NC1 domain of type 4 collagen antigen
PLA2R antigen
Mesangial antigens
Others
Describe NC1 domain type 4 collagen antigen disease ?
Disease name = anti GMB nephritis ( cuz the antigen is along the entire membrane )
Antigen name : Non collagenous domain (NC1) of alpha 3 chain of collagen type 4
antigen is found on the glomerular basement membrane ( found in a linear pattern in the membrane )
Antibodies will come and bind to it FORMING A DIFFUSE LINEAR PATTERN ( seen as a green lingeage line in IF) –>IMP THIS IS THE ONLY PATHOLOGY THAT SHOWS THIS
the antibody will destroy the glomerulus and patient will present with HEMATURIA
The antibody will also go and attack the MEMBRANE OF ALVEOLI = HEMOPTYSIS ( bleeding cough ) —> CALLED GOOD PASTRUE SYNDROME
describe PLA2R antigen disease ?
Disease name : Membranous glomerulopathy
Antigen = M type phospholipase A2 receptors ( PLA2R )
antigen is found on the epithelial cells membrane —> UNDER PODOCYTES
antibody will bind to it —->
DAMAGE GLOMERULAR + INCREASES THE THICKNESS OF THE MEMBRANE —-> called membrane glomeruopathy (increases thickness cuz it binds under the podocyte n pushes it upward–>increases thickness )
it will form granular sub-epithelial pattern under IF
what are the examples of in-situ planted antigens ?
Exogenous : infectious agents, drugs
Endogenous : DNA, nuclear proteins, igs, immune complexes, igA
these are introduced in the kidney, rest in the glomeruli’s then form complexes in the glomeruli
the antibody will bind to the antigen in granular pattern —-> GRANULAR PATTERN UNDER IF
what are the examples of circulating immune complex deposition ?
these complexes circulate in the blood then come and deposit in the glomeruli
Endogenous antigens : DNA, tumor antigens
Exogenous antigens : Infectious products
in circulating immune complex deposition, why does the immune complex prefer to deposit in the glomeruli even thought it was formed in blood and could have deposited anywhere?
we dont know but there are factors that contribute to this:
1- the glomerulus basement membrane charge is NEGATIVE —> SO the immune complex has to be POSITIVE in order to easily deposit in glomeruli , if it was negative it would get repulsed
2- If it is negative charged w m3nda eno it want to deposit in the glomeruli where would it deposit ? ENDOTHELIAL , the only place where a negative charge immune complex can deposit in glomeruli is the ENDOTHELIAL ( cant go past the it and move to basement )
3- Size, the smaller the immune complex the further it can go deep ( smaller complex indicates less immunoglobulins around it therefore escapes the immune system destruction )
if the one complex is deposited in the endothelial ( could be + or - ) and another is deposited under podocyte ( its only - that can reach this deep ), which one is more likely to attract neutrophils and cause endocapillary proliferation?
the one in the endothelium
Cuz its closer to the blood and closer to the WBCs in the blood
what can you expect the microscopic features of Acute proliferative glomerulonephritis ?
proliferative means
Endocapillary proliferation only
means immune complex is only endothelial ( Doesnt reach membrane or podocyte ) ( could be - or + )
means proliferation of endothelium, mesangial ,+ NEUTROPHILS
what do you expect the microscopic features of membrano glomerulonephritis ?
membrano glomerulonephritis means
membrane thickening
which means the immune complex reached far beyond the epithelium and now is in under the podocyte which led to the thickness ( only negative immune complexes can reach this far )
what do you expect the microscopic features of membrano proliferative glomerunephritis ?
means both thickening and endocapillary proliferation
where is the immune complex deposited ?
describe complement activation in glomerular disease ?
activation of alternative complement pathway
these ppl have autoantibody called C3 nephritic factor
Which binds to an enzyme making it more available to keep on breaking down C3
it skips C1 and C2 and imme go C3 and activate it then break it down —> persistent C3 degradation and hypocomplementemia
the broken C3 build up and deposit in the glomeruli
IF U DO IF on these PPL YOU ONLY FIND C3 and C2,C1
Dense deposit disease = C3 GN = membranoproliferative glomerulonephritis (MPGN ) type 2
What happens in epithelial cell injury glomerular disease ?
Podocytopathy :
Disease with different etiologies whos principal manifestation is injury to podocytes
Changes in visceral epithelial cells ( podocyte ) include :
Effacement of foot process —> disappearance of foot process
straight up detachment of cells from the GBM
you cant see effacement of foot process by LM so you need to use electron microscopy –> so its called minimal change disease
what happens if you lose foot processes ?
proteinuria
foot processes are one of the most imp factors that gives the membrane its selective permeability without it = protein escapes = proteinuria
describe ANCA cell injury in glomerular disease?
ANCA = anti neutrophilic cytoplasmic antibodies
these antibodies are directed against intra-cellular contents of neutrophil
these antibodies will target specific granules in the leukocytes
BUT
instead of destroying them, it will activate the leukocyte
ANCAs will activate neutrophils
then
Activated neutrophils cause endothelial cell injury
ANCA titers n disease activity
what are some ANCA antibodies ?
anti-proteinase 3 ANCA ( PR3-ANCA )
anti-myeloperoxidase ANC ( MPO-ANCA)
describe anti-proteinase 3 ANCA ( PR3-ANCA )?
its directed against PR3 ( antigen, component of neutrophil )
once it the antibody binds to the antigen it stains the THE CYTOPLASM of the neutrophils —-> its called CYTOPLASMIC ANCA
PR3 –> Rhymes with C = cytoplasmic
describe anti-myeloperoxidase ANC ( MPO-ANCA )?
the antigen is myeloperoxidase
usually found surrounding the nuclei
so when we stain it will be around the nuclei
so we call it PERINUCLEAR ANCA
MPO-ANCA —> PPPP perinuclear
describe nephron loss injury in Glomerular disease?
whenever GFR is reduced to 30-50% of normal you cannot stop it , its end stage renal disease why?
if you have 10 glomeruli and you lose 3 due to a disease
then the blood weight of the 3 lost glomeruli will be moved to the remaining 7
this will cause hypertension of the glomerulus
this hypertension will push proteins to the glomeruli = HYALINOSIS and SCLEROSIS
this will make you lose 2 nephrons and then the same happens until khalas its over
whats the main cause of nephron loss?
Glomerulosclerosis –>
Focal segmental glomerulosclerosis which can happen a disease by itself or problem in adaptation ( maladaptation)
what is nephritic syndrome?
Acute :
Oliguria ( low urine output )
Hematuria ( grossly or microspcic )
Hypertension
Mild proteinuria
what causes oliguria?
decreased GFR = Obliterated capillary lumen
what causes obliterated capillary lumen?
1- ENDOCAPILLARY PROLIFERATION
2- Crescents ( proliferation of parietal cells )
in cases of endocapillary proliferation wheres the immune complex will be found? ENDOTHELIUM
So in nephritic syndrome = immune complex is is in the subendothelium/mesangium
what does hematuria indicates?
Damage to glomerulus
how does hypertension happen?
capillary lumen are obliterated = less filtrate = increased plasma volume
+
Renin = salt and water retention
why do we have red cell casts?
red cell casts indicate that site of injury is at glomerular level
So when blood passes through the ducts
it assumes the shape of the duct
if the injury was below glomerular lvl , we will see normal RBCS
what is acute proliferative post-streptococcal/post-infectious glomerulonephritis ?
Acute = acute
Proliferative = endocapillary proliferation ( endothelial, mesangial, neutrophils )
Post-streptcoccal/post infection = after strept or infections
Glomerulonephritis = inflammation = neutrophils
what causes acute proliferative post-streptococcal/post-infectious glomerulonephritis ?
1 to 4 weeks after
PHARYNX
or
SKIN ( only no other sites )
infections with nephritogenic strains of group A,B hemolytic streptococci
antigens are :
Streptococcal pyogenic exotoxin B ( SpeB )
Streptococcal glyceraldehyde-3-phosphate dehydrogenase ( GAPDH )= nephritis associated plasmin receptor ( NAPlr)
What is the location of the immune complex deposition ?
ENDOTHELIAL ( SUB-ENDOTHELIAL )
THEN AFTERWARDS AT THE END IT, they will migrate to across glomerular basement membrane to be at :
SUB-EPITHELIAL ( BELOW PODOCYTES)
before it migrates to sub-epithelial, they are subendothelial and they produce abscess there and form immune complexes and initiates inflammation there
what you will find in the serology of acute proliferative post-streptococcal/post-infectious glomerulonephritis patient?
LOW level of serum complements ( cuz they move to the glomeruli cuz theres inflammation there )—> YOU WILL FIND ALL 3, C1,C2,C3 cuz here its classical activation and no abnormality
High level of anti streptolysin O antibodies ( cuz of infection of streptococcal)
describe light microscopy of acute proliferative post-streptococcal/post-infectious glomerulonephritis ?
Hypercellular glomeruli by :
Proliferation of mesangial or endothelial cells
Leukocytic infiltration of neutrophils, monocytes, lymphocytes
Crescent formation in severe cases ( parietal cells proliferation )
Obliterated capillary lumen due to the above
what do you see in IFA of acute proliferative post-streptococcal/post-infectious glomerulonephritis ?
granular deposition of immune complexes :
IgG, igM, C3 in mesangium and basement membrane
what do you see in electro microscope of acute proliferative post-streptococcal/post-infectious glomerulonephritis ??
dense deposits on the EPITHELIAL SIDE OF THE MEMBRANE
sub epithelial
called HUMPS
what rapidly progressive crescentic glomerulonephritis ?
rapidly progressive = rapidly progressing toward renal failure
Crescentic = parietal proliferation = membrane ruptures
what are classification of rapidly progressive crescentic glomerulonephritis?
Type 1 = anti GBM antibody
Type 2 = immune complex
Type 3 = Pauci-immune
describe type 1?
Antibodies against NC1 of the alpha 3 chain of collage type 4
linear diffuse pattern along the GBM
Antibodies also affect alveoli = hemapytsis
Good pasture syndrome
describe type 2?
immune complex
Literally any immune complex can cause this
Idiopathic
Postinfection
Lupus, iga , etc
its a complication of any immune complex disorder
Granular deposition of immune complexes
describe type 3?
Pauci-immune = Absence of immune complexes so you wont find any complexes
we see it with ANCA ( cytoplasmic/perinuclear )
or
Idiopathic
if you do IF u wont find anything ( lack of anti GBM, or any other immune complexes )
what do you see in light microscope of rapidly progressive crescentic glomerulonephritis?
Formation of crescents ( proliferation of parietal )
what do you see in electro microscope? rapidly progressive crescentic glomerulonephritis?
Deposits of immune complexes ( Type 1 and 2 )
RUPTURE OF GBM = crescentic
what do you see in IFA of rapidly progressive crescentic glomerulonephritis?
Type 1 = linear immune deposits ( anti GBM )
Type 2 = granular immune deposits
Type 3 = nothing
what is IgA nephropathy ? Berger disease ?
Most common type of glomerulonephritis worldwide
MAJOR CAUSE OF RECURRENT HEMATURIA
what causes igA nephropathy? berger disease?
Genetic or acquire defects of MUCOSAL IGA
abnormally glycoslyated igA1 ( galactose deficient igA1)
this abnormal igA will produce autoimmune response ( autoantibodies form immune complexes with circulating igA)
these complexes will deposit in MESANGIUM
also activate alterantive complement pathway
what is characteristic clinical presentatation of igA nephropathy ?
Hematuria following any MUCOUSAL INFECTION
like respiratory, GI, urinary infection
cuz mucousal infection = produce igA
RECURRENT HEMATURIA –> KEYFACTOR
what do you see in Light microscope? in IgA nephropathy ?
Mesangial hypercellularity ( Cuz igA deposition )
what do you see in IF of igA nephropathy?
IgA
C3
both deposited in mesangial
what do you see electro microscope?
mesangial deposition
what nephrotic syndrome?
OTI = EDEMA = most important feature is edema
Heavy proteinuria ( severe protein loss )
Hypoalbuminemia ( cuz its being lost in urine )
Hyperlipidemia ( high lipids in blood )
Lipiduria
Location of edema ? = orbits , around the eye
what causes nephrotic syndrome?
Increased glomerular capillary permeability via
PODOCYTE INJURY ( most imp thing that prevent protein secretion )
what are the results nephrotic syndrome?
Increased infection—–> ( cuz proteins including immunoglobulins are lost in urine )
thromosis and thromboembolic complications —-> cuz anti-coagulants are proteins and are lost in urine
why do we have hyperlipidemia ?
unknown but theories say :
Liver tries to compensate for lack of proteins and with them it starts increasing lipoprotiens in blood
what is minimal change disease ?
aka lipoid nephrosis
Most frequent cause of nephrotic syndrome in children 1-7 years
no immune complexes js loss of foot of processes of podocyte ( EFFACEMENT)
what is etiology and pathogenesis of minimal change disease ?
No immune deposits in glomerulus
an immunologic mechanism is suggested
what is special about minimal change disease ?
Dramatic response to corticosteroids therapy ( respond to steroids )
what do you see under LM in minimal change disease ?
Normal glumerili
Pct cells show cytoplasmic lipid droplets
what do you see under Electro microscope in minimal change disease?
effacement of foot process of podocytes
what do you see in IF?
no immunoglobulins or complement deposit
what is focal segmental glomerulosclerosis ?
Common cause of nephrotic syndrome in ADULTS AND CHILDREN
DOESNT RESPOND WELL TO CORTICOSTEROID ( UNLIKE MINIMAL CHANGE DISEASE)
What are the classifications of focal segmental glomerulosclerosis ?
Primary disease ( Idiopathic )
HIV infection
Heroin abuse
what is the pathogenesis of focal segmental glomerulosclerosis ?
Degeneration of visceral epithelial cells = PODOCYTES
what do you see under light microscope of focal segmental glomeruli?
Sclerosis of some glomeruli ; the affected glomeruli only portion of it is affected ( hence segmental )
Sclerotic segments : Collapse of basement membrane, deposition of hyaline proteins, obliterated capillary
what do you see under the electro microscope of focal segmental glomerulisclerosis ?
Diffuse effacement of foot process
Focal deatachment of podocytes
what do you see under IF in focal segmental glomerulosclerosis ?
igM and C3 in sclerotic area or in the mesagnium
what is membranous glomerulopathy?
Membranous = thickening of wall
Most common cause of nephrotic syndrome in ADULTS ( only )
Poor response to corticosteroids ( like focal seg…)
what is the cause of primary membranous glomerulopathy?
autoantibodies against podocytes antigens :
Phoshopilpase A2 receptors ( PLA2R )
Thrombospondin type 1 domain containing 7A ( THSD7A)
these will get deposited below podocytes = thickening
what causes secondary membranous glomerulopathy?
Drugs
malignant tumor
SLE
Infections
what is the pathogenesis of membranous glomerulopathy?
Immune complex in the subepithelial zone of glomerular capillaries
How do the capillaries become leaky even though membrane is thickened? ?
C5b-C9 complements will directly attack the capillary wall and injure it to increase protein leakage
what do you see under the light microscope of membranous glomerulipathy?
Uniform
Diffuse thickening of capillary wall
what do you see under the IF of membrane glomerupathy?
Granular deposits of immunoglobulins and complenents ( C5b - C9 )
wat do you see the under electro microscope?
Sub= epithelial immune complexes
what is membranoproliferative GN?
Membrane = thickening
Proliferative = endocapillary proliferation
what are 2 types of membrano-proliferative GN?
1- immuneglobulin- mediated MPGN :
ig and C3 deposits
associated with SLE; heptatis B, malignant
2- C3 glomerulopathy : ONLY C3 DEPOSITS without Ig DEPOSITION
Dense deposit disease
C3 glomerulonephritis
what is the pathogenesis of 1st type?
Immunoglobulin-Mediated MPGN :
Immune complexes deposit in :
Mesangium
+
Subendothelial zone of capillary
what is the pathogenesis in the 2nd type of GN?
C3 glomerulopathy :
Abnromal activation of complement pathway =
C3 NEPHRITIC FACTOR
what do you see in LM of membranoproliferative GN?
GBM is thickened ( membrano ) —> Duplicated = double contour or tram track appearance
Glomeruli are large and hypercellular = Endocapillary cell proliferation
Epithelial crescent
what do you see under EM and IF of membranoproliferative GN of immunoglobulin mediated ? MPGN
Subendothelial deposits
C3 is deposited in granular pattern
IgG, Clq and C4 are PRESENT ( CUZ MEDIATED BY BOTH )
what do you see under EM and IF of dense deposit disease ( C3 mediated )?
Deposits of dense material in GBM —> gbm BECOMES RIBBON LIKE
Similar deposits will also be found : Spleen, eye , mesangium, bowmans, tubular bm
C3 is deposited in both granular or linear foci in the BM
Ig ,C1q and C4 are ABSENT ( ONLY C3 )
What are the systemic disease that cause glomerular injury?
Diabetes mellitus
Hypertension
Thromobtic micro angiopathy : HUS, TTP
what the glomerular lesions that happen in diabetic nephropathy ?
1- Capillary basement membrane thickening
2- Diffuse mesangial sclerosis
3- Nodular sclerosis ( KIMMELSTIEL WILSON DISEASE
Nodulular scrleosis is pathognomic of diabetes —> DOESNT HAPPEN IN ANY OTHER DISEASE OTHER THAN DIABETE, DIABETES EXLUSIVE
the nodules will contain mesangial cells at the periphery of glomerulus
what are renal arteries effects during diabetic nephropathy ?
atherosclerosis
hyaline arteriosclerosis of EFFERENT ( diabetes exclusive only )
and
Hyaline arteriosclerosis of afferent arterioles ( could be by many disease
what is the last possible lesion caused by diabetic nephropathy?
Pyelonephritis ( inflammation of renal pelvis )
Papillary necrosis ( MOST COMMON WITH DIABETES )
what is the pathogenesis that led to the lesions of diabetic nephropathy ?
Advanced glycation end product ( AGE):
Increase endothelial permeability
Cross link collagen type IV in basement membrane …. increases fluid filtration
Modify basement membrane and trap plasma protein albumin—> thickened basement membrane
what are 3 characteristics of diabetes nephropathy ?
1- kIMMELSTIEL WILSON ( nodular sclerosis )
2- Hyaline arteriosclerosis of EFFERENT
3- Papillary necrosis
what are 2 types of hypertensive nephropathy ?
Npehrosclerosis ( Benign nephrosclerosis )
Accelerated/ malignant nephrosclerosis
Describe nephrosclerosis ( benign nephrosclerosis )?
Sclerosis of small renal arteries and arterioles
Causes, ischemia, interst fibrosis , tubular atrophy, glomersclerosis
what is the pathogenesis of nephrosclerosis ?
Endothelial dysfunction + platelet activation
Medial and intimal thickening
Hyalinization of arteriolar walls by extravasation of plasma proteins through injured endothelium
what is the morphology of Nephrosclerosis ?
Grossly :
Symmertically atorphic, renal surface will show diffuse granularity
Microscopy :
1- Hyaline arteriolesclerosis ( afferent ) –> homogenous pink wall thickening
Large blood vessels : Intimal thickening + replication of internal elastic lamina + fibrosis of media = 2- FIBROELASTIC HYPERPLASIA
Glomeruli become sclerossed
Tubules atrophy
Interstitial fibrosis
what is the pathogenesis of accelerated/malignant nephrosclerosis ?
Long standing HTN :
Endothelial injury + platelet aggregation
Intravascular thrombosis
Mitogenic factors from platelet ( PDGF ) —> HYPERPLASTIC ARTERIOSCLEROSIS
Fibrinoid necrosis of arterioles and small arteries = necrotizing arteriolitis
what is the morphology of malignant nephrosclerosis ?
Grossly :
Small hemorrhage on cortical surface ( Rupture of arterioles or glomeruli ) = FLEA BITTEN KIDNEY
Microscope :
1- Hpyerplastic arteriosclerosis : Prliferation of intima smooth muscles cells = onion skin appearance
2- Fibrinoid necrosis = small vessels/arteriole damage
3- Necrosis may involve glomeruli with microthrombi within glomeruli
what is thrombotic microangipathy ? TMA?
Lesions seen in various clinical syndrome characterized by :
Microvascular thrombosis
Microangiopathic hemolytic anemia—> on blood smear : Schistocyte ( Fragmented RBC)
Thrombocytopenia
Renal failure in certain instances
what are types of TMA?
Primary TMA
Secondary TMA
how does TMA happen?
Thrombosis in small bv by some pathological process
so now we have thrombi in small bv
so the platelets have been consumed = thromobcytopenia
then the RBCS will go n hit the thrombus damaging them = forming schistocytes = HEMOLYTIC ANEMIA
What are primary TMA?
Shiga-toxin-mediated hemolytic uremic syndrome ( HUS )
Atypical HUS ( Complement mediated TMA )
Thrombotic thromocytopenic purpura ( TTP)
What causes secondary TMA?
Malignant HTN
Drugs , pregnancy, chemotherapy, transplant rejetion
what is the morphology of all TMAS?
Grossly :
Patchy or diffuse cortical necrosis
Microscopic :
Early : Thrombi in glomeruli and small arteries and arterioles
Later : Thickening in glomeruli wall and small arteries and arterioles
how is shiga toxin mediated hemolytic uremica syndrome happen?
After intestinal infection :
By shiga toxin producing E.coli ( usually undercooked burgers )
or
Shigella
Shiga toxin will cause :
Endothelial damage
Directly actiavting the alternative complement way
Diagnosis is based on :
Diarrhea
Shigalike exotoxin in stool ( identified with vero cell assay )
Serum antibodies against shiga toxin ( with elisa detected)
how does atypical hemolytic uremic syndrome happen?
abnormalities of factors that decrease the activation of complement by alternative pathway
how does TTP happen?
Acquired inhibitory autoantibodies or inherited mutation —> deficiency in ADAMTS13 ( plasma protease that cleaves vWF )
