MedEd Histo 2 Flashcards
what is AKI
acute decline in renal function leading to fall in urine output
how is AKI captured in clinical setting
rise in creatinine / urea seen on U&Es
what is CKD
decreased kidney function or kidney damage, present for more than 3 months
how is CKD captured in clinical setting
fall in eGFR
normal eGFR
> 90
eGFR of each stage of kidney disease
1 = >90 (normal)
2 = 60 - 89 (mild)
3A = 45 - 59 (mod)
3B = 30 - 44 (mod)
4 = 15 - 29 (severe)
5 = <15 (ESRF)
2 most common causes of CKD
DM
HTN
other causes of CKD except DM and HTN
ADPKD (PCKD)
untreated AKI
- pyelonephritis
- ATN
- obstruction
how do categorise AKI
pre renal
renal
post renal
general cause of pre renal AKI
decreased blood flow to kidneys
causes of pre renal AKI
hypovolaemia
sepsis
CCF
renal artery stenosis
ACEi
general cause of renal AKI
direct damage to nephrons
causes of renal AKI
ischaemia
nephrotoxins
GN
interstitial nephritis
hepatorenal syndrome
HUS / ITP
general cause of post renal AKI
physical blockage to outflow
causes of post renal AKI
stones
tumours
prostate problems
blocked catheter
of the 3, which type of AKI is the most to least common
most common = pre renal
2nd = post renal
3rd = renal
what diseases affect the glomerulus
nephrotic and nephritic syndromes
name 4 nephrotic syndromes
minimal change
membranous
FSGS
secondary causes
name 5 nephritic syndromes
IgA vasculitis
post strep GN
Alports syndrome
benign familial haematuria
rapidly progressive GN - goodpastures, pauci immune, immune complexes
name 2 conditions which can affect BVs of kidney
HUS
TTP
name 2 tubule disorders
acute tubular necrosis
acute interstitial nephritis
what is mesangium
connective tissue (ESM) between capillaries in kidneys
what cells actually do the filtering in kidney
podocytes
triad of nephrotic syndrome
peripheral oedema
proteinuria
low serum albumin
define proteinuria
3g/day or PCR >300mg
what other 2 associated features often come with nephrotic syndrome
increased cholesterol
increased clotting tendency
what is the actual issue in nephrotic syndromes
issue with podocytes which form the filtration barrier
treatment of nephrotic syndromes
steroids
who gets minimal change disease
kids
Ix of minimal change disease
light microscopy
electron microscopy
immunoflurescence
what does light microscopy / immunoflurescnce of minimal change disease show
NOTHING
what does electron microscopy of minimal change disease show
loss of podocyte foot processes
tx and prognosis of minimal change disease
steroids (prednisolone) - very good response
what does immunoflurescence look for
immune complexes
who gets membranous GN
adults
histology of membranous GN
diffuse basement membrane thickening
what can you see on EM of membranous GN
spikey immune complexes deposited
what can you see on immunoflurescence of membranous GN
immune complexes across all the BM
tx and prognosis of membranous GN
poor response to steroids
2 associations of membranous GN
SLE
anti phospholipase a2 ABs
what is FSGS
focal segmented glomerulonephritis
characteristic finding of FSGS
only SOME parts of kidney affected (focal)
who gets FSGS
adults
histology of FSGS
focal and segmental scarring
EM of FSGS
loss of foot processes
immunoflurescence of FSGS and why
NOTHING - no immune complexes involved
steroid response to FSGS
not great but not as bad as membranous
secondary causes of nephrotic syndromes
DM
amyloidosis
buzzword for DM causing nephrotic syndrome
Kimmelsteil Wilson nodules
buzzword for amyloidosis
apple green birefringence with Congo red stain
2 types of amyloidosis & what they are
AA (chronic inflam eg RA)
AL (light chains -> MM)
triad of nephritic syndrome
HTN
haematuria
peripheral oedema
what do you see in urine of nephritic syndrome
red cell cast
what is the actual problem with nephritic syndrome
large proteins / immune complexes causing damage to delicate kidney BVs
what is the commonest cause of GN worldwide
IgA nephropathy
what preceeds IgA nephropathy
group A strep infection
how long after strep infection do you get IgA nephropathy
1-2 days
what is the problem in IgA nephropathy
deposition of IgA immune complexes within glomeruli
immunoflurescence of IgA nephropathy
IGA immune deposits in MESANGIUM
what is the 1/3rds rule with IgA nephropathy
1/3 get better
1/3 get CKD
1/3 need dialysis
difference between IgA nephropathy and post strep GN presentation
same Sx but post strep GN occurs 1-3 WEEKS after group A strep, but IgA nephropathy is 1-2 days
what is the problem in post strep GN
antigen mimicry and immune complex deposition
2 blood results seen in post strep GN
reduced c3
raised anti streptolysin O titre
immunoflurescence of post strep GN
granular IgG deposits in BASEMENT MEMBRANE
mx of post strep GN
supportive
name cresentic (rapidly progressive) GN
goodpastures
immune complex mediated
pauci-immune (ANCA-associated ie vasculitis)
what are cresentic (rapidly progressive) GN
most aggressive type of GN, causing renal failure in weeks
what is characteristic of cresentic (rapidly progressive) GNs on histology (inc what this actually is)
severity and presence of crescents (macrophages in Bowman’s space)
buzzword for goodpastures
anti glomerular BM ABs
what does histology of goodpastures show
crescents
what does immunoflurescence of goodpastures show
linear deposition of IgG in GBM
sx of goodpastures
nephritic syndrome
pulmonary haemorrhage
causes of immune complex mediated GN
SLE
IgA nephropathy
post infectious
HSP
histology of immune complex mediated GN
crescents
immunoflurescence of immune mediated GN
bumpy deposition of immune complexes in GBM or mesangium
name 2 pauci-immune / ANCA associated GNs
granulomatosis with polyangiitis
eosinophilic granulomatosis with polyangiitis
buzzword for granulomatosis with polyangiitis
cANCA
buzzword for eosinophilic granulomatosis with polyangiitis
pANCA
where do pauci-immune GNs effect
vasculitis affecting small micro blood vessels
immunoflurescence of pauci-immune GN
no / scanty immune complexes
–> this one isnt immune complex mediated
sx of pauci-immune GN
skin rashes
pulmonary haemorrhage
nephritic syndrome
what is alports syndrome
hereditary cause of CKD
how is alports inherited
X linked (affects boys)
what is the defect in alports
type 4 collagen problem
triad of alports sx
nephritic syndrome
bilateral sensorineural deafness
lens dislocation
prognosis of alports
progressive
causes ECKD in young adults
inheritance of benign familial haematuria
AD
what is the defect in benign familial haematuria
type 4 collagen
aka benign familial haematuria
thin basement membrane disease
sx of benign familial haematuria
asymptomatic haematuria
no other issues generally
most common cause of renal AKI
acute tubular necrosis
sign of acute tubular necrosis and why
brown casts in urine
- tubule cells die and shed into urine
causes of acute tubular necrosis
hypovolaemia
toxins
- gentamicin
- myoglobin (rhabdomyolysis)
- IV contrast
what is acute interstitial nephritis
kind of like an allergic reaction
-see interstitial infiltrate and eosinophils
what sign is seen in acute interstitial nephritis
sterile pyuria
(white cell casts / white cells in urine with no infection)
also rash / fever
what causes acute interstitial nephritis
penicillins
allopurinol
NSAIDs
when can you get chronic interstitial nephritis
taking paracetamol / NSAIDs for ages
triad of HUS
progressive renal failure
MAHA
low platelets
most common specific cause of HUS (esp in kids <5)
e.coli O157:H7
describe the 4 steps of pathophysiology of HUS
gastroenteritis (e.coli) - produces toxins
endothelial damage
thrombosis, platelet consumption, fibrin strand deposition
destruction of RBCs - schistocytes / anaemia
where can kids get e.coli O157:H7 from
petting zoos
what is TTP
thrombotic thrombocytopaenic purpura
pentad of TTP
MAHA
thrombycytopaenia
uraemia
fever
neuro Sx
(ie HUS + fever + neuro sx)
mortality of TTP if untreated
> 90%
describe pathophysiology steps of TTP
deficiency of protease that cleaves vWF
large vWF multimers form
platelet aggregation and fibrin deposition
microthrombi
how are the microthrombi different in TTP and HUS
HUS - microthrombi just in liver
TTP - microthrombi occur everywhere esp in CNS
what protease enzyme is deficient in TTP
ADAMTS13
inheriatnce of PCKD
AD
defect in PCKD
PKD gene defect encoding polycystin
sx of PCKD
haematuria
kidney failure
extra renal manifestations of PCKD
** buzzwords
liver cysts (most common)
berry aneurysms ** key buzzword
–> SAH
what is lupus nephritis
damage due to immune complex deposition
buzzwords of histology seen in lupus nephritis
wire loop capillaries
lumpy immune complex deposition
6 stages of lupus nephritis
1 = minimal mesangial disease only
2 = mesangial disease
3 = focal deposits
4 = diffuse deposits
5 = subepithelial membranous disease
6 = advanced sclerosis (>90%)
ABs to phsopholipase a2 R are associated with which form of GN
membranous
ABs to minimal change disease
none
ABs to goodpastures
anti BM
histology of kidney biopsy of MM pt
amyloid deposition
describe the liver anatomy zones from portal triad to central vein
portal triad: hepatic artery, portal vein, bile duct
zone 1 (periportal)
zone 2
zone 3 (periventricular)
central vein
which zone is least / most oxygenated
zone 1 is most
zone 3 is least
which zone does viral hepatitis / toxins affect first
zone 1
which zone is most sensitive to metabolic toxins and why
zone 3 - has the most hepatocytes
which zone is most sensitive to ischaemia and why
zone 3 - least oxygenated
3 causes of massively raised LFTs
viral hepatitis
ischaemia
metabolic toxins eg paracetamol
causes of acute hepatitis
viral - A&E
drugs
AID
what is the pattern of inflammation in acute hepatitis
*** buzzword
spotty necrosis
what is spotty necrosis
small foci of inflammation and necrosis with inflammatory infiltrates
causes of chronic hepatitis
viral (C)
drugs
PBC, PSC
Wilsons / haemachromatosis
what is the pattern of inflammation in chronic hepatitis
*** buzzword
piecemeal necrosis / interface hepatitis
what is piecemeal necrosis / interface hepatitis
loss of border between portal tract and surrounding parenchyma
what histological sign in lvier signals evolution to cirrhosis
**buzzword
bridging fibrosis (portal triad to central vein)
what are the causes of micronodular vs macronodular replacement of hepatocytes
micro = alcohol
macro = everything else
describe the pathophysiology of cirrhosis
- hepatocyte damage leads to necrosis
- fibroblasts replace hepatocytes, some areas of regenerating hepatocytes remain
- increased resistance to blood flow within liver leads to portal HTN
- increases resistance causes fibrotic bridges to form –> intrahepatic shunting (bypasses the hepatocytes)
- portal HTN causes extrahepatic shunts due to backlog of blood
where are the portal anastomoses
oesophagus
anorectal
umbilicus
spleen
3 main histological patterns of alcoholic liver disease
hepatic steatosis –> alcoholic hepatitis –> cirrhosis
3 key features of hepatic steatosis
fully reversible if ETOH stopped
large, pale, yellow, greasy liver
fat droplets in hepatocytes
3 key histological features of alcoholic hepatitis
**buzzwords
hepatocyte ballooning
mallory denk bodies
fibrosis
which zone is most affected in alcoholic hepatitis
3
features of alcoholic cirrhosis
shrunken brown organ
micronodular cirrhosis
how is NAFLD distinguished from alcoholic liver disease
history - histology is the same
cause of NAFLD
insulin resistance associated with obesity / DM
who gets PSC
males
buzzwords for histology of PSC
periductal intra / extra hepatic bile duct fibrosis
3 associations of PSC
** buzzwords
UC
cholangiocarcinoma
pANCA
who gets PBC
females with other AIDs
histology buzzwords of PBC
chronic BD inflammation
granulomas
buzzword for AB association of PBC
anti mitochondrial ABs
who gets AI hepatitis
young / post menopausal women with other AIDs
2 AB associations buzzwords for AI hepatitis
anti smooth muscle AB
anti liver kidney microsomal (LKM) Ig
inheritance of haemochromatosis
AR
sx of haemachromatosis
bronzed skin
DM
hepatomegaly
buzzword histology stain for haemachromatosis
prussian blue stain
pathophysiology of haemochromotosis
increased gut iron absorption
pathophysiology of wilsons
failure of copper excretion by hepatocytes to bile
buzzword histology stain for wilsons
rhodanine stain
buzzword ix result for wilsons
reduced serum caeroplasmin
reduced serum copper
alpha 1 antitrypsin deficiency pathophysiology
failure to secrete alpha 1 antitrypsin into blood –> massive build up in hepatocytes –> forms globules in hepatocytes –> chronic hepatitis
buzzword histology stain and result for alpha 1 antitrypsin deficiency
periportal red hyaline globules using periodic acid schiff stain
most common form of liver cancer
mets
3 benign liver cancers
haemangioma
liver cell adenoma
bile duct adenoma
association of liver cell adenoma
OCP
most common benign liver cancer
haemangioma
2 malignant liver cancers
HCC
cholangiocarcinoma
tumour marker for HCC
AFP
RFs for HCC
viral hepatitis
alcoholic cirrhosis
NAFLD
aflatoxin
haemochromatosis
association of cholangiocarcinoma
PSC
histology of cholangiocarcinoma
capillary ingrowth
inheritance for
haemochromatosis
wilsons
alpha 1 antitrypsin
AR
AR
AD
most common examination finding in someone with portal HTN
splenomegaly
liver biopsy reveals spotty necrosis, which is most likely cause?
hep A
hep B
hep C
TB
HIV
Hep A
what are neutrophils raised in
acute inflam
what do neutrophils look like
multilobed and granulated
what are macrophages released in
late acute inflammation to clear debris
chronic inflammation
what are lymphocytes released in
chronic inflam
what are eosinophils raised in
allergy
parasitic infection
what do eosinophils look like
bi-lobed nuclei with red granules
what are mast cells raised in
allergy
what do mast cells look like
large cells with lots of granules
key buzzwords of SCC
keratin production
intercellular bridges
NOT gland forming
where can you get SCC
skin
H&N
oesophagus - upper/middle 1/3
anus
cervix / vagina
buzzwords of adenocarcinomas
forms glands
secretes mucin
where can you get adenocarcinomas
viscera
- lung / breast / stomach / colon / pancreas
where can you get transitional cell carcinoma
kidney pelvis
ureters
bladder
2 key histo stains
haematoxylin
eosin
what does haematoxylin and eosin stain and what colour
haematoxylin = basic parts PURPLE
eosin = acidic parts PINK
MI histopath at <6hrs
normal
CK-MB also normal
MI histopath at 6 - 24hrs
loss of nuclei
homogenous cytoplasm
necrotic cell death
MI histopath 1-4 days
infiltration of polymorphs then macrophages to clear up debris
MI histopath 5 - 10 days
further removal of debris
MI histopath 1-2 weeks
granulation tissue
new blood vessels
myofibroblasts
collagen synthesis
Mi histopath weeks to months
strengthening
decellularising scar tissue
inheritance of FAP
AD
where is the mutation in FAP
APC TSG
how does FAP present
100s to 1000s of polyps in childhood
prognosis of untreated FAP
100% risk of adenocarcinoma in early adulthood
what is gardeners syndrome
subtype of FAP with extra-intestinal features
what are the extra-intestinal features of gardner’s syndrome
osteomas of skull
epidermoid cysts
desmoid tumours
dental caries
inheritance of gardners
AD
inheritance of lynch
AD
what is the gene defect in lynch
DNA mismatch repair gene
number of polyps in lynch vs FAP
much less in lynch in the 10s
FAP in 100s-1000s
why does lynch progress to cancer even if there are less polyps than FAP
can’t repair errors as defect is in DNA mismatch repair gene
extra-colonic cancers seen in lynch
endometrial (2nd most common)
ovarian
small bowel
gastric
how are FAP / lynch / gardners mx
regular monitoring
+/- colectomy
what features of polyps increases the risk of cancer
larger polyps (key one)
more polyps
higher villous component
dysplastic features
what % of colorectal cancers are adenocarcinomas
98%
what is the medical name of colon polyps
adenoma
3 types of neoplastic polyps
tubular
tubulovillous
villous
features of MEN1
pituitary adenoma
parathyroid hyperplasia
pancreatic tumour
features of MEN2a
parathyroid hyperplasia
medullary thyroid carcinoma
pheochromocytoma
features of MEN2b
mucosal neuromas
marfanoid body habitus
medullary thyroid carcinoma
phaeochromocytoma
what hormone can be monitored in MEN2a to assess treatment response
calcitonin
what type of cancer is prostate cancer
adenocarcinoma
how do you work out the gleason score for prostate cancer
1-5 based on differentiation of cells on histology (1 = normal looking, 5 = poorly differentiated and aggressive)
take a biopsy and classify the most common and worst pattern seen
add these 2 numbers together to get score /10
