Histology MC Flashcards
1
Q
Squamous cell carcinomas - tumour types
A
Histological features:
Keratin production
Intracellular bridges
NO glands
Site: head+neck, skin, oesophagus (squamous cells), anus, cervix, vagina
2
Q
Adenocarcinoma - tumour types
A
Histological features:
Form glands, secrete glandular fluid
Mucin production
Site: lung, breast, colon, pancereas, stomach
3
Q
Histo chemical stains
A
Fontana + melanin
Congo red + amyloid (apple green briefringence)
Prussian blue + iron (haematochromatosis)
4
Q
Immuno histo stains
A
CD45 + lymphoid cells
Cytokeratin epithelial marker
5
Q
Fontana histochemical stain
A
Melanin
6
Q
Congo Red histochemical stain
A
Amyloid
7
Q
Prussian blue histochemical stain
A
Iron (haematochromatosis)
8
Q
CD45 +ve immunohisto stain
A
Lymphoid cells
9
Q
Cytokeratin positive immunohisto stain
A
Epithelial marker
10
Q
What are the 3 components of atherosclerotic plaques?
A
Cells - SMC, macrophages, leukocytes
ECM including collagen
Intracellular and extracellular lipid
11
Q
What are the histological findings of MI chronologically?
A
<6 h - normal histology
6-24 h - loss of nuclei, necrotic cells, homogenous cytoplasm
1-4 days - polymorph infiltration + macrophages
5-10 d - removal of debris
1-2 w - granulation tissue, novo angiogenesis, myofibroblasts
weeks-month strenghtening, scarring
12
Q
What does nut met liver imply?
A
Congestive hepatopathy, also known as nutmeg liver and chronic passive congestion of the liver, is liver dysfunction due to venous congestion, usually due to congestive heart failure.
13
Q
Hyperthrophic cardiomyopathy (HCM)
A
Thick walled, heavy, hyper contracting heart.
Histology: myocyte dissaray +/- arrhytmia
Autosomal dominant mutation in beta MHC gene.
14
Q
Rheumatic fever
epidemiology, clinical features, ix, tx
A
Peak age 5-15 yo
Multisystem - heart, joints, skin (erythema marginatum), CNS (enchephalopathy)
Clin features: 2-4 weeks post strep throat infection
Lancefield group A strep - main pathogen
May affect mitral valve
Histology: verrucae vegetations, aschoff bodies, antischkov myocytes
Tx: Benzylpenicillin
Erythromycin if allergic to penicillin
15
Q
What is the main pathogen associated with Rheumatic fever?
A
Lancefield group A strep
16
Q
What is the Jones Major Criteria?
A
Criteria for diagnosis of group A strep infection Major criteria: CASES Carditis Arthritis Sydenham's chorea Erythema marginatum Subcutaneous nodules
17
Q
What is Erythema marginatum and what is it associated with?
A
pink rings on the torso and inner surfaces of the limbs which come and go for as long as several months. It is found primarily on extensor surfaces.
Group A streptococcal infection, otherwise known as Streptococcus pyogenes infection
Rheumatic fever
18
Q
What is the treatment for rheumatic fever?
A
Benzylpenicillin
Erythromycin if penicillin allergy (bacteriostatic, binding to the 50s subunit of the bacterial rRNA complex, protein synthesis and subsequent structure and function processes critical for life or replication are inhibited)
19
Q
What is the pathology of rheumatic heart disesae
A
young 5-15 yo
antigen mimicry - cross reaction of anti streptococcal antibodies with myocardial antigens
Causes verrucae (beady fibrous vegetations) on mitral valve (70%) or both mitral and aortic (25%)
20
Q
What is Libman Sacks endocarditis associated with?
A
SLE and antiphospholipid syndrome
Small, warty vegetations, sterile, platelet rich
21
Q
What is non bacterial thrombotic endocarditis associated with?
A
DIC/ Hypercoagulable states
Small vegetations formed of thrombi
22
Q
What are the clinical features of bacterial endocarditis
A
Systemic illness
Cardiac murmurs (MR/AR)
Immune response: Roth spots, oslers nodes, haematuria - glomerulonephritis
Thromboembolic phenomena: Janeway lesions, septic abscesses, splenomegaly
23
Q
What valves are affected in bacterial endocarditis
A
Tricuspid in IVID
Mitral/aortic otherwise
24
Q
What are some of the causative organisms for bacterial endocarditis?
A
Staph aureus (esp IVID) Strep pyogenes
Unusual bacteria
HAECK - haemophilus, aggregatibacter, cardiobacterium, eikenella, kingella
25
What is the Duke criteria and what is it used for?
Bacterial endocarditis
Major:
- positive blood cultures
- echo confirming vegetation
Minor
- RF: prosthetic valve, IVDU, congenital heart valve abnormalities
- fever
- immune stuff
- thromboembolic criteria
26
What is the Rx for bacterial endocarditis
Broad spect until cultures confirm
Flucloxacillin (MSSA)
Rifampicin, vancomycin, gentamicin MRSA
Subacute
Benzylpenicillin + gentamicin
Vancomycin 4 weeks
27
Which valve issue is associated with rheumatic fever?
Mitral stenosis, mitral regurgitation
28
Which valve issue is associated with infective endocarditis?
Aortic regurgitation,
| Mitral regurgitation
29
What histological features do you expect in chronic bronchitis?
1. Dilatation of airways
2. Goblet cell hyperplasia
3. Hyperthrophy of mucous glands
30
What histological features do you expect in Bronchiectasis?
permanent dilatation of bronchi
31
What histological features do you expect in asthma?
Curschman spirals
Eosinophils
Leyden crystals
32
Curschman spirals
Eosinophils
Leyden crystals
What do these histological findings confirm?
Asthma
33
What RF and pathogen is associated with:
| Farmer's lung
mouldy hay/grain/ silage
Saccharopolyspora rectivirgula
Gram-positive rod. It was formerly known as Micropolyspora faeni. Inhalation of the bacteria can cause the disease farmer's lung, a type of hypersensitivity pneumonitis
34
What RF and pathogen is associated with:
| Humidifier's lung
Heated water reservoirs
| Thermactinomyces spp f Gram-positive endospore-forming bacteria
35
What RF and pathogen is associated with:
Malt workers lung
+TX
Germinated barely
Aspergillus calvatus/ fumigatus
TX: amphotericin B liposomal
caspofungin
36
What RF and pathogen is associated with:
| Cheese washer's lung
mouldy cheese
Aspergillus calvatus
Penicillium casei
37
```
Histology report:
keratinisation
Intracellular prickles (desmosomes)
Smoker male
Squamous cells on cytology
```
Squamous cell carcinoma of lung
38
Histology report:
non smoking woman
glandular differentiation (gland formation + mucin production)
cytology: mucin vacuols
Adenocarcinoma of lung
39
Management of oesophageal varices
Emergency endoscopy -> sclerotherapy / banding
40
Gastric ulcer vs duodenal ulcer
Worse with food vs relieved by food
41
Gastric lymphoma
| Pathology rx
```
H pylori - chronic antaigen stimulation
Remove cause - H Pylori using triple therapy
PPI
Clarithromycin
Amoxicillin or Metronidazole
```
42
Coeliac disease
| Pathology
T cell mediated autoimmune disease
| Gluten intolerance - villous atrophy and malabsorption
43
Coeliac clinical findings
Steatorrhoea, abdo pain, failure to thrive
Dermatitis herpetiformis
Chronic blistering skin condition, characterised by blisters filled with a watery fluid that can be very itchy. Despite its name, DH is neither related to nor caused by herpes virus: the name means that it is a skin inflammation having an appearance similar to herpes.
44
What condition are these serological investigations used for
Anti endomysial ab
Anti tissue transglutaminase IgA
Anti gliadin
Coeliac
45
Upper GI endoscopy and duodenal biopsy is the gold standard for?
Coeliac
46
```
Histological report:
Skil lesions
cobblestone appearance of mucosa
Rosethorn ulers
non caseating granulomas
transmural inflammation
aphthosus ulcer - first lesion
```
Crohn's disease
47
Backwas ileitis
no granulomas/fissures/fistulae
islands of regenerating mucosa bulge into lumen causing pseudopolyps
Ulcerative cholitis
48
What conditions are the following skin manifestations associated with:
Erythema nodosum, pyoderma gangrenosym, erythema multiforme, clubbing
UC and Crohn's
49
What is the Mx for Crohn's disease?
Ix Systemic markers of inf (ESR, CRP)
Barium contrast
Endoscopy
Rx:
Mild: Prednisolone
Severe: IV hydrocortisone, metronidazole
Additional: Azathiopine, Infliximab
50
What is the Mx for UC?
Ix Rectal biopsy, flexible sig/colonoscopy, AXR, stool culture
Rx:
Mild Prednisolone + Mesalazine (5 ASA)
Moderate Prednisolone + mesalazine + steroid enema bd
Severe: admit, NBM, fluids, IV hydrocortisone, rectal steroids
51
Which antibiotics are associated with C difficile and why?
Ciprofloxacin and Cephtriaxone
Because it kills commensals allowing for C Diff to flourish
Exotoxins cause pseudomembranous colitis
52
RX and Ix for C Diff infection?
Stool sample
Metronidazole (covers anaerobes)
or
Vancomycin as 2nd line
53
Carcinoid syndrome
Diverse group of tumours
Enterochromaffin cell origin
Produce 5-HT
Carcinoid syndrome: bronchoconstriction, flushing, diarhorrea
Carcinoid crisis: Life threatening, unstable (vasodilation, hypotensive, tachycardic, bronchoconstriction, hyperglycaemia)
IX: 24 hr urine 5HIAA main serotonin metabolite
RX Octreotide somatostatin analogue
54
Chronic gastritis with lymphocyte infiltration +/- neutrophils suggests?
+/- Marginal B cell lymphoma
MALT/Mucosal associated lymphoid tissue
usually associated with H pylori inflammation
Risk of developing into adenocarcinoma or MALT lymphoma
If caught early - triple therapy: PPI, clarithromycin, amoxicillin or metronidazole
55
What cancer is Duke staging used for?
What are the stages ? A-D
Colorectal cancer
98% are adenocarcinomas
Ix proctoscopy, sigmoidoscopy, barium enema, bloods
Carcinoembryonic antigen CEA to monitor disease
```
Duke staging
A, B1, B2, C1, C2, D
A - confined to mucosa
B1 - extending into muscularis propria
B2 -transmural invasion, no lymph node
C1 - muscularis propria, LN mets
C2 - transmural invasion, LN mets
D - distant mets
```
56
What marker is used to monitor colorectal cancer?
CEA carcioemrbyonic antigen
57
What is Peutz-Jeghers syndrome?
A type of hamartomatous polyp disease.
Multiple polyps, hyperpigmentation of mucosa, freckles everywhere
Autosomal dominant disease - LKB1
risk of intussusception and malignancy
58
What is Familial Adenomatous Polyposis?
FAP is a familial syndrome causing colorectal cancer
70% autosomal dominant with APC gene mutation C5Q1
30% autosomal recessive mutation in DNA mismatch repair genes
Presents at around 10-15 yrs with more than 100 adenomatous polyps
59
HNPCC - hereditary non polyposis colorectal cancer
Autosomal dominant mutation in DNA mismatch repair genes
usually in right colon
few polyps
rapid malignant progression in under 50 yo
associated with endometrial, ovarian, small bowel, transitional cell (bladder) and stomach carcinoma
60
What are the endocrine functions of the islets of Lnagerhans?
Alpha cells - glucagon increases blood glucose
Beta cells: insulin decreases blood glucose
Delta cells: somatostatin, regulates alpha and beta cells
D1: Vasoactive peptide, stimulates secretion of H2O in pancreas
PP: pancreatic polypeptide - self regulates
61
What is metabolic syndrome?
cluster of conditions that occur together, increasing your risk of heart disease, stroke and type 2 diabetes.
```
Fasting hyperglycaemia >6 mmol/L
HTN >140/90
Central obesity
Dyslipidaemia low HDL, high TGs
Microalbuminaemia
```
62
How do you diagnose diabetes?
Fasting plasma glucose >7 mmol/L
| Random plasma glucose >11 mmol/L
63
Features of T1DM?
Autoimmune destruction of beta cells by CD4 + and CD8 + T cells
Complication: DKA - lack of insulin => increased plasma glucose => increase need for muscle ketones
64
Features of T2DM?
linked to obesity and insulin resistance
65
What is the GLASCOW scale and what is it used for?
Used to determine severity of acute pancreatitis
PaO₂ <59.3 mmHg (7.9 kPa)
Age >55 years
WBC >15 x 10³/µL (10⁹/L)
Calcium <8 mg/dL (2 mmol/L)
BUN >44.8 mg/dL (serum urea >16 mmol/L)
LDH >600 IU/L
Albumin <3.2 g/dL (32 g/L)
Glucose >180 mg/dL (10 mmol/L)`
66
What is painless jaundice associated with?
Pancreatic carcinoma at the head of the pancreas
67
What is multiple endocrine neoplasia?
MEN are a group of syndromes with functioning hormone producing tumours in multiple organs.
MEN1 - PPP parathyroid hyperplasia, pancreatic tumor, pituitary adenoma
MEN 2 A - parathyroid, thyroid, phaeochromocytoma
MEN 2 B medularry thyroid, phaeochromocytoma, neuroma (MARFANOID phenotype)
68
What does nutmeg liver suggest?
hronic passive congestion of the liver, is liver dysfunction due to venous congestion, usually due to congestive heart failure.
69
What is the investigation of choice for hepatocellular carcinoma?
alpha-fetoprotein
| USS
70
What is modified child's pugh score used for?
```
To indicate prognosis of cirrhosis,
Includes:
Ascites
Enchephalopathy
Bilirubin
Albumin
PTT
```
Results
Child Pugh A <7 50% 5 yr survival
Child Pugh B 7-9 20% 5 yr survival
Child Pugh C >10 <20% 5 yr survival
71
What are the causes of portal hypertension?
Pre hepatic
Portal vein thrombosis (factor V lieden)
Hepatic
Pre-sinusoidal - schoistosomiasis, PBC
Sinusoidal - cirrhosis
Post sinusoidal - veno occlusive disease
Post hepatic
Budd Chiari syndrome - occlusion of hepatic vein
RX thrombolytic
72
Which of the following is now the most common cause for hepatic steatosis?
Metabolic syndrome is very common because of obesity. It is defined as central obesity, or BMI >30, with hypertriglyeridemia, decreased HDL cholesterol, hypertension, and hyperglycemia.
Steatosis = fat droplets in hepatocytes
Chronic alcohol abuse may lead to hepatic steatosis. The carbohydrate deficient transferrin (CDT) test measures isoforms of iron transport protein transferrin. Consumption of ethanol more than 50 to 80 g/day for 2-3 weeks may increase serum CDT. The CDT may be higher in chronic heavy drinkers than light social drinkers.
Steatosis is reversible over weeks to months. Reduce alcohol consumption. Adopt a diet and exercise program to lose weight (a 10% weight reduction helps to prevent progression of steatosis to steatohepatitis and to cirrhosis).
73
Case:
40 yo obsese man shows mild to moderately elevated serum alanine transferase (ALT) on bloods and no other signs on examination.
What is the most likely diagnosis?
Non alcoholic fatty liver disease from metabolic syndrome aka obesity
The lipid accumulates in the hepatocytes as vacuoles. These vacuoles have a clear appearance with H&E staining
74
What genetic factors may cause liver steatosis?
Polymorphisms in the patatin-like phospholipase domain containing 3 (PNPLA3) gene encoding for a triacylglycerol lipase involved in lipid regulation may explain greater propensity to develop steatosis in some populations.
75
Histology - what might the following histological findings suggest?
Hepatocyte ballooning,
Hepatocyte necrosis
Mallory bodies
Alcoholic liver cirrhosis
Mallory body, Mallory-Denk body, and Mallory's hyaline, is an inclusion found in the cytoplasm of liver cells. Mallory bodies are damaged intermediate filaments within the hepatocytes.
Can be seen acutely after a binge episode
76
What are some causes for macronodular cirrhosis?
Hepatitis B and C - most common
Alpha 1 anti trypsin deficiency
Wilsons disease
77
What are transaminase values with alcoholic liver disease?
AST and ALT high
AST > ALT
On CT: micronodular signs of cirrhosis + spleen enlargement from portal hypertension
78
Which of the following cells plays the greatest role in fibrogenesis of the liver?
A Bile duct epithelial cell
B Endothelial cell
C Hepatocyte
D Ito cell
E Kupffer cell
The hepatic stellate (Ito) cell, which resides in the space of Disse, normally stores vitamin A. However, it can respond to injury and express alpha-smooth muscle actin as well as differentiate into myofibroblasts.
79
What are the histological findings in primary biliary cholangitis?
loss of bile duct associated with chronic inflammation
| early stages - granulomas
80
What antibody is used to diagnose primary biliary cholangitis?
Anti mitochondrial antibodies AMA
81
What do you use to treat primary biliary cholangitis?
ursodeoxycholic acid
82
What are the histological findings in primary sclerosing cholangitis?
inflammation of extrahepatic and intrahepatic bile ducts forming multiple strictures.
The sclerosis of surrounding tissue squeezes life out of bile ducts
associated with UC
83
What IX are needed to confirm primary sclerosing cholangitis?
USS - bile duct dilation
| ERCP gold standard shows beading of bile duct due to many strictures
84
What is haemochromatosis?
Genetic condition which increases absorption of iron from the gut
Causes chocolate brown organs
Autosomal recessive mutation
Signs: bronze, diabetes, hepatomegaly
HHC results from a mutation involving the hemochromatosis gene (HFE) that leads to increased iron absorption from the gut. The prevalence is between 1:200 and 1:500 persons in the U.S. About 1 in 10 persons of northern European ancestry carries the abnormal recessive HFE gene, and most of these are the C282Y mutation.
TX
venesetion
desferrioxamine
85
What is wilsons disease?
Failure to excrete copper
autosomal recessive defect in chr 13
low levels of ceruloplasmin
KEYSER FLEISCHER RINGS
Rhodanine stain on histology - mallory bodies and fibrosis seen on microscopy
TX lifelong penicillamine
86
Alpha 1 antitrypsin deficiency ?
Failure to secrete alpha 1 antitripsin
autosomal dominant - accumulates in hepatocyytes causing inclusions in cytoplasm
Intra cytoplasmic inclusions of A1AT which stain with periodic acid schiff
Kids: neonatal jaundice
Adults: emphysema and Chronic liver disease
87
What does Periodic acid schiff stain for?
alpha 1 antitrypsin intra cytoplasmic inclusions for A1AT deficiency
88
What antibodies are used to diagnose autoimmune hepatitis?>
Anti smooth muscle actin Anti SMA
89
What is the most common cause of cystitis ?
80% caused by Gram -ve bacilli from gut
E coli
Proteus
Klebsiella
Enterobacter
90
What is the treatment for cystitis?
Trimethoprim or Nitrofurantoin
91
What are the RF, clin features and diagnosis of transitional cell tumours?
```
bladder cancer
male
>50
smoking
painless haematuria
DX: cystoscopy + biopsy
```
92
Bladder suqamous cell carcinoma is associated with?
Schistosomiasis in endemic regions
93
BPH tx?
TURP, 5 alpha reductase inhibitors
94
What grading system is used for prostate cancer?
Gleason system based on degree of differentiation and glandular patterns
95
What is the cut off of PSA for prostate cancer?
4 ng/ML
96
What are the biological markers for teratomas?
AFP, HCG, LDH
97
What stain is used for histology in haemochromatosis?
Prussian blue
98
What organs are affected in haemochromatosis and what does it cause?
Excessive iron deposition in persons with HH can affect many organs, but heart (congestive failure), pancreas (diabetes mellitus), liver (cirrhosis and hepatic failure), and joints (arthritis) are the most severely affected.
99
What are RF for liver adenomas?
Oral contraceptive use is the most common risk for hepatic adenoma, but even then it is rare. Anabolic steroid usage may increase the risk in men. Congenital glycogen storage diseases are a risk as well.
100
What is the most likely tumor marker detected in the blood of a patient with hepatocellular carcinoma?
AFP alpha feto protein
biomarker found in up to 80% of hepatocellular carcinomas. It is also a biomarker of the testicular carcinomas with a 'yolk sac' element, including yolk sac carcinomas and embryonal carcinomas.
101
What are some tx for Hep B?
Pegylated interferon alfa (PEG-IFN-a), entecavir (ETV), and tenofovir disoproxil fumarate (TDF) are the agents primarily used for treatment of chronic active hepatitis B, suppressing, but not clearing the virus. Interferons have antiviral, antiproliferative, and immunomodulatory effects. Entecavir is a guanosine analogue inhibitor of hepatitis B viral polymerase. Tenofovir is a nucleotide analogue reverse transcriptase and HBV polymerase inhibitor.
102
What histological changes may you see in viral hepatitis?
| Actue stage and chronic stage findings
Individual hepatocytes are affected by viral hepatitis. Viral hepatitis A rarely leads to signficant necrosis, but hepatitis B can result in a fulminant hepatitis with extensive necrosis. A large pink cell undergoing "ballooning degeneration" is seen below the right arrow. At a later stage, a dying hepatocyte is seen shrinking down to form an eosinophilic "councilman body" below the arrow on the left.
103
What stain can be used in histology for viral hepatitis?
This trichrome stain demonstrates the collapse of the liver parenchyma with viral hepatitis. The blue-staining areas are the connective tissue of many portal tracts that have collapsed together.
104
What do you use to treat paracetamol overdose?
N-acetylcysteine helps regenerate glutathione stores to counteract the effect of toxic metabolites generated from acetaminophen poisoning.
105
What are the most common causes of renal calculi?
```
Calcium oxalate (or phosphate) 75%
Magnesium ammonium phosphate (struvite, or "triple phosphate") 12%
Uric acid 6%
Cystine 1%
Other 6%
```
Struvite refers to bacterial calculi, usually caused by proteus bacteria
Uric acid stones may be associated with gout
Urinary tract calculi are usually unilateral and about 1 to 3 mm in size. Their passage is marked by intense abdominal or back or flank pain. This pain can be paroxysmal, known as renal or ureteral "colic". Hematuria may also be present. Larger stones that cannot pass may produce hydronephrosis or hydroureter.
106
What is an example of a complex renal calculi and how does this affect the kidney?
"staghorn calculus" is a massive stone that nearly fills the calyceal system, rendering the kidney non functional. needs nephrectomy as this is a risk to infection.
Leucocytes ++
Blood ++
Protein trace
Nitrite ++
107
What is nephrotic syndrome? What are the characteristics?
Key words in EMQ - swelling (face of kids, feet of adults)
KEY WORDS: Frothy urine
Nephrotic syndrome is the breakdown of glomerular filtration barrier. It is one step away from end stage kidney failure.
4 clinical features:
1. Oedema
2. Proteinuria (>3.5 mg/day)
3. Hypoalbuminaemia
4. Hyperlipidaemia - liver produces lipoproteins to compensate for loss of albumin)
108
What are some of the primary causes for nephrotic syndrome?
Minimal change disease (children, podocytes, prednisolone)
Membranous glomerular disease (podocytes only in basement membrane, spikey subepithelial deposits)
1ry associated with phospholipase A2 receptor on podocytes
2ry associated with SLE, infection, drugs, malignancy
Focal segmental glomerulosclerosis (podocytes, scars, immunosuppresion)
109
What are the histological findings associated with diabetic glomerulosclerosis?
Diffuse glomerular basement membrane thickening.
Kimmelstein Wilson nodules - where mesangial matrix takes over the whole glomerulus
EMQ KEY WORD ASIAN
110
What are the histological findings associated with amyloid inducing nephrotic syndrome?
Deposition of extracellular proteinaceous material. Seen as apple green under polarised light due to Congo red stain.
Commonest proteins associated:
Amyloid associated protein and amyloid light.
111
What are the most common proteins associated with amyloid deposition in the kidneys?
Serum amyloid associated protein - AA
from chronic inflammation such as rheumatoid arhtritis, chronic infections TB
Amyloid light protein - derived from immunoglobulin light chains
associated with multiple myeloma
112
What are some of the clinical findings in amyloidosis
Macroglossia - large tongue
Heart failure
Hepatomegaly
113
What is amyloid light protein associated with?
Multiple myeloma - blood cancer arising from plasma cells
Patients with plasma cell dyscrasias (multiple myeloma) can have an excess of immunoglobulin light chains that form the AL amyloid.
114
What is nephritic syndrome and what is it characterised by?
```
Manifestation of glomerular inflammation i.e. glomerulonephritis
Characteristics PHAROH
Proteinuria
Haematuria
Azootemia high urea and creat
Red cell casts in urine
Oliguria
HTN
```
115
What is trichrome stain used for?
3 colours
A trichrome stain can colour the muscle tissue red, and the collagen fibres green or blue. Liver biopsies may have fine collagen fibres between the liver cells, and the amount of collagen may be estimated based on the staining method. Trichrome methods are now used for differentiating muscle from collagen, pituitary alpha cells from beta cells, fibrin from collagen, and mitochondria in fresh frozen muscle sections, among other applications. It helps in identifying increases in collagenous tissue
116
What 3 serologic tests have high sensitivity for post-streptococcal GN?
Anti streptolysin O ASOT
anti hyalouridase
anti DNase B
117
What are the characteristics of post streptococcal GN?
occurs 1-3 weeks post strep infection (throat or impetigo, usually Group A alpha haemolytic strep = pyogenes)
Immune complex deposition
Haematuria, proteinuria, oedema, HTN
High anti streptolysin O titre
On microscopy - granular depositions of IgG, subendothelial lumps
The deposits are seen here with bright breen fluorescence in a granular, bumpy pattern because of the focal nature of the immune complex deposition process. In type III hypersensitivity, antigen-antibody complexes tend to filter out and become trapped along basement membranes, such as those in glomerular capillaries.
118
What type of hypersensitivity reaction is post strep GN?
Type 3 hypersensitivity
119
What is the most common cause of nephrotic syndrome?
Membranous glomerular disease
In most cases there is no underlying condition present (idiopathic). However, some cases of membranous GN can be linked to a chronic infectious disease such as hepatitis B, a carcinoma, or SLE.
Diffuse BM thickening in glomerulus
IgG and complement deposits along entire GBM
Urianalysis: frothy cloudy urine, proteinuria
Membranous nephropathy is an immunologically mediated disease in which deposts of mainly IgG and complement collect in the basement membrane and appear in a diffuse granular pattern by immunofluorescence, as seen here. Membranous nephropathy can be secondary to an underlying malignancy, infection, drug ingestion, or SLE. It can be idiopathic. About 3/4 of persons with the idiopathic form have antibodies to phospholipase A2 receptor, a transmembrane cell surface receptor. Levels of this antibody can indicate the severity of disease.
120
What antibodies can be associated with membranous glomerular disease (nephrotic syndrome)?
Phospholipase A2 receptor antibodies - transmembrane cell surface receptor
Can indicate severity of disease
121
What is the commonest cause of glomerulonephritis?
IgA nephropathy (BERGER disease)
122
What are the characteristics of IgA nephropathy?
Deposition of IgA immune complexes in glomeruli
1-2 d post URTI with frank haematuria
May progress to end stage renal failure
Biopsy - fluorescent microscopy shows deposition of IgA in glomeruli and complenment in mesangium
May also cause isolated microscopic haematuria with no associated sx
123
What is the pathogenesis of IgA nephropathy
In IgA nephropathy, there is abnormally glycosylated IgA1. Anti-glycan antibodies form and lead to immune complexes deposited within the mesangium of the glomeruli. These complexes attach to fibronectin or type IV collagen in the extracellular matrix and activate mesangial cells to produce extracellular matrix, leading to mesangial hypercellularity, segmental glomerulosclerosis or adhesion, tubular atrophy, and interstitial fibrosis.
The IgA is deposited mainly within the mesangium, which then increases mesangial cellularity as shown at the arrow. Patients with IgA nephropathy usually present with hematuria (nephritic syndrome). Older adults may also have proteinuria, microscopic hematuria, and hypertension. Most cases are idiopathic. Some cases occur when there is defective clearance of IgA with liver disease. Some cases occur in patients with celiac disease.
124
What is rapidly progressive glomerulonephritis? (crescentic GN)
Aggressive form of nephritic syndrome that may develop into end stage renal failure within weeks.
Main clinical features:
oliguria = urine output that is less than 1 mL/kg/h in infants, less than 0.5 mL/kg/h in children, and less than 400 mL or 500 mL per 24h in adults - this equals 17 or 21 mL/hour.
renal failure
Classified based on immunological findings
Type 1 - Anti GBM (Goodpastures syndrome)
Type 2 - immune complex mediates (SLE, IgA nephropathy, post infectious GN)
Type 3- ANCA associated (c ANCA, p ANCA)
Present of crescents on light microscopi in glomeruli
crescents composed of proliferating epithelial cells
125
What are the characteristics of type 1 rapidly progressive/crescentic GN?
Type 1 = Anti GBM antibody against collagen type 4
Goodpasture syndrome most common cause
Can see crescents on light microscopy with proliferating epithelial cells
Fluorescent microscopy: linear deposition of IgG in GBM (* immunofluorescence pattern shows positivity with antibody to IgG and has a smooth, diffuse, linear pattern that is characteristic for deposition of glomerular basement membrane antibody with Goodpasture syndrome)
May see lung involvement - pulmonary haemorrhage
126
If Goodpasure syndrome is suspected, what serologic test should be obtained?
Anti GBM antibody
127
What are the characteristics of type 2 rapidly progressive/crescentic GN?
Immune complex mediated - SLE, IgA, post infectious
Crescents on light microscopy
Fluorescent microscopy: granular IgG complexes on GBM and mesangium
128
What are the characteristics of type 3 rapidly progressive/crescentic GN?
Pauci immune - no Anti GBM no immune complex
ANCA associated - cANCA Wegners granulomatosis
pANCA microscopic polyangiitis
Crescent on light microscopy
nothing on fluorescent microscopy
Usually associated with vasculitis - presenting with skin rashes or pulmonary haemorrhage
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What is Wegner's granulomatosis?
It is a type of rapidly progressive crescentic glomerulonephritis associated with c-ANCA. has kidney + URT involvement.
anuria (increase creat and urea)
oliguria
Inflamed glomerular capillaries
Associated with vasculitis - skin rashes and pulmonary haemorrhages.
rare multisystem autoimmune disease of unknown etiology. Its hallmark features include necrotizing granulomatous inflammation and pauci-immune vasculitis in small- and medium-sized blood vessels
130
What does ANCA stand for and what is is associated with?
anti-neutrophil cytoplasmic autoantibody
C-ANCA - Wegner's granulomatosis - vasculitis in skin and lung
P-ANCA - microscopic polyangitis
131
What is Alport syndrome?
Hereditary nephritis - X linked condition where there is a mutation in Collagen alpha 5 chain
Causes nephritic syndrome, deafness, eye disorder (lens dislocation + cataract)
Young onset - 5-20 yo
Progresses to ESRF
This is a type of hereditary nephritis known as Alport syndrome in which patients may also manifest nerve deafness and eye problems. The glomeruli show irregular thickening and thinning and splitting of basement membranes due to an inherited abnormality in collagen. Most cases are X-linked and have mutations of the COL4A5 gene. In addition, as shown below, the renal tubular cells appear foamy because of the accumulation of neutral fats and mucopolysaccharides.
132
What is benign familial haematuria?
Thin basement disease
Rare cause of nephritic syndrome
Autosomal dominant condition where there is thinning of GBM leading to isolated haematuria with no functional defect of the kidneys
133
What drugs may cause acute interstitial nephritis?
Antibiotic: meticillin, penicillin, cephalosporins
NSAIDS
Thiazide diuretics (furosemide)
H2 blocker cimetide
Allopurinol - GOUT medication used to decrease high blood uric acid levels. It is specifically used to prevent gout, prevent specific types of kidney stones and for the high uric acid levels that can occur with chemotherapy. It is taken by mouth or injected into a vein
Sulphonamides - antibacterial sulfonamides act as competitive inhibitors of the enzyme dihydropteroate synthase (DHPS), an enzyme involved in folate synthesis. Sulfonamides are therefore bacteriostatic and inhibit growth and multiplication of bacteria, but do not kill them.
134
What do you expect to find on U&E in acute renal failure?
Reduced GFR, increase creat and urea
135
What are the histological findings for membranoproliferative glomerulonephritis? What serologic test is often positive with MPGN?
Silver stain showing tram track BM, double contour BM
C3 nephritic factor autoantibody that targets C3 convertase
136
What are the inflammatory disorders causing tubulointerstitial nephritis?
1. Acute pyelonephritis - E coli (leukocytic casts in urine)
2. Chronic pyelonephritis + reflux nephropathy
Chronic inflam + scarring from recurrent or persistent infection.
Urine reflux
3. Acute interstitial nephritis - hypersensitivity 1 or 4 reaction to drugs (antbx: methicillin, cephalosporins; NSAIDs; diuretics e.g thiazide)
4. Chronic interstitial nephritis/ Analgesic nephritis (old using NSAIDs or paracetamol)
137
What are the 2 thrombotic microangiopathies?
HUS (haemolytic uraemic syndrome) and TTP (thrombotic thrombocytopenic purpura)
138
What is HUS?
Haemolytic uraemic syndrome
in children
triad: uraemia, thrombocytopaenia, MAHA (haemolytic anaemia)
Associated with diarrhorea caused by E coli O157:H7
Thrombi is confined to kidneys
can present with bleeding due to low platelets from MAHA
139
What is TTP?
Thrombotic thrombocytopaenia purpura
Adults
Pentat: uraemia, thrombocytopaenia, MAHA (haemolytic syndrome), neuro signs (headache/coma), fever
can present with bleeding due to low platelets (petichae)
140
What are some of the diagnostic signs of HUS or TTP?
Low HB, Low Plt
signs of haemolysis - increased bilirubin, increased reticulocytes
fragmented RBC on blood smear
COOMBS TEST NEGAIVE NO AIHA
141
Causes and complications of Acute renal failure?
Pre renal - sepsis, hypovolaemia, burns
Renal - Acute tubular necrosis, acute glomerulonephritis, thrombotic microangiopathy (HUS, TTP)
Post renal - obstruction - stones, tumours, BPH
Complications: metabolic acidosis, hyperkalcaemia, fluid overload, HTN, uraemia
142
What is chronic renal failure?
Progressive, irreversible loss of renal function. Sx of uraemia (itching, fatigue, anorexia)
Causes:
Diabetes, glomerulonephritis, HTN, vascular changes, reflux nephropathy, PCKD
143
What are the stages of chronic renal failure? How is it classified?
```
By GFR
>90 kidney damage, N function
60-89 Mild
30-59 moderate
15-29 Severe
<15 - renal failure - needs replacement therapy
```
144
Adult PCKD?
Autosomal dominant
PKD1 on chr 16 - multiple renal cysts, liver cysts, beryr aneurysm
PKD2 on Chr 4
Clinical manifestation as complication of cyst rupture
145
What are the 2 types of amyloidosis? What is amyloidosis?
Multisystem disorder caused by abnormal folding of proteins + deposition of amyloid fibrils in tissue, disrupting normal function.
```
Primary AL amyloidosis
Associated with multiple myeloma
Amyloid L proteins forming free light chains in serum and urine (Bence Jones)
monoclonal Ig
increased bone marrow plasma cell
```
Secondary AA amyloidosis
Amyloid formed from serum amyloid A - acute phase protein, so 2ry to infection/ inflam
Autoimmune - rheumatoid arthritis
Chronic inf - TB
Non immune- renal carcinoma, hodgkins
146
What proteins are associated with haemodialysis amylodosis?
Deposition of beta 2 microglobulin
147
What is familial amyloidosis?
Diff kinds of genetic amyloidosis
Most common - Familial mediterranean fever
Production of IL-1 CAUSING FEVER AND INFLAMMATION of serosal surfaces
AA amyloid - renal deposition
148
What are the clinical features of Amyloidosis?
```
Organ specific:
Kidney - nephrotic syndrome
1. . Oedema
2. Proteinuria (>3.5 mg/day)
3. Hypoalbuminaemia
4. Hyperlipidaemia
```
Heart - conduction, HF
Liver/spleen - hepatosplenomegaly
Tongue - MACROGLOSSIA
neuropathies - carpal tunnel
149
What stain would you use for Amyloidosis and what do you expect to see?
Congo red stain showing apple green birefringence under polarised light/fluorescent microscopy.
If pink/red - caused by beta pleated sheet configuration
150
What is sarcoidosis?
Multisystem disease of unknown cause, usually found in young patients.
Non-caseating granulomas.
```
Multi organ involvement
Skin - erythema nodosum
Lung - bilateral lymph adenopathy on CXR
Joins - arthritis
Eyes - uveitis, visual loss, keratoconjunctivitis, Heerfordt's Syndrome)
Hepatosplenomegaly
Hear - rythm disturbance
CNS involvement
```
DIAGNOSIS OF EXCLUSION
151
What investigations should you do to diagnose sarcoidosis?
Calcium high
ESR high
ACE high
Transbronchial biopsy
152
What are the histological findings in Alzheimers? What is the gross pathology?
```
Gross pathology:
Widened sulci
Narrow gyri
Enlarged ventricles
Generalised atrophy
```
Histological:
Senile beta amyloid plaques - cause inflammatory reaction
Neurofibrilary tangles of Tau protein
*intracellular beta amyloid misfolding may be more toxic than extracellular
153
What are some of the treatments available for AD?
Anti-cholinesterases
nAChR agonists
Glutamate antagonists
154
What are the diagnostic characteristics of dementia?
```
Impaired cognitive function and personality without impariment of consciousness.
Memory impairment + 1 of the following:
Aphasia - language disorder
Apraxia - no tasks done
Agnosia - losing recognition ability
```
155
Which pathological proteins are associated with AD?
Neurofibrilary tangles of tau
| beta amyloid
156
Which pathological proteins are associated with Dementia with Lewy bodies?
Alpha synuclein - aggregates called lewy bodies
| Ubiquitin
157
Which pathological proteins are associated with Corticobasal degeneration?
Tau in astrocytes (post mortem diagnosis)
| Parkinsonism
158
Which pathological proteins are associated with frontotemporal dementia?
Tau
159
Which pathological proteins are associated with Pick's disease?
Tau
160
Which pathological proteins are associated with Progressive supranuclear palsy?
Tau in astrocytes ( post mortem diagnosis)
| Parkinsonism
161
Which pathological proteins are associated with Multiple system atrophy?
Alpha synuclein in oligodendrocytes- clinically similar to PD, can be diagnosed when alive
162
What are the Parkinson plus syndromes?
Lewy Body dementia - fluctuating cognition, visual hallucination, early dementia
Progressive supranuclear palsy -limited vertical gaze, early falls
Corticobasal syndrome - unilateral parkinsonism
Multiple system atrophy - may be cerebellar predominant or parkinsonims predominant - early autonomic dysfunction
Vascular parkinsonism - multi infarct presentation with gait instability and lower body parkinsonism
163
What is Lewy Body dementia?
A type of parkinsonism where you have fluctuating cognition and may have visual disturbances.
Alpha synuclein aggregates
164
What is characteristic to Progressive supranuclear palsy?
Tautopathy with limited downgaze, early falls
165
What is characteristic to Corticobasal syndrome ?
Tautopathy
| Classical unilateral parkinsonysm, apraxia +/- alien limb
166
What is characteristic to Multiple system atrophy?
Synucleinopathy
Cerebellar predominant
or
Parkinsonism predominant
Associated with early autonomic dysfunction
167
What is characteristic to Vascular Parkinsonism?
Multiple infarct presentation
Gait instability
Lower body parkinsonism
Rare - tremour
168
Why is Tau important?
gene responsible for frontotemporal dementia proteins on chr 17 q 21
a bunch of pathologies
169
What is characteristic to Pick's disease?
Tau positive pick bodies
Fronto temporal atrophy
Marked gliosis and neuronal loss = WALNUT APPEARANCE
Balloon neurons
170
Histological findings:
Walnut appearance of gliosis and neuronal loss
Balloon neurons
What is it?
Pick's disease
171
What is Braak's staging used for?
Parkinsons and AD
172
What is characteristic to Multiple sclerosis?
Autoimmune demyelinating disease
young onset - F 20-40 yo
Relapsing remitting - better between episodes, progressive
Primary progressive - just keeps getting worse
173
What pathology is associated with MS?
MS plaques showing sharp margins of myelin loss
Myelin Basic Protein
Proteo-lipid protein
174
What is prion disease and how does it work?
Proteinaceous infectious disease. Transmissible by infected protein.
Misfolding of alpha prion protein into beta, which potentiates further misfolding.
Humans - variable CJD - linked to bovine spongiform enchephalopathy - late incubation period of years
Deposits in cerebellum and motor cortices
Other syndromes:
Kuru - Papa new guinea
fatal familial insomnia
