1
Q
Layers of the skin
A
Epidermis
- Stratum corneum
- Stratum lucidum
- Stratum granulosum
- Stratum spinosum (langerhans cells)
- Startum basale (melanocytes)
- Keratinocytes move up as they age
Dermis
- made of collagen and elastic fibres
- contains sweat glands, sebaceous glands, hair follicles, neurovascular bundles, blood vessels
Subcutaneous fat
- yum insulation
2
Q
What are the inflammatory reaction changes and examples of vesiculobullous conditions?
A
Forms bullae
- Bullous pemphigoid
- Pemphigus vulgaris
- Pemphigus foliaceus
3
Q
What are the inflammatory reaction changes and examples of spongiotic conditions?
A
Becomes oedematous due to intracellular oedema
- Eczema
- Contact dermatitis
4
Q
What are the inflammatory reaction changes and examples of psoriasiform conditions?
A
Becomes thickened
- Psoriasis
5
Q
What are the inflammatory reaction changes and examples of lichenoid conditions?
A
Forms a sheeny plaque
- Lichen planus
6
Q
What are the inflammatory reaction changes and examples of vasculitic conditions?
A
Associated with vasculitides
- Pyoderma gangrenosum
- Small vessel vasculitis
7
Q
What are the inflammatory reaction changes for granulomatous conditions?
A
Associated with granulomas
8
Q
What do the following words mean?
a) hyperkeratosis
b) parakeratosis
c) acanthosis
d) acantholysis
e) lentiginous
A
a) increase in S. corenum/ keratin
b) nuclei in S corneum
c) increase in S. spinosum
d) decreased cohesions between keratinocytes
e) linear pattern of melanocyte proliferation within epidermal basal cell layer
9
Q
Compare acute and chronic histology of dermatitis/eczema
A
Acute
- spongiosis
- inflammatory infiltrate in dermis
- dilated dermal capillaries
Chronic
- acanthosis
- crusting, scaling
10
Q
Differences between atopic, contact, and seborrhoeic dermatitis
A
Clinical presentation
Atopic
- infants (face + scalp) and older (flexural areas) affected
- lichenification if chronic
- FHx of atopy
Contact
- type IV hypersensitivity
- erythema, swelling, pruritus
- affect ear lobes, neck, wrists, feet (jewellery, watches, shoes)
Seborrhoeic
- inflammatory reaction to yeast
- infants (cradle cap) and adults (face, eyebrow, eyelid, chest)
- mild erythema, fine scaling, mildy pruritic
11
Q
What would you see in histology of psoriasis?
A
Parakeratosis
Loss of granular layer
Clubbing of rete ridges giving ‘test tubes in a rack’ appearance
Munro’s microabscesses
12
Q
What other conditions/signs are associated with psoriasis?
A
Nail changes (POSH)
- Pitting
- Onycholysis
- Subungual Hyperkeratosis
Arthritis (5-10%)
13
Q
Describe lesions seen in lichen planus?
A
Pruritic, Purple, Polyglonal, Papules and Plaques with mother-of-pearl sheen
Wickam’s striae also seen - fine white network on surface
14
Q
What would you see in histology of lichen planus?
A
Hyperkeratosis with saw-toothing of rete ridges and basal cell degeneration
15
Q
Name causes of erythema multiforme
A
Infections
- HSV, mycoplasma
Drugs (SNAPP)
- Sulphonamides
- NSAIDs
- Allopurinol
- Penicillin
- Phenytoin
16
Q
Pt has annular target lesions on the extensor surfaces of their hands and feet
Combination of macules, papules, urticarial weals, vesicles, bullae and petechiae noted
What is this?
A
Erythema multiforme
17
Q
Based on where IgA Abs bind to, which bullous disease is it?
a) Basement membrane -> subepidermal bulla
b) Desmoglein 1 + 3 -> intraepidermal bulla
c) Hemidesmosomes of basement membrane -> subepidermal bulla
A
a) Dermatitis herpetiformis
- associated w coeliac
b) Pemphigus vulgaris
- pemphiguS - bullae are SUPERFICIAL
c) Bullous pemphigoid
- pemphigoiD - bullae are DEEP
18
Q
Histology shows microabscesses w coalesce to form supepidermal bullae, and neutrphil + IgA deposits as tips of dermal papillae
What is it?
A
Dermatitis herpetiformis
19
Q
Histology shows supepidermal bullae with eosinophils, and linear depositiong og IgG along basement membrane
What is it?
A
Bullous pemphigoid
20
Q
Histology shows intraepidermal bulla with netlike pattern of intercellular IgG deposits, and acantholysis
What is it?
A
Pemphigus vulgaris
21
Q
Compare clinical presentation of bullous diseases
A
Dermatitis herpetiformis
- itchy vesicles on extenson surfaces of elbows, buttocks
- associated w coeliac
Bullous pemphigoid
- large tense bullae on erythematous base, do not rupture easily
- forearms, groin, axillae
- occur in elderly
Pemphigus vulgaris
- easily ruptured bullae
- raw red surface found on skin and mucosal membranes
- +ve Nikolsky’s sign (top layer of skin slips away from lower layer when rubbed)
22
Q
Salmon pink rash appears followed by oval macules in Christmas tree distribution. Pt had a cold last week.
What is it?
A
Pityriasis rosea
- first patch is known as Herald patch
- remits spontaenously
23
Q
Name two derm emergencies and what you would see
A
Stevens Johnson Syndrome
Toxic Epidermal Necrolysis
- sheets of skin detachment (<10% in SJS and >30% in TEN)
- Nikolsky sign positive
- commonly caused by reaction to drugs, i.e. sulfonamide abx, anticonvulsants
24
Q
Rough plaque, waxy, ‘stuck on’ appearing in middle age/elderly
Histo shows entrapped keratin with orderly proliferation of epidermis
A
Seborrhoeic keratosis
- entrapped keratin = horn cysts
- benign
25
Scaly lesion biopsied on nose of elderly pt
Histo shows solar elastosis, parakeratosis, atypia/dysplasia, inflammation, not full thickness
Actinic (solar/senile) keratosis
- premalignant
- sandpaper like texture
- sun-exposed area
26
Rapidly growing dome shaped nodule develops necrotic, crusted centre on pt back of hand
Grew over 2-3 weeks then went away, pt shows pictures and wants to know what it was
Keratocanthoma
- similar histology to SCC
- premalignant
27
Pt comes in with flat, red, scaly patches on lower leg
Wants to know what it is and should they be worried?
Bowen's disease
- premalignant
- intra-epidermal squamous cell carcinoma in situ
- histo: basement membrane INTACT so not invading dermis
28
Compare BCC and SCC
BCC
- 'rodent' ulcer
- slow growing, rarely mets
- pearly surface w telangiectasia
- mass of basal cells push down into dermis
- histo: palisading (nuclei align in outermost layer)
SCC
- when Bowen's spreads to dermis
- flat, red, scaly, can ulcerate
- histo: atypia/dysplasia throughout epidermis, nuclear crowding, spreads through basement membrane into dermis
29
What would histology of a melanoma show?
Atypical melanocytes
- intially grow horizontal in epidermis then vertically into dermis
- vertical growth produces 'buckshot appearance' = pagetoid cells
30
What is most important prognostic factor for melanomas?
Breslow thickness
- depth which tumour cells have invaded skin
- the deeper, the worse the prognosis
- stage 1 <1mm = 80=90%
- stage 4 >4mm = 50% 5-year survival
31
Subtypes of melanomas
Lentigo maligna melanoma
- sunexposed area of old white ppl
- slow growing black lesion
Superficial spreading malignant melanoma
- irregular borders, variations in colour
Nodular malignant melanoma
- occur all sites, common in younger ppl
Acral lentiginous melanoma
- occur on palms, soles and subungual areas
32
Name the conditions that affect the bronchus of the lungs and compare their pathology
Chronic bronchitis
- dilatation of airways and excess mucus production
- tobacco, smoke, air pollution
Bronchiectasis
- airway dilatation and scarring
- post-inflammation, asthma, systemic disease, congenital disease
Asthma
- smooth muscle cell hyperplasia, excess mucus, inflammation
- immunological; allergens, drugs, cold air, exercise
33
Pt suffering from productive cough over last two years every winter, multiple hospital admissions for chest infections
Histo show dilatation of airways, goblet cell hyperplasia and hypertrophy of mucous glands
What is this likely to be?
Chronic bronchitis
34
Pt suffers from recurrent chest infections, and recently started coughing blood, background of sarcoidosis
Histo shows permanent dilation of the bronchi
What is this likely to be?
Bronchiectasis
35
What would you see in histology of asthamatic lungs?
Curschm ann spirals
- whorls of shed epithelium
Eosinophils and mast cells in surface epithelium
Goblet cell hyperplasia
Mucus plugs seen within airways
Bronchial smooth muscle thick and blood vessels dilated
Charcot-Leyden crystals
- breakdown of eosinophils
36
Name a lung condition that affects the acinus and its pathology
Emphysema
- airspace enlargement, wall destruction
- tobacco smoke*, alpha-1 antitrypsin deficiency
*Neutrophils and macrophages activated by smoking, will release proteases which degrade tissues
37
Pt has pneumothorax and dies
Autopsy histo of lung shows loss of alveolar parenchyma distal to terminal bronchiole
What did they likely suffer from?
Emphysema
38
Name lung condition that affects bronchiole and its pathology
Small airway disease/bronchiolitis
- inflammatory scarring/obliteration
- tobacco smoke, air pollutants
- suffer from dyspnoea, cough
39
Congenital causes of bronchiectasis
Cystic fibrosis
Primary ciliary dyskinesia
Hypogammaglobulinemia
Young's syndrome (rhinosinusitis, azoospermia, bronchiectasis)
40
Chronic changes of asthma
Muscular hypertrophy
Airway narrowing
Mucus plugging
41
Presentation and investigation findings of interstitial lung disease
PC
- chronic SOB
- end-inspiratory crackles
- cyanosis, pulmonary HTN, cor pulmonale
RESTRICTIVE lung disease in spirometry
- decreased CO diffusion capacity, lung volume, compliance
42
Histology of fibrosing lung disease subtype of ILD
Idiopathic pulmonary fibrosis, pneumoconiosis etc
- progressive patchy interstitial fibrosis with loss of lung architecture and honeycomb change
- begins at periphery of lobule, sub-pleural
- hyperplasia of type II pneumocytes causing cyst formation (honeycomb fibrosis)
43
Histology of granulomatous lung disease subtype of ILD
Granuloma = collection of histiocytes, macrophages, multi-nucleate giant cells
44
Histology of extrinsic allergic alveolitis/hypersensitivty pneumonitis subtypes of ILD
Polypoid plugs of loose connective tissue within alveoli/bronchioles
Granuloma formation (think TB!!) and organising pneumonia
Immune-mediated lung disorders due to organic antigens cause widespread ALVEOLAR inflammation
45
Based on these occupations/equipment/things, what aspect of them causes ILD?
a) Coal mines
b) Farmer
c) Bird owner
d) Water tanks
e) Malt worker
f) Cheese maker
a) Asbestos exposure -> benign pleural lesions -> fibrosis
Rest of them cause hypersensitivity pneumonitis
b) mouldy hay/grain -> Saccharopolyspora rectivirgula
c) proteins in excreta/feathers
d) heated water reservoirs - thermactinomyces spp.
e) germinating barley - Aspergillus clavatus/fumigatus
f) mouldy cheese - Aspergillus clavatus/penicillum casei
By removing antigen, can prevent progression to fibrosis
46
Types of pneumonia
Bronchopneumonia
- patchy bronchial/peri-bronchial distrubtion
- low virulence organisms, seen in elderly/frail
Lobar pneumonia
- fibrinosuppurative consolidation
Atypical
- interstitial penumonitis
- no intra-alveolar inflammation
47
Name common bacterial pneumonia organisms
Community-acquired
- Strep pneum
- Haem influ
- Mycoplasma
Hospital-acquired
- Klebsiella
- Pseudonomas
Aspiration
- mixed aerobic and anaerobic organisms
48
What would you see in the histo of a lobar pneumonia?
1. Congestion
- hyperaemia and intra-alveolar fluid
2. Red hepatisation
- hyperaemia, intra-alveolar NEUTROPHILS
3. Grey hepatisation
- intra-alveolar connective tissue, FIBROSIS
4. Resolution
- restoration of normal tissue architecture
49
Male pt, smoker since teens, coughing up blood, SOB last 3 months, tumour noted by proximal bronchi on CXR
Biopsy shows keratinisation, intercellular prickles (desmosomes)
Which Ca?
Squamous cell carcinoma (30-50%)
- local spread w late mets
- less responsive to chemo
- cytology: squamous cells
50
Female pt, never smoked, coughing blood, tumour on CXR
Biopsy shows gland formation and mucin production, cells contain mucin vacuoles, and EGFR mutations noted on molecular testing
Which Ca?
Adenocarcinoma (20-30%)
- malignant epithelial tumour
- can have atypical adenomatous hyperplasia; non-mucinous BAC, mixed pattern adenocarcinoma
51
Pt with 40 yr pack hx, cushingoid, bone pain, CXR shows central tumour by proximal bronchi
Which Ca?
Small cell carcinoma (20-25%)
- arises from neuroendocrine cells
- associated w ectopic ACTH secretion, Lamber-Eaton, cerebellar degeneration
- highly malignant, mets early to bone, adrenal, liver and brain
- p53 and RB1 common mutations
52
Tumour noted on CXR
Biopsy shows large cells, large nuclei, prominent nucleoli, no evidence of glandular or squamous differentiation
Which Ca?
Large cell carcinoma (10-15%)
- poorly differentiated malignant epithelial tumour
- poor prognosis
53
Name potential paraneoplastic syndromes seen in lung Ca
Excess of the following:
ADH -> SIADH
ACTH -> Cushing's syndrome
PTH/PTHrP -> primary hyperparathyroidism, hypercalcaemia + bone pain
Calcitonin -> hypercalcaemia
Serotonin -> carcinoid syndrome (flushing + diarrhoea + bronchoconstriction)
Bradykinin -> coughing
54
How is lung Ca staged?
Tumour 1-4
- based on size and invasion of pleua, pericardium
Lymph node mets N0-2
- N1/2 = lymph node involved, depends on extent of involvement
Distant mets M0-1
- tumour spread to distant sites
55
Pt worked in coal mines 40 years ago
What signs would be suggestive of mesothelioma?
Extensive pleural effusion
Chest pain
Dyspnoea
*asbestos exposure
56
What do the molecular findings mean for lung Ca tx?
a) ERCC1 - NSCLC
b) EGFR
c) Kras
d) EML4-ALK
a) poor response to cisplatin
b) usually adeno, target for anti-EGFR for tyrosine kinase inhibitor therapy
c) adeno/squamous, poor prognosis, non-response to TKI
d) usually adeno, no benefit from TKI
57
Classification of pulmonary hypertension
Classified according to aetiology
1. Pulmonary arterial hypertension
- idiopathic, hereditary, drugs/toxins, associated congenital heart disease
2. Pulmonary hypertension associated with left heart disease
- systolic/diastolic dysfunction, valve disease
3. Pulmonary hypertension due to lung disease
4. Chronic thromboembolic pulmonary hypertension
5. Pulmonary hypertension w unclear multifactorial mechanisms
- metabolic disorders, systemic disorders, haematological disorders
58
Pathophysiology of pulmonary HTN
Pre-capillary
- chronic hypoxia/embolus
Capillary
- pulmonary fibrosis
Post-capillary
- left heart disease, veno-occlusive disease
Pulmonary vasoconstriction of arterioles
- intimal firbosis, thickened walls
Complications
- RHF, venous congestion of organs (nutmeg liver), peripheral oedema
59
Risk factors for PE
Anything that contributes to Virchow's triad (stasis + vessel wall injury + hypercoagulability)
- female
- immobile
- cardiac disease
- cancer
- childbirth
- polycythaemia
- contraceptive pill
- DIC
- anti-phospholipid syndrome
- trauma/surgery
- obesity
60
Path of pulmonary oedema
Intra alveolar fluid accumulation leads to poor gas exchange
Usually result of left heart filure
Histo: intra-alveolar fluid, iron laden macrophages (heart failure cells)
61
Path of diffuse alveolar damage
ARDS in adults
- infection, aspiration, trauma
HMD in neonates
- hyaline membrane
- insufficient surfactant production in prems
- rapid onset resp failure
Histo: lung expanded, firm, plum-coloured, airless
62
How is breast disease investigated?
Triple Assessment
1. Clinical examination
2. Imaging - sonography, mammography, MRI
3. Pathology - cytopathology, histopathology
63
Who do we offer mammograms to?
35+
Pts have less glandular tissue and more fat, contrast more visible
64
How is cytopathology obtained and coded for suspected breast disease?
Fine needle aspiration via 16/18 gauge needle
```
C1 - inadequate sample
C2 - benign
C3 - atypia
C4 - sus of malignancy
C5 - malignant
```
65
What is the diagnostic gold standard of breast cancer?
Core biopsy for histopathology
66
What would you see on normal breast histology?
Branching ducts ending in terminal-duct lobular units (functional unit of breast)
Duct-lobular system lined by an inner glandular epithelium and an outer myoepithelium
67
Painful, red breast, hot to touch
Pt has fever and recently gave birth, finding it difficult to breastfeed
What caused this and its tx?
Lactational acute mastitis
Staphylococcal infection via cracks in nipple and stasis of milk
Tx: continue breastfeeding + abx +/- surgical drainage
68
What causes non-lactational acute mastitis?
Keratinising squamous metaplasia blocking lactiferous ducts leading to peri-ductal inflammation and rupture
69
What FNA cytology findings do you expect from the following benign breast conditions:
a) acute mastitis,
b) mammary duct ectasia,
c) fat necrosis,
d) fibroadenoma,
e) intraductal papilloma?
a) abundance of neutrophils
b) proteinaceous material and macrophages
c) empty fat spaces, histiocytes and giant cells
d) branching sheets of epithelium, bare bipolar nuclei and stroma
e) (of nipple discharge) - branching papillary groups of epithelium
70
45 yr old woman comes in with green nipple discharge. She is a smoker and has 4 children.
Poorly defined periareolar mass palpated.
What caused this and its possible complications?
Mammary duct ectasia
Inflammation and dilation of large breast ducts that fill up with stagnant brown/green secretion
Fluids can be irritant and lead to
- periductal mastitis
- abscess
- fistula formation
- fibrosis (slit-like nipple retraction)
71
54 year old obese woman comes in after noticing breast mass and skin tethering. There is no breast pain and she was involved in a recent car accident.
What is this and its causes?
Fat necrosis
Inflammatory reaction to damaged adipose tissue
Causes
- trauma
- radiotherapy
- surgery
- nodular panniculitis
72
What is the most common benign breast tumour and its clinical findings?
Fibroadenoma
- spherical, freely mobile, variable size and rubbery tumour
- occur in reproductive period
73
How could intraductal papilloma present and what does it affect?
Bloody nipple discharge
Benign papillary tumour in duct system of breast
- small terminal ductules => peripheral papillomas
- larger lactiferous ducts => central papillomas
74
Pt presents with palpable lump in breast
Stellate mass seen on mammography
Histology shows central, fibrous, stellate area
What is this?
Radial scar
Benign sclerosing lesion - central scarring surrounded by proliferating glandular tissue in stellate pattern
75
What is a Phyllodes tumour?
Breast: interlobular stroma mass with increased cellularity and mitoses
Presents >50yrs as palpable mass
Most benign, can be aggressive thus excised with wide local excision/mastectomy to limit recurrence
76
32 year old woman comes in with lumpiness in breasts that comes and goes every month
What would histology show?
Fibrocystic disease, changes w menstrual cycle
Dilated large ducts which may become calcified
77
Name three proliferative breast conditions that risk becoming malignant
Usual epithelial hyperplasia
- slight increase risk Ca
Flat epithelial atypia
- x4 risk of Ca
In situ lobular neoplasia
- x7-12 risk of Ca
78
How many breast Ca present?
Hard fixed lump
Paget's disease (eczema of nipple then areola)
Peau d'orange
Nipple retraction
79
Compare breast carcinoma in situ types and histology
Neoplastic epithelial proliferation limited to ducts/lobules by basement membrane
Lobular
- cells lack adhesion protein E-cadherin
- no microcalcifications or stromal reactions
Ductal
- ducts filled with atypical epithelial cells
- high risk progressing to invasive Ca
80
How can invasive breast carcinomas be categorised and their histology?
Malignant epithelial tumours
Ductal
- most common
- big, pleiomorphic cells, invade into stroma
Lobular
- cells aligned in single file chains/strands
Tubular
- well-formed tubules with low grade nuclei
- <1cm rarely palpable
Mucinous
- produce abundance of extracellular mucin, dissects into surrounding stroma
81
What medication types are used to treat breast Ca?
Tamoxifen
- mixed agonist/antagonist of E2 receptors
Herceptin/trastuzumab
- monoclonal Ig to Her2
- needs LVEF monitoring due to toxic effect on myocardium
82
Which genes and receptors impact breast Ca mx?
BRCA1/2
- susceptibility gene
- prophylactic treatment
+ve ER/PR receptor
- associated with good prognosis, predicts response to tamoxifen
+ve HER2 receptor
- associated w bad prognosis
83
What is basal-like carcinoma in breast associated with and what would histology show?
Associated with BRCA, vascular invasion and distant mets
Triple negative: EP/PR/Her2 negative
Histo: sheets of markedly atypical cells w lymphocytic infiltrate, +ve stain for CK5/6/14
84
How are breast biopsies coded for in the screening programme?
Screening programme for 47-73 year old women every 3 years
```
Core biopsy of abnormal area:
B1 = normal breast tissue
B2 = benign abnormality
B3 = lesion of uncertain malignant potential
B4 = sus of malignancy
B5 = malignant
```
B5a -> DCIS
B5b -> invasive Ca
85
What is the role of the pancreas?
Produces enzymic HCO3- rich fluid stimulated by secretin and CCK
86
What does secretin do?
Produced by s-cells in the duodenum
Controls gastric acid secretion and buffering with HCO3-
87
What does CCK do?
Made by l-cells in the duodenum
Stimulates digestion of fast and protein by causing release of digestive enzymes
88
What are the exocrine functions of the pancreas?
Digestive function by secreting proteases, lipases, amylases into ducts
89
What are the endocrine functions of the pancreas?
Secretes the following into the bloodstream
- glucagon
- insulin
- somatostatin
- D1 (vasoactive peptide)
- pancreatic polypeptide
90
What do D1 and PP do for the pancreas?
```
D1 = stimulates secretion of H2O into pancreatic system
PP = self regulates secretion activities (pancreatic polypeptide)
```
91
Where are the following hormones made by the Islets of Langerhans in the pancreas?
a) glucagon
b) insulin
c) somatostatin
a) Alpha cells
b) Beta cells
c) Delta cells
92
Features of metabolic syndrome
```
Fasting hyperglycaemia > 6 mmol/l
BP > 140/90
Central obesity (> 94cm M, > 80cm F)
Dyslipidaemia (decreased HDL < 1 mmol/l, increased TGs > 2 mmol/l)
Microalbuminaemia
```
93
Complications of diabetes
Macrovascular
- cardiac = MI
- renal = glomerulonephritis, pyelonephritis
- cerebral = CVA
Microvascular
- ocular = diabetic retinopathy
- PVS = claudication, change in colour/temp, poor healing ulcer
94
Diagnosis of diabetes mellitus
Fasting plasma glucose > 7 mmol/l
Random plasma glucose > 11.1 mmol/l
95
Compare T1DM and T2DM
T1DM
- autoimmune destruction of beta cells by CD4+ & CD8+ T-lymphocytes, may present with DKA, insulin dependent
T2DM
- strongly linked to obesity and insulin resistance
Both
- polyuria due to osmotic diuresis
- polydipsia due to raised plasma osmolality
- hyperglycaemia, predisposing to recurrent infections
96
54 yo male presents with severe epigastric pain radiating to the back, relieved by sitting forward, and has associated prominent vomiting
Ix: increased amylase and lipase
What are the possible causes of his presentation?
Acute pancreatitis (*most common*)
Idiopathic
Gallstones*
Ethanol*
Trauma
```
Steroids
Mumps
Autoimmune
Scorpion venom
Hyperlipidaemia
ERCP
Drugs (thiazides)
```
97
What would you see on histology of acute pancreatitis?
Coagulative necrosis
98
Complication of alcoholic pancreatitis
Formation of pseudocyst (pathological collection of fluid)
99
What would you see on histology of chronic pancreatitis?
Fibrosis and loss of exocrine tissue
Duct dilatation with thick secretions
Calcification
*similar to Ca pancreas
100
Complications of chronic pancreatitis
Pseudocysts
Diabetes
Pancreatic Ca
101
64 yo presents with epigastric pain radiating to their back, complain of white stool and weight loss, and have a hx of diabetes
What are possible causes of their presentation?
Chronic pancreatitis
- wt loss & steatorrhea = malabsorption
- 2o diabetes = lack of enzymes to digest food
```
Alcoholism
CF
Hereditary
Pancreatic duct obstruction (stones/tumours)
Autoimmune (IgG4 sclerosing)
```
102
What would you see on the histology of acinar cell carcinoma of the pancreas?
Neoplastic epithelial cells with eosinophilic granular cytoplasm
+ve immunoreactivity for lipase, trypsin, chymotrypsin
103
What is acinar cell carcinoma and its presentation?
Rare, arises from acinar cells and leads to enzyme production by neoplastic cells
Causes non-specific sx, abdo pain, wt loss, N&V
10% get multifocal fat necrosis and polyarthralgia due to lipase secretion
104
Prognosis of acinar cell carcinoma
Median survival from diagnosis: 18 months
| 5 year survival: < 10%
105
What is the most common pancreatic Ca?
Ductal adenocarcinoma of the pancreas (85% cases)
| - usually affects the head of the pancreas
106
Risk factors for ductal adenocarcinoma of pancreas
Smoking
BMI, diet
Chronic pancreatitis
Genetic = FAP, HNPCC
107
Signs and sx of ductal adenocarcinoma of pancreas
```
Wt loss, anorexia
Upper abdo and back pain (chronic, persistent, severe)
Painless jaundice, pruritus, steatorrhoea
DM
Trousseau's syndrome (25%)
Ascites
Abdominal mass
Virchow's node
Courvoisier's sign
```
108
What is Trousseau's syndrome?
Acquired blood clotting disorder that results in migratory thrombophlebitis (inflammation of a vein due to a blood clot) in association with an often undiagnosed malignancy
109
What is Courvoisier's sign?
In the presence of a palpably enlarged gallbladder and accompanied with mild/painless jaundice, the cause is unlikely to be gallstones (malignancy instead)
110
Ix seen in ductal adenocarcinoma of pancreas
```
Low Hb
High bilirubin
High Ca2+
CT/MRI/ERCP for imaging
CA19.9 > 70 IU/mL
```
111
Mx of ductal adenocarcinoma of pancreas
```
Palliative chemo (5-FU)
Surgical resection (15% cases) = Whipple's procedure
5 year survival rate = < 5%
```
112
What is MEN?
Multiple endocrine neoplasia
- group of genetic syndromes where functioning hormone-producing tumours appear in multiple organs
- MEN1, MEN2A, MEN2B
113
Which organs are affected in MEN1?
'PPP'
Parathyroid hyperplasia/adenoma
Pancreatic endocrine tumour (often phaeo)
Pituitary adenoma
114
Which organs are affected in MEN2A?
Parathyroid, thyroid, phaeo
115
Which organs are affected in MEN2B?
Medullary thyroid, phaeo, neuroma
| Marfanoid phenotype
116
Functional neuroendocrine tumour presentations
Present with sx related to hormone excess:
- insulinoma = hypoglycaemic attack
- gastrinoma = Zollinger-Ellison syndrome, high acid so recurrent ulceration
- glucagonoma = necrolytic migrating erythema
- VIPoma = diarrhoea
117
Non-functional neuroendocrine tumour presentation
Picked up incidentally on imagine or when grow large enough to produce sx of local disease or mets
118
What do the following pancreatic malformation mean?
a) ectopic pancreas
b) pancreas divisum
c) annular pancreas
a) commonly in stomach, small intestine instead
b) dorsal and ventral buds fail to fuse, increased risk of pancreatitis
c) bad shape that can constrict duodenum, presents with duodenal obstruction around 1yo
119
Which mutation is present in most ductal pancreatic carcinomas?
K-Ras (95% cases)
120
Where does ductal pancreatic Ca spread?
```
DIRECT: bile ducts, duodenum
LYMPHATIC: lymph nodes
BLOOD: liver
SEROSA: peritoneum
Nerves
```
121
Common pathology of the gallbladder
Gallstones
Inflammation
Cancer
122
Complications of gallstones
Bile duct obstruction = painful, reflux of bile and acute pancreatitis
Acute and chronic cholecystitis
Gallbladder cancer
Pancreatitis
123
What are Rokitansky-Aschoff sinuses?
Pressure diverticula involving muscularis that form in chronic cholecystitis as a result of the gallbladder contracting against an obstruction
124
Which cells are affected in gallbladder cancer?
Adenocarcinoma – mucin-secreting epithelium
125
Which pathological protein is present in the following diseases that cause dementia?
a) Alzheimer's
b) Lewy body dementia
c) Corticobasal degeneration
d) Frontotemporal dementia
e) Pick's disease
a) Tau, beta-amlyoid
b) Alpha-synuclein, ubiquitin
c) Tau
d) Tau, progranulin (linked to chr 17)
e) Tau
126
Rx of Alzheimer's
Symptomatic based
- anti-cholinesterases
- nAChR agonists
- glutamate antagonists
127
What is seen on imaging of Alzheimer's?
*MRI and PET may be done though clinical diagnosis*
Generalised atrophy of brain
Widened sulci
Narrowed gyri
Enlarged ventricles
Most marked in temporal and frontal lobes with loss of cholinergic neurons
128
What presentation of dementia points towards Lewy body?
```
Psychological disturbances early
Day-to-day fluctuation in cognitive performance
Visual hallucinations
Spontaneous motor signs of Parkinsonism
Recurrent falls and syncope
Pathologically indistinguishable from PD
```
129
What causes Parkinson's disease?
Decreased stimulation of motor cortex by basal ganglia
Due to death of dopaminergic neurons in substantia nigra
130
Parkinsonism symptoms
T remor
R igidity
A kinesia
P ostural instability
Psychiatric features late in disease (hallucinations, anxiety)
131
Fluctuating cognition, visual hallucinations, early dementia
Which dementia type is this?
Lewy Body Dementia
| - parkinson plus syndrome
132
Downgaze, early falls, early rigidity and akinesia, dysarthria and dysphagia
Which dementia type is this?
Progressive supranuclear palsy
| - parkinson plus syndrome
133
Unilateral parkinsonism, dystonia/myoclonus, apraxia 'alien limbs', progressive non-fluent aphasia
Which dementia type is this?
Corticobasal syndrome
| - parkinson plus syndrome
134
What are the two presentations of multiple system atrophy?
Cerebellar predominant or parkinsonism predominant
| - both associated with early autonomic dysfunction
135
Multi-infarct presentation, gait instability, lower body parkinsonism, less likely to have a tremor
Which dementia type is this?
Vascular parkinsonism
| - parkinson plus syndrome
136
What causes multiple sclerosis?
Autoimmune demyelinating disease
| - gets rid of myelin produced by oligodendrocytes that wraps around axons for axon conduction
137
How can MS be classified?
Primary progressive
- 10% cases, continually getting worse
Relapsing remitting
- better between episodes but progresses over years
138
What proteins are seen in MS?
Myelin basic protein
| Proteo-lipid protein
139
32 yo presents with blurry vision and a previous admission of loss of sensation on their R side of their body
What pathology would you expect to see?
MS plaques showing sharp margins of myelin loss
140
Neuropathology seen due to Alzheimer's disease
Extracellular plaques
Neurofibrillary tangles
Cerebral amyloid angiopathy
Neuronal loss (cerebral atrophy)
141
When does tau protein start causing problems?
Tau protein becomes hyperphosphrylated -> accumlates inside the cell -> causes cell death
Found throughout the brain
142
Benign bone disease findings on X ray
No periosteal reaction
Thick endosteal reaction
Well developed bone formation
Intraosseous and even calcification
143
Malignant bone disease findings on X ray
Acute periosteal reaction (Codman's triangle, onion skin, sunburst)
Broad border between lesion and normal bone
Varied bone formation
Extraosseous and irregular calcification
144
16 yo presents with right knee pain
X ray shows an elevated periosteum and sunburst appearance of the right knee
What would you expect to see on histology?
Osteosarcoma
- malignant mesenchymal cells
- ALP +ve
*common in adolescents and affects knee in 60% cases*
145
Osteosarcoma X ray findings
```
Elevated periosteum (Codman's triangle)
Sunburst appearance
```
146
45 yo presents with leg pain and swelling
X ray shows lytic lesion wit fluffy calcification
What would you expect to see on histology?
Chondrosarcoma
- malignant chondrocytes
- affects axial skeleton, femur/tibia/pelvis in > 40yos
147
Chondrosarcoma X ray findings
Lytic lesions with fluffy calcification
| Axial skeleton affected
148
14 yo presents with leg pain
X ray shows onion skinning of periosteum
What would you expect to see on histology?
Ewing's sarcoma
- sheets of small round cells
- CD99 +ve
- T11:22 translocation
- affects long bones, pelvis in < 20 yos
149
Ewing's sarcoma X ray findings
Onion skinning of periosteum
150
32 yo female presents with knee pain
X ray shows lytic lesions up to the articular surface
What would you expect to see on histology?
Giant cell borderline malignancy
- osteoclast-type multinucleate giant cells on background of spindle/ovoid cells
- sheets of osteoclast cells
- knee-epiphysis affected
- occurs in 20-40 yo, F > M
151
Giant cell X ray findings
Lytic/lucent lesions right up to articular surface
152
Small benign bone forming lesion of which its night pain is relieved by aspirin
Osteoid osteoma
153
Osteoid osteoma X ray finding
Radiolucent nidus with sclerotic rim 'Bull's-eye'
154
Osteoid osteoma features
Affects tibia diaphysis/proximal femur
Arises from osteoblasts
Affects adolescents, M:F = 2:1
155
Bony outgrowths attached to normal bone commonly occurs in middle aged pts
Osteoma
| - head + neck commonly affected
156
Gardner syndrome
GI polyps
Multiple osteomas
Epidermoid cysts
157
Benign tumours of cartilage commonly occurs in middle aged pts
Enchondroma
| - hands mainly affected
158
Enchondroma X ray findings
Lytic lesions
Cotton wool calcification
Expansile, O ring sign
159
Ollier's syndrome
Multiple enchondromas
160
Maffuci's syndrome
Multiple enchondromas
| Haemangiomas
161
Cartilage capped bony outgrowth
Osteochondroma/exostosis
- most common benign tumour
- affects metaphysis of long bones near tendon attachment sites
- occurs in adolescents
162
Osteochondroma X ray findings
Well defined bony protuberance from bone
Cartilage capped bony spur on surface of bone 'mushroom' on X ray
163
Hereditary multiple exostoses
aka diaphyseal aclasis
- multiple exostoses (osteochondromas)
- short stature
- bone deformities
164
Bit of bone replaced by fibrous tissue commonly occurs in middle aged pts
Fibrous dysplasia
- F > M
- misshapen bone trabeculae on histology (chinese letters)
165
Fibrous dysplasia X ray findings
Soap bubble osteolysis
| Shepherd's crook deformity
166
Fluid filled unilocular with well defined lytic lesion on X ray
Simple bone cyst
| - humerus or femur commonly
167
X ray shows speckled mineralisation of small benign bone forming lesion
Osteoblastoma
168
Albright syndrome
Polyostotic dysplasia
Cafe au lait spots
Precocious puberty
169
Pt has serositis, arthritis, red rash on their nose and cheeks, and has had a history of kidney issues
Which autoantibody do you expect to find?
SLE pts have anti-nuclear antibodies (ANA, 95% cases)
- anti dsDNA
- anti-SM
170
Which HLA is associated with SLE?
HLA DR3 or 2
171
Which HLA is associated with scleroderma?
Both limited and diffuse: HLA DR5 & DRw8
172
Pt recently struggling with swallowing, lumps in hands, and hard skin changes on face and elbows and knees as well as hands that go white when it is cold
Which autoantibody do you expect to find?
```
Limited scleroderma (CREST)
- anti-centromere
```
173
Which pulmonary complications are limited and diffuse scleroderma associated with?
```
Limited = pulmonary hypertension
Diffuse = pulmonary fibrosis
```
174
Which autoantibodies are present in diffuse scleroderma?
Anti Scl-70
Fibrillarin
RNA pol I, II, III
PM-Scl
175
Which connective tissue disorder is +ve for anti-Jo-1?
Polymyositis
Dermatomyositis
*anti Jo-1 = tRNA synthetase
176
What are polymyositis and dermatomyositis associated with?
Underlying malignancy
| Pulmonary fibrosis
177
Histology shows increased collagen in skin and organs as well as onion skin thickening of arterioles
What is this?
Limited scleroderma
178
What would histology show for diffuse scleroderma?
Inflammation within or around muscle fibres
179
What would histology show for polymyositis and dermatomyositis?
Endomysial inflammatory infiltrate
| 'Drop out' of capillaries and myofibre damage
180
Histology expected in SLE
```
Lupus Erythematosus (LE) Cells
- neutrophils that engulfed lymphocyte nuclei coated with and denatured by antibody to nucleoprotein
```
Affects kidneys, CNS, spleen, heart
- kidney: nephrotic syndrome
- CNS: small vessel angiopathy
- spleen: onion skin lesions
- heart: Libman-Sack endocarditis
181
Signs & sx of SLE
4/11 ACR criteria needed => SOAP BRAIN MD
Serositis
Oral ulcers
Arthritis
Photosensitivity
```
Blood disorders (AIHA, ITP, leucopenia)
Renal involvement
ANA +ve
Immune phenomena (dsDNA, anti-Sm, antiphospholipid Ab)
Neuro sx
Malar rash
Discoid rash
```
182
Signs & sx of limited scleroderma
Skin changes on face and distal to elbows and knees + CREST syndrome
```
Calcinosis
Raynaud's
Esophageal dysmotility
Sclerodactyly
Telangiectasia
```
183
Signs & sx of diffuse scleroderma
Thickening of skin occurs anywhere
Widespread organ involvement
184
Signs & sx of polymyositis and dermatomyositis
Proximal muscle weakness
- increased CK and abnormal EMG
DM has cutaneous features
- heliotrope rash
- gottron papules
185
Name large vessel vasculitides
```
Takayasu's arteritis
Temporal arteritis (GCA)
```
186
Name medium vessel vasculitides
Polyarteritis nodosa (PAN)
Kawasaki's disease
Buerger's disease (thrombangitis obliterans)
187
Name small vessel vasculitides
Granulomatosis with polyangiitis (wegener's = nazi)
Eosinophilic granulomatosis with polyangiitis (Church Strauss)
Microscopic polyangiitis
Henoch Schonlein Purpura
188
Woman comes in with absent pulse, low BP in arms, cold hands, bruits and claudication
Which vasculitides?
Takayasu's arteritis
189
72 year old with painful shoulders and hips comes in with scalp tenderness and a temporal headache
ESR is raised
What ix would be diagnostic?
Temporal artery biopsy for temporal arteritis (GCA)
190
72 year old with painful shoulders and hips comes in with scalp tenderness and a temporal headache
ESR is raised
What would histology show?
Granulomatous transmural inflammation
Giant cells
Skip lesions
*for temporal arteritis (GCA)
191
72 year old with painful shoulders and hips comes in with scalp tenderness and a temporal headache
ESR is raised
What is the mx?
Oral prednisolone
192
What would you see on angiography of a patient with polyarteritis nodosa?
'Strings of pearls/rosary bead' appearance due to microaneurysms
193
What would histology show for polyarteritis nodosa?
Fibrinoid necrosis
| Neutrophil infiltration
194
Features of polyarteritis nodosa
Systemic inflammation
Renal involvement
Lungs usually spared
30% have underlying hep B
195
Would would you see on angiogram of a patient with Buerger's disease?
Corkscrew appearance from segmental occlusive lesions
196
32 year old man with a heavy smoking hx presents with painful inflammation of his arms and legs, as well as ulceration on his toes, feet, and fingers
Which vasculitides could this be?
Buerger's disease (thrombangitis obliterans)
197
Pt presents with saddle nose due to chronic sinusitis, pulmonary haemorrhage as well as haematuria and proteinuria
Which autoantibody would they be +ve for?
Granulomatosis with polyangiitis -> cANCA (anti-PR3) +ve
198
What features are seen in granulomatosis with polyangiitis?
Triad
1. Upper resp tract: sinusitis, epistaxis, saddle nose
2. Lower resp tract: cavitation, pulmonary haemorrhage
3. Kidney: cresenteric glomerulonephritis (blood & protein)
199
Features of eosinophilic granulomatosis with polyangiitis
Asthma, allergic rhinitis
Eosinophilia
Later systemic involvement
200
Which autoantibodies are seen in the following vasculitides?
a) Granulomatosis with polyangiitis
b) Eosinophilic granulomatosis with polyangiitis
c) Microscopic polyangiitis
a) cANCA (anti-PR3)
b) pANCA (anti-MPO)
c) pANCA (anti-MPO)
ANCA = antinuclear cytoplasmic antibody
201
Features of microscopic polyangiitis
Pulmonary renal syndrome
- pulmonary haemorrhage
- glomerulonephritis
202
Features of Henoch Schonlein Purpura
```
IgA mediated
Occurs in children < 10 years
Preceding URTI
Palpable purpuric rash (lower libs extensors + buttocks)
Glomerulonephritis
Colicky abdo pain, arthritis, orchitis
```
203
Features of primary amyloidosis
Deposition of amyloid L protein
Associated with plasma cell dyscrasias with paraproteins, i.e. multiple myeloma
Monoclonal Ig, free light chains in serum and urine (Bence Jones)
Increased bone marrow plasma cells
204
Features of secondary amyloidosis
Amyloid formed from serum amyloid A (acute phase protein)
Secondary to chronic infections/inflammation
- AI disease: TA, ank spond, IBD
- Infection: TB, osteomyelitis, IVDU (skin)
- Non-immune: renal cell carcinoma, Hodgkin's
205
What is haemodialysis associated amyloidosis?
Deposition of beta2-microglobulin resulting in amyloidosis due to longstanding chronic renal failure, especially when on peritoneal dialysis
Associated with carpal tunnel syndrome
206
Most common familial amyloidosis
Familial Mediterranean Fever (AR)
- +++ production of IL-1 attacks serosal surfaces (pleura, peritoneum, synovicum)
- associated gene encodes pyrin
- AA amyloid, predominant renal deposition
207
Clinical features of amyloidosis
Kidney: nephrotic syndrome (main presentation)
Heart: conduction defects, heart failure, cardiomegaly
Liver/spleen: hepatosplenomegaly
Tongue: macroglossia in 10%
Neuropathies: carpal tunnel syndrome
208
What staining is used for amyloidosis and what does it show?
Apple green birefringence with Congo red stain under polarised light (otherwise pink/red)
- this is due to beta-pleated sheet configuration
- misfolded proteins unstable and self-associated to form fibrils
209
Characteristic feature of sarcoidosis
Non-caseating granuloma in many tissues
| - also get Schaumann and asteroid bodies (includes proteins and calcium)
210
Typical presentation of sarcoidosis
F>M, more severe disease in black pts
Lungs commonly involved
- Bilateral hilar lymphadenopathy
- Pulmonary infiltrates (fine nodular shadowing in mid zones)
Insidious SOB, cough, chest pain and night sweats
211
Ddx of bilateral hilar lymphadenopathy
TB
Sarcoidosis
Lymphoma
Bronchial Ca
212
Extrapulmonary manifestations of sarcoidosis
Skin: erythema nodosum, lupus pernio, skin nodules
Eyes: anterior/posterior uveitis, keratoconjuctivitis, lacrimal gland enlargement
Blood: leucopoenia, anaemia
Heart: dysrhythmias, cardiomyopathy, conduction defects, pericarditis, valvular lesions
Lymphadenopathy, hepatosplenomegaly, arthritis, bone cysts, FLAWS, hypercalcaemia/hypercalciuria
213
How is sarcoidosis diagnosed?
Diagnosis of exclusion
- CXR: bilateral hilar lymphadenopathy, fine nodular shadowing mid zones (pulmonary infiltrates)
- hypercalcaemia
- increased ESR, ACE
- transbronchial biospy
214
Stain for melanoma
Fontana stain
215
+ve Fontana stain
+ve for melanin -> melanoma
216
Stain for amylodosis
Congo red + apple green birefringence
217
Congo red stain with apple green birefringence
+ve for amyloid -> amyloidosis
218
Stain for Wilson's disease
Rhodanine stain
*golden brown against blue counterstain
219
+ve Rhodanine stain
+ve for copper -> Wilson's disease
*golden brown against blue counterstain
220
Stain for haemachromatosis
Prussian blue
| Perl's stain
221
+ve Prussian blue stain
+ve for iron -> haemochromatosis
222
+ve Perl's stain
+ve for iron -> haemochromatosis
223
Stain for epithelial carcinoma
Cytokeratin
224
Stain for lymphoid cells
CD45
225
Stain for TB
Ziehl-Neelson
*red against a blue background
Auramine stain
*bright yellow
226
+ve Ziehl-Neelson
+ve for acid-fast bacilli -> TB
*red against a blue background
227
+ve Auramine stain
bright yellow -> TB
228
Which stain shows flying saucer shaped cysts?
Gomori's methanamine silver stain
229
Which stain diagnoses Pneumocystic jirovecii?
Gomori's methanamine silver stain
230
+ve Gomori's methanamine silver stain
Flying saucer shaped cysts -> Pneumocystic jirovecii
231
+ve modified Kinyoung acid fast stain
Cryptosporidium parvum
232
Which stain shows yeast cells surrounded by halos?
India ink stain
233
Which stain diagnoses Cryptococcus neoformans?
India ink stain
234
+ve India ink stain
Yeast cells surrounded by halos -> Cryptococcus neoformans
235
Which stain shows cystoplasmic inclusions?
Giemsa stain
236
Which stain diagnoses Chlamydisa psittaci?
Giemsa stain
237
+ve Giemsa stain
Cystoplasmic inclusion -> Chlamydisa psittaci
238
+ve Fite stain
Mycobacterium leprae
239
Stain for Mycobacterium leprae
Fite stain
240
Histology seen for osteoporosis
Loss of cancellous bone
241
Histology seen for osteomalacia
Excess of unmineralise bone (osteoid)
242
Histology seen for primary hyperparathyroidism
Osteitis fibrosa cystica
- marrow fibroisis + cysts
- aka Brown Tumour
243
Histology seen for Paget's disease
Huge osteoclasts w >100 nuclei
| Mosaic pattern of lamellar bone (jigsaw due to re-modelling)
244
What would you see in the x-ray of ostemolacia?
Looser's zones
- pseudo fractures
Splaying of metaphysis
Bowing of legs in Ricket's
245
What would you see in the x-ray of primary hyperparathryoidism?
Brown's tumours
- collection of multinucleate giant cells
Salt and pepper skull
Subperiosteal bone resorption in phalanges
246
What would you see in the x-ray of Paget's disease?
Mixed lytic and sclerotic
Skull
- osteoporosis circumscripta
- cotton wool appearance
Vertebrae
- picture frame
- ivory vertebra
Pelvis
- sclerosis and lucency
247
Stages of Paget's disease
Osteolytic
Mixed
Osteosclerotic
=> results in lytic and sclerotic lesions
248
Diagnosis of osteoporosis
DEXA scan
- T-score < -2.5 = osteoporosis
- T score -1 to -2.5 = osteopenia
* T-score compares to healthy population
* *Z-score compares age-matched control (useful for bone loss in younger pts)
249
Sx of Paget's disease
```
Bone pain
Microfractures
Nerve compression
- sensorineural deafness
- sciatica
Skull changes cause larger head size
Deafness
High output cardiac failure
```
250
Sx of vit D deficiency in children
```
Bone pain
Bowing tibia
Rachitic rosary
Frontal bossing
Pigeon chest
Delayed walking
```
251
Skeletal changes associated with CKD
```
Increased bone resorption (osteitis firbosa cystica)
Osteomalacia
Osteosclerosis
Growth retardation
Osteoporosis
```
252
Clinical features of RA
```
Symmetrical joints affected
DIP joints SPARED
Mild anaemia
Raised ESR
Rheumatoid nodules (25%)
Can be multisystem disease
```
253
Serology for rheumatoid arthritis
Rheumatoid factor +ve 60-70% cases
| anti-CCP more sensitive + specific
254
Characteristic deformities in RA
Radial deviation of wrist
Ulnar deviation of fingers
Swan neck = hyperextension of PIP & flexion of DIP
Boutonniere = flexion of PIP & hyperextension DIP
Z shaped thumb
Synovial swelling
255
Extra-articular features
Pulmonary fibrosis
Vasculitis
Amyloidosis
Pericarditis
Subcutaneous nodules
DVT
256
Histopathology seen with RA
Proliferative synovitis
- thickening of synovial membranes
- hyperplasia of surface synoviocytes
- intense inflammatory cell infiltrate
- fibrin deposition and necrosis
Pannus formation
- inflamed synovium overlies articular surface
257
X-ray features of osteoarthritis
LOSS
Loss of joint space
Osteophytes
Subchondral sclerosis
Subchondral cysts
258
What nodes are seen in osteoarthritis?
Heberden's nodes on DIP
Bouchard's nodes on PIP
259
Crystal type in gout
Urate crystals
Needle shaped
Negatively birefringent crystals
260
Crystal type in pseudogout
Calcium pyrophosphate crystals
Rhomboid shaped
Positively birefringent crystals
261
How does fracture repair occur?
1. Organisation of haematoma (pro-callus)
2. Formation of fibrocartilaginous callus
3. Mineralisation of fibrocartilaginous callus
4. Remodelling of bone along weight bearing lines
262
Which organisms are most likely to cause osteomyelitis in the following groups?
a) adults
b) sickle cell patients
c) children
a) Staph aureus
b) Salmonella
c) Haemophilus influenza, Group B strep
263
Compare bones affected in osteomyelitis between adults and children
Adults
- vertebrae
- jaw (secondary to dental abscess)
- toes (secondary to diabetic skin ulcer)
Children
- long bones
264
X-ray changes in osteomyelitis
Early changes
- sub-periosteal new bone formation
~10 days post-onset
- lytic destruction of bone
265
Rare causes of osteomyelitis
TB
- immunocompromised patients
Syphilis
- congenital or acquired
266
Diseases affecting the glomerulus that present with nephrotic syndrome
Primary
- Minimal change disease
- Membranous glomerular disease
- Focal segmental glomerulosclerosis
Secondary
- diabetes
- amyloidosis
- SLE
267
Diseases affecting the glomerulus that present with nephritic syndrome
```
Acute post-infections (post-strep)
IgA nephropathy (Berger disease)
Rapidly progressive
Alport's syndrome (hereditary)
Thin basement membrane disease (benign familial haematuria)
```
268
Diseases affecting the tubules and interstitium
Acute tubular necrosis
Tubulointerstitial nephritis
269
Diseases affecting the blood vessels of the renal system
Thrombotic microangiopathies
- haemolytic uraemic syndrome (HUS)
- thrombotic thrombocytopenic purpura (TTP)
270
Proteinuria
Hypoalbuminaemia
Hyperlipidaemia
Oedema
Which syndrome is this?
Nephrotic syndrome
271
Proteinuria
Haematuria
Hypertension
Which syndrome is this?
Nephritic syndrome
| - also see oliguria
272
Features of nephrotic syndrome
```
Proteinuria (frothy urine)
Hypoalbuminaeima
Oedema (periorbital)
Hyperlipidaemia
Thrombotic disease
```
273
Features of nephritic syndrome
```
Proteinuria
Haematuria
Azootemia
Red cell casts
Oliguria
Hypertension
```
274
Compare pathology of nephrotic and nephritic syndrome
NephrOtic
- pOdocyte damage leading to glomerular change-barrier disruption
NephrItic
- Inflammation disrupting glomerular basement membrane
275
Acute changes in asthma
Bronchospasm
Oedema of mucosa
Hyperaemia
Inflammation
276
Chronic change in asthma
Muscular hypertrophy
Airway narrowing
Mucus plugging
277
Condition results in smooth muscle cell hyperplasia, excess mucus, and inflammation
What histological features would you see?
ASTHMA
Curschmann's spirals (whorls of shed epithelium)
Eosinophils and mast cells
Goblet cell hyperplasia
Charcot-Leyden crystals (eosinophilic protein buildup)
Blood vessel dilation
278
Condition results in dilatation of the airways and excess mucus production
What histological features would you see?
```
CHRONIC BRONCHITIS
Dilated airways
Mucus gland hyperplasia
Goblet cell hyperplasia
Mild inflammation
```
279
Condition results in airspace enlargement and wall destruction
What histological features would you see?
EMPHYSEMA
Loss of alveolar parenchyma distal to the terminal bronchiole
Centrilobular (centred on bronchiole) damage if caused by smoking
Panacinar (diffuse loss of alveolae) damage if caused by alpha-1 antitrypsin deficiency
280
Condition results in airway dilatation and scarring
What histological features would you see?
BRONCHIECTASIS
| Permanent dilatation of the bronchi
281
Inflammatory causes of bronchiectasis
```
Post-infectious/inflammatory
Abnormal host defence
- hypogammaglobulinemia
- chemotherapy, NG
Obstruction
Secondary to bronchiolar disease and interstitial fibrosis
Systemic disease
Asthma
```
282
Congenital causes of bronchiectasis
Cystic fibrosis
Primary ciliary dyskinesia
Hypogammaglobulinemia
Young's syndrome = rhinosinusitis, azoospermia, bronchiectasis
283
Most common CF mutation
Delta F508
| - chromosome 7q3 = CFTR gene
284
Stages of lobar pneumonia
1. Consolidation
- hyperaemia and intra-alveolar fluid
2. Red hepatisation
- hyperaemia, intra-alveolar neutrophils
3. Grey hepatisation
- intra-alveolar connective tissue (fibrosis vibes)
4. Resolution
- restoration of normal tissue architecture
285
Interstitial pneumonitis pneumonia describes a...
...n atypical pneumonia
286
Patchy bronchial/peri-bronchial distribution pneumonia describes a...
...bronchopneumonia
287
Fibrinosuppurative consolidation pneumonia describes a...
...lobar pneumonia
288
Owl's eye inclusions
Big, eosinophilic viral inclusion seen in CMV infections
289
Steps of atherosclorosis
Endothelial injury
LDL enters and converted into oxidised LDL causing inflammation
Macrophages eat it up and become foam cells
Apoptosis of foam cells create cholesterol core of plaque
Adhesion molecules attract more macrophages and T cells into plaque
Vascular smooth muscle cell forms fibrous cap
290
Which part of the aorta is more affected by atherosclerosis?
Abdominal > thoracic
291
Complications of MI
```
Contractile dysfunction
Congestive heart failure
LV infarct
Cardiac rupture of ventricular wall, septum, papillary muscle
Ventricular aneurysm
Arrhythmias
Pericarditis
Pericardial effusion
Dressler's syndrome
Fibrinous pericarditis
Mural thrombus embolisation
```
292
Common cause of sudden death post-MI
Ventricular fibrillation
293
What histological changes do you see 24 hours post-MI?
under 6 hours
- normal by histology
- CK-MB normal
6-24 hours
- loss of nuclei, homogenous cytoplasm, necrotic cell death
294
What histological changes do you see between 1-10 days post-MI?
1-4 days
- infiltration of polymorphs then macrophages (clear up debris)
5-10 days
- removal of debris
295
What histological changes do you see weeks post-MI?
1-2 weeks
- granulation tissue, new blood vessels, myofibroblasts, collagen synthesis
Weeks-months
- strengthening, decellularising scar tissue
296
Common causes of heart failure
```
Ischaemic heart disease
Valve disease
Myocarditis
Hypertension
Dilated cardiomyopathy
Arrhythmias
```
297
Complications of heart failure
Sudden death
Systemic emboli
Arrhythmias
Deep vein thrombosis and pulmonary embolism
298
What causes fluid overload in heart failure?
Cardiac damage -> decreased CO -> activates RAS -> salt and water retention
This compensatory mechanism to maintain perfusion eventually leads to fluid overload
299
What causes dilatation and poor contractility in heart failure?
Cardiac damage -> decreased stroke volume -> activation of sympathetic nervous system via baroreceptors (low BP)
This mechanism to maintain perfusion eventually leads to increased total peripheral resistance -> increased afterload -> LVH and increased EDV -> dilatation and poor contractility
300
What ix are done for heart failure?
BNP
CXR
ECG
ECHO
301
LVHF signs
Dyspnoea, orthopnoea, PND, wheeze, fatigue
*pooling of blood in pulmonary circulation -> decreased peripheral BP and flow
302
RVHF signs
Engorgement of systemic and portal venous systems: peripheral oedema, ascites, facial engorgement
*chronic severe pulmonary HTN/secondary to LVF
303
What is Arrhythmogenic Right Ventricular Cardiomyopathy (ARVC)?
Myocyte loss with fibrofatty
| replacement typically affecting the right ventricle
304
What is Hypertrophic obstructive cardiomyopathy (HOCM)?
Septal hypertrophy resulting in an
outflow tract obstruction
Cause of sudden death in young people
305
Histology of hypertrophic cardiomyopathy
Myocyte disarray
| - arrhythmogenic
306
Which mutation causes hypertorphic cardiomyopathy?
beta-MHC gene
- autosomal dominance
- affects sarcomeric proteins
MYBP-C and Trop-T gene mutations
307
What are the mechanisms of the following patterns of cardiomyopathy?
a) dilated
b) hypertrophic
c) restrictive
a) dilated - systolic dysfunction
b) hypertrophic - diastolic dysfunction
c) restrictive - diastolic dysfunction
308
What are the causes of the following patterns of cardiomyopathy?
a) dilated
b) hypertrophic
c) restrictive
a) dilated
- IHD, valvular heart disease, HTN, congenital HD
b) hypertrophic
- HTN, AS
c) restrictive
- pericardial constriction
309
What does acute rheumatic fever affect?
Heart: pancarditis i.e. endocarditis, myocarditis, pericarditis
Joints: arthritis and synovitis
Skin: Erythema marginatum, subcutaneous nodules
CNS: Encephalopathy, Sydenham’s chorea
310
What criteria is used to diagnose acute rheumatic fever?
```
Jones' Major Criteria:
Carditis
Arthritis
Sydenham's chorea
Erythema marginatum
Subcutaneous nodules
```
```
Minor:
Fever
Raised ESR or CRP
Migratory arthralgia
Prolonged PR interval
Previous rheumatic fever
Malaise
Tachycardia
```
311
Which valve is affected by rheumatic fever?
Mitral 70%
| Mitral & aortic 25%
312
Main pathogen causing rheumatic fever
Lancefield group A strep
313
Histology seen in rheumatic fever
```
Beady fibrous vegetations
- verrucae
Aschoff bodies
- small giant-cell granulomas
Antischkov myocytes
- regenerating myocytes
```
314
What immunological mechanism results in rheumatic fever?
Antigenic mimicry
| - cell-mediated immunity and antibodies to streptococcal antigen cross-react with myocardial antigens
315
Tx of rheumatic fever
Benzylpenicillin
Erythromycin if allergic
316
Small, warty vegetations found along the
lines of closure of valve leaflet -
‘verrucae’
Dx?
Rheumatic heart disease
317
Large, irregular masses on valve cusps,
extending into the chordae
Dx?
Infective endocarditis
318
Small, bland vegetations attached to
lines of closure. Formed of thrombi
Dx?
Non-bacterial thrombotic endocarditis (marantic)
319
Small (up to 2mm), warty vegetations
that are sterile and platelet-rich
Dx?
Libman-Sacks endocarditis
| - associated with SLE and anti-phospholipid syndrome
320
```
Narrowed
aortic valve
high velocity,
high pressure
flow
```
Causes?
Aortic stenosis
- calcification (old age)
- congenital bicuspid valve
321
Incompetent aortic
valve blood flows
back into LV after
systole
Causes?
Aortic regurgitation
- infective endocarditis
- aortic aneurysm
- LV dilation
- connective tissue disorder (Marfan's, ank spond)
322
```
Narrowed mitral
valve high
velocity, high
pressure flow.
Back pressure
in left atrium
dilatation
```
Causes?
Mitral stenosis
| - rheumatic fever
323
Incompetent mitral
valve blood flows
back into left atrium
during systole
Causes?
Mitral regurgitation
- infective endocarditis
- connective tissues disease
- post-MI
- rheumatic fever
- left ventricular dilatation (functional MR)
324
Middle aged woman presents with SOB and chest pains
O/E Mid systolic click and late systolic murmur
Dx?
Mitral valve prolapse
325
Causes of pericarditis
```
Fibrinous
- MI, uraemia
Purulent
- Staphylococcus
Granulomatous
- TB
Haemorrhagic
- tumour, TB, uraemia
Fibrous
- constrictive
```
326
What causes pericardial effusion?
Chronic heart failure
| - serous fluid in pericardial sac
327
Myocardial rupture from myocardial infarction or trauma
Haemopericardium
328
3 main types of renal stones
Calcium oxalate 75%
Magnesium ammonium phosphate 15%
Uric acid 5%
329
Staghorn calculi cause
Magneisum ammonium phosphate
Commonly due to urease producing organisms which alkanise urine
promoting precipitation of magnesium ammonium phosphate salts
330
Histology seen for BPH
Nodule formation
| Prostatic epithelial ducts with duct spaces
331
Tx for BPH
TURP
| 5-alpha reductase inhibitors
332
Most common prostate cancer
Adenocarcinoma
| - develops from PIN
333
Grading system for prostate cancer
Gleason system
334
30 yo with testicular mass. Radiosensitive.
Which tumour?
Seminoma
335
18 yo with testicular mass. Chemosensitive. Markers presents are AGP, HCG and LDH.
Which tumour?
Teratoma
336
Germ cell testicular tumours
```
Seminoma
Embryonal carcinoma
Yolk sac tumour
Choriocarcinoma
Teratoma
```
337
Predisposing factors to germ cell testicular tumours
Cryptochordisim
Testicular dysgenesis
Genetic factors
- Klinefelter's, testicular feminisation
338
Non germ cell testicular tumours
```
Leydig (from stroma)
Sertoli cell (from sex cord)
```
339
Most common bladder tumour
Transitional cell (urothelial)
90% cases, 3:1 M:F
340
Bladder tumour associated with schistosomiasis
Squamous cell carcinoma
341
```
Renal biopsy of tumour:
- Bland epithelial cells
growing in a papilliary or
tubopapilliary pattern
- Well circumscribed
cortical nodules
```
What is it?
Papillary adenoma
- benign
- < 5mm
342
```
Renal biopsy of tumour:
- Macroscopic:
mahogany brown
- Microscopic: sheets of
cells, pink cytoplasm,
form a nest of cells
```
What is it?
Oncocytoma
| - benign
343
Renal biopsy of tumour:
- Fat spaces, thick blood vessels and spindle cell components
What is it?
Angiomyolipoma
| - mesenchymal benign tumour composed of fat, blood vessels, and muscle
344
```
Renal biopsy of tumour:
Microscopic –
1. Small round blue
cells (very
undifferentiated)
2. Epithelial
component – cells
trying to differentiate
and form primitive
renal tubules
```
What is it?
Nephroblastoma
| - childhood renal malignancy
345
```
Renal biopsy of tumour:
- Macroscopic: golden yellow with
haemorrhagic areas
- Microscopic: nests of epithelium
with clear cytoplasm
```
What is it?
Clear cell renal cell carcinoma
- epithelial tumour
- 70% cases
346
Renal biopsy of tumour:
- macroscopic: friable brown tumour
- microscopic: papillary/tubopapilliary growth pattern
What is it?
Papillary renal cell carcinoma
| - 15% cases
347
Renal biopsy of tumour:
- macroscopic: solid brown tumour
- microscopic: sheets of large cells, distinct cell borders
What is it?
Chromophobe renal cell carcinoma
| - 5% cases
348
Conditions that cause nephrotic syndrome
Primary
- minimal change disease
- membranous glomerular disease
- focal segmental glomerulosclerosis
Secondary
- diabetes, amyloidosis, SLE
349
Conditions that cause nephritic syndrome
```
Acute post-infectious (post-strep)
IgA nephropathy (Berger)
Rapidly progressive
Alport's syndrome (hereditary nephritis)
Thin basement membrane disease (benign familial haematuria)
```
350
Proteinuria
Hypoalbuminaemia
Oedema
What this?
Nephrotic syndrome
| - may also see hyperlipidaemia, thrombotic disease
351
Child comes in with swelling around their eyes and frothy urine
Renal biopsy would show loss of podocyte foot processes and no immune deposits
Pt responds to steroids
What this and mx?
Minimal change disease
- common in children
Mx
- Steroids
- Cyclosporin 2nd line
*generally AVOID renal biopsy in children
352
Pt comes in with swollen feet and frothy urine
Renal biopsy shows loss of podocyte foot processes and spikey deposits as well as Ig deposits along entire GBM
No response to steroids
What this and mx?
Membranous glomerula disease
- spikey deposits = subepithelial deposits
Mx
- steroids
- ACEi/ARB for BP
353
Pt comes in with swollen feet and frothy urine
Renal biopsy shows loss of podocyte foot processes and Ig and complement in scarred areas
Partial response to steroids
What this and mx?
Focal segmental glomerulosclerosis
Mx
- steroids
- ACEi/ARB control BP
- calcineurinin inhibitors 2nd line
354
When do you see Kimmelstiel Wilson nodules?
Nephrotic syndrome cause by diabetes due to diffuse glomerular basement membrane thickening with _mesangial matrix nodules_
355
Which renal syndrome do you see red cell clasts in?
Nephritic syndrome
| - in urine as red cells clumped together and leaked out into tubules
356
When does acute post-infectious glomerulonephritis occur and why?
1-3 weeks after strep throat infection or impetigo due to immune complex deposition damaging glomeruli
357
When does IgA nephropathy present and why?
1-2 days after URTI with frank haematuria due to deposition of IgA immune complexes in glomeruli
358
Most aggressive form of glomerulonephritis and how does it present
```
Rapidly progressive (cresenteric) glomerulonephritis
- oliguria and renal failure more pronounced in this nephritic syndrome presentation
```
359
Types of rapidly progressive GN
Type 1
- anti-GBM antibody (Goodpasture's)
Type 2
- immune complex mediated
Type 3
- pauci-immune/ANCA-associated
360
Pt presents with nephritic syndrome, sensorineural deafness and cataracts at age 18
What is this caused by?
ALPORT'S SYNDROME
- X-linked recessive disorder
- Mutation in type IV collage alpha 5 chain
- eye disorders: lens disolcation, cataracts
361
Pt comes in and + blood found on dipstick
Tells GP dad has same problem
What is this?
Thin basement membrane disease/benign familial haematuria
362
What causes benign familial haematuria?
Diffuse thinning of GBM due to mutation in type IV collage alpha 4 chain
- autosomal dominant
- renal function typically unaffected
- chill vibes, no woz, usually asx
363
Ddx if pt presents with asx haematuria
1. Benign familial haematuria
- more likely microscopic haematuria
2. IgA nephropathy
- more likely frank haematuria, Cr raised, happens in Asians
3. Alport syndrome
- well rare, deafness & eye problems too
364
Renal biopsy shows necrosis of short segments of tubules
What this?
Acute tubular necrosis
365
Causes of acute tubular necrosis
Hypovolaemia
- ischaemic of nephrons
- despite cured hypovolaemia pt may present with persistent acute renal failure
Nephrotoxins
- aminoglycosides, NSAIDs
- radiographic contrast agents
- myoglobin
- heavy metals
366
Renal tumour biopsy shows well differentiated transparent cells
Clear cell carcinoma
367
Renal tumour in pt with dialysis-associated cystic disease
Papillary carcinoma
368
Renal tumour biopsy shows pale, eosinophilic cells
Chromophobe renal carcinoma
369
Renal histology shows wire loop capillaries and GBM has a lumpy-bumpy granular fashion
What this and how would it present?
Lupus nephritis
- immune complex deposition in capillaries and GBM cause this
- present with renal failure, nephrotic syndrome, urinary abnormalities
370
Chronic renal failure stages GFRs
1. >90
2. 60-89
3. 30-59
4. 15-29
5. <15 or treated with renal replacement therapy
371
Which mutations cause adult polycystic kidney disease and how is it inherited?
Autosomal dominant
- PKD1, chr16
- PKD2, chr14
372
Clinical features of adult polycystic kidney disease
```
MISHAPES
abdominal Mass
Infected cysts & Increased BP
Stones
Haematuria
Aneurysms (berry)
Polyuria & nocturia
Extra-renal cysts
Systolic murmur (mitral valve)
```
373
What causes acute interstitial nephritis?
Hypersensitivity reaction to drugs
| - abx, NSAIDs, diuretics
374
Histology seen in acute interstitial nephritis
Inflammatory infiltrate with tubular injury, eosinophils & granulomas
375
HUS features
TRIAD
- MAHA
- thrombocytopenia
- renal failure
376
TTP features
PENTAD
- MAHA
- thrombocytopenia
- renal failure
- fever
- neurological sx: confusion, seizures, headaches
377
Cells that make up oesophagus
```
Squamous epithelium (proximal 2/3 - bottom bit)
Columnar epithelium (distal 1/3 - top bit)
```
Joined by squamo-columnar junction/Z-line
378
Most common cause of oesophagitis and its complications
GORD
- ulceration
- haemorrhage
- haematemesis/melaena
- Barrett's oesophagus
- stricture
- perforation
379
Tx for GORD
Stop smoking
Weight loss
PPI/H1 antagonists
380
How does oesophageal adenocarcinoma occur?
1. Metaplasia of squamous -> columnar (Barrett's)
2. Dysplasia
3. Cancer rip
RFs: smoking, obesity, prior radiation therapy
381
Pt presents with progressive dysphagia, odynophagia, anorexia, and severe wt loss
They are a known alcoholic and heavy smoker
What this?
Squamous cell carcinoma
| - rapid growth usually found in middle
382
What are squamous cell oesophageal carcinomas associated with?
```
Alcohol, smoking
Achalasia of cardia
Plummer-Vinson syndrome
Nutritional deficiencies
Nitrosamines
HPV
x6 more common in black people
M > F
```
383
What causes varices?
Portal HTN leading to back pressure forming engorged dilated veins
384
Cells of stomach
Lined by gastric mucosa, columnar epithelium (mucin secreting) and glands
385
Epigastric pain that is worse with food
What ix needed?
Gastric ulcer
Biopsy for H pylori histology status (punched out lesion with rolled margins)
386
RFs for gastric ulcers
```
H pylori
Smoking
NSAIDs
Stress
Delayed gastric emptying
Elderly
```
387
Tx for gastric lymphomas
Caused by H pylori due to chronic antigen stimulation so remove cause!
Triple therapy: PPI + clarithromycin + amox/metro
388
Causes of acute gastritis
Neutrophil mediated
- aspirin
- NSAIDs
- corrosives (bleach)
- acute H pylori
- severe stress (burns)
389
Causes of chronic gastritis
Lymphocyte and plasma cell mediated
- H pylori
- pernicious anaemia
- alcohol
- smoking
390
Epigastric pain worse at night and relieved by food and milk
What is this and its possible causes?
Duodenal ulcer
RFs:
- H pylori
- drugs (aspirin, NSAIDs, steroids)
- smoking
- acid secretion
391
Gold standard ix for coeliac disease and its findings
Upper GI endoscopy and duodenal biopsy
- villous atrophy
- crypt hyperplasia
- lymphocyte infiltrates
392
Cancers associated with coeliac disease
Enteropathy-associated T cell lymphomas (duodenal)
Non-Hodgkin's lymphoma
Adenocarcinoma of small intestine
393
Which parts of the GI tract are most commonly affected by ischaemic colitis?
Splenic flexure
- SMA transition to IMA
Rectosigmoid
- IMA transition to internal iliac
394
Histology seen in Crohn's
```
Skip lesions
Cobblestone appearance
Aphthous ulcer - rosethorn ulcers as they join to form serpentine ulcers
Non-caseating granulomas
Transmural inflammation
Fistula formation
```
395
Histology seen in UC
```
Continous involvement of mucosa
Backwash ileitis if severe
Superficial inflammation
No granulomas/fissures/fistulas
Pseudopolyps (can fuse to form mucosal bridges)
```
396
Complications of Crohn's
Strictures
Fistulae
Abscess formation
Perforation
397
Complications of UC
Severe haemorrhage
Toxic megacolon
Colectomy
Adenocarcinoma
398
Tx for Crohn's
Mild
- prednisolone
Severe
- IV hydrocortisone, metronidazole
Additional
- azathioprine
- methotrexate
- infliximab
399
Tx for UC
Mild
- prednisolone + mesalazine (5 ASA)
Moderate
- prednisolone + 5-ASA + steroid enema bd
Severe
- admit, NBM, IV fluids, IV hydrocortisone, rectal steroids
Remission
- 5-ASA 1st line, azathioprine 2nd line
400
Tx for C diff
Metronidazole or Vancomycin
401
Complications of diverticular disease
Diverticulitis (fever, peritonism)
Gross perforation
Fistula
Obstruction (due to fibrosis)
402
Carcinoid syndrome features
Serotonin release from enterochromaffin cell origins in tumours:
- Bronchoconstriction
- Flushing
- Diarrhoea
403
Carcinoid crisis features
```
Life threatening vasodilation
Hypotension
Tachycardia
Bronchoconstriction
Hyperglycaemia
```
404
Tx of carcinoid syndrome
Octreotide (somatostatin analogue)
405
RFs for neoplastic polyps to become malignant
Large size
Degree of dysplasia
Increased villous component
406
Which gene mutation causes neoplastic polyps?
APC gene
407
Once APC gene first mutated in colon, which following genes being hit progress to carcinoma?
KRAS, LOF mutations of p53
408
Peutz-Jeghers syndrome features
Autosomal dominant - LKB1
= multiple hamartomatous polyps
= mucocutaenous hyperpigmentation
= freckles on mouth, palms, soles
= risk of intussusception and malignancy
409
Most common type of colorectal cancer
Adenocarcinoma (98% cases)
410
Compare right and left-sided colorectal cancer presentations
Right
- iron deficiency anaemia
- wt loss
Left
- change in bowel habit
- crampy LLQ pain
411
Colorectal cancer staging
Duke's staging
A: confined to mucosa (5yr survival >95%)
B1: extending into muscularis propria (5yr survival 67%)
B2: transmural invasion, no lymph nodes involved (5yr survival 54%)
C1: extending to muscularis propria, with LN metastases (5yr survival 43%)
C2: transmural invasion, with lymph node metastases (5yr survival 23%)
D: distant metastases (5yr survival <10%)
412
Which chemotherapy is used for terminal colorectal cancer?
Fluorouracil
413
Which familial syndromes increase the risk of colorectal cancer?
Familial adenomatous polyposis (FAP)
Gardners
Hereditary non-polyposis colorectal cancer/Lynch syndrome (HNPCC)
414
What cancers is Lynch syndrome associated with?
```
Colorectal
Endometrial
Ovarian
Small bowel
Transitional cell
Stomach carcinoma
```
415
What makes up a hepatic lobule?
Think of like hexagon
- at the centre is hepatic vein = centrilobular vein
- points of hexagon = portal tracts
Portal tracts made up of portal triad
1. branches of bile ducts
2. hepatic artery
3. portal vein
416
3 zones of the liver
Zone 1 (closest to portal triad)
- periportal hepatocytes
- more oxygen
Zone 2 (mid zone)
Zone 3 (closest to terminal hepatic vein)
- perivenular hapetocytes
- most mature and metabolically active
- most liver enzymes
417
Functions of the liver
```
Metabolism
Protein synthesis
Storage
Hormone metabolism
Bile synthesis
Immune function
```
418
Spotty necrosis of liver on histopathology with small foci of inflammation and infiltrates
Cause?
Acute hepatitis
419
Histopathology of chronic hepatitis
1. Portal inflammation
2. Peicemeal necrosis (no clear border between portal tract and parenchyma)
3. Lobular inflammation
4. Bridging between portal vein to central vein which evolves into cirrhosis
420
Histopathology of cirrhosis
Hepatocyte necrosis
Fibrosis
Nodules of regenerating hepatocytes
Disturbance of vascular architecture
421
Major causes of cirrhosis
1. Alcoholic liver disease
2. Non-alcoholic fatty liver disease
3. Chronic viral hep (B+/-D, C)
4. Autoimmune
5. Biliary (PBC, PSC)
6. Genetic
7. Drugs (methotrexate)
422
Genetic causes of cirrhosis
1. Haemochromatosis- HFE gene Chr 6
2. Wilson’s disease- ATP7B gene Chr 13
3. Alpha 1 antitrypsin deficiency (A1AT)
4. Galactosaemia
5. Glycogen storage disease
423
Micronodular causes of cirrhosis
Alcoholic hepatitis
| Biliary tract disease
424
Macronodular causes of cirrhosis
Viral hepatitis
Wilson's disease
Alpha 1 antitrypsin deficiency
425
What score is used for cirrhosis?
Modified Child's Pugh Score (ABCDE)
- Albumin
- Bilirubin
- Clotting prothrombin time
- Distention (ascites)
- Encephalopathy
*determines prognosis*
426
Large, pale, yellow and greasy liver with accumulation of fat droplets in hepatocytes
Hepatic steatosis (fatty liver)
427
Large, fibrotic liver with hepatocyte ballooning and necrosis alongside Mallory Denk bodies
Alcoholic hepatitis
| = seen acutely after heavy night of drinking
428
Yellow-tan, fatty and enlarged liver that transforms into shrunken, non-fatty, brown sad boy
Alcoholic cirrhosis
| - micronodular = small nodules & bands of fibrous tissue
429
What are Mallory Denk bodies?
Cytoplasmic hyaline inclusions of hepatocytes
430
NAFLD histology
Simple steatosis
- fatty infiltrates, relatively benign
NASH
- steatosis + hepatitis
- can progress to cirrhosis
431
Types of autoimmune hepatitis
Type 1
- ANA, anti-SMA, anti-actin Ig, anti-soluble liver antigen Ig
Type 2
- anti-LKM Ig
Associated with HLA-DR3 all
432
Autoimmune inflammatory destruction of medium sized intrahepatic bile ducts
What is this and what can it progress to?
Primary biliary cirrhosis
Leads to cholestasis and slow development of cirrhosis
433
Inflammation and obliterative fibrosis of extrahepatic and intrahepatic bile ducts
What is this and what can it progress to?
Primary sclerosing cholangitis
Leads to multi-focal stricture formation with dilation of preserved segments
Increased incidence of cholangiocarcinoma in the long-term
434
Ix findings in primary biliary cirrhosis
Increased serum ALP, cholesterol, IgM, bilirubin (late)
Anti-mitochondrial antibodies
US: no bile duct dilatation
435
Ix findings in primary sclerosing cholangitis
Increased serum ALP, associated with auto-Ig (p-ANCA)
Associated with UC
US: bile duct dilatation
ERCP: beading of bile ducts (strictures)
436
Compare histology of PBC and PSC
PBC
- bile duct loss with granulomas
PBS
- onion skinning fibrosis (concentric fibrosis)
437
Benign tumours in the live
Hepatic adenoma
- associated w OCP
Haemangioma
- most common
438
Most common malignant liver lesion
Metastasis
| - secondary tumours from GI tract, breast or bronchus
439
Causes of hepatocellular Ca
Chronic liver disease
- viral hep
- alcoholic
- haemochromatosis
- NAFLD
- aflatoxin
- androgenic steroids
440
Ix for hepatocellular Ca
alpha-fetoprotein
| USS
441
Causes of cholanigiocarinoma
```
Primary sclerosing cholangitis
Parasitic liver disease
Chronic liver disease
Congenital liver abnormalities
Lynch syndrome type II
```
442
Highly invasive liver cancer affecting the vascular epithelium
Haemangiosarcoma
443
Liver cancer that originates from immature liver precursor cells seen in children
Hepatoblastoma
444
How are the following genetic causes of cirrhosis inherited?
a) Haemochromatosis
b) Wilson's diease
c) Alpha 1 antitrypsin deficiency
a) autosomal recessive
b) autosomal recessive
c) autosomal dominant/codominant
445
Periodic acid Schiff detects which liver disease?
Alpha 1 antitrypsin deficiency
| = intracytoplasmic inclusions of A1AT stained by it
446
What are the intracytoplasmic inclusions of alpha 1 antitrypsin stained by?
Periodic acid Schiff
447
Features of haemochromatosis
```
Skin bronzing (melanin deposition)
Diabetes
Hepatomegaly with micronodular cirrhosis
Cardiomyopathy
Hypogonadism
Pseudogout
```
448
Features of Wilson's disease
Liver disease: acute hepatitis, fulminant liver
failure or cirrhosis
Neuro disease: parkinsonism, psychosis,
dementia (basal ganglia involvement)
Kayser Fleischer rings: copper deposits in
Descemet’s membrane in cornea
449
Features of alpha 1 antitrypsin deficiency
Kids: neonatal jaundice
Adults: emphysema and chronic
liver disease
450
Tx of haemochromatosis
Venesection
| Desferrioxamine
451
Tx of Wilson's disease
Lifelong penicillamine
| May require liver transplant
452
Breast Ca monoclonal antibody if HER2 receptor present (poor prognosis)
Trastuzumab
453
Tram track opacities in lung
Bronchiectasis
454
Fitz Hugh Curtis syndrome features
Complication of PID:
- RUQ pain from peri-hepatitis
- Violin string peri-hepatic adhesions
455
Histological findings in endometriosis
Macro
- red-blue to brown nodules = powder burns
- chocolates cysts in ovaries
Micro
- endometrial glands and stroma
456
Sharply circumscribed, discrete, round, firm, gray-white tumour found in the uterus containing bundles of smooth muscle cells
Leiomyoma (fibroid)
457
Which system is used to stage endometrial Ca?
FIGO
458
Endometrial Ca types
Endometrioid
- peri-menopausal, related to E2
= ADENOCARCINOMA
Non-endometrioid
- post-menopausal, not related to E2
= PAPILLARY, SEROUS, CLEAR CELL
459
HPV associated with VIN
HPV-16
460
What cell type is Paget's of the vulva?
Adenocarcinoma in situ
461
Normal vulva hsitology
Squamous epithelium
462
Epithelial ovarian tumours
Serous cystadenoma
Mucinous cystadenoma
Endometrioid
Clear cell
463
Germ cell ovarian tumours
Dysgerminoma (female testicular seminoma)
Teratoma
Choriocarcinoma
464
Sex cord/stroma ovarian tumours
Fibroma
Granulosa-theca cell tumour
Sertoli-Leydig cell tumour
465
Metastatic ovarian tumour and its histology
Krukenberg tumour
| = signet ring cells from gastric/colonic cancer
466
Psammoma bodies and columnar epitherlium of ovarian tumour
Serous cystadenoma
| - most common type of epithelial tumour
467
Ovarian tumour that causes pseudomyxoma peritonei
Mucinous cystadenoma
| - 75% K-ras mutation
468
Abundanct clear cytoplasm and hobnail appearance of ovarian tumour
Clear cell
| - poor prognosis
469
What do the following ovarian tumours produce?
a) teratoma
b) chroriocarcinoma
c) granulosa-theca cell tumour
d) sertoli-leydig cell tumour
a) teratoma = AFP
b) chroriocarcinoma = hCG
c) granulosa-theca cell tumour = E2
d) sertoli-leydig cell tumour = androgens
470
Which ovarian tumour is associated with Meig's - and what is it?
Fibroma
Meig's = ascites + pleural effusion + ovarian tumour
471
FIGO ovarian staging system
Stage I: limited to ovaries (75-90%)
Stage II: limited to pelvis (45-60%)
Stage III: limited to abdomen (including regional LN metastases) (30-40%)
Stage IV: distance metastases outside abdominal cavity (<20%)
472
Most common type of cervical carcinoma
Squamous cell carcinoma
473
FIGO cervical staging system
Stage 0: CIN
Stage I: limited to cervix (80-95%)
Stage II: extended beyond uterus but not to pelvic side wall or lower 1/3 vagina
(75%)
Stage III: extension to pelvic side wall and/or lower 1/3 vagina (50%)
Stage IV: extension beyond true pelvis or involvement of bladder/bowel mucosa
(20-30%)
474
What is the transformation zone of the cervix?
Area where columnar epithelium transforms into squamous cells
- normal physiological process
- susceptible to
malignant change
475
Which HPV strains cause CIN?
HPV 16 & 18
476
CIN histology findings
CIN 1 = dysplasia confined to lower 1/3 of epithelium
CIN 2 = lower 2/3
CIN 3 = full thickness, but basement membrane intact
477
Most common cause of strokes
Atherosclerosis
478
Most common artery affected in strokes
Middle cerebral artery
479
Most common vascular territories affected by TIA
Embolic atherogenic debris from carotid artery travels to ophthalmic branch of internal carotid
480
Contralateral leg paresis, sensory loss, cognitive deficits
Which vascular territory affected?
Anterior cerebral artery
481
Contralateral weakness and sensory loss of face and arm, cortical sensory loss, aphasia
Which vascular territory affected?
Middle cerebral artery
482
Contralateral hemianopia/quadrantanopia, CN III and IV palsy, hemiparesis, sensory loss, amnesia, decreased level of consciousness
Which vascular territory affected?
Posterior cerebral artery
483
Impaired extraocular muscles, vertical nystagmus, reactive miosis, hemi/quadriplegia, dysarthria, locked-in syndrome, coma
Which vascular territory affected?
Proximal basilar artery (usually thrombosis)
484
Somnolence, memory and behaviour abnormalities, oculomotor deficit
Which vascular territory affected?
Distal basilar artery (usually emoblic)
485
Lateral medullary syndrome
Ipsilateral
- ataxia
- Horner's
- facial sensory loss
Contralateral
- limb impairment of pain temperature, sensation
Nystagmus
N&V
Dysphagia, dysarthria
Hiccups
486
Contralateral hemiparesis that is facial sparing, contralateral impaired proprioception and vibration sensation, ipsilateral tongue weakness
Which vascular territory affected?
Medial medullary infarct (anterior spinal artery assoc w anterior cord infarct also)
487
What would you see with lacunar infarcts?
1. Pure motor hemiparesis (posterior limb of internal capsule): contralateral arm, leg,
and face
2. Pure sensory loss (ventral thalamic): hemisensory loss
3. Ataxic hemiparesis (ventral pons or internal capsule): ipsilateral ataxia and leg
paresis
4. Dysarthria-clumsy hand syndrome (ventral pons or genu of internal capsule):
dysarthria, facial weakness, dysphagia, mild hand weakness and clumsiness
488
Skull fracture → rapid arterial bleed → lucid interval → LoC
Extradural haemorrhage
489
History of minor trauma → damaged bridging veins with slow
venous bleed → fluctuating
consciousness
Subdural haemorrhage
490
Which artery is commonly affected in extradural haemorrhages?
Middle meningeal artery (superficial)
491
Who's at risk of subdural haemorrhages?
Elderly
Alcoholics
Associated w brain atrophy
492
When does subacute sclerosing panencephalitis occur?
Post-measles infection
493
Most common form of adult brain tumour
Metastatic lesions
| - come from lung, breast, malignant melanoma
494
Primary brain tumour in pt with neurofibromatosis type II
Meningioma
495
Primary brain tumour affecting the ventricles and causing hydrocephalus
Ependymoma
496
Primary brain tumour presenting in a child with an indolent presentation
Pilocytic astrocytoma
497
Primary brain tumour that is soft, gelatinous, and calcified
Oligodendroma
498
Most common types of nervous system tumours
Astrocytomas
Meningiomas
Pituitary adenomas
Metastatic tumours (small cell, breast)
499
Tumours seen in Von Hippel-Lindau syndrome
```
Haemangioblastoma of cerebellum
Brainstem and spinal cord
Retina
Renal cysts
Phaeochromocytomas
```
500
Tumours seen in tuberous sclerosis
Giant cell astrocytoma
Cortical tuber
Supependymal nodules
Calcifications on CT
501
Tumours seen in neurofibromatosis type I
Optic glioma
| Neurofibroma astrocytoma
502
Tumours seen in neurofibromatosis type II
Vestibular schwannoma
Meningioma
Ependymoma
Astrocytoma
503
Tumours seen in multiple endocrine neoplasia type I affecting the CNS
Pituitary adenoma
Year 5 Pathology
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