1
Q
Layers of the GI tract
A
1) Epithelium, lamina propria, muscularis mucosa
2) Submucosa
3) Muscularis propria (types include circular, longitudinal, oblique)
4) Serosa
2
Q
Adenocarcinoma of oesophagus
A
GORD Barrettâs Developed countries Caucasian Lower 1/3 of oesophagus
3
Q
Squamous cell carcinoma of oesophagus
A
Smoking and alcohol
Middle 1/3 oesophagus
Developing countries
4
Q
What is Barrettâs and what is a poor prognostic marker
A
Metaplasia from squamous to columnar
Goblet cells - intestinal metaplasia (more cancer risks)
No goblets cells - gastric metaplasia
5
Q
Where in stomach does H.pylori occur?
A
Pyloric antrum and canal
6
Q
Causes of acute gastritis
A
Chemicals, aspirin, NSAIDs, alcohol, corrosives, h.pylori
7
Q
Causes of chronic gastritis
A
A - autoimmune (pernicious anaemia)
B - bacterial (h.pylori)
C - chemicals (NSAIDS, bile reflux)
8
Q
Describe H.pylori
A
- Spiral flagellated gram negative bacteria
- 90% of chronic gastritis cases
- can lead to development of lymphoid follicles + lymphoma (MALToma - Bcell)
- can also lead to intestinal metaplasia (goblet cells) and cause adenocarcinoma
9
Q
What is an ulcer?
A
Loss of tissue beyond the muscularis mucosa into the sub serosa
Chronic - scarring and fibrosis
10
Q
Gastric vs duodenal ulcer
A
Gastric - worse when eating, older patients,
Duodenal- relieved by eating, worse on empty stomach, at night, younger patients
Biopsy all ulcers
11
Q
Gastric cancer- adenocarcinoma and other types
A
M>F, Japan very high
Adenocarcinoma is >95%
Leather bottle stomach on endoscopy
Intestinal-> glands, well differentiated, mucin forming
Diffuse - no gland formation, signet ring cells, poor differentiation, poor prognosis
Others- MALToma, SCC, neuroendocrine, gastrointestinal stromal tumour
12
Q
Menetriers disease
A
Hyperplasia of gastric pitts and increase in mucosal thickness
13
Q
What is the histology of the duodenum?
A
Intestinal type epithelium, glandular columnar with goblet cells, has villi
14
Q
What can H.pylori do in the duodenum?
A
It can cause gastric metaplasia and result in ulcers -> duodenitis
15
Q
What is coeliacs disease?
Investigations and histology
A
IgA anti- tTG
Gold standard is duodenal biopsy and histology
Histology - villus atrophy, crypt hyperplasia, more infra epithelial lymphocytes
Enteropathy associated T cell lymphoma (EATL) risk increases
16
Q
Liver histology, also describe the zones of the liver
A
- Hepatic lobules, hexagonal shape
- In each corner of lobule there is a portal triad of bile duct, portal venue and arteriole
- Blood from portal triad to central vein (in centre of lobule from edges to centre) via sinusoids
- Bile goes via caniculi away from, central vein to bile ducts
Zones:
- Area between the triad and central vein is divided
- 1 has most oxygen and highest ALP
- 3 has most metabolically active cells so at risk of hypoxia
17
Q
Acute hepatitis histology?
A
Spotty necrosis
Can be caused by viruses, drugs etc
18
Q
Describe histology of chronic hepatitis
A
Piecemeal necrosis (Interface hepatitis)
Causes: viruses, drugs, PBC, PSC, Wilsonâs, haemochromatosis
19
Q
Features of obstructive jaundice
A
- Itching
- Pale stool
- Dark urine (conjugated bilirubin in urine)
- Lack of urinary urobiliogen (itâs is colourless)
20
Q
What is urinary urobilinogen?
A
Bilirubin that has been converted by gut bacteria and reabsorbed by enterohepatic circulation for kidney excretion
Bilirubin must be conjugated by liver before excretion via bile or kidneys
21
Q
What is transudate and some causes?
A
Protein <30g/L
Causes: cardiac failure, renal failure, cirrhosis, hypoalbuminaemia (like pressure is forcing it)
22
Q
What is exudate and some of the causes?
A
Protein>30g/L
Inflammation, infection and malignancy, e.g. TB, malignant infiltration of peritoneum
This is to do with secretion
23
Q
Histology of alcohol induced liver disease including the stages of steatosis, fibrosis and cirrhosis
A
Steatosis - fat, neutrophils (NASH looks like alcoholic fatty liver disease but is different based on Hx)
Alcoholic hepatitis - neutrophils, bile accumulation, bile flow blocked, balloon cells
Fibrosis - collagen blue stain chows collagen deposited, indicates scarring
Cirrhosis - regenerative nodules and cuff of fibrous connective tissue. Fibrous tissue between portal tracts too, distortion of vasculature architecture (disorganised regeneration that leads to portal HTN)
24
Q
Features of CLD
A
Palmar erythema, gynaecomastia, spider naevi, dupytrens contracture
25
Features of portal HTN
Caput Medusae (swollen abdomen veins) splenomegaly, ascites
26
Feature of hepatic encephalopathy
Asterixis
27
Types of autoimmune hepatitis and the sequlae
Interface hepatitis
Inflammation, necrosis, fibrosis, cirrhosis and liver failure
1 - anti smooth muscle Abs and +- ANA, steroids Tx, from 10 years old onwards
2 - anti liver kidney microsomal Abs, poor steroid response, paeds
3 - anti soluble liver antigens Abs
28
PBC - antibodies, symptoms and associations
- Antimithochondrial Abs
- Intrahepatic bile ducts destroyed
- Other AI disorders: scleroderma, RA
- High ALP, bilirubin and cholesterol
- Chronic granulomatous inflammation of bile duct
- Itching, fatigue, abdo pain
29
Most common drug cause of hepatic adenoma
COCP
Hemangioma is most common benign lesion
30
What is portal inflammation vs interface vs lobular?
Portal - within the portal
Interface - between portal tract and parenchyma
Lobular - across whole lobe
31
Stages of fibrosis
0: no fibrosis
F1: portal fibrosis without septa
F2: portal fibrosis with few septa
F3: numerous septa without cirrhosis
F4: cirrhosis
32
What is Wilsonâs disease and the signs?
Recessive, copper transport gene mutation, copper accumulated causing Parkinsonism features, liver disease, Kayser Fleisher rings, psychiatric problems
Rhodanine stain
33
Hereditary haemochromatosis - symptoms, management and pathophysiology
Recessive, excess iron absorption and deposition, haemosiderin deposited in organs causing rusty brown appearance
Brown bronze skin colour, steatorrhoea, diabetes, therapeutic phlebotomy
34
What is Gilbertâs?
Recessive, reduces UDP glucoronyl transferase and reduced bilirubin conjugation
Normal LFTs, raised unconjugated bilrubin
Fasting is trigger
35
What is Budd chiari syndrome?
Hepatic vein thrombosis, outflow obstruction, associated with polycythaemia rubra vera, hepatosplenomegaly, ascites
36
Pemphigus vulgaris
```
Superficial
Easily ruptures
Nikolsky sign
Antibodies to desmoglein 1/3
Acantholytic cells - separation of keratinocytes due to loss of cadherin
```
37
Bullpus pemphigoid
Elderly
Flexor surfaces
Anti-hemidesmosome Abs
Tense bullae do not repute easily, sub epidermal
38
Pemphigous foliaceus
So superficial rarely see intact bullae, stratum corneum separates from epidermis
39
Dermatitis herptiformis
Coeliac disease, itchy bullous rash on extensor surfaces
40
Epidermolysis bullosa
Collagen autoantibodies, induced by trauma
41
Vitiligo
Anti melanocytes antibodies
42
Psoriasis
Parakeratosis - thick keratin layer, silvery scales
Munro microabscess
Loss of stratum granulosum - auspitz sign
Clubbing of rete ridges - test tube rack on histology
43
Lichen planus
Purple, pruritic, papules and plaques
White lacy appearance of mouth
Inner surface of wrists
44
Pyoderma gangrenosum
Form of vasculitis not gangrene
45
Seborrheic keratosis
Elderly, benign
Pigmented, stuck on appearance, cauliflower
Over proliferation of epidermis
46
Actinic keratosis
Pre malignant -> SCC
| Sun exposed areas, sandpaper like, warty
47
Sebaceous cyst
Smooth, non mobile, punctum, smelly
48
Pityriasis rosea
Salmon pink lesion, multiple oval machines in fir tree distribution, follow an URTI
49
BCC
Smooth, pearly, central ulcer and fine telangiectasia, sun exposed area, elderly, locally invasive
50
SCC
Invasion through BM, can metastasise, sun exposed areas,
51
Bowenâs disease
SCC in situ, full thickness, no BM invasion
52
Erythema multiforme
Macules, papules, urticaria
Stevens Johnsonâs syndrome - affects mucosa too
53
What are two key functioning parts of the pancreas
Islet of langeehans
Acini- glandular functional units
54
Acute pancreatitis sequale
What is the most sensitive marker of pancreatitis?
Causes
Histology
Insult, necrosis, enzyme release, acute inflammation
Lipase
I GET SMASHED- idiopathic, gallstones, ethanol, trauma, steroids, mumps, autoimmune, scorpion venom, hyperlipiadaemia, hypercalcaemia, hypothermia, ERCP, drugs (thiazides)
Acute inflammation and necrosis
55
What is a pseudocyst and what causes it?
Collection of fluid after acute pancreatitis. Lined by fibrous tissue containing enzymes and necrotic material. Can get infected and form abscess,
Causes abdominal discomfort
Spontaneous resolution
56
Chronic pancreatitis causes, histology, symptoms and investigations
Alcohol, haemochromatosis, gallstones, CF, tumours
Parenchyma fibrosis, atrophic acini, dilation of ducts, duct strictures, intrapancreatic caliculi
Severe epigastric pain radiating to back, steatorrhoea, malabsorption
Pancreatic calcifications on AXR/CT
57
Pancreatic cancer, presentation, epidemiology, investigations
Ductal adenocarcinoma is most common
>60, M>F
5 year survival 5%
At head >body>tail
Due to location causes jaundice
Weight loss, abdo and back pain, painless jaundice, pruritis, steatorrhoea, DM, ascites, VTE
Tumour marker CA19-9
Whipples for head of cancer, palliative chemo
Acinar cell adenocarcinoma, pancreatoblastoma (childhood, rare)
No SCC
58
Neuroendocrine tumours
Tail>body>head
Men1 associated
Chromoganin levels in blood
Can be functioning or non - e.g. insulinoma, gastrinoma
59
Gallstones - RF, types
Female, Native American, OCP, rapid weight loss e.g. surgery
Cholesterol (wonât show on x ray), pigmented (calcium salts, unc bilirubin)
60
Acute vs chronic cholecystitis
Acute- lots of neutrophils, due to stones
Chronic - fibrosis, rokitansky aschoff sinuses (diverticula)
61
Gallbladder cancer
Mostly due to gallstones, uncommon though
62
Diverticulitis
Old
Rectal bleeding
Fever
LIF
63
UC
Continuous from rectum proximally, no granulomas, mucosal inflammation
Blood and mucus, associated with PSC, can have pseudo polyps in bowel, can get ulcers
64
Crohns
Patchy inflammation, full thickness, non caseating granulomas, anywhere in GI tract, common at terminal ileum, thickness wall (rubber hose)
Cobblestone mucosa
Tend to get fistula and fissures
65
Colorectal cancer
Older age, western populations, mostly adenocarcinoma, CFA tumour marker
66
Adenomas (polyps)
Sequence to adenocarcinoma and types of polyps
Precursor to colorectal ca
Types: tubular, tubolovillous, villus
First mutation in APC, then second puts at risk of adenoma. Kras or p53 then turns into adenocarcinoma
67
Peutz jegher syndrome
dominant, multiple polyps, bleeding, freckles around mouth, palm and soles, increased risk of intususception, mucocutanenous pigmentation
68
Juvenile polypsosis
Dominant inheritance, lots of polyps, may need colectomy
69
FAP
APC gene mutation most common, lots of adenomatous polyps, high risk of adenocarcinoma, prophylactic colectomy.
At birth have hypertrophy of retinal pigment epithelium
70
Lynch syndrome (HNPCC)
Dominant inheritance, carcinomas before 30, few polyps, associated with endometrial/ovarian/small bowel/stomach ca
71
Acute mastitis
Red, painful, tender, hot, neutrophils
Lactational - cracked skin, stasis of milk, staph aureus, must continue expressing milk, surgically drain if abscess
Non-lactational - peri ductal inflammation
72
Duct ectasia
40-60, multiparous, smoker
Inflammation and dilation of breast ducts, nipple greeny brown discharge, breast pain, nipple retraction, periareolar mass
Mammography may mimic cancer, no risk of malignancy
73
Fat necrosis of breast
After trauma, in middle aged women, obese, after surgery or radiotherapy too, painless for, breast mass, can cause nipple retraction
Empty fat spaces, histocytes, multinucleated giant cells
74
Fibroadenoma
20-30, freely mobile breast lump
Changes in size with hormones
Stromal and glandular tissue
Has stromal, glandular cells
75
Fibrocystic disease
Hormone responsive, lumpy, common in premenopausal women, may be related to menstruation, dilated large calcified ducts
76
Intraductal papilloma
Bloody nipple discharge
Middle aged
Not seen on mammogram
Papillary mass within dilated duct
77
Flat epithelial atypia and in situ lobar neoplasia
FEA - earliest presentation of DCIS potentially, 4x increased cancer risk, cribriform areas (punched out holes)
ISLN - solid proliferation of cells, 7-12x times increased risk of cancer
78
Breast cancer
- carcinoma in situ, invasive breast carcinoma and basal like carcinoma
Most common ca in women, gold standard for diagnosis is histopathology
Carcinoma in situ:
- not invaded BM
Complete excision with clear margin in curative
- lobular(no necrosis, pre menopausal) and ductal (necrosis, pre or post, ducts with atypical cells)
Invasive breast carcinoma:
Ductal, lobular, tubular, mucinous
Indications: peau dâorange, tethering, pagers disease (eczema), nipple retraction, lymphadenopathy, bloody discharge, ulceration
Basal-like carcinoma: sheets of atypical cells, lymphocytic infiltrate and central necrosis
79
Grading of invasive breast cancer and immunotyping
Grading: core biopsy & histological analysis of 3 things = mitotic figures, nuclear pleomorphism, tubule
formation
Higher grade = poorly differentiated
Once diagnosed all are assessed for ER/PR/HER2 receptors
ER/PR +ve = good prognosis - will respond to Tamoxifen
HER2 +ve = worse prognosis - treat with Herceptin
Most important prognostic factor for BC = status of the axillary LNs
80
PSC
Inflammation causes scars within the bile ducts - makes the ducts hard and narrow and gradually causes liver damage.
Associated with UC
81
Pathogenesis of atherosclerosis
Pathogenesis: endothelial injury â LDL adhesion â oxidised LDL â monocyte
adhesion to the endothelium â macrophages take up LDL & form foam cells â platelet adhesion & smooth muscle recruitment â smooth muscle cells form fibrous cap
82
Histology following an MI
- Under 6 hours â normal by histology
- 6â24 hrs - loss of nuclei, homogenous cytoplasm, necrotic cell death, contraction band necrosis (dark
red/pink wavy lines extending across the myocardial fibres)
- 1-4 days â infiltration of polymorphs (neutrophils) then macrophages (clear up debris), cytoplasm is
homogenous so it is difficult to see outlines between myocardial fibres
- 5-10: days removal of debris
- 1-2 weeks: granulation tissue, new capillaries, myofibroblasts & macrophages present in large numbers,
collagen synthesis, young scar
- Weeks-months: strengthening, decellularising scar - a pale white collagenous area within the interstitium
between myocardial fibres
83
Dilated, hypertrophic, restrictive cardiomyopathy
Dilated - progressive loss of myocyte
Idiopathic, infective, alcohol, chemo, diabetes, thyroid issues, haemochromatosis
Hypertrophic - LVH,, familial, cause of sudden death in young person
Restrictive -too stiff, idiopathic, amyloidosis, sarcoidosis, IBD
84
Rheumatic heart disease
Follows from rheumatic fever, mostly affects mitral valves
Antigenic mimicry and cross reactivity -> mitral stenosis or prolapse
Beady/warty fibrous vegetation, granulomas, regenerating myocytes
85
Mitral valve disease causes of each
AS: Elderly, Calcification, ejection-systolic murmur
AR: Causes = rheumatic HD, microbial endocarditis, Marfanâs, dissecting aneurysm, AS
MR: Left ventricular dilation, IE, CTD, post-MI, Rheumatic fever
Mitral valve prolapse (aka myxomatous mitral valve): middle-aged women, mid systolic click + late systolic
murmur
86
Non bacterial thrombotic endocarditis
>40, no inflammation or bacteria, mitral
Associated with malignancy, Dic, hyperccoagulable state
RECURRENT EMBOLI
87
Infective endocarditis - acute
Staph aureus, strep pyogenes, IVDU, tricuspid valve, larger thrombi, flucoxacillin IV
FOR MRSA: rifampicin, vancomycin, gentamicin
88
Subacute infective endocarditis- more common
PUO for months, strepviridans, aortic and mitral valves, post dental treatment soft thrombi
Microscopic haematuria, splenomegaly, heart murmurs
Benzypenicilln and gentamicin IV
89
Histology of thyroid gland
Follicles containing colloid, stroma between follicles, parafollicular cells secrete calcitonin
90
Histology of Hashimotoâs thyroiditis
Lymphoid cells, germinal centres
Epithelial cells enlarge and develop eosinophilic cytoplasm - hurthle cells
91
Histology of adrenal gland
Zona glomerulosa - aldosterone
Zone fasciculata - glucocorticoids
Zona reticularis - androgens and glucocorticoids
Medulla - noradrenaline and adrenaline
92
Thyroid carcinoma
Papillary - most common, IR, psammoma bodies, non functional, any age, good prognosis, may have cervical nodes mets
Follicular - middle aged,looks like normal thyroid, metastasise v blood
Medullary - parafollicular cell origin, produce calcitonin, staining positive with Congo red and apple green, CEA and calcitonin tumour marker
Anaplastic - aggressive, early mets, elderly, poor prognosis
93
Men syndrome
MEN 1: pituitary tumours, parathyroid tumours, pancreatic neuroendocrine tumours, facial angiofibromas &
collagenomas
MEN 2A: pheochromocytoma, hyperparathyroidism, medullary thyroid cancer
MEN2B: phaeochromocytoma, medullary thyroid cancer, marfanoid phenotype, neuromas of the GI tract
94
Fibrous dysplasia
- Females, age<30
- Proximal femur/tibia/skull/ribs
- Bone pain from early adulthood
- Soap bubble osteolytis
- Shepherds crook deformity
- Marrow replaced by fibrous stroma, rounded trabecular bone
95
Osteochondroma
10-20, males
End of long bones, common benign tumour
Bony protuberance with cartilage cap
96
Osteitis osteoma
Bone forming, adolescent, dull pain at night, relieved by aspirin, bulls eye x ray, normal bone
97
Enchondroma
Fingers and hands
Middle aged
Risk of malignant transformation
Popcorn/cotton wool calcification
98
Osteoma
Middle aged
Head and neck
Bony outgrowths
Associated with Gardner syndrome
99
Bone cyst
Fluid filled cyst, asymptomatic
| Lytic well defined lesion
100
Osteoblastoma
Speckled mineralisation
101
Osteosarcoma
```
Forms bone
10-30
End of long bones, most common is knee
Pain and mass
Elevated periosteum - codmans triangle
Sun-burst appearance
ALP positive
Poor prognosis
```
102
Chondrosarcoma
```
Cartilage producing
>40
Axial skeleton, proximal femur/tibia/pelvis
Lytic lesions with fluffy calcification
Surgery
```
103
Ewings sarcoma
<20
Diaphysis and metaphysics of long bones or pelvis
Onion skinning or periosteum,
Sheets of small round cells, ALP negative
Translocation of 11:22
104
Giant cell tumour
```
Knee
20-40
Lytic lesions, soap bubble appearance
Giant multinucleate osteoblasts
Tumour cells are the stromal cells
```
105
What is a green stick fracture?
Paediatric fracture, transverse but partial, remains attached
106
What is a comminuted fracture?
Segmental fracture, bone is splintered
107
What is a compound fracture?
Penetration of skin surface, open fracture
108
What is an impacted fracture?
Fracture site is crushed inwards
109
What is cancellous and cortical bone?
Cortical - calcified, long bones, mechanical and protective
| Cancellous - axial Skelton, vertebrae, pelvis etc
110
What is osteoarthritis?
Loss of joint space, subchondral cysts and subchondral sclerosis
111
What is RA? Signs, diagnosis and characteristic deformities
| Histology
Symmetrical, small joints of hands and feet and ankles, elbows and knees.
Serology â RF +ve in 60-70%, anti-CCP is more sensitive & specific than RF
Characteristic deformities:
- Radial deviation of wrist and ulnar deviation of fingers.
- swan neckâ and âBoutonniereâ deformity of fingers
- Z shaped thumb
- Synovial swelling
Swan neck = hyperextension of PIPJ & flexion of DIPJ
Boutonniere = flexion of PIPJ & hyperextension of DIPJ
Extra-articular features: Pulmonary fibrosis, vasculitis, amyloidosis, pericarditis, subcutaneous nodules, DVT
Histopathology â thickening of synovial membrane, hyperplasia of surface synoviocytes, intense inflammatory cell infiltrate & fibrin deposition & necrosis
112
What is ankylosing spondylitis?
An inflammatory disease
Can cause some of the bones in the spine (vertebrae) to fuse - bamboo spine
113
What is psoriatic arthritis?
New fluffy bone. Associated nail changes like pitting
114
Osteoporosis
Reduction in bone density
Normal biochemistry
Increased translucency
115
What is reactive arthritis?
HLA B27
Sacroiliac and knee joints, feet, ankles
Joint pain and swelling triggered by an infection in another part of the body â most often the intestines, genitals or urinary tract.
116
Small cell carcinoma
```
20%
Smoking, poor prognosis
Paraneoplastic syndromes (SIADH, hyponatraemia, ectopic ACTH)
Oat shaped cells
P53, RB1 mutation
Central
```
117
Squamous cell lung cancer
Smoking, most common subtype, central from bronchial epithelium, males, keratin and intracellular bridges, spread locally and metastasise late, kras - poor prognosis
118
Adenocarcinoma lung cancer
Non smokers, females, Asians, peripherally located, glandular differentiation, cells with mucin vacuoles, EGFR mutation, early mets, kras is poor prognosis
119
Large cell lung carcinoma
Poor differentiated large cells and large nuclei, no squamous or glandular differentiation, diagnosis of exclusion, poor
120
Asbestos lung conditions
Plumber and ship workers
Plaques are benign
Mesothelioma - thickened
pleura, malignant, latency or 25-45 years
Pneumoconiosis - fibrosis, benign, affects lower lobe
121
Extrinsic allergic alveolitis
Persistent productive cough, SOB, clubbing, weight loss
| Mouldy hay, farmers lung
122
Heart failure - right and left sequence
LHF â pulmonary oedema â intra-alveolar fluid & iron-laden macrophages
RHF â systemic oedema â venous congestion in organs â nutmeg liver
123
Pulmonary oedema
Presentation of PO = SOB, coughing up pink frothy sputum
Main cause = LHF
Nom-cardiac causes = fluid overload, RF, alveolar injury, neurogenic, high altitude
Cardiac causes on CXR â Kerley B-lines, bats wing appearance, cardiomegaly, upper lobe diversion of blood vessels, effusion
124
Pattern or acute lung injury - causes in adults and neonates
3 phases and histology
Rapid respiratory failure due to damage to alveolar epithelium & endothelium
Adults - ARDS
- 24-48 hrs post-trauma, burns or sepsis
Neonates - RDS (hyaline membrane disease)
Histology â diffuse alveolar damage, lungs are plum coloured, heavy & airless
3 phases of the acute lung injury pattern:
- Exudative phase: lungs become leaky
- Hyaline membrane phase: hyaline membranes line the alveolar spaces
- Organising phase: organisation of exudates to form granulation tissue
125
Asthma
Eosinophils and mast cells.muscular hypertrophy, airway narrowing, mucus plugging
Charcot Leyden crystals - eosinophils inflammation
Goblet cell hyperplasia
126
COPD - emphysema and chronic bronchitis
Complications, sequence and symptoms
Chronic bronchitis and emphysema
Chronic Bronchitis:
Chronic productive cough present on most days for 3 months over 2 consecutive years
Airway damage â dilated airways, goblet cell hyperplasia, inflammation, hypertrophy of mucous
glands
Complications: lung cancer (independent of smoking), recurrent infections, chronic respiratory failure,
pulmonary hypertension â cor pulmonale (RHF)
Emphysema:
Smoking â activation of macrophages & neutrophils â release of proteases â permanent loss of alveolar
parenchyma
Main 2 causes = smoking, alpha-1 antitrypsin deficiency
Smoking â loss centred around a bronchiole (centrilobular)
Doesnât cause a productive cough / recurrent infections - just causes SOB
Complications: bullae â pneumothorax, respiratory failure, PH â cor pulmonale
127
Bronchiectasis
Permanent abnormal bronchial dilation with inflammation and fibrosis
Causes: infection, CF, immunodeficiency,obstruction, asthma, sarcoidosis, obstruction
Complications: haemoptysis, infections, amyloidosis, RHF
Signer ring sign, tram track opacities
128
Lobar and bronchopulmomary pneumonia
Bronchopulmonary: infection is centred around an airway
Elderly, H.influenzae, Staph, Strep, Pneumococcus, patchy bronchial and peribronchial distribution
Lobar: infection within a specific lobe
Strep.pneumoniae
Histology: congestion (intra-alveolar fluid) â red hepatisation (intra-alveolar neutrophils) â grey
hepatisation (dry and firm as cells disintegrate & formation of intra-alveolar connective tissue) â
resolution (back to normal architecture)
129
Seminoma
Radiosensitive, germinal tumour, most common
130
SLE
Malar rash histology: lymphocytic infiltration of dermis, vacuolation of the basal epidermis, extravasation of RBCs in the upper dermis, immune complex deposition at dermal-epidermal junction
Kidney histology: Immune complex deposition in capillaries â âwire loop capillariesâ, deposition of immune
complexes & complement in GBM in a lumpy-bumpy granular fashion
Libman-Sacks Endocarditis: non-infective endocarditis associated with SLE, vegetations are made of immune cells & fibrin strands â murmur
131
Alzheimerâs disease
Beta amyloid, NFTS made of tau
| Generalised brain atrophy, widened sucks, narrowed gyri, enlarged ventricles
132
Parkinsonâs disease
What is it, signs and symptoms?
Loss of DA neurones from substantia migraine which project to basal ganglia. â stimulation of the motor cortex
âTRAPâ Tremor, Rigidity, Akinesia, Postural instability
Some develop psychiatric features later in disease e.g. Parkinsons Disease Dementia, hallucinations, anxiety
Lewy bodies present in affected neurons (alpha synuclein protein is main component; mutations reported in familial PD)
Familial Parkinsonâs - worse
133
Huntingtons disease
Cerebral atrophy in caudate nucleus and putamen
Number of repeats increases, earlier onset, dominant
134
Multiple sclerosis
Autoimmune demyelinating disease Usually presents with focal sx: optic neuritis, poor coordination.
Myelin basic protein & proteolipid protein = what is targeted
MRI: Demyelinating plaques - number of plaques is indicative of the severity of the disease
Females, 20-40 yrs of age
135
Oligodendroma
Soft gelatinous, calcified
136
Medulloblastoma
Always Grade 4, from embryonal cells - neuroepithelial precursors of brainstem / cerebellum, in the cerebellum! 2nd most common primary CNS tumour in children
Histology â high grade, small blue round cells with hyperchromatic cytoplasm, stains +ve for synaptophysin
137
Ependymoma
From ependymal cells lining the ventricles, hydrocephalus and ventricular tumour
138
Meningioma
Most benign, >40, mass under dura, mostly frontal lobe, focal symptoms, doesnât really invade brain
Neurofibromatosis type 2
139
Schwannoma
Acoustic neuroma
140
Glioma types
Oligodendrogliomas
Diffuse astrocytoma
Pilocytic astrocytoma
Glioblastoma multiformw
Can be diffuse or circumscribed
141
Pilocytic astrocytoma
Most common type of primary CNS tumour in children
Slowly growing benign tumour
MRI â well-circumscribed, cystic enhancing lesion
Histology â piloid (hairy) cells, Rosenthal fibres, low mitotic activity,
well-differentiated astroglial cells
142
Diffuse Astrocytoma
20-40
Cerebral hemispheres
Ill defined non enhancing lesion
Can become gliobastoma
143
Glioblastoma multiforme
Can arise from astrocytomas
Most common primary CNS tumors in adults
>50 yrs
MRI â heterogeneous enhancement, neoangiogenesis
Histology â large cells, highly polymorphic, high mitotic activity, microvascular proliferation and necrosis, pathological blood vessels
144
Oligodendroglioma
Diffuse, 20-40, slow growing, less aggressive, long hx of neurological signs, fried egg cells on histology
145
Subfalcine, subtentorial, tonsillar herniation
Subfalcine: cortex pushed under rigid falx cerebri of the dura, usually due to a SOL
Subtentorial (Uncal): herniation of medial temporal lobe through the tentorial notch, most common type
Tonsillar: cerebellar tonsils herniate through the foramen magnum - death due to pressure on medulla
146
Grading of CNS tumours
Classified according to tumour type & grade (level of
differentiation)
```
NO staging - primary CNS tumours donât spread
WHO Grading system:
- LOW Grades:
Grade 1: benign, long-term survival
Grade 2: survival > 5 years
```
- HIGH Grades:
Grade 3: survival <5 years
Grade 4: survival <1 year
147
Symptoms of Stroke :
ACA
MCA
PCA
ACA: contralateral hemiplegia & sensory loss leg>arm/face, personality
changes
MCA: contralateral hemiplegia & sensory loss arm/face>leg, if on the left - Brocaâs aphasia & Wernickeâs
aphasia, if on the right - neglect
PCA: contralateral hemianopia or quadrantopia, CN palsies
148
common cause of SAH
SAH: due to congenital berry aneurysm (most common at bifurcation of internal carotid), sudden onset thunderclap
headache
149
HIV tuberculoma
Ring enhancing lesion
150
Tuberous sclerosis
Epileptic with patch on back and lumps in brain
151
Neurofibromatosis 1
Characterized by changes in skin coloring (pigmentation) and the growth of tumors along nerves in the skin, brain, and other parts of the body
152
Ovarian tumours
Epithelial most common
- serous cystadenoma
- mucinous cystadenoma
- endometriod carcinoma
- clear cell carcinoma
Germ cell tumours
- dysgerminoma
- cystic teratoma
- choriocarcinoma
Sex chord /stromal
- granulosa/thecal cell
- sertoli leydig cell tumour
- fibroma
Metastases
- krukenberg tumour
153
Serous cystadenoma - ovary
Most common, usually unilocular, can be benign, borderline or malignant
Histology: columnar epithelium, psammoma bodies (concentric laminated calcifications)
154
Mucinous cystadenoma- ovary
Mucin secreting cells, epithelium may resemble GI or endocervix, benign borderline or malignant, Kras mutation
155
Endometriod carcinoma
Malignant, mimics endometrium, better than mucinous or serous for prognosis, tubular glands on histology, endometriosis risk factor
156
Clear cell carcinoma
Clear cells with lots of glycogen, hobnail appearance- bulbous nucleus and nuclear projections into cytoplasm,malignant, poor prognosis, endometriosis association
157
Dysgerminoma
Most commmon ovarian ca in young women, no differentiation, can give raise to any cancer if malignant
158
Cystic teratoma or dermoid cyst
```
Mature:
Aka dermoid cyst
Benign usually
Differentiation into mature tissues e.g. skin, teeth, hair, bone, cartilage
Usually bilateral & asymptomatic
Most common type of germ cell tumour
```
Immature:
Tend to be malignant
Solid
Contain immature embryonal tissue - tends to be neural tissue
Secrete AFP
159
Choriocarcinoma
Mimics pregnancy secretes hcG
160
Sertoli Leydig cell tumour
Secrete androgens -> virilisation, breast atrophy, hirsutism, enlarged clitoris
161
Granulosa/thecal cell tumour
Secrete oestrogen â PMB, IMB, endometrial cancer, breast cancer, breast enlargement
162
Krukenberg tumour
Malignancy of the ovary due to metastasis from usually gastric/colonic/breast cancer
Signet ring cells - mucin producing
163
Endometrial cancer
Endometrioid (85%):
Subtypes - mucinous adenocarcinoma, secretory adenocarcinoma
Younger patients
Related to excess oestrogen
```
Non-Endometrioid (15%):
Subtypes - papillary, clear cell, serous
Older patients
Less oestrogen dependent
Tend to have a higher grade, deeper invasion & higher stage
```
164
Naming malignancies
Histology of cells: large nuclei, lots of mitoses, large nucleo-cytoplasmic ratio
Carcinoma: derived from epithelial cells
Squamous cell carcinoma: keratin (swirly appearance), intercellular bridges
Adenocarcinoma: from glandular epithelium, glands, mucin producing
Sarcoma: derived from connective tissue
165
Granulomas
An organised collection of activated epithelioid macrophages
Epithelioid - look like epithelial cells; can also be called histiocytes
Lymphocytes around the outside
Giant Cells of Langhans (multinucleate) may be present - these are just
multiple epithelioid macrophages fused together, nuclei may have a
horseshoe appearance around outside of cell
Caseating granuloma (cheesy area) = TB
Non-caseating granuloma = sarcoidosis, leprosy, cat scratch fever, fungal infections
166
Congo red and apple green birefringence stain
Positive for amyloidosis
167
Fontana stain
Positive for melanin and melanoma
168
Rhodanine
Golden brown, positive for copper in Wilsonâs disease
169
Prussian blue stain
Positive for iron, haemochromatosis
170
Cytokerarin stain
Epithelial marker, immunohistochemical stain = Carcinoma
171
Zeihl neeson stain
Red against blue background, acid-fast bacilli = TB
172
Fite stain
Mycobacterium leprae
173
India ink stain
Cryptococcosus neoformams
174
Auramine stain
Bright yellow fluorescence for TB
175
Different cell types and what it means histology
Neutrophils - Acute inflammation (sterile or non-sterile)
Lymphocytes - Chronic inflammation, lymphoma
Macrophages - Late acute inflammation, chronic inflammation (including granulomas e.g. Sarcoidosis)
Plasma Cells - Chronic inflammation, myeloma
Eosinophils - Allergic reactions, parasitic infections
Tumours e.g. Hodgkinâs disease
176
What three categories can renal pathologies be divided into? Give examples of each
Those affecting the glomerulus, tubes and insterstitium, and blood vessels
Glomerulus - nephrotic syndrome, nephritic syndrome
Tubules and interstitium - acute tubular necrosis, tubulointerstitial nephritis
Blood vessels - HUS, TTP
177
What is nephrotic syndrome?
Can be primary or secondary (diabetes, SLE)
Characterised by triad of proteinuria (pcr>300), hypoalbuminaemia (<30) and oodema
Swelling classically periorbital in children and frothy urine
Loss of podocyte foot processes, may have immune deposits, may have glomerulae BM thickening, scarring
Management with steroids generally and ACEi/ARN for BP control
178
Nephrotic syndrome diagnosis
* Urine dip â proteinuria, NO haematuria
* Urine PCR - >300mg/mmol
* Serum albumin â low
* Total cholesterol â high
* Immunoglobulins â low
* Renal biopsy â diagnostic investigation of choice in adults (avoided in children)
179
What is nephritic syndrome?
Glomerular inflammation characterised by
PHAROH
proteinuria, haematuria, azootemia (high urea and creatinine), red cell blasts, oliguria and hypertension
180
Causes of nephritic syndrome
1) Post strep throat infection or impetigo (1-3 week), granular deposits of IgG in GBM
2) Berger disease - IgA deposits in glomeruli, 1-2 days after URTI with frank haematuria, can progress to ESRF, South Asians
3) Rapidly progressive GN - most aggressive, can go to ESRF, more pronounced oliguria and renal failure, crescents in glomeruli (from macrophages and parietal cells Iâm Bowmanâs space). Can get vascularised as rashes.
4) Hereditary - alports syndrome, x linked, sensorineural deafness, eye disorders e.g. cataracts, 5-20 yo
5) Thin basement membrane disease- dominant, microscopic haematuria usually asymptomatic
181
Describe the types of rapidly progressive GN
Type 1 - goodpastures disease with anti GBM antibodies
Type 2 - immune complex mediated and associated with SLE, post infection and IgA
Type 3 - lack of immune complex c-ANCA associated (Webberâs granulomatosis) or pANCA (microscopic polyangilitis)
182
Causes of asymptomatic haematuria
Thin basement membrane disease aka benign familial haematuria (renal functional normal and excellent prognosis)
IgA nephropathy - Berger disease, more likely than TBMD to cause haematuria and is more common in Asians
Alports syndrome
183
Acute tubular necrosis/injury, causes and sequence
Most common cause of ARF
Damage to tubular epithelial cells -> reduced flow and increased haemodynamic pressure in nephron -> reduced pressure gradient across BM -> acute renal failure -> tubular glomerular feedback reduces blood supply to kidneys further
Causes include:
- hypovaelamia
- drugs (amino glycosides, NSAIDs), radiographic contrast agents, myoglobin (e.g. secondary to rhabdomyolysis), heavy metals
Histopathology: necrosis of short segments of tubules
184
What is tubulointerstitial nephritis? Give types too
Renal inflammatory disorders affecting tubules and interstitium
Acute pyelonephritis - e.coli, fever chills sweats flank pain renal angle tenderness and leukocytosis with maybe urinary symptoms and even haematuria
Chronic pyelonephritis - caused by recurrent infections, scarring and inflammation, can be from urine reflux, chronic obstruction from calculi
Acute interstitial nephritis - hypersensitivity reaction to drug e.g. NSAIDs, begins a day after with fever skin rash haematuria proteinuria and esosinophilia
Chronic interstitial nephritis - in elderly on long term analgesics, late in disease get symptoms like HTN, proteinuria and haematuria
185
HUS
Children,
MAHA, thrombocytopenia, renal failure
Associated with diarrhoea from e.coli
Thrombi confined to kidneys
186
TTP
Affects adults
MAHA, thrombocytopenia, fever, renal failure, neurological signs
Generic ADAMTS13 mutation, thrombi throughout circulation
187
Diagnosis of TTP or HUS
Low hb, platelets,
Signs of haemolytic: high bilirubin, reticulocytes, ldh
fragmented red cells
Coombs negative
Differentiate on symptoms
188
Acute renal failure
| Pre renal, renal and post renal causes
A rapid loss of renal function manifesting as increased serum creatinine and urea.
1. PRE-RENAL
Caused by renal hypo-perfusion e.g. hypovolaemia, sepsis, burns, acute pancreatitis, and renal
artery stenosis.
2. RENAL
Acute tubular necrosis, acute glomerulonephritis and thrombotic microangiopathy.
3. POST-RENAL
Obstruction to urine flow as a result of stones, tumours (primary & secondary), prostatic hypertrophy and retroperitoneal fibrosis
189
Chronic renal failure - what is it and list itâs causes
Progressive, irreversible loss of renal function characterized by prolonged symptoms and signs of uraemia (fatigue, itching, anorexia and if severe eventually confusion).
Causes: diabetes, glomerulonephritis, hypertension, vascular disease, chronic pyelonephritis, polycystic kidney disease
190
5 stags old chronic renal failure
Classified into 5 stages by GFR:
```
1 - normal renal function, proteinuria maybe, GFR>90
2 - 60-89
3 - 30-59
4 - severely impaired function, 15-29
5 - renal failure, <15
```
191
Polycystic kidney disease
Group of disorders characterised by renal cysts and numerous systemic extra-renal manifestation
```
Clinical features: MISHAPES
o Abdominal Mass
o Infected cysts & increased BP
o Stones
o Haematuria
o Aneurysms (Berry)
o Polyuria & nocturia
o Extra-renal cysts e.g. liver, ovaries, pancreas, seminal vesicles
o Systolic murmur â due to mitral valve prolapse
```
192
Renal cell carcinoma
Types:
1. Clear cell carcinoma â well differentiated
2. Papillary carcinoma â commonest in dialysis-associated cystic disease
3. Chromophobe renal carcinoma â pale, eosinophilic cells
Risk factors: smoking, obesity, HTN, unopposed oestrogen, heavy metals, CKD
Clinical features: costovertebral pain, palpable mass, haematuria
Paraneoplastic syndrome: polycythaemia, hypercalcaemia, HTN, Cushingâs syndrome, amyloidosis
193
Temporal arteritis
Elderly, scalp tenderness, temporal headache, jaw claudication, blurred vision, high ESR, biopsy needed, granulomatous and giant cells
Prednisolone
194
Takayasu arteritis
Pulseless disease, low Bp in arms, cold hands, high in Japanese women
195
Kawasaki disease
Children under 5, fever, red rash on palms and soles with desquamation, conjunctivitis, strawberry tongue, aneurysm formation
196
Polyarteritis nodosa
Renal involvement, micro aneurysm, string of pearls
197
Wegners granulomatosis
Triad of:
(1) Upper resp tract: sinusitis, epistaxis, saddle nose
(2) Lower resp tract: cavitation, pulmonary haemorrhage
3) Kidneys: crescentic glomerulonephritis-> haematuria & proteinuria
cANCA (anti-PR3) +ve
198
Churg strauss or eosinophilic granulomatosis with polyangiitis
Asthma, allergic rhinitis, eosinophilia
pANCA positive
199
Henoch Schlonein Purpura
```
IgA mediated vasculitis
In children < 10 years
Preceding URTI
Palpable purpuric rash (lower libs extensors + buttocks)
Colicky abdo pain
Glomerulonephritis
Arthritis
Orchitis
```
200
Microscopic polyangitis
Pulmonary renal syndrome:
(a) Pulmonary haemorrhage
(b) Glomerulonephritis
pANCA (anti-MPO) +ve
201
Amyloidosis
Multisystem disorder caused by abnormal folding of proteins that are deposited as amyloid fibrils in tissues, disrupting their normal function.
Clinical features:
KIDNEY: nephrotic syndrome = most common presentation
HEART: conduction defects, heart failure, cardiomegaly
LIVER/SPLEEN: hepatosplenomegaly
TONGUE: macroglossia in 10%
NEUROPATHIES: incl carpal tunnel
202
Sarcoidosis - what is it and the signs and diagnosis
A multisystem disease of unknown cause, commonly affecting young adults, characterized by non-caseating granulomas in many tissues
Bilateral hilar lymphadenopathy, worse in Afro Caribbean, females, fine modular mid zone shadowing, SOB, cough, chest pain, night sweats
SKIN: erythema nodosum, lupus pernio (red/purple
lesions around nose), skin nodules
LNs: lymphadenopathy, painless and rubbery
JOINTS: arthritis, bone cysts
EYES: anterior uveitis, keratoconjunctivitis, lacrimal gland enlargement
LIVER/SPLEEN: Hepatosplenomegaly
BLOOD: Leukopaenia/ anaemia
Hypercalcaemia/hypercalciuria â renal calculi + nephrocalcinosis
HEARTâ dysrhythmias, cardiomyopathy, conduction defects, pericarditis, valvular
lesions
CONSTITUTIONAL SX: malaise, fever, wt loss, night sweats
DIAGNOSIS OF EXCLUSION
Investigations: âCa2+, âESR, âACE
203
Perl stain
Positive for haemachromatosis
204
Lewy body dementia
Psychological disturbances occur early. Day-to-day fluctuations in cognitive performance, visual hallucinations, spontaneous motor signs of Parkinsonism, recurrent falls and syncope, pathologically indistinguishable from PD
205
What is dementia?
| What are the different types of cognitive disturbances?
A global impairment of cognitive function and personality without impairment of consciousness.
Includes memory impairment and at least one of the following cognitive disturbances: aphasia, apraxia, agnosia or a disturbance in executive functioningâ.
* Aphasia= language disorder (may be expressive or receptive)
* Apraxia= loss of ability to carry out learned purposeful tasks
* Agnosia= loss of ability to recognise object, people etc.
206
Acute rheumatic fever - what is it ask what systems does it affects
Occurs at a peak age of 5-15years. It is a multisystem illness affecting:
Heart: pancarditis i.e. endocarditis, myocarditis, pericarditis;
Joints: arthritis and synovitis;
Skin: Erythema marginatum, subcutaneous nodules
CNS: Encephalopathy, Sydenhamâs chorea
Clinical features:
- develop 2-4 weeks after strep throat infection.
- diagnosis: group A strep infection + 2 major criteria or 1 major + 2 minor criteria
207
Diagnostic criteria for rheumatic fever
Need two major or one major and two minor
Jonesâ Major Criteria (CASES):
- Carditis
- Arthritis
- Sydenhamâs chorea
- Erythema marginatum
- Subcutaneous nodules
Minor criteria:
- fever
- raised ESR or CRP
- migratory arthralgia
- prolonged PR interval
- previous rheumatic fever
- malaise
- tachycardia
Commonly affects mitral valve only
Pathology Year 5
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