Histopathology Flashcards
1
Q
Definition of Atherosclerosis
A
an arteriosclerosis characterized by atheromatous deposits in and fibrosis of the inner layer of the arteries: intimal lesions
2
Q
Major risk factors for atherosclerosis
A
Age Gender Genetics Hyperlipidaemia Hypertension Smoking Diabetes Mellitus
3
Q
What are the 3 stages of atheromatous plaque formation?
A
1 - Raised lesion
2 - Soft lipid core
3 - White fibrous cap
4
Q
How does gender affect risk of artherosclerosis?
A
Premenopausal women protected (HRT no protection)
Postmenopausal risk increases (older ages greater than men)
5
Q
Other (not major) risk factors for atherosclerosis
A
Inflammation Hyperhomocyteinaemia Metabolic syndrome Lipoprotein (a) Haemostasis (procoagulation) Lack of exercise Stress Obesity
6
Q
What are the pathological steps of the response to injury hypothesis?
A
- Endothelial injury
- Lipoprotien accumulation (LDL)
- Monocyte adhesion to endothelium
- Monocyte migration into intima -> macrophages & foam cells
- Platelet adhesion
- Factor release
- Smooth muscle cell recruitment
- Lipid accumulation -> extra & intracellular, macrophages & smooth muscle cells
7
Q
What is the earliest for of atheroslerotic lesion
A
Fatty streak Lipid filled foamy macrophages No flow disturbance In virtually all children >10yrs Relationship to plaques uncertain Same sites as plaques
8
Q
What are the 3 principle components of an atherosclerotic plaque?
A
Cells - including smooth muscle cells, macrophages and leukocytes
Extra Cellular Matrix - including collagen
Intracellular and extracellular lipid
9
Q
When cardiac demand becomes greater than arterial supply, this is know as?
A
Critical stenosis
Occurs at ~70% occlusion (or diameter <1mm)
Causes “stable” angina
10
Q
In what kind of plaque does acute change prodominantly occur and what kind of change can happen?
A
Majority of plaques that show acute change show only mild to moderate luminal stenosis prior to acute change.
1) Rupture – exposes prothrombogenic plaque contents
2) Erosion - exposes prothrombogenic subendothelial basement membrane
3) Haemorrhage into plaque – increase size
11
Q
What are the characteristics of a vulnerable plaque?
A
Lots foam cells or extracellular lipid
Thin fibrous cap
Few smooth muscle cells
Clusters inflammatory cells
12
Q
How does IHD present?
A
Angina pectoris
Myocardial infarction
Chronic IHD with heart failure
Sudden cardiac death.
13
Q
What is the pathogenesis of IHD
A
insufficient coronary perfusion relative to myocardial demand due to chronic progressive atherosclerotic narrowing of epicardial coronary arteries and variable degrees of superimposed plaque change, thrombosis and vasospasm
14
Q
What is Prinzmetal angina?
A
Chest pain caused by coronary vasospasm
15
Q
What is the histological evolution of and MI?
A
< 6 hours - normal histology (CK-MB also normal)
6-24 hrs - loss of nuclei, homogenous cytoplasm, nerotic cell death
1-4 days - infiltration of polymorphs then macrophages (clear up debris)
5-10 days - removal of debris
1-2 weeks - granulation tissue, new blood vessels, myofibroblasts, collagen synthesis
Weeks-months - strengthening, decellularising scar
16
Q
What % of MI’s are asymptomatic and who gets them?
A
10-15%
common in elderly and diabetics
17
Q
What factors predict a worse prognosis from MI?
A
Older age
Female
DM
Previous MI
18
Q
What are the main complications of an MI?
A
- Contractile dysfunction: cardiogenic shock
- Arrhythmias
- Myocardial rupture
- Pericarditis: Dressler syndrome
- RV infarction
- Infarct extension - new necrosis adjacent to old
- Infarct expansion - ventricular aneurysm
- Mural thrombus - embolisation
- Papillary muscle rupture - valve disfunction
19
Q
How long after a MI does myocardial rupture usually occur?
A
Mean 4-5 days, range 1-10 days
20
Q
What is sudden cardiac death?
A
Unexpected death from cardiac causes in individuals without symptomatic heart disease or early (1hr) after onset of symptoms
21
Q
What causes sudden cardiac death?
A
Acute myocardial ischaemia triggers lethal arrhythmia on a background of asympotmatic IHD. MI usually causes electrical instability at sites distant from conduction system often near scars from old MIs
10% have non-atherosclerotic causes (e.g. long QT)
22
Q
What causes nutmeg liver?
A
Right-sided heartfailure due to increased pressure
23
Q
What are the causes of cardiac failure?
A
Ischaemic heart disease Valve disease Hypertension Myocarditis Cardiomyopathy Left sided heart failure causes Right failure
24
Q
Complications of cardiac failure
A
Sudden Death
Arrhythmias
Systemic emboli
Pulmonary oedema with superimposed infection
25
What are the histological findings of cardiac failure?
Macroscopically - dilated ventricles with scarring and thinning of walls
Microscopically - fibrosis and replacement of ventricular myocardium
26
What are the different patterns of cardiomyopathy?
```
Too thin (dilated)
Too thick (hypertrophic)
Too stiff (restrictive)
```
27
What are the causes of dilated cardiomyopathy?
```
Caused by a progressive loss of mycocytes.
Idiopathic
Infective - myocarditis
Toxic - alcohol, chemotherapy
Hormonal - thyroid, DM, peripartum
Genetic - haemochromatosis
Immunological - myocarditis, sarcoidosis
```
28
What are the causes of hypertrophic cardiomyopathy (HOCM)?
50% familial (AD) beta-myosin heavy chain mutation.
Leading cause of sudden cardiac death in young athletes.
Left ventricular hypertrophy without dilation narrows left ventricular outflow tract.
29
What are the causes of restrictive cardiomyopathy?
Impaired ventricular compliance.
Idiopathic
Secondary to amyloidosis, sarcoidosis, radiation-induced fibrosis.
30
In what order does chronic rheumatic valvular disease affect the different heart valves?
Mitral > Aortic > Tricuspid > Pulmonic
| Predominately left-sided, 48% mitral alone.
31
What is the commonest causes of aortic stenosis?
Calcific aortic stenosis, calcium deposits in valve impairs opening causing outflow tract obstruction.
32
What are the causes of aortic regurgitation?
```
Rigidity - rheumatic, degenerative
Destruction - microbial endocarditis
Disease of aortic valve ring causing dilation;
- Marfan's Syndrome
- Dissecting aneurysm
- Syphilitic aortitis
- Ankylosing spondylitis
```
33
Examples of drugs which can induce SLE
Hydralazine and procainamide
| Drug-induced SLE rarely affects kidneys and is associated with anti-histone antibodies
34
What characteristic histology is seen in the blood with SLE?
LE cells - a neutrophil or macrophage that has phagocytized the denatured nuclear material of another cell - LE body
35
What are the diagnostic criteria for SLE?
```
4 out of 11 of;
Serositis (pericarditis, pleuritis)
Oral ulcers
Arthritis
Photosensitivity
Blood disorders (AIHA, ITP)
Renal involvement
ANA +ve
Immune phenomena (dsDNA, anti-sm etc)
Neuro symptoms
Malar rash
Discoid rash
```
36
Which antibodies are associated with Sjögren's syndrome?
Anti-Ro
| Anti-La
37
How can SLE affect the heart valves?
Libman–Sacks endocarditis is a form of nonbacterial (sterile) endocarditis that is seen in SLE. It is one of the most common cardiac manifestations of lupus (most common = pericarditis).
38
Which autoantibodys are associated with systemic scleroderma?
Limited (CREST) = anti-centromere
| Diffuse = Anti Scl-70 (DNA topoisomerase)
39
What does CREST stand for?
```
Calcinosis
Raynauds
Esophageal dysmotility
Sclerodactyly
Telagiectasia
Also associated with Pulmonary hypertension
```
40
What is a form of scleroderma localised to the skin also know as?
Morphoea
41
What are the characteristics of systemic scleroderma?
- Fibrosis and accumulation of collagen in skin and organs
- Vascular alterations: 'onion skin' intimal thickening of small arteries
- Autoantibodies
42
What is the skin involvement in limited systemic scleroderma?
Face and distal to elbows and knees.
43
What are polymyositis and dermatomyositis associated with?
25-50% have underlying malignancy, male predominance. Bronchus, breast and GI malignancy most commonly.
44
What are the signs and symptoms of polymyositis and dermatomyositis?
- Proximal muscle weakness, raised CK & abnormal EMG
| - DM also has heliotrope rash and Gottron's papules
45
Which autoantibody is associated with dermatomyositis?
Anti-Jo-1 (tRNA synthetase)
46
What does a young child with a week long fever, eythematous palms and soles, conjunctivitis and a swollen tongue have?
Kawasaki's disease
47
What are the clinical features of Kawasaki's disease?
```
Affects children < 5 yrs
High fever > 5 days
plus 4 of;
- non-purulent conjunctivitis
- red mucous membranes (strawberry tongue)
- cervical lymphadenopathy
- rash (polymorphous)
- red, oedematous palms and soles or later desquamation
```
48
What possible complications are there with Kawasaki's disease?
Coronary artery aneurysms, MI and sudden death.
49
What is the treatment for Kawasaki's disease?
IVIG within first 10 days reduces risk of coronary artery aneurysms.
Aspirin reduces thrombosis risk.
Self-limiting
50
Which infection is associated with polyarteritis nodosa?
30-40% have underlying Hepatitis B infection
51
Which organs are commonly affected in polyarteritis nodosa?
```
Any organ but most common are:
kidneys (80%)
heart (70%)
liver (65%)
GIT (50%)
Spares lungs
```
52
What are the clinical features of polyarteritis nodosa?
```
PUO, weight loss
Muscle aches
Neuropathy
Haematuria, renal failure
Hypertension
Abdominal pain, melaena
```
53
What might be the diagnosis in a patient with features of polyarteritis nodosa + lung involvement and an eosinophilia?
Churg-Strauss syndrome
54
What are the histological features of polyarteritis nodosa?
Rosary sign (beading)
Nodular appearance to medium sized vessels on angiography - microaneurysms
Microscopically necrotising arteritis with inflammation
55
What is the commonest form of arteritis?
Temporal arteritis
56
What type of hypersensitivity reaction is temporal arteritis?
Type IV reaction to vessel wall components
57
What is amyloid?
Deposition of an abnormal proteinaceous substance in non branching fibrils.
Beta-pleated sheet structure.
Resistant to enzymatic degradation.
Variety of different proteins can be involved.
58
What is the most common form of amyloidosis?
AL (light-chain) amyloidosis, associated with multiple myeloma. Bence-Jones protein in blood and urine.
59
What is AA amyloidosis?
Serum Amyloid A (SAA) acute phase protein deposited as amyloid, often secondary to chronic infections / inflammation.
60
What type of amyloid is deposited in Alzheimer's disease?
Amyloid-beta (Aβ)
61
What is always present in amyloid?
Serum amyloid P component (SAP), ~10%
| Pentagonal constituent of amyloid deposits
62
How can amyloid be visualised in a tissue sample?
Stains with Congo red dye.
| Shows apple green birefringence under polarised light.
63
What are the common clinical features of amyloidosis?
```
Kidney: nephrotic syndrome
Heart: conduction defects, restrictive cardiomyopathy, heart failure
Hepatosplenomegaly
Macroglossia
Neuropathies: e.g. carpal tunnel
```
64
Which type of amyloidosis is associated with haemodialysis?
Beta-2-microglobulin amyloid deposition
65
What is the most common form of familial amyloidosis?
Familial Mediterranean Fever (autoinflammatory disease) - AA amyloid deposition
66
What is sarcoidosis?
Multisystem disorder based on a cell mediated immune response and characterised by non-caseating granulomas in many tissues
67
Which organ systems are characteristically involved in sarcoidosis?
Skin, lymphoid system and lungs (most common)
68
How can sarcoidosis present in the skin?
Erythema nodosum
Lupus pernio
Skin nodules
69
How can sarcoidosis affect the eyes?
Uveitis
Uveoparotitis - bilateral uveitis, parotid enlargement +/- facial nerve palsy.
Retinal inflammation
70
What systemic effects are there with sarcoidosis?
Hypergammaglobulinaemia
Raised serum ACE
Hypercalcaemia due to increased activation of Vit D by granulomas
71
What histological findings are there when looking at a sacroid granuloma?
Non-caeseating granuloma with Schaumann and asteroid bodies
72
Definition of neurodegenerative disease
Progressive, irreversible conditions that lead to neuronal loss – often caused by intra or extracellular accumulation of a misfolded protein; usually sporadic (less than 10% genetic); lead to dementia.
73
Definition of dementia
A serious loss of global cognitive ability in a previously unimpaired person, beyond what might be expected from normal ageing. It may be static, the result of a unique global brain injury, or progressive due to neurodegeneration
74
What are the pathological correlates of neurodegeneration?
```
Macroscopically: brain atrophy (diffuse or selective)
Microscopically: often misfolded protein
- neuronal loss
- damage of synapses (early)
- exocytotoxicy (excess of NTs)
- microglial activation
- reactive astrocytosis
```
75
What is a Lewy body?
Abnormal aggregates of protein (mostly alpha-synuclein) that develop inside nerve cells in Parkinson's disease (PD), Lewy body dementia and some other disorders.
76
How does multiple sclerosis usually present?
In patients 20-40 yrs old with focal symptoms, optic neuritis and poor coordination.
77
How is Multiple sclerosis classified?
```
Primary progressive (10% - get continually worse)
Relapsing remitting (better between episodes but progresses over years)
Rare variants (neuromyelitis optica (Devic disease), Marburg disease, Balo disease)
```
78
What can cause demyelinating lesions?
- Viral infections (PML, HIV)
- Genetic (Leukodystrophies)
- Autoimmune (multiple sclerosis, acute haemorrhagic encephalomyelitis, acute disseminated encephalomyelitis)
- Nutritional/metabolic (central pontine myelinolysis, B12 deficiency)
- Toxic (radiotherapy, chemical agents)
79
How does multiple sclerosis appear histologically?
MS plaques showing sharp margins of myelin loss with central veins.
Inactive plaques = glial scar
80
Which pathological proteins are associated with Alzheimer's disease?
Tau and Beta-amyloid
81
What is bone made of?
INORGANIC - 65%
- calcium hydroxyapatite (10Ca 6PO4 OH2)
ORGANIC - 35%
- bone cells and protein matrix
82
What two main types of bone are there and give examples?
Cortical: long bones e.g. femur 80-90% calcified
Cancellous: vertebrae & pelvis 15-25% calcified
83
Which type of bone cell is multinucleate?
Osteoclast
84
What does RANK stand for?
Receptor Activator for nuclear factor kB
| Important for osteoclastogenesis
85
Which cell type expresses RANK ligand and RANK?
RANK ligand: stromal cell / osteoblast
| RANK: osteoclast precursor and osteoclast
86
Definition of metabolic bone disease
Disordered bone turnover due to imbalance of various chemicals in the body (vitamins, hormones, minerals etc)
Overall effect is reduced bone mass (osteopaenia) often resulting in fractures with little or no trauma
87
What are the three main categories of metabolic bone disease?
1. Non-endocrine (e.g. age related osteoporosis)
2. Related to endocrine abnormality (Vit D; Parathyroid hormone)
3. Disuse osteopaenia
88
What is the usual site for a bone biopsy?
Iliac crest
89
What are the causes of osteoporosis?
1º - age, post-menopause
2º - drugs, systemic disease
90% cases due to insufficient Ca intake and post-menopausal oestrogen deficiency
90
What DEXA scan scores define osteoporosis?
T score >2.5 SD below normal peak bone mass = osteoporosis
| T score between 1 & 2.5 SD below normal peak bone mass = osteopaenia
91
What is the effect of increased PTH secretion on the kidenys and bone?
Kidney: stimulates Ca reabsorption & VitD activation
Bone: Stimulates osteoclasts hence resorption
92
What are the different types of osteomalacia?
1. Deficiency of vitamin D
2. Deficiency of PO4
Osteomalacia = Defective bone mineralisation
93
What type of fractures can be seen in osteomalacia?
Horizontal fractures / pseudofractures, also called Looser's zones.
94
Symptoms of hyperparathyroidsm/hypercalaemia
Stones (Ca oxalate renal stones)
Bones (osteitis fibrosa cystica, bone resorption)
Abdominal groans (acute pancreatitis)
Psychic moans (psychosis & depression)
95
What underlying changes occurs in renal osteodystrophy?
```
PO4 retention – hyperphosphataemia
Hypocalcaemia as a result of decreased vit D
2o hyperparathyroidism
Metabolic acidosis
Aluminium deposition
```
96
What are the different phases of Paget's disease?
1. Osteolytic
2. Osteolytic-osteosclerotic
3. Quiescent osteosclerotic
97
What is the clinical presentation of Paget's disease?
Pain, microfractures, nerve compression (incl. Spinal N and cord)
Skull changes may put medulla at risk
+/- haemodynamic changes, cardiac failure
Development of sarcoma in area of involvement 1%
98
What type of patients usually get Paget's disease?
Onset > 40y
M=F
Rare in Asians and Africans
99
What is Hirschsprung's disease associated with?
Down's syndrome and RET proto-oncogene Cr10
100
What would a biopsy of affected bowel in Hirschsprung's disease show?
Hypertrophied nerve fibres but no ganglia
101
Which segments of bowel are prone to volvulus in the young and elderly?
Infants - small bowel
| Elderly - sigmoid colon
102
What is pseudomembranous colitis?
Acute, antibiotic associated colitis with pseudomembrane formation, caused by protein exotoxins of C. difficile
103
Non-caseating granulomas in the bowel are found with which disease?
Crohn's disease
104
What are the histological features of Crohn's disease?
```
Whole GI tract can be affected
Skip lesions
Transmural inflammation
Non-caseating granulomas
Sinus/fistula formation
Cobblestone mucosa
```
105
What are the extra-intestinal manifestations of Crohn's disease?
Arthritis
Uveitis
Stomatitis/cheilitis
Skin lesions: pyoderma gangrenosum, erythema multiforme, erythema nodosum
106
What major complications are there with ulcerative colitis?
Severe haemorrhage
Toxic megacolon
Adenocarcinoma 20-30 x increased risk
107
What are the extra-intestinal manifestations of ulcerative colitis?
```
Arthritis
Myositis
Uveitis/iritis
Erthema nodosum, pyoderma gangrenosum
Primary sclerosing cholangitis
```
108
What different types of colorectal polyps are there?
Non-neoplastic: Hyperplastic, inflammatory (pseudo-polyps), hamartomatous (juvenile, Peutz Jeghers)
Neoplastic: Tubular adenoma, Tubulovillous adenoma, Villous adenoma
109
What are the risk factors for cancer with regard to bowel adenomatous polyps?
- Size
- Proportion of villous component
- Degree of dysplastic change within polyp (low or high)
110
What is familial adenomatous polyposis coli?
AD mutation in APC tumour suppressor leading to 1000's of adenomatous polyps by 25, ~100% develop cancer within 10-15 years
111
Which gene causes FAP and where is it located?
APC, chromosome 5q21
112
What is Gardner's syndrome?
Same clinical, pathological and etiological features and Ca risk as FAP but with extra-intestinal manifestations.
113
What extra-intestinal manifestations are there with Gardner's syndrome?
- Multiple osteomas of skull and mandible
- Epidermoid cysts
- Desmoid tumours
- Dental caries, unerrupted supernumery teeth
- Post-surgical mesenteric fibromatoses
114
What is HNPCC?
Hereditary non-polyposis colorectal cancer.
AD mutation of mismatch repair genes leading to DNA replication errors.
3-5% of all colorectal cancers
115
Apart from bowel, what other cancers are associated with HNPCC?
Endometrium, prostate, breast, stomach.
116
What is the most common form of colorectal cancer?
98% adenocarcinoma
117
What are the symptoms of colorectal cancer?
Bleeding, change in bowel habit, anaemia, weight loss, pain, fistula.
118
What is the staging system for colorectal cancer?
```
Dukes' staging
A - confined to wall of bowel
B - through wall (muscular layer) of bowel
C - lymph node metastases
D - distant metastases
```
119
What are the 4 key features of liver cirrhosis?
1. whole liver involved
2. fibrosis
3. nodules of regenerating hepatocytes
4. distortion of liver vascular architecture (shunting of blood
120
What are the causes of and histological changes in acute hepatitis?
Mainly caused by drugs and viruses.
Get 'spotty necrosis'
Acute defined as lasting < 6 months
121
What are the main causes of chronic hepatitis?
Viruses
Drugs
Auto-immune
122
What do grade and stage relate to r.e. chronic hepatitis?
Severity of inflammation = grade
| Severity of fibrosis = stage (most important)
123
What different classifications of liver inflammation are there?
Portal inflammation
Interface hepatitis (piecemeal necrosis)
Lobular inflammation
124
What are Mallory-Denk bodies?
An inclusion found in the cytoplasm of liver cells most common in alcoholic hepatitis and alcoholic cirrhosis
125
Is alcohol toxic to the liver?
Not directly, it is converted to acetaldehyde which is toxic, affects zone 3 hepatocytes most as they are most metabolically active
126
Is alcoholic liver cirrhosis macro- or micronodular?
Micronodular
127
What is the histological picture in primary biliary cirrhosis?
Bile duct loss associated with chronic inflammation (with granulomas)
128
What auto-antibody is specific for primary biliary cirrhosis?
Anti-mitochondrial antibodies
129
What is the histological picture in primary sclerosing cholangitis?
Periductal bile duct fibrosis (onion-skinning) and scarring causing cholestasis
130
Which disease increases the risk of cholangiocarcinoma?
Primary sclerosing cholangitis
131
What defect is there in haemochromatosis?
HFE gene mutation on chromosome 6 leads to unregulated gut iron absorption - 'chocolate liver'
132
What is the difference between haemochromatosis and haemosiderosis?
Haemochromatosis - gut absorped iron deposited in hepatocytes leading to fibrosis
Haemosiderosis - RBC iron (repeat transfusions) stored in kuffer cells with no risk of fibrosis
133
What is the defect in Wilson's disease?
AR gene mutation on chromosome 13 which prevents copper excretion into bile leading to accumulation in tissues (liver and CNS)
134
What auto-antibody is specific for autoimmune hepatitis?
Anti-smooth muscle actin antibodies
135
What is the defect in alpha-1-antitrypsin deficiency?
Not with the enzyme itself, but there is a failure to secrete the enzyme from hepatocytes leading to intra-cytoplasmic inclusions and hepatitis
136
What is the commonest liver cancer?
Metastatic liver adenocarcinoma
137
What different primary hepatic tumours are there?
From hepatocytes: hepatocellular carcinoma, hepatoblastoma
From bile duct cells: cholangiocarcinoma
From blood vessels: haemangiosarcoma
138
Does viral hepatitis cause macro- or micronodular cirrhosis?
Macronodular
139
What is inflammation / infection of the Fallopian tubes and ovaries called?
Fallopian tube: salpingitis
| Ovary: oopheritis
140
Which organisms cause infections of the female genital tract but are not associated with any serious complications?
– Candida: Diabetes mellitus, oral contraceptives and pregnancy enhance development of infection
– Tichomonas vaginalis: protozoan
– Gardenerella: gram negative bacillus causes vaginitis
141
Which organisms are a major cause of infertility in females?
Chlamydia and Gonorrhoea
142
What complications can occur with mycoplasma infection of the female gential tract?
Spontaneous abortion and chorioamnionitis
143
What two main causes of PID are there?
- lower genital tract infection spreading upwards (mucosal)
| - secondary infection following abortion: starts in uterus (deeper tissues)
144
Which organisms cause PID secondary to abortion?
Staph, stept, coliform bacteria and clostridium perfringens
145
What complications can there be with PID?
* Peritonitis
* Intestinal obstruction due to adhesions
* Bacteremia
* Infertility
146
What complications can there be with salpingitis?
* Plical fusion
* Adhesions to ovary
* Tubo-ovarian abscess
* Peritonitis
* Hydrosalpinx
* Infertility
* Ectopic pregnancy
147
What is the mean age of patients who get cervical cancer?
45-50 years
| 2nd most common cancer affecting women
148
What are the main risk factors for the cervical cancer?
* Human Papilloma Virus - present in 95%
* Many sexual partners
* Sexually active early
* Smoking
* Immunosuppressive disorders
149
Which are the most common types of HPV that are associated with cancer and which cancers are they associated with?
16 and 18
Cervical cancer
Also, vulval, vaginal, penile, and anal cancer
150
Which are the most common types of low risk HPV and what do they causes?
6 and 11
| Oral and genital warts
151
What main types of cervical carcinoma are there are what is the most common?
Squamous cell carcinoma
| Adenocarcinoma (20% of all invasive cases)
152
What staging system is used for cervical cancer?
FIGO stage (International Federation of Gynecology and Obstetrics) also used for other gynecological cancers
153
How does HPV transform cells?
It expresses proteins E6 and E7 which bind to and inactivate P53 and Retinoblastoma gene (Rb), respectively.
This interferes with apoptosis and increases unscheduled cellular proliferation which contributes to oncogenesis.
154
What are the 2 distinct biological states of HPV infection?
- Non productive or latent infection: infection can only be identified by molecular methods
- Productive viral infection: has characteristic cytological and histological features
155
What are the screening intervals for the cervical screening program?
```
25 = First invitation
25-49 = 3 yearly
50-64 = 5 yearly
65+ = Only screen those who have not been screened since age 50 or have had recent abnormal tests
```
156
Which types of HPV does the cervical cancer vaccine protect against?
6, 11, 16, 18
157
What is the commonest uterine tumour?
Leiomyoma: smooth muscle tumour of myometrium aka fibroid. May be intramural, submucosal or subserosal. Malignant counterpart rare = Leiomyosarcoma
158
What causes endometrial hyperplasia?
A state of persistent oestrogen production e.g. PCOS, Granulosa cell tumours, etc.
159
What are the risk factors for endometrial carcinoma?
– Excessive oestrogen stimulation
– Nulliparity
– Obesity
– Diabetes mellitus
160
What are type I endometrial carcinomas?
Endometrioid, mucinous and secretory adenocarcinomas
Younger age
Oestrogen dependent
Often associated with atypical endometrial hyperplasia
Low grade tumours, superficially invasive
161
What are type II endometrial carcinomas?
```
Serous and clear cell carcinomas
Older, postmenopausal
Less oestrogen dependent
Arise in atrophic endometrium
High grade, deeper invasion, higher stage
```
162
What are the different FIGO stages for endometrial carcinoma?
Stage 1 – confined to uterus
Stage 2 – spread to cervix
Stage 3 – spread to adnexae, vagina, local lymph nodes (pelvic or para-aortic)
Stage 4 – other pelvic organs distant spread inc any other distant lymph node groups
163
What is gestational trophoblastic disease?
A spectrum of tumours and tumour like conditions characterised by proliferation of of pregnancy associated trophoblastic tissue. Includes:
– Complete and partial mole
– Invasive mole
– Choriocarcinoma
164
What are the characteristics of complete and partial moles?
1 in 1000 pregnancies
Most present with spontaneous abortion
Excessive level of HCG hormone
Risk of malignant development only with complete moles (2.5%)
165
How do hydatidiform moles form?
Complete: An empty egg fertilised by 1 or 2 sperms (46XX or 46XY)
Partial: A normal egg fertilised by 2 sperms (XXX, XXY, XYY) or a normal egg fertilised by a sperm carrying unreduced paternal genome (XXY)
166
What are the characteristics of choriocarcinoma?
* 1 in 20,000-30,000 pregnancies
* Rapidly invasive, widely metastasising (lung, vagina, brain, liver, kidney)
* Responds well to chemotherapy
* 50% arise in moles
* 25% arise in previous abortion
* 22% arise in normal pregnancy
167
What is endometriosis?
Presence of endometrial glands and stroma outside the uterus which is functional and bleeds at time of menstruation -> pain, scarring and infertility.
Affects 10% of premenopausal women.
168
What is the origin of endometrial tissue in endometriosis?
* Metaplasia of pelvic peritoneum
| * Implantation of endometrium, retrograde menstruation
169
What is adenomyosis?
Ectopic endometrial tissue deep within the myometrium.
| Causes dysmenorrhoea.
170
What risk factors are associated with ovarian cancer?
* Most significant is genetic predisposition
* Family history of ovarian and breast cancers
* Infertility
* Endometriosis
* Hormone replacement therapy
* Pelvic inflammation
* Nulliparity, early menarche, late menopause
171
What is the commonest type of malignant ovarian tumour?
95% Epithelial tumours - 65% of all ovarian tumours
| Serous most common subtype.
172
What is the incidence pattern of ovarian cancers?
* Germ cell tumours have bimodal distribution; 15-21 and 65-69 (95% benign)
* 50% of epithelial are 45-65
* Sex cord tumours most common in post-menopausal women
173
What is the difference between type I and type II ovarian tumours?
```
Type I (20%) - Low grade, relatively indolent, arise from well characterised precursors (BOT) and endometriosis
Type II - High grade, mostly serous type, aggressive, >75% have p53 mutations, no precursor lesions
```
174
What are the different sub-types of epithelial ovarian cancer?
* Serous (most common)
* Mucinous (gastrointestinal or endocervical type)
* Endometrioid (associated with endometriosis)
* Clear cell (strong association with endometriosis)
* Transitional
* Mixed types
175
What are the types of benign ovarian tumours?
* Serous Cystadenomas
* Cystadenofibromas
* Mucinous cystadenomas
* Brenner tumour
176
A patient newly diagnosed with an endometrioid ovarian tumour should also be investigated for..?
Endometrioid carcinoma in uterus as co-existance is common
177
What are the different subtypes of sex cord stromal tumour?
Fibromas: benign
Granulosa cell tumor: may produce estrogen
Thecoma: benign, may secrete oestrogen, or rarely androgens
Sertoli-Leydig cell tumor: may be androgenic
178
What is the difference between a mature and immature teratoma?
Mature: benign, all mature adult type tissues (e.g. teeth, hair) transformation rare
Immature: malignant, presence of embryonic elements, grows rapidly, penetrates the capsule, forms adhesions and spreads to lymph nodes, lung, liver etc.
179
Germ cell tumour subtypes?
```
Teratoma
Dysgerminoma
Yolk sac tumour
Embryonal carcinoma
Choriocarcinoma
```
180
What are Krukenberg tumours?
A malignancy in the ovary (often bilateral) that metastasised from a primary site, commonly colorectal, gastric or breast.
May be composed of signet ring, mucin-rich cells.
May be first presentation of primary tumour.
181
What familial syndromes are associated with an increased risk of ovarian cancer?
1 - familial breast-ovarian cancer syndrome
2 - site-specific ovarian cancer
3 - cancer family syndrome (Lynch type II)
All are autosomal dominant, 1+2 associated with BRCA1 mutations and account for 90% familial ovarian cancers
182
What type of ovarian cancers are associated with HNPCC and BRCA mutations?
- Serous tumours: BRCA - commonest
- Mucinous tumours: HNPCC
- Endometrioid carcinoma: HNPCC
Ovarian cancer <30 yrs more likely to be due to HNPCC mutations (MSH2 and MLH1) than BRCA1/2
183
What is a papillary hidradenoma?
A benign nodule of ectopic breast tissue usually found on the labia majora or the interlabial folds. May ulcerate and be confused with carcinoma of the vulva.
184
What is the commonest vulval malignancy?
SCC
| May be associated with or secondary to HPV or lichen sclerosus.
185
What type of vaginal cancer was associated with an old treatment to prevent adverse pregnancy outcomes?
Clear cell adenocarcinoma in daughters if mother was treated during pregnancy with Diethyl stilbosterol (DES) for threatened abortion.
186
BCR-ABL is associated with which disease?
CML
187
What are myeloproliferative neoplasms (MPNs)?
A group of neoplastic/clonal disorders of haemopoeitic stem cells characterised by the overproduction of one or more of the mature myeloid cellular elements of the blood. There is often increased BM fibrosis and cases may progress to acute leukaemia.
188
How do leukaemia, MPN and MDS differ?
Leukaemia: Proliferation without differentiation
MPN: Proliferation and full differentiation
MDS: Ineffective proliferation and differentiation
189
What cell counts are increased in polycythaemia vera?
Predominantly increased RBCs
| Also platelets and granulocytic cells and a true increase in plasma volume
190
What symptoms do patients with polycythaemia vera present with?
```
Symptoms of increased hyper viscosity:
- Headaches, light-headedness, stroke
- Visual disturbances
- Fatigue, dyspnoea
Increased histamine release:
- Aquagenic pruritus
- Peptic ulceration
```
191
What signs do patients with polycythaemia vera present with?
- Variable splenomeagaly
- Plethora
- Erythromelalgia: red painful extremeties
- Thrombosis
- Retinal vein engorgement
- Gout due to increased red cell turnover and overproduction of uric acid
- Absence of other causes of increased haematocrit
192
What mutation is diagnostic for polycythaemia vera?
JAK2 V617F
193
What is pseudopolycthaemia?
Also has a high haematocrit but reduced plasma volume and normal RBC mass
194
What does a patient with a purely raised RBC count and exon 12 mutation have?
Erythrocytosis
| No raised WBCs or PLTs
195
What is the target haematocrit with treatment in polycythaemia vera? And what treatment is used?
<45%
Venesection and Cytoreductive therapy (e.g. hydroxyurea)
Aspirin used to decrease risk of thrombosis
196
How is idiopathic erythrocytosis managed?
Venesection only
| Less likely to transform to MF or AML
197
What is essential thromocythaemia?
Chronic MPN mainly involving megakaryocytic lineage
| with sustained thrombocytosis >600x10^9/L
198
What symptoms do patients with essential thromocythaemia present with?
- Incidental finding in half the patients
- Thrombosis: arterial or venous
- Bleeding: mucous membrane and cutaneous
- Minor: headaches, dizziness visual disturbances
- Splenomegaly usually modest
199
What conditions are associated with mutations of JAK2?
Polycythaemia vera ~100%
Essential thromocythaemia ~50%
Myelofibrosis ~50%
200
What treatment is available for essential thromocythaemia?
- Aspirin: to prevent thrombosis
- Anagrelide: specific inhibition of platelet formation, side effects include palpitations and flushing, increases MF
- Hydroxycarbamide/urea: antimetabolite. Suppression of other cells as well. Possible mildly leukaemogenic
- Alpha interferon: may have a place in the treatment of patients below 40 years of age or in pregnancy.
201
How are patients with essential thromocythaemia risk stratified?
- Low risk: 60, Thrombosis, ischaemic or haemorrhagic symptoms, Platelets >1000x10^9/L, Other thrombotic risk factors
202
What is chronic idiopathic myelofibrosis?
A clonal myeloproliferative disease with proliferation mainly of megakaryocytes and granulocytic cells, associated with reactive bone marrow fibrosis and extramedullary haematopoieisis.
Can be primary or secondary to PV or ET
203
What symptoms and signs do patients with essential thromocythaemia present with?
- Incidental in 30%
- Cytopenias: anaemia or thrombocytopenia
- Thrombocytosis
- Splenomegaly: may be massive e.g. Budd-Chiari syndrome
- Hepatomegaly
- Hypermetabolic state: weight loss, fatigue, dyspnoea, night sweats, hyperuricaemia
204
What signs in a peripheral blood film are there with myelofibrosis?
```
Leucoerythroblastic picture
Tear drop poikilocytes
Giant platelets
Circulating megakaryocytes
Basophilia
```
205
What treatment is available for patients with myelofibrosis?
- Transfusions: may become increasingly difficult because of splenomegaly, platelet transfusions often ineffective.
- Splenectomy for symptomatic relief: often hazardous and followed by worsening of condition
- Cytoreductive: hydroxycarbamide for thrombocytosis but may worsen anaemia
- Thalidomide with or without prednisolone for select patients
- Bone marrow transplant for young patients
206
What type of biopsy are preferable for suspected bone tumours?
(Jamshidi) Needle biopsy guided by US or CT
| Prevents local contamination
207
Examples of tumour-like conditions which would be part of a differential for a suspected bone tumour
```
Fibrous dysplasia
Metaphyseal fibrous cortical defect/non-ossifying fibroma
Reparative giant cell granuloma
Ossifying fibroims
Simple bone cyst
```
208
What condition may have a 'soap bubble' osteolytic appearance on x-ray? What is seen on histology?
Fibrous dysplasia
Hip may also get shepherd's crook deformity.
Histology shows thin, irregular (Chinese character-like) bony trabeculae
209
What is McCune–Albright syndrome?
- Endocrine disease, such as in precocious puberty
- Polyostotic fibrous dysplasia
- Unilateral Café-au-lait spots
210
What mutation is associated with fibrous dysplasia?
GNAS on chromosome 20q13
211
What is the commonest site of an enchondroma?
Hands and feet.
| They are a cartilage cyst found in the bone marrow and may cause a fracture.
212
What is the commonest site of an osteochondroma?
Knee and proximal ends of long bones.
| They are a type of benign tumour that consists of cartilage and bone usually on a peduncle.
213
What are the commonest sites affected by fibrous dysplasia?
Fibrous dysplasia can occur in any part of the skeleton but the bones of the skull, thigh, shin, ribs, upper arm and pelvis are most commonly affected.
214
What is the commonest site of a Giant cell tumour of bone?
The epiphyseal/metaphyseal region of long bones, most commonly around the knee.
It is characterised by the presence of multinucleated giant cells (osteoclast-like cells).
215
What are the commonest sites of an osteosarcoma?
```
Osteosarcoma tends to affect regions around the;
knee 60%
hip 15%
shoulder 10%
jaw 8%
```
216
What is Codman's triangle?
Triangular area of new subperiosteal bone that is created when a lesion, often a tumour, raises the periosteum away from the bone. Can be seen with osteosarcoma.
217
What is osteosarcoma and what does it look like histologically?
The most common type of primary malignant bone tumour that exhibits osteoblastic differentiation and produce malignant osteoid.
Malignant mesenchymal cells +/- bone and cartilage formation
218
What are the commonest sites of a chondrosarcoma?
Pelvis, shoulder, proximal ends of long bones, base of skull.
Affects older patients >40 yrs
219
What does an chondrosarcoma look like histologically?
Malignant chondrocytes =/- chondroid matrix.
| May dedifferentiate to high grade sarcoma
220
What are the commonest sites of Ewing's sarcoma?
Pelvis, femur, humerus, ribs and clavicle.
Occurs in middle of bones - diaphysis
80% patients <20
221
What is Ewing's sarcoma and what does it look like histologically?
A malignant small, round, blue cell tumour.
| Sheets of small round cells.
222
What mutation is associated with Ewing's sarcoma?
Specific chromosome translocation 11:22 (EWS/Fli1)
223
What are the commonest sites of a soft-tissue sarcoma/tumour?
Can affect anywhere but majority occur in large muscles of limbs, chest wall, mediastinum, retroperitoneum.
224
What risk factors are associated with soft-tissue sarcomas?
```
Genetic - Retinoblastoma gene
Chemical carcinogens e.g. agent orange
Physical (asbestos, foreign body)
Viruses (HIV - kaposi's)
Immunodeficiency
```
225
What different types of soft-tissue sarcomas are there?
Spindle cell tumours
Myxoid tumours
Pleomorphic tumours
226
What cells are seen with a normal cervical smear?
Superficial and intermediate squamous cells
227
How are samples collected in exfoliative cytology?
Cells are dislodged or spontaneously shed from a surface ie. Bronchial washings and brushings, serous cavity effusions etc. Not FNA's
228
What possible side effects could there be from FNA?
```
Typically nothing
Bruising
Fainting
(Pneumothorax – site dependent!)
(Infarction of lesion)
```
229
What are the acute and chronic dangers with cocaine use?
– Acute dangers : cardiac dysrythmias, acute heart failure, myocardial infarction
– Slowly developing damage to the myocardium, ventricular arrhythmias, sudden death
– Lethal syndrome of excited delirium, occurs in regular users within 24 hrs of last dose
– Effects prolonged if used with ethanol, get cocaethylene formed
230
What are the major points of forensic toxicology concern for ecstasy?
aka. MDMA.
– Few deaths
– Large OD causes direct toxic effect on heart
– Can cause hyperthermia, leads to rhabdomyolysis, leads to muscle necrosis and renal failure
231
What are the major points of forensic toxicology concern for Methadone?
– Tolerance
– After ingestion fatal amount takes 4-6 hours to die
– Additive effects other respiratory depressant drugs
– 5 mL can kill a child, 60 mL can kill healthy adult male
– Maintenance dose can vary from 5 to 200 mL
232
Under Section 3 of the Coroner’s Act 1887, which deaths are reported to the coroner?
Violent
Unnatural or sudden
Cause of death is unknown
233
What problems are there with interpreting forensic toxicology?
* Tolerance
* Site dependence
* PM redistribution of drugs (NB PM blood concentration cannot be used to calculate the dose)
* Individual variation in response
* Stability of drugs
234
Why is hair used for analysis of drugs?
* Can only detect drugs <12 hrs in blood
* Urine, typically 2-3 days
* Hair: only specimen good for long term drug use
* Drugs incorporated into hair from blood during the growth phase
* Hair growth ~1cm/month – “tape-recording of drug use”
235
What are the applications of hair drug analysis?
* Child custody cases
* Investigating spiked drinks defences
* Drug naïve deaths
* Monitoring drug use prior to return of driving license – Germany, Italy
* Investigation of drug use in exhumed/putrefied bodies
* Employment, pre-employment screening - USA
236
What are the features of chronic pancreatitis?
- progressive fibroinflammatory disease
- diabetes, steatorrhoea & radiographic calcifications
- permanent impairment of function
- irreversible morphological changes
237
What are the non-alcohol related causes of chronic pancreatitis?
- hereditary
- autoimmune
- metabolic (hypercalcaemia, hyperlipidaemia)
- idiopathic
- anatomic abnormalities (e.g. paraduodenal pancreatitis)
- obstructive (e.g. gallstones)
- trauma
238
What is the pathogenesis of alcohol related chronic pancreatitis?
- chronic alcohol consumption increases protein concentration within pancreatic juice
- intraductal precipitation of plug-forming secretions
- subsequent calcification
- intraductal calculi -> duct obstruction
- secondary acinar atrophy & periductal fibrosis
239
What are the microscopic features of alcohol related chronic pancreatitis?
- preservation of normal lobular architecture
- irregular loss of acinar and ductal tissue
- ductal dilatation (ectasia)
- chronic inflammation & fibrosis
- fibrosis is irregular in distribution in periductal, intralobular & interlobular areas
- hyperplasia & hypertrophy of nerve fibres
240
What are the macroscopic features of alcohol related chronic pancreatitis?
- focal, segmental or diffuse involvement
- involved areas are indurated & fibrotic
- distorted cystically dilated ducts
- plugs of calcified protein (calculi)
- pancreas may become rock hard & undergo atrophy
- shrunken & irregular contour in advanced cases
- pseudocysts of variable size (up to 10cm) lined by fibrous tissue, inflammation & granulation tissue (no epithelial lining)
241
What microscopic feature is helpful in differentiating chronic pancreatitis from duct type adenoCa?
preservation of lobular architecture
242
What are PanIN 1A and 1B?
Cellular changes that can be observed in chronic pancreatitis
PanIN 1A - mucous cell metaplasia
PanIN 1B - papillary epithelial hyperplasia
243
What are the features of hereditary pancreatits?
- usually begins in childhood or early adolescence
- rare: 2% of chronic pancreatitis pts
- recurrent pancreatitis
- family history of pancreatic disease
- characteristic PRSS1 mutation (cationic trypsinogen gene)
- 50-fold increased risk of ductal adenoCa
244
What is Lymphocytic Sclerosing Pancreatitis?
Autoimmune duct-centric pancreatitis with high serum IgG4, (obliterative) phlebitis of medium-sized veins and IgG4+ plasma cells around ducts.
Often associated with other systemic AI diseases
245
What is groove pancreatitis?
AKA paraduodenal pancreatitis - within & surrounding duodenal wall near minor ampulla
‘groove’ - usually involves an area located between the CBD, pancreas & duodenum
Chronic inflammation of duodenum that extends to pancreatic parenchyma
246
What is a pancreatic pseudocyst?
- consequence of severe acute on chronic pancreatitis or secondary to trauma, surgical complication
- thick walled fibrous capsule without epithelial lining
- sequela of extensive liquefactive necrosis of peripancreatic fat tissue and/or intrapancreatic parenchyma due to activated pancreatic enzymes
- can be anywhere in pancreas
- cyst fluid analysis – high amylase levels >500U/L
247
What different types of tumour are there of the pancreas?
- Ductal adenocarcinoma
- Pancreatic Intraepithelial neoplasia (PanIN)
- Cystic Tumours: serous or mucinous cystic neoplasm
- Intraductal Papillary Mucinous Neoplasm (IPMN)
- Pancreatic Endocrine Neoplasm: well or poorly dif
248
What are the risk factors for pancreatic ductal adenocarcinoma?
- smoking & high dietary fat intake
- acquired chronic pancreatitis & diabetes
- hereditary chronic pancreatitis
- heritable genetic syndromes - BRCA2, FAMMM, P-J syndrome, familial pancreatitis, HNPCC
249
What is the T staging for pancreatic ductal adenocarcinoma?
Tis – Ca in situ (PanIN 3)
T1 – tumour limited to pancreas, 20mm
T3 – tumour extends directly into any of the following: duodenum, bile duct, peripancreatic tissues
T4 – tumour extends into stomach, spleen, colon, adjacent large vessels
250
What type of pancreatic tumour is composed of large stromal mucin lakes within which are suspended relatively scanty strips and clusters of cells with individual cells having a signet ring configuration?
Colloid carcinoma (mucinous non cystic Carcinoma)
251
What type of pancreatic tumour is poorly differentiated, lacks gland formation & has a pushing growth pattern at the periphery with large, syncytial tumour cells?
Medullary Carcinoma
252
What type of pancreatic tumour contains neoplastic glands resembling conventional ductal adenoCa as well as large nests of cells with squamous differentiation?
Adenosquamous carcinoma
253
What type of pancreatic tumour has enormous tumour cells growing in solid sheets & have markedly atypical nuclei?
Undifferentiated carcinoma
254
What is Pancreatic Intraepithelial Neoplasia?
- precursor of ductal adenoCa
- series of increasingly proliferative changes within the epithelium of pancreatic ducts
- graded as PanIN 1A, 1B, 2 & 3
255
What type of pancreatic lesion is grossly well circumscribed & composed of small cysts, each measuring <1cm, separated by thin translucent septa?
Serous cystic neoplasm e.g. Microcystic serous cystadenoma
256
What are the microscopic features of a serous cystic neoplasm?
- cysts lined by flattened cuboidal epithelium
- clear cytoplasm & well defined cytoplasmic borders
- small round uniform nuclei with dense chromatin
- accumulation of glycogen
257
What type of pancreatic lesion is grossly well circumscribed, often involves the tail of pancreas & contains numerous large 1-5cm cysts?
Mucinous cystic neoplasm
258
What are the microscopic features of a mucinous cystic neoplasm?
- similar to ovarian mucinous neoplasm
- tall columnar cells with abundant apical mucin
- bland with uniform, basally oriented nuclei
- minimal architectural complexity
- subepithelial hypercellular spindle cell stroma (ovarian-like) – must be present for diagnosis
- stromal cells express oestrogen, progesterone and inhibin
259
What is an Intraductal Papillary Mucinous Neoplasm?
- characterized by intraductal proliferation of mucinous cells usually arranged in a papillary pattern (intestinal, gastric foveolar, pancreatobiliary)
- multilocular cystic mass or abundant papillary nodules
- mucin extrusion through the ampulla diagnostic
- radiographic finding of ectatic (dilated) ducts
- 2 main types: Main and Branch duct type
- Good prognosis, most managed by conservative resection
260
What is the normal lining of the oesophagus?
- Proximal 2/3 squamous epithelium
- Distal 1/3 columnar epithelium
- Join at squamo-columnar junction / Z-line
261
What is the normal lining of the body of the stomach?
- Foveolar epithelium (columnar, mucin secreting)
| - Specialised glands (parietal and chief cells)
262
What is the normal lining of the antrum of the stomach?
- Foveolar epithelium (columnar, mucin secreting)
| - Non-specialised glands
263
What is the normal lining of the duodenum?
- Glandular epithelium with goblet cells
| - Villous architecture (villus:crypt ration >2:1)
264
A tissue sample with Brunners glands is from where?
Proximal part of duodenum. They are seen in the lamina propria.
265
What is the grading system for oesophagitis?
Los Angeles classification (A-D)
266
What is the commonest cause of oesophagitis?
Gastro-oesophageal reflux disease (GORD) / reflux oesophagitis
267
What are the complications of GORD?
Ulceration -> Haemorrhage, Perforation
Fibrosis -> Stricture
Barrett's oesophagus
268
What is Barrett's oesophagus?
Metaplasia of squamous mucosa to columnar epithelium with goblet cells (intestinal type epithelium) due to chronic GORD.
Can lead to adenocarcinoma: metaplasia -> dysplasia -> Ca
269
What are the risk factors for squamous cell oesophageal carcinoma?
- alcohol and smoking
- achalasia of cardia
- Plummer-Vinson syndrome
- nutritional deficiencies
- nitrosamines
- HPV
270
How does squamous cell oesophageal carcinoma present?
- 6x more common in afro-carribeans, M>F
- 50% in middle 1/3
- progressive dysphagia
- odynophagia
- anorexia
- severe weight loss
- grows and spreads rapidly to liver and local structures
271
What are common causes of acute gastritis?
- 0 NSAIDs: Aspirin, Ibuprofen etc
- Corrosives (bleach)
- Infection (acute H.pylori)
272
What are common causes of chronic gastritis?
- H.pylori, H.heilmanni
- Autoimmune (pernicious anaemia)
- Alcohol
- Smoking
- Other infection (CMV, HSV, Strongyloides)
- Crohn's Disease
273
How are H.pylori often described in biopsies?
Seagull shapped
274
What possible complications are there from a gastric ulcer?
- Bleeding: iron def anaemia, shock
- Perforation: peritonitis, abscess formation
- Malignancy
275
What is commonest type of gastric cancer?
90% carcinomas
| Also MALTomas / Lymphoma
276
What is the cause and treatment of gastric lymphoma?
Chronic inflammation due to H/pylori
| Treat with PPIs + antibiotics to eradicate infection and hence chronic antigen stimualtion
277
What auto-antibodies are present in pernicious anaemia?
Parietal cell antibodies 90%
| Intrinsic factor antibodies 60%
278
What complications can occur with pernicious anaemia?
- Vit B12 deficiency
- Stomach body atrophy
- Malignancy
279
What other pathogens can cause duodenitis, esp in immunosuppressed?
```
CMV
Microsporidiosis
Cyryptosporidiosis
Giardia lamblia
Tropheryma whippelii (Whipples disease)
```
280
How does pain experienced with duodenal and gastric ulcers differ?
Gastric: worse with food, better with antacids
Duodenal: better with food and milk, worse at night
281
What does endoscopy and a duodenal biopsy show in coeliac disease?
- Scalloping with smooth shiny mucosa
| - Villous atrophy, crypt hyperplasia, intraepithelial lymphocytes
282
How is partial villous atrophy graded?
Marsh Criteria 0-4
283
Why might serology be inaccurate in coeliac disease?
Because (irish) patients are likely to have IgA deficiency also, need duodenal biopsies on and off gluten diet
284
What malignancy are patients with poorly controlled coeliac disease at an increased risk of?
Duodenal T-cell MALToma/lymphoma
| ~10% progress if not treated adequately
285
What is the commonest type of urinary calculi and why do patients get them?
75% = calcium oxalate
Most related to absorptive hypercalciuria, some to renal hypercalciuria
15% = Magnesium ammonium phosphate
5% = uric acid
286
What are magnesium ammonium phosphate urinary calculi associated with?
Infections with urease-producing organisms e.g. Proteus which alkalinises the urine. Can form very large 'staghorn calculi'
287
What are the common points of renal stone impaction?
Pelvic-uriteric junction, pelvic brim and Vesico-uriteric junction
288
What is a renal papillary adenoma?
Benign renal epithelial tumour with a papillary or tubular architecture and size of 5mm or less
Often found incidentally
289
What is a renal oncocytoma?
Completely benign oncocytic renal epithelial neoplasm. Most cases sporadic and discovered incidentally.
Mahogany brown colour.
290
What is a renal angiomyolipoma?
Benign mesenchymal tumour of the kidney composed to variable amount of fat, smooth muscle and thick-walled blood vessels
Most sporadic, some associated with tuberous sclerosis
May present with flank pain due to haemorrage
291
What is the commonest renal malignancy and what risk factors are associated with it?
Renal cell carcinoma - malignant epithelial tumour
Risk factors include smoking, hypertension, obesity, environmental chemicals, long-term dialysis
Genetic syndromes e.g. von Hippel Lindau
292
What different subtypes of renal cell carcinoma are there?
70% clear cell - golden yellow tumours with haemorrgaic areas
15% Papillary - friable brown tumour, >5mm papillary adenoma
5% Chromophobe - solid brown tumour
293
Which renal tumour often shows loss of genetic material at chromosome 3p?
Clear cell renal cell carcinoma
294
Which renal tumour often genetically shows trisomy of chromosomes 7 and 17?
Papillary renal cell carcinoma
295
What grading system is used for renal cell carcinoma?
Fuhrman system 1-4
296
What is the overall 5 year survival rate for renal cell carcinoma?
~60%
297
What is Wilm's tumour?
aka Nephroblastoma, a malignant childhood (2-5yr) renal neoplasm which presents as an abdominal mass.
Histologically see 'small round blue cells'
Good prognosis
298
What are transitional cell carcinomas?
aka urothelial carcinomas are a group of epithelial neoplasms arising in the urothelial tract, most commonly the bladder. Associated with smoking.
299
How are urothelial carcinomas classified?
- Non-invasive papillary urothelial carcinomas
| - Invasive (infiltrating) urothelial carcinomas
300
What are non-invasive papillary urothelial carcinomas and how are they treated?
Frond-like growths projecting from bladder mucosa, present with haematuria.
Resection at cystoscopy +/- intravesical chemotherapy depending on grade. Follow up.
301
What are invasive (infiltrating) urothelial carcinomas and how are they treated?
Malignant / invasive urothelial tumour.
Tumours only invading lamin propria can be treated with resection and intravesical chemotherapy.
Tumours invading detrusor muscle or beyond required cystectomy +/- radiotherapy +/- systemic chemotherapy.
302
What treatment is available for benign prostatic hyperplasia?
Medical
- alpha-blockers: doxazosin
- 5-alpha-reductase inhibitors: finasteride, dutaseride
Surgical
- transurethral resection of the prostate (TURP)
303
What mutations are often found in prostatic carcinoma?
```
GST-pi
PTEN
AMACR
p27
E-cadherin
```
304
How is prostate cancer usually diagnosed?
From needle biopsy following a raised serum prostate specific antigen (PSA) level in an asymptomatic patient
305
What prognostic indicator is used for prostate cancer?
Gleason score (6-10) - higher the score mean more aggressive behaviour
306
What are the main treatment options for early stage prostate cancer?
Active surveillance
Radical prostatectomy
Radical radiotherapy
307
What risk factors are there for testicular germ cell tumours?
Cryptorchidism increases risk 3-5 fold
Prenatal risk factors include low birth weight and small for gestational age
Most arise from precursor lesion - intratubular germ cell neoplasia (ITGCN)
308
What different types of testicular germ cell tumour are there?
Seminoma - resembles germ cells
Embryonal carcinoma - resembles embryonic tissue
Yolk sac tumour - resembles yolk sac tissue
Immature teratoma - resembles foetal tissue
Mature teratoma - resembles adult tissues
Choriocarcinoma - resembles placental tissue
Often mixed
309
What types of testicular non-germ cell tumours are there?
Testicular lymphoma - older men, high grade, poor survival
Leydig cell tumours - most benign
Sertoli cell tumours - most benign
310
What are the stages of fracture repair?
1. Organisation of haematoma at # site (pro-callus)
2. Formation of fibrocartilaginous callus
3. Mineralisation of fibrocartilaginous callus
4. Remodelling of bone along weight-bearing lines
311
What are the common sites of osteomyelitis?
```
Adults:
- vertebrae
- jaw (2º to dental abscess)
- toe (2º to diabetic skin ulcer) (>3mm)
Children
- long bones (usually metaphysis)
```
312
What are the common causative organisms of osteomyelitis?
```
Adults:
- Staph Aureus (90%)
- E. Coli
- Klebsiella
- Salmonella (associated with sickle cell disease)
- Psuedomonas (IVDA)
Neonates:
- Haemophilus influenzae
- Group B Streptococcus
- Occasionally entrobacter
```
313
When does osteomyelitis show x-ray changes and what are they?
- usually appear 10 days or so post onset
- Mottled rarefaction and lifting of periosteum
- >1week - involucrum: irregular sub-periosteal new bone formation
- Later - irregular lytic destruction (takes 10-14days)
- Some areas of necrotic cortex may become detached called sequestra (takes 3-6 weeks)
314
How might TB osteomyelitis present?
- Affects immunocompromised patients
- Spinal disease (50% cases) may result in psoas abscess and severe skeletal deformity (Pott’s disease)
- Systemic amyloidosis may result in protracted cases
315
What type of cell is associated with TB osteomyelitis?
Langhans type Giant cell
316
What problems can syphilitic osteomyelitis causes?
```
Congenital skeletal lesions:
- Osteochondritis
- Osteoperiostitis
- Diaphyseal osteomyelitis
Acquired late skeletal lesions:
- Non-gummatous periostitis
- Gummatous inflammation of bone and joints
- Neuropathic joints (Tabes Dorsalis)
- Neuropathic shaft fractures
```
317
What main sites are affected by osteoarthritis?
```
Vertebrae
Hips
Knees
DIPJ hand
Carpometacarpal joints
Metatarsophalangeal joints
```
318
How many patients with rheumatoid arthritis are rheumatoid factor positive?
80%
| RF mostly IgM, forms immunocomplexes with IgG
319
What are the histological findings in rheumatoid arthritis?
Proliferative synovitis with;
1. Thickening of synovial membranes ( villous)
2. Hyperplasia of surface synoviocytes
3. Intense inflammatory cell infiltrate
4. Fibrin deposition and necrosis
Pannus is the exuberant inflamed synovium on the articular surface
320
What subsets of pseudogout are there?
a) Sporadic
b) Metabolic
c) Hereditary
d) Traumatic
321
What are the clinical effects of a prolactinoma?
- Amenorrhea, galactorrhea, loss of libido, infertility
| - Usually diagnosed earlier in females of reproductive age
322
What are the clinical effects of a growth hormone adenoma?
- Prepubertal children - gigantism
- Adults - acromegaly
- Diabetes mellitus, muscle weakness, hypertension, congestive cardiac failure
323
What are the causes of hypopituitarism?
Nonsecretory pituitary adenomas (commonest)
Ischaemic necrosis:
- Most commonly post-partum (Sheehan’s syndrome)
- DIC, sickle cell anaemia, elevated intracranial pressure, shock.
Ablation of pituitary by surgery or irradiation
324
What are the clinical manifestation of anterior pituitary hypofunction?
- Children: growth failure (pituitary dwarfism)
- Gonadotrophin deficiency - amenorrhea and infertility in women. Decreased libido and impotence in men
- TSH and ACTH deficiency - hypothyroidism and hypoadrenalism
- Prolactin deficiency - failure of post-partum lactation
325
What are the causes of a non-toxic goitre?
Common if there is impaired synthesis of thyroid hormone - most often due to iodine deficiency.
May be seen at puberty particularly in females.
May be due to ingestion of substances that interfere with thyroid hormone synthesis e.g. brassicas.
May be due to hereditary enzyme defects.
326
What are the primary causes of thyrotoxicosis?
Grave's disease
Hyperfunctioning multinodular goitre
Hyperfunctioning adenoma
Thyroiditis
327
What are the non-primary causes of thyrotoxicosis?
Secondary: TSH secreting pituitary adenoma (rare)
Not associated with thyroid disease:
- Struma ovarii (ovarian teratoma with ectopic thyroid)
- Factitious thyrotoxicosis (exogenous thyroid intake)
328
What are the causes of hypothyroidism?
```
Primary:
- Postablative (after surgery or radioiodine therapy)
- Primary idiopathic
- Hashimoto’s thyroiditis
- Iodine deficiency
- Congenital biosynthetic defect
Secondary:
- Pituitary or hypothalamic failure (uncommon)
```
329
What are the types of thyroid carcinoma?
Papillary (75-85%) associated with radiation exposure
Follicular (10-20%)
Medullary (5%)
Anaplastic (<5%)
330
What are the diagnostic features of a papillary thyroid carcinoma?
- Optically clear nuclei
- Intranuclear inclusions
May have papillary architecture
May be psammoma bodies - accumulations of calcium
Lymphatic spread
331
How does follicular thyroid carcinoma spread?
Usually metastasise via bloodstream to lungs bone and liver
332
What is medullary thyroid carcinoma and what is characteristic about it?
Neuroendocrine neoplasm derived from parafollicular C cells
80% sporadic - adults 5-6th decade
20% familial - MEN - younger patients
Characteristically has amyloid deposits of calcitonin
333
What are the characteristics of anaplastic thyroid carcinoma?
Occur in elderly patients
Very aggressive
Metastases common
Most cases death within one year due to local invasion
334
What are the causes of primary hyperparathyroidism?
80-90% - solitary adenoma
10-20% hyperplasia of all 4 glands
- Sporadic or component of MEN type 1
<1% carcinoma
335
What are the causes of hypoparathyroidism and the clinical manifestations?
- Surgical ablation (majority), Congenital absence, Autoimmune
- Neuromuscular irritability: tingling, muscle spasms, tetany
- Cardiac arrhythmias
- Fits
- Cataracts
336
What are the endogenous causes of Cushing's syndrome?
- Cushing's disease >50% ACTH-producing adenoma in pituitary: nodular coritcal adernal hyperplasia
- Primary adrenal neoplasm ~30%
- Bilateral hyperplasia
- Ectopic ACTH by non-endocrine tumours e.g. small cell lung carcinoma
337
What are the causes of primary adrenal insufficiency?
Acute:
- Haemorrhage
- Sepsis (Waterhouse-Friderichson syndrome)
- Sudden withdrawal of corticosteroid therapy
Chronic (Addison’s disease):
- Autoimmune (75-90%)
- TB
- HIV
- Metastatic tumour (lung and breast particularly)
- Rarely amyloid, fungal infections, haemochromatosis, sarcoidosis
338
What is important to know about phaeochromocytomas?
- 10% associated with familial syndrome inc. MEN 2A and 2B, von Hippel-Lindau disease and Sturge-Weber syndrome
- 10% are bilateral
- 10% are malignant
- 10% of catecholamine-secreting tumours arise outside the adrenal (paragangliomas)
339
What features of endocrines tumours might suggest multiple endocrine neoplasia?
- Occur at a younger age than sporadic tumours
- Arise in multiple endocrine organs
- Often multifocal in one organ
- Often preceded by hyperplasia
- Usually more aggressive than sporadic tumours
340
How is cytopathology used and coded in breast disease?
```
- investigating nipple discharge and palpable lumps
C1 = inadequate
C2 = benign
C3 = atypia, probably benign
C4 = suspicious of malignancy
C5 = malignant
```
341
How does duct ectasia normally present and what findings are there?
* Inflammation and dilation of large breast ducts that presents with nipple discharge, sometimes breast pain, breast mass and nipple retraction
* Discharge cytology shows macrophages and proteinaceous material
* Histology shows dilated ducts with periductal inflammation and filled with secretions
* Benign condition with no increased risk of malignancy
342
How does acute mastitis normally present and what findings are there?
* Painful red breast often seen in lactating women due to cracked skin and stasis of milk
* Staphylococci the most common causative organism.
* FNA cytology shows abundant neutrophils.
* Histology shows acute inflammation +/- abscess formation
343
How does fat necrosis normally present and what findings are there?
* A firm breast lump associated with trauma, surgery, or radiotherapy
* FNA cytology shows degenerate fat, foamy macrophages and giant cells
* Histology shows degenerate adipocytes surrounded by foamy macrophages, giant cells, lymphocytes and plasma cells. Later changes include fibrosis and calcification.
344
How does fibrocystic breast change normally present and what findings are there?
* A spectrum of changes which reflect normal, albeit exaggerated, hormonal responses
* Very common, >1/3 of premenopausal women
* Presents with cyclical breast lumpiness and nodularity
* Histological changes include cysts, apocrine metaplasia, adenosis, mild usual epithelial hyperplasia and stromal hyperplasia
* No increased risk of malignancy
345
How does a fibroadenoma normally present in the breast and what findings are there?
* Common benign fibroepithelial tumour
* Circumscribed mobile lump in women 20-30 yrs
* FNA cytology shows branching sheets of epithelium, bare bipolar nuclei and stroma
* Histology shows a multinodular mass composed of expanded intralobular stroma and compressed slit-like ducts
346
What are phyllodes tumours?
- An uncommon group of potentially aggressive fibroepithelial neoplasms of the breast
- Present as enlarging masses in women aged over 50.
- May arise within pre-existing fibroadenomas
- Vast majority behave in a benign fashion but a small proportion can behave more aggressively
347
How does an intraductal papilloma normally present in the breast and what findings are there?
* Common benign papillary tumour arising with the duct system in women 40-60 yrs
* Presents with nipple discharge or a mass
* Discharge cytology = branching papillary groups of epithelium
* Histology = papillary mass within a duct lined by epithelium and myoepithelium
348
What is a radial scar?
* Benign sclerosing lesion of the breast characterised by a central zone of scarring surrounded by a radiating zone of proliferating glandular tissue
* Presents as a stellate mass on mammography, closely mimicking carcinoma
* Histology = a central elastotic nidus surrounded by a proliferative corona
349
What are proliferative breast diseases?
• A diverse group of intraductal epithelial proliferations associated with an increased risk, of greatly varied magnitude, for subsequent development of invasive breast carcinoma.
• Picked up on mammography or incidentally in breast tissue excised for other reasons.
• Includes:
- florid usual epithelial hyperplasia (1.5-2x risk)
- flat epithelial atypia (4x risk)
- in situ lobular neoplasia (7-12x risk)
350
What is ductal carcinoma in situ (DCIS) and what findings are there?
* A neoplastic intraductal epithelial proliferation associated with an inherent, but not inevitable, risk of progression to invasive breast carcinoma
* Histology shows ducts filled with atypical epithelial cells
* Graded into low, intermediate or high grade according to degree of nuclear atypia
* 85% detected as microcalcification on mammography
351
What is the lifetime risk of invasive breast carcinoma in women?
- 1 in 8/9
| - Incidence rates rise rapidly with increasing age: most cases occur in older women.
352
What risk factors are there for breast cancer?
- early menarche
- late menopause
- increased weight
- high alcohol consumption
- oral contraceptive use
- positive family history
- BRCA mutations: lifetime risk up to 85%
353
What are the two genetic pathways that lead to invasive breast cancer?
* “Low grade” breast carcinomas tend to arise from low grade DCIS or in situ lobular neoplasia and show 16q loss
* “High grade” breast carcinomas arise from high grade DCIS and show complex karyotypes with many unbalanced chromosomal aberrations
354
What different histological types of breast carcinoma are there?
- ductal (80%)
- lobular (15%)
- tubular (5%)
- mucinous (5%)
355
What FNA cytology and histology findings are there for invasive breast carcinoma?
* FNA cytology shows many poorly cohesive atypical epithelial cells
* Histology shows infiltrating atypical epithelial cells
356
How are invasive breast cancers graded?
1) tubule formation
2) nuclear pleomorphism
3) mitotic activity
Each scored 1-3, added together:
3-5 points = grade 1 (well differentiated)
6-7 points = grade 2 (moderately differentiated)
8-9 points = grade 3 (poorly differentiated)
357
What receptors are tested for in breast cancer and what do they suggest?
* oestrogen receptor (ER), progesterone receptor (PR) and Her2 status
* Low grade types tend to be ER, PR positive and Her2 non-amplified
* High grade types tend to be ER, PR negative and Her2 amplified
358
What prognostic factors are there for breast cancer?
* most important prognostic factor = status of axillary lymph nodes
* tumour size
* histological type
* histological grade
359
What is the aim of the NHS Breast Screening Programme and who is targeted?
- to pick up DCIS or early invasive carcinomas
| - women aged 47-73 are invited for screening every 3 years
360
What % of women have an abnormal screening mammogram? How are they assessed?
- ~5%
- they are recalled to an assessment clinic for further investigation
- may include more mammograms or an ultrasound plus core biopsy or FNA
361
How are core biopsies taken as part of the breast screening program coded?
```
B1 = normal breast tissue
B2 = benign abnormality
B3 = lesion of uncertain malignant potential
B4 = suspicious of malignancy
B5 = malignant (B5a = DCIS, B5b = invasive carcinoma)
```
362
What are the histological findings of gynaecomastia?
Breast ducts show epithelial hyperplasia with typical finger-like projections extending into the duct lumen. The periductal stromal is often cellular and oedematous.
363
Where do immune complexes deposit in the kidney?
- mesangial
- subendothelial
- subepithelial
Related to size and charge
Complexes may be formed with endogenous (auto) antigens e.g. SLE, or exogenous antigens e.g. from infective organisms and deposit at different rates.
364
What are the common congenital disorders of the kidneys?
Bilateral or unilateral agenesis
Ectopic kidney e.g. pelvic
Horseshoe kidney (1:500 to 1:1000)
365
What is adult polycystic kidney disease?
- AD (1:400-1:1000), 10% of ESRF patients.
- Cysts arise from any portion of the nephron
- Renal failure develops from 40-70 years.
- PKD1 and PKD2 genes have been identified
- Also get cysts in liver and beri-aneurysms in brain
366
Which group of patients acquire renal cysts and what are they associated with?
- Cysts commonly arise in the kidneys of patients with ESRF after a prolonged period on dialysis (acquired cystic disease).
- Carcinoma may occur in these cysts (7% of patients at 10 years)
367
What are the causes of acute kidney injury?
```
Pre-renal:
- Failure of perfusion
Renal:
- Acute tubular injury
- Acute glomerulonephritis
- Thrombotic microangiopathy
Post-renal:
- Obstruction to urine flow
```
368
What causes acute tubular injury?
aka acute tubular necrosis
- Ischaemia or toxins e.g. myoglobin, drugs
- NSAIDs and cox2 inhibitors predispose
369
What morphological changes are there to tubular epithelial cells in acute tubular injury and why does renal function decrease?
- They show a range of changes from loss of brush border to detachment from the basement membrane with formation of intraluminal granular casts.
- Reduction in GFR is due to a combination of tubular obstruction, tubular leak and haemodymic changes. Tubules have excellent capacity to repair if the underlying insult is corrected
370
What are glomular crescents and what are they associated with?
Glomerulonephritis sufficient to cause acute renal failure is almost always associated with glomerular crescents which form in response to holes in the GBM caused by macrophages and neutrophils.
371
What are the causes of crescentic glomerulonephritis?
- Immune complex disease
- Anti-GBM disease
- Pauci-immune (scanty antibody deposits)
Crescentic glomerulonephritis leads rapidly to irreversible renal damage but is often treatable. Therefore diagnosis and treatment are urgent!
372
What are the commonest causes of immune complex-associated crescentic glomerulonephritis?
- SLE
- IgA nephropathy
- Post-infectious glomerulonephritis
Immune complexes can be detected by immunohistochemistry and electron microscopy
373
What antibodies are associated with pauci-immune crescentic glomerulonephritis?
Circulating anti-neutrophil cytoplasm antibodies (ANCA) cause neutrophil activation leading to glomerular necrosis. Typically patients also have vasculitis in other organs – e.g skin rash, lung haemorrhage
374
What is thrombotic microangiopathy?
- Damage to endothelium of glomeruli and vessels leading to thrombosis.
- Associated with damage to RBCs causing haemolytic anaemia with red cell fragments on the blood film = haemolytic uraemic syndrome (HUS)
375
What forms of thrombotic microangiopathy are there?
1. Diarrhoea associated. Caused by bacterial (usually E.coli) infection of the gut that releases a toxin that targets renal endothelium
2. Atypical (non-diarrhoeal) – often associated with abnormalities of proteins that control activation of the alternative pathway of complement – may be familial.
376
What is the definition of nephrotic syndrome?
Breakdown of selectivity of the glomerular filtration barrier leading to massive protein leak
- Proteinuria > 3.5g/day
- Hypoalbuminaemia
- Oedema
- Hyperlipidaemia
377
What are the causes of nephrotic syndrome?
```
Systemic:
- Diabetes mellitus
- Amyloidosis
- SLE
Primary glomerular disease:
- Minimal change disease
- Focal and segmental glomerulosclerosis
- Membranous glomerulonephritis
```
378
What histological changes are seen with diabetes associated nephrotic syndrome?
Diabetic glomerulosclerosis - glomeruli show capillary wall thickening and mesangial increase with nodule formation. Arterioles show hyaline deposition
379
What are the characteristics of renal amyloidosis?
- Deposition of extracellular proteinaceous material that stains with Congo red to give green bifrefringence.
- May be derived from many precursor proteins – commonest in the kidney are:
AA – derived from serum amyloid A protein which is elevated in chronic inflammation e.g. rheumatoid arthritis, chronic infections
AL - derived from immunoglobulin light chains
380
What is minimal change disease?
Primary disease of podocytes. Glomeruli look normal apart from effacement of podocyte foot processes on EM. Commonest in children. Generally responds to immunosuppression
381
What is focal and segmental glomerulosclerosis?
Similar to minimal change disease but glomeruli develop segmental scars. Less likely to respond to immunosuppresssion
382
What is membranous glomerulonephritis?
Associated with immune complex deposition on the outside of the GBM.
May be primary (idiopathic or auto-antibodies to phospholipase A2 receptor) or secondary to SLE, infection, malignancy or drugs
383
An asymptomatic patient with microscopic haematuria may have what?
- Thin basement membranes due to hereditary defect in type IV collagen
- IgA nephropathy
384
What is IgA nephropathy?
- Commonest form of glomerulonephritis worldwide
- Predominant IgA deposition in glomeruli
- Often presents with microscopic or macroscopic haematuria
- May cause proteinuria, acute renal failure
- Up to 30% progress to end stage renal failure
385
What are the commonest causes of chronic renal failure by prevalence?
- Diabetes (19.5%)
- Glomerulonephritis (15.3%)
- Hypertension & Vascular disease (15%)
- Reflux nephropathy (chronic pyelonephritis) (9.5%)
- Polycystic kidney disease (9.4%)
386
What are the main subtypes of brain oedema?
- Vasogenic oedema – When integrity of blood brain barrier is disrupted, made worse due to lack of lymphatic drainage in brain, can be local or general
- Cytotoxic oedema – Secondary to cellular injury e.g. due to general hypoxic-ischaemic injury
387
What is the normal volume of CSF and normal pressure?
90-150 ml
| 7–15 mmHg for a supine adult
388
How can hydrocephalus be classified?
```
Non-communicating/obstructive:
- Actual obstruction to flow of CSF
Communicating/Non-obstructive:
- Impaired reabsorption
- No obstruction to flow
```
389
What different types of brain herniation are there?
* Transtentorial (uncal gyral, mesial temporal) – medial temporal lobe compressed against the free margin of the tentorium cerebelli
* Subfalcine (cingulate gyrus) – cingulate gyrus displaced under the falx cerebri
* Tonsillar – cerebellar tonsils through the foramen magnum, this causes brain stem compression
390
What are the causes of intraparenchymal haemorrhage (non traumatic)?
» Hypertension accounts for 50% of clinically significant haemorrhages
» Other factors include clotting disorders, neoplasms, amyloid, vasculitis, vascular malformations
391
What are Charcot–Bouchard aneurysms?
Microaneurysms most often located in the lenticulostriate vessels of the basal ganglia that are associated with chronic hypertension. They are a common cause of cerebral hemorrhage.
392
What types of vascular malformation are there in the brain?
- Arteriovenous (AV) malformations: high pressure massive bleeds
- Capillary telangectases
- Venous angiomas
- Cavernous angiomas: low pressure recurrent bleeds
393
What is the commonest cause of a subarachnoid haemorrhage?
- Rupture of a Berry aneurism
- present in 1% of general population
- 80% occur at internal carotid artery bifurcation
- 30% patients have multiple
- Higher incidence in people with polycystic kidney disease, coarctation of the aorta, fibromuscular dysplasia and AV malformations in the brain
394
What inflammatory skin reaction patterns are there?
```
Vesiculobullous
Spongiotic
Psoriasiform
Lichenoid
Vasculitic
Granulomatous
```
395
What is seen on immunofluorescence in bulous pemphigoid?
IgG and C3 deposition along dermoepidermal junction
396
What is Pemphigus foliaceus?
look up
397
What does a classical BCC look like?
A raised, smooth, shiny, pearly nodule which may have ulcerated
398
What does a classical SCC look like?
A red, scaling, thickened patch on sun-exposed skin
399
What congenital diseases of the lungs are there?
- Lung agenesis or hypoplasia
- Tracheal & bronchial stenosis
- Congenital cysts
400
What are the causes of acute respiratory distress syndrome?
Infection (local or generalised sepsis), aspiration, trauma, inhaled irritant gases, shock, blood transfusion, DIC, drug overdose, pancreatitis, idiopathic.
401
What does insufficient surfactant production cause in premature babies?
Hyaline membrane disease of newborn
402
What is the basic pathology in ARDS and hyaline membrane disease of newborn?
Diffuse alveolar damage
403
What are the risk factors / associations with hyaline membrane disease?
```
Prematurity
Maternal diabetes
Second twin
Caesarean section
Birth asphyxia
```
404
What complications can hyaline membrane disease cause?
- Respiratory failure and death within 48 hours
- Pneumonia
- Interstitial emphysema
- Bronchopulmonary dysplasia: fibrous scarring
405
What are Charcot–Leyden crystals?
Microscopic crystals found in people who have allergic diseases such as asthma or parasitic infections.
406
What are Curschmann's spirals?
Desquamated epithelium seen in biopsies from asthmatic patients.
407
What is the definition of chronic bronchitis?
> Chronic cough productive of sputum
| > Most days for at least 3 months over at least 2 consecutive years
408
What are the histological features of chronic bronchitis?
> Dilatation of airways
> Hypertrophic mucous glands
> Goblet cell hyperplasia
409
What main complicatiosn arise from chronic bronchitis?
> Repeated infections
> Chronic hypoxia and reduced exercise tolerance
> Chronic hypoxia results in pulmonary hypertension and right sided heart failure (cor pulmonale)
> Increased risk of lung cancer independent of smoking
410
What is the definition of emphysema?
Emphysema is a permanent loss of the alveolar parenchyma distal to the terminal bronchiole.
411
How does the pattern of emphysema differ between a cause of smoking or alpha-1-antitrypsin deficiency?
Smoking > Loss centred on bronchiole - CENTRILOBULAR
| Alpha-1-antitrypsin deficiency > Diffuse loss of alveolae - PANACINAR
412
What main complicatiosn arise from emphysema?
Bullae > rupture = pneumothorax
Respiratory failure
Pulmonary hypertension > cor pulmonale
413
What is the definition of bronchiectasis?
Permanent abnormal dilatation of bronchi - site depends upon cause.
414
What are the causes of bronchiectasis?
- Congenital
- Post-infectious (esp children or cystic fibrosis)
- Immunodeficiency: 1º [hypogammagl.] and 2º [chemotherapy, NG]
- Ciliary dyskinesia: 1º [Kartagener’s] and 2º
- Obstruction (extrinsic/intrinsic/middle lobe syn.)
- Post-inflammatory (aspiration)
- Secondary to bronchiolar disease (OB) and interstitial fibrosis (CFA, sarcoidosis)
- Systemic disease (connective tissue disorders)
- Asthma
415
What are the main complications from bronchiectasis?
- Recurrent infections
- Haemoptysis
- Pulmonary Hypertension > cor pulmonale
- Amyloidosis
416
What is the location of the cystic fibrosis gene?
CFTR gene (Cystic Fibrosis Transmembrane Conductance Regulator) = 7q3
417
What are the main systemic effects of cystic fibrosis?
Lung -> airway obstruction, respiratory failure, recurrent infection
GI tract -> meconium ileus, malabsorption
Pancreas -> pancreatitis, malabsorption
Liver -> cirrhosis
Male reproductive system -> infertility
418
What organisms do patients with cystic fibrosis get repeatabley infected with?
S.aureus, H. influenzae, P.aeruginosa, B.cepacia
419
What are the main complications from cystic fibrosis?
Recurrent infections
Haemoptysis
Pneumothorax
Chronic respiratory failure and cor pulmonale
Allergic bronchopulmonary aspergillosis (ABPA)
Atelectasis
BRONCHIECTASIS
420
What are the histological features of bronchopneumonia?
- Patchy bronchial and peribronchial distribution
- Often lower lobes
- Acute inflammation surrounding airways and within alveoli
421
What are the histological features of lobar pneumonia?
1. Congestion: Hyperaemia, Intra-alveolar fluid
2. Red hepatization: Hyperaemia, Intra-alveolar neutrophils
3. Grey hepatization: Intra-alveolar connective tissue
4. Resolution: Restoration normal architecture
422
What are the main complications from pneumonia?
- Abscess formation
- Pleuritis and pleural effusion
- Infected pleural effusion (EMPYEMA)
- Fibrous scarring
- Septicaemia
423
What is the lung involvement in sarcoidosis?
Discrete epithelioid and giant cell granulomas, preferential distribution in upper zones with tendency to be perilymphatic, peribronchial.
Advanced disease may be fibrotic and cystic.
424
What is the definition of pulmonary hypertension?
Mean pulmonary arterial pressure > 25mmHg at rest
425
What are the morphological changes in pulmonary vessels with chronic hypoxia?
Eccentric intimal fibrosis,
| Thickening of muscle wall.
426
What is the effect of a small pulmonary embolus?
- Small peripheral pulmonary arterial occlusion > haemorrhagic infarct
- Repeated emboli cause increasing occlusion of pulmonary vascular bed > pulmonary hypertension
- Patients present with pleuritic chest pain or chronic progressive shortness of breath
427
What is the effect of a large pulmonary embolus?
- Large emboli can occlude the main pulmonary trunk (saddle embolus)
- Sudden death, acute right heart failure, or cardiovascular shock occurs in 5% of cases when >60% of pulmonary bed is occluded
- If patient survives, the embolus usually resolves
- 30% develop second or more emboli
428
Examples of non-thrombotic emboli
```
Bone marrow
Amniotic fluid
Trophoblast
Tumour
Foreign body (e.g. talc in IVDU)
Air
```
429
What are the causes of pulmonary veno-occlusive disease?
Fibrotic/collagenous occlusion of pulmonary veins. Causes:
- IDIOPATHIC
- Some “herbal” teas and diet pills
- Chemotherapy
- Radiotherapy
- Bone marrow transplantation
- Renal transplantation
- HIV infection
- Systemic sclerosis
430
What are the main complications of pulmonary hypertension?
Right sided heart failure:
- Venous congestion of organs – “nutmeg liver”
- Peripheral oedema
- Pleural effusions and ascites
- Poor lung perfusion and hypoxia
431
What is idiopathic pulmonary fibrosis also know as?
Cryptogenic fibrosing alveolitis
432
What is farmers lung?
Aka Extrinsic allergic alveolitis
Reaction to inhaled antigen, acute or chronic.
Responds well to avoiding antigen and steroids. Some develop fibrosis.
433
What is dusty lung?
```
Aka Pneumoconiosis = permanent alteration of lung structure by inhaled inorganic dust and the tissue reaction of the lung to its presence, excluding bronchitis and emphysema.
Coal workers’ lung
Silicosis
Asbestosis
Berylliosis, Kaolin, haematite
```
434
What are the histological features of asbestosis?
- Fine subpleural basal fibrosis with asbestos bodies in tissue
- May also see pleural disease - fibrosis, pleural plaques
- Increased risk of lung cancer in the presence of asbestosis
435
What are the frequencies of the most common lung cancers?
```
Small cell carcinoma 20%
Non-small cell lung cancer:
> Squamous cell carcinoma 35%
> Adenocarcinoma 27%
> Large cell carcinoma – uncommon 10%
```
436
What types of lung cancer are most strongly associated with smoking?
Squamous cell carcinoma and small cell carcinoma
437
What are the risk factors for lung cancer, other than smoking?
> Asbestos exposure (Asbestos + smoking = 50x risk)
> Radiation (Radon, theraputic, uranium miners)
> Heavy metals (Chromates, arsenic, nickel)
> Family history (familial lung cancers rare)
438
What is the pathway of development for squamous cell carcinoma of the lung?
```
Normal epithelium
Hyperplasia
Squamous metaplasia
Dysplasia
Carcinoma in situ
Invasive carcinoma
```
439
What is the pathway of development for adenocarcinoma of the lung?
Atypical adenomatous hyperplasia
Non-mucinous BAC
Mixed pattern adenocarcinoma
440
What does histology of lung adenocarcinoma show?
Evidence of glandular differentiation, stains mucin positive
441
What molecular pathways are involved in adenocarcinoma pathogenesis?
Smokers: K-ras mutation, DNA methylation and p53
| Non-smokers: EGFR mutation/amplification
442
What mutations are common in small cell carcinoma?
p53 and RB1
443
What drug targets EGFR and is sometimes used to treat adenocarcinoma lung cancer?
Cetuximab
444
Which paraneoplastic syndromes are strongly associated with small cell carcinoma?
SIADH and Cushing's syndrome (ACTH)
445
Which paraneoplastic syndromes are strongly associated with squamous carcinoma?
Parathyroid hormone-related peptide -> hypercalcaemia
