Pathology Flashcards
(317 cards)
1
Q
Define Infective endocarditis
A
Inflammation of endothelial surfaces of the heart, including heart valves caused by certain microorganisms
2
Q
Name 3 types of endocarditis
A
Infective
Non-bacterial thrombotic
Libman sacks
3
Q
When does libman sacks endocarditis occur?
A
Cancer ie adenocarcinoma
4
Q
Why are rheumatic heart and valve replacements more susceptible to IE?
A
Blood flows smoother over valves, but when damaged or replaced there’s an increase chance for bacterial colonisation
5
Q
Pathophysiology of Rheumatic Heart Disease
A
- results from host immune response to group A streptococcus antigens that cross react with host proteins
- antibodies and CD4+ T cells directed against streptococcus M proteins
- complement systems activated as is Fc receptor bearing cells (neutrophils and macrophages)
- cytokine production by stimulated t cells = macrophage activation
- heart cells damage by antibody and t cell mediated reactions
- recurrent inflammation, fibrosis, narrow and stiff heart valve, valve thickening, calcification = stenosis
6
Q
A
7
Q
What gross findings are associated with rheumatic heart disease?
A
Acute = valvular vegetation along lines of closure, little effect on cardiac function
Chronic = commissural fibrosis, valve thickening and calcificati, shortened and fused chordae tendinea
8
Q
What are the microscopic findings of rheumatic heart disease?
A
Aschoff bodies - granulomatous inflammation- central zone of degenerate ECM infiltrated by lymphocytes, plasma cells and Anitschkow cells
9
Q
What is the most common type of breast cancer?
A
Invasive ductal carcinoma – accounts for approximately 70-80% of all breast cancers
10
Q
What is the classic presentation of a colon carcinoma?
A
Change in bowel habits, rectal bleeding, and weight loss; typically presents with left-sided colonic obstruction
11
Q
What are the most common causes of acute pancreatitis?
A
Gallstones, alcohol use, hyperlipidemia, and certain medications
12
Q
What is the clinical presentation of a gastric ulcer?
A
Epigastric pain (especially after eating), nausea, vomiting, and potential weight loss
13
Q
What is the most common benign liver tumor?
A
Hemangioma
14
Q
What is the most common malignant liver tumor?
A
Hepatocellular carcinoma (HCC), often in the setting of cirrhosis
15
Q
What is the most common type of thyroid cancer?
A
Papillary thyroid carcinoma (PTC), which is typically slow-growing and presents with a thyroid nodule
16
Q
What is the common presentation of a pulmonary embolism?
A
Sudden onset chest pain, dyspnea, tachypnea, and hypoxia
17
Q
What is the most common form of endometrial cancer?
A
Endometrioid carcinoma, often presenting with abnormal uterine bleeding in postmenopausal women
18
Q
What is the classic triad of symptoms in polycystic kidney disease?
A
Hypertension, hematuria, and palpable abdominal masses (due to enlarged kidneys)
19
Q
What is the most common cause of liver cirrhosis?
A
Chronic alcohol use and hepatitis C infection
20
Q
How is the diagnosis of myocardial infarction confirmed?
A
Elevated cardiac biomarkers (troponins, CK-MB) and characteristic ECG changes (e.g., ST-segment elevation)
21
Q
What is the classic presentation of acute appendicitis?
A
Right lower quadrant abdominal pain (McBurney’s point), nausea, vomiting, and fever
22
Q
What is the most common type of lung cancer?
A
Adenocarcinoma, particularly in non-smokers
23
Q
What is the hallmark finding in rheumatoid arthritis?
A
Symmetric joint swelling, morning stiffness, and presence of rheumatoid factor (RF) and anti-CCP antibodies
24
Q
What are the classic features of Crohn’s disease?
A
Abdominal pain, diarrhea (often bloody), weight loss, and possible perianal disease; associated with ‘skip lesions’ on colonoscopy
25
What is the most common site for metastasis of colorectal cancer?
Liver
26
What is the pathophysiology of type 1 diabetes?
Autoimmune destruction of beta cells in the pancreas, leading to insulin deficiency
27
What is the most common cause of community-acquired pneumonia?
Streptococcus pneumoniae
28
What is the classic presentation of a brain tumor?
Headache, nausea, vomiting, and neurological deficits (e.g., hemiparesis, seizures)
29
What is the most common cause of secondary hypertension?
Renal artery stenosis
30
What is the characteristic feature of a myocardial infarction on ECG?
ST-segment elevation or depression, T-wave inversion, and pathological Q-waves
31
How does non-small cell lung cancer typically present?
Progressive cough, hemoptysis, weight loss, and fatigue
32
What are the key histopathological features of Hodgkin's lymphoma?
Reed-Sternberg cells, often found in lymph nodes
33
What is the pathophysiology of acute glomerulonephritis?
Immune-mediated damage to the glomeruli, often following a streptococcal infection, leading to hematuria, proteinuria, and edema
34
What is the most common cause of upper gastrointestinal bleeding?
Peptic ulcer disease (gastric or duodenal)
35
What is the characteristic feature of aortic dissection on imaging?
A "double lumen" appearance seen on chest CT or aortic angiography
36
What is the most common primary tumor of the brain?
Glioblastoma multiforme (GBM), a highly aggressive glioma
37
What is the management for a tension pneumothorax?
Immediate needle decompression followed by chest tube insertion
38
What is the classic presentation of hyperthyroidism?
Weight loss, heat intolerance, palpitations, tremors, and exophthalmos (in Graves' disease)
39
What are the characteristic findings in diabetic nephropathy?
Microalbuminuria progressing to proteinuria, glomerulosclerosis, and eventually end-stage renal disease
40
What is the most common cause of acute cholecystitis?
Gallstones obstructing the cystic duct, leading to inflammation and infection of the gallbladder
41
What is the classic presentation of acute cholecystitis?
Severe right upper quadrant pain, fever, nausea, vomiting, and positive Murphy’s sign
42
What is the first-line investigation for suspected acute cholecystitis?
Ultrasound, showing gallstones, gallbladder wall thickening, and pericholecystic fluid
43
What is the management of acute cholecystitis?
Initial conservative management with IV fluids, antibiotics, followed by cholecystectomy (either open or laparoscopic)
44
What are the common causes of small bowel obstruction?
Adhesions (most common), hernias, Crohn's disease, and tumors
45
What is the classic presentation of small bowel obstruction?
Abdominal distention, vomiting, colicky abdominal pain, and inability to pass flatus or stool
46
What are the complications of untreated small bowel obstruction?
Bowel ischemia, perforation, sepsis, and death
47
What is the most common cause of large bowel obstruction?
Colorectal cancer (particularly left-sided), diverticular disease, and volvulus
48
What is the classic presentation of large bowel obstruction?
Abdominal distention, constipation, vomiting, and colicky lower abdominal pain
49
What are the typical findings of diverticulitis on CT scan?
Pericolonic fat stranding, bowel wall thickening, and possible abscess formation
50
What is the management of uncomplicated diverticulitis?
Conservative management with antibiotics, bowel rest, and pain control
51
What is the management of complicated diverticulitis (e.g., perforation, abscess)?
Surgical intervention may be required for perforation, abscess drainage, or resection
52
What are the signs and symptoms of acute pancreatitis?
Severe epigastric pain radiating to the back, nausea, vomiting, elevated amylase/lipase, and jaundice in some cases
53
What is the most common cause of acute pancreatitis?
Gallstones and alcohol use
54
What is the most common cause of chronic pancreatitis?
Chronic alcohol use
55
What is the management of acute pancreatitis?
Supportive care (IV fluids, pain control), monitoring for complications (e.g., pancreatic necrosis), and addressing underlying causes (e.g., cholelithiasis)
56
What is the most common type of bowel cancer?
Adenocarcinoma, usually arising from polyps in the colon or rectum
57
What is the classic presentation of colorectal cancer?
"Rectal bleeding, change in bowel habits, weight loss
58
Types of necrosis
Fat
Gangrenous
Liquifactive
Fibrinoid
Coagulative
Caseous
59
What do you look for in a 2D echo for infective endocarditis?
valve regurg
leaflet prolapse
pericardial effusion
ventricular dilatation
60
Commonest organisms for Infective endocarditis?
staph aureus
viridans streptococcus
HACEK organisms from the mouth
coagulase neg staph
61
how do you diagnose infective endocarditis
dukes criteria - 2 maj + 0 minor, 1 maj + 3 minor or 0 maj + 5 minor
62
What are major criteria for dukes criteria for IE
+ve blood cultures
evidence of endocardial involvement
63
what is minor criteria for dukes IE
heart condition/IVDU
fever
Vasc. phenomena - emboli, septic infarcts, janeway lesions
immune phenomena - oslers nodes, roths spots
single positive blood culture
ECHO findings
64
Causes & risk factors for IE
- valvular disease/replacement
- previous IE
HOCM
IVDU
Malignancy
DM
Alcohol
65
Complications of IE
Cardiac - pericarditis, valvular insufficiency, CCF, aneurysm, arterial emboli
Non-cardiac - stroke, AKI, glomerulonephritis
66
What are osler's nodes
painful raised red lesions in hand due to immune complex deposition in IE
67
what are janeway lesions
non-painful, nodular/macular red lesions due to septic emboli
68
Treatment for IE
IV ABx for 6/52
normally iv ceftriaxone & vanc
valves don't have specific blood supply so difficult to treat
if medical treatment fails - valve replacement/heart transplant
69
how do you prevent graft rejection
tacrolimus
mycophenolate
steroids
70
How do immunosuppressants work
4 classes
1. corticosteroids - anti-inflam, kill T cells
2. cytotoxic drugs - block cell division
3. immunophilins - block t cell responses
4. lymphocyte depleting therapies - kills t cells and kills activated t cells
71
MOA of warfarin
vit k antagonist
inhibits 1972
72
What is the cause of sudden death in AS
MI
Aortic dissection
73
how does aortic stenosis occur
lipid accumulation
inflammation & calcification = valve thickening and stenosis
74
Why does AS cause LVH?
as sclerosis progresses to stenosis, the left ventricle encounters resistance therefore develops hypertrophy (thickening of wall)
then decreased left vent myocardial elasticity and coronary blood flow and increased myocardial workload, O2 consumption and mortality
75
Why might you get arm weakness after aortic valve endocarditis?
thromboembolism leading to CVA
76
define thrombus
blood clot formed of constituents of blood within a blood vessel whilst someone is living
77
surgical options for valve replacement
mechanical valve
transcatheter aortic valve replacement
tissue valve
78
if we found microscopic branching hyphae on a removed metallic valve whats the cause?
fungal infection
candida, aspergillus
79
differences between mechanical and tissue valve
mechanical - excellent durability, warfarin, easy insertion, bleeding and thromboembolism risk
tissue - quiet, no warfarin, low bleeding and thromboembolism risk
80
What is GCA?
inflammatory disease of the large and medium blood vessels in the head, mainly branches of ECA
81
which part of the vessel is mostly affected in GCA?
tunica medium
82
What microscopic pathological changes do you expect with GCA/
intimal thickening, therefore reduced lumen diameter
elastic lamina fragmentation
infiltrate of T cells & macrophages
multinucleated giant cells
82
blood test for GCA
ESR
82
why might you go blind with GCA
ophthalmic artery involvement
83
how do you treat GCA
prednisolone or IV methylprednisolone
2 year course
84
Pathological changes in osteoporosis
histologically normal bone decreased in quantity
increase in osteoclast activity post-menopausal
trabecular plates have perforated, thinned and lose interconnections - progressive microfractures
85
What is OP
metabolic bone disease characterised by low bone mass, micro-architectural deterioration of bone tissue, loss of bone matrix
86
pathogenesis of OP
inadequate peak bone mass
excessive bone resorption
inadequate formation of new bone
87
How do steroids cause OP?
Direct inhibition of osteoblast formation
direct stimulation of bone resorption
inhibition of GIT Ca2+ absorption
stimulation of renal Ca2+ loss
inhibition of sex steriods
88
Causes of OP
primary - postmenopausal, age
secondary - steroids, alcohol, immobilisation, chemo, pituitary tumours
89
Causes for a pathological #
OP
Mets
paget's
multiple myeloma
90
what is multiple myeloma
plasma cell neoplasm
associated with lytic bone lesions, hypercalcaemia, renal failure
large amounts of IgG and IgA
most common primary bone tumour in elderly
91
How do you diagnose multiple myeloma
M spike on protein electrophoresis
Bence Jones proteins in urine
punched out lytic skull lesions
hypercalcaemia
anaemia
92
what are bence jones proteins
monoclonal globulin proteins or Ig light chains in urine
produced by neoplastic plasma cells
93
Causes of fat embolism
long bone #
major burns
acute pancreatitis
orthopaedic surgery including IM nail/arthroplasty
94
how do you manage a fat embolism
mainly supportive - resp (O2), fluids, sepsis, nutrition
Unproven rx = ethanol, heparin
95
How do you define gangrene
type of necrosis caused by critically insufficient blood supply
96
define necrosis
accidental and unregulated form of cell death resulting from damage to cell membranes & loss of iron homeostasis
97
pathogenesis of necrosis
severe/prolonged ischaemia
= severe swelling of mitochondria, Ca2+ influx into mitochondria, rupture of lysosomes and plasma membrane
death by necrosis due to release of cytochrome C from mitochondria
98
Difference between wet & dry gangrene
wet = commonly bowel, venous obstruction, moist, soft, swollen, rotten, no clear demarcation, numerous bacteria, poor prognosis
dry = limbs, arterial occlusion, dry, black, clear demarcation, minimal bacteria, better prognosis
99
define atherosclerosis
pathological process of vasculature in which an artery wall thickens as a result of accumulation of fatty materials (cholesterol)
100
risk factors for atherosclerosis
smoking
HTN
DM
Increased LDL
FHx
101
what might pleural plaques on a CXR demonstrate?
most common manifestation of asbestos exposure = increased risk of mesothelioma and lung adenocarcinoma
102
one classification of lung cancer
non-small cell - adenocarcinoma, squamous, large cell
small cell
103
if a lung cancer tumour was epidermal growth factor +ve, what's the chemotherapeutic agent?
tyrosine kinase inhibitor
104
what are signs of an aggressive lung cancer on a report
invading pleura
LN involvement
105
pathogenesis of clubbing
various hypotheses
- higher plasma growth hormone levels
-megakaryocyte or platelet clusters in peripheral vasculature of the digits and release platelet derived growth factor
= increased vascularity, permeability and connective tissue changes = clubbing
106
pancoast paraneoplastic syndrome involves which hormone
ACTH = cushing syndrome
107
What is FISH technique
fluorescence in situ hybridisation
fluorescent probes bind to chromosome showing sequence complementarity
108
define adenocarcinoma
cancer in mucus secreting glands
109
define emphysema
lung pathology causing SOB
alveoli are damaged
inner walls are weakened and rupture causing larger air sacks
110
define paraneoplastic syndrome
symptom complexes occur in patients with cancer than cant be explained by local or distant tumour spread
111
common paraneoplastic syndromes
cushing syndrome - small cell lung ca secreting ACTH like hormone
SIADH - Small cell lung ca
Hypercalcaemia - squamous lung ca, breast, renal
hypoglycaemia - ovarian
nonbacterial thrombotic endocarditis
112
TB Investigations
sputum culture
ziehl neelsen stain
mantoux test
PCR
FNAC of LN
113
how do you label TB sputum samples
Category B UN3373
114
what are the organisms of TB
mycobacterium tuberculosis
avium intracellulare
bovis
115
what is the culture media for mycobacteria
solid - lowenstein jensen
liquid - BACTEC
116
how long does it take to culture TB
1-8 weeks
117
what is the protein deposition in TB
amyloid
118
what are giant cells
multinucleated cells comprising of macrophages forming granulomas
langerhan's giant cells
119
what is a granuloma
organised collection of macrophages fusing to form langerhan's giant cells
120
causes of granuloma
TB
crohns
RA
sarcoidosis
121
What does a C4 lesion mean on an FNAC
C1 = inadequate sample
C2 = benign
C3 = equivocal
C4 = suspicious
C5 = malignant
122
What do you look for on an excision report for breast Ca
type of cancer
positive LN
margins status
HER2 receptor status - poor prognosis
ER/PR receptor status - good
Ki 67 proliferation index
123
Most common site of breast Ca
upper outer quadrant - more glandular tissue
124
what is HER2?
oncogene
biomarker
human epidermal growth factor receptor 2
bad prognosis
125
how do you test for HER2
immunohistochemistry (IHC)
FISH (fluorescence in situ hybridisation)
126
How does herceptin work at a cellular level
aka trastuzumab = monoclonal antibody
interferes with HER2 receptor
turns genes on and off
normally HER protein binds to human EGF and stimulates cell proliferation
therefore trastuzuman = cell destruction
127
how can you manage breast ca
radiotherapy
chemotherapy
premenopausal - tamoxifen - blocks oestrogen
post menopausal - anastrozole (aromatase inhibitor)
128
pathophysiology of paget disease in breast
extension of ductal carcinoma in situ up the lactiferous ducts and into skin of nipple
produces unilateral crusting exudate over the nipple
129
Define hyperplasia
increase number of cells in tissue/organ in response to a stimulus
130
what is the microscopic appearance of hyperplasia in the parathyroid glands
chief cell hyperplasia
islands of oxyphils and poorly developed delicate fibrous strands may envelop nodules
131
pt develops stupor, confusion and hypoglycaemia with a pancreatic mass - why?
insulinoma
132
causes of unresponsive hypoglycaemia
abnormal insulin sensitivity
diffuse liver disease
ectopic insulin production
133
lab diagnosis of insulinoma
high circulating insulin
high insulin to glucose ratio
134
What make up MEN1
pancreatic tumour
parathyroid hyperplasia
pituitary adenoma
135
what makes up MEN 2
A - parathyroid hyperplasia
medullary thyroid ca
pheochromocytoma
B - medullary thyroid ca
pheochromocytoma
marfanoid habitus
mucosal neuromas
136
What are the gene mutations in insulinoma
MEN1
loss of tumor suppressor genes such as PTEN & TSC2
inactivating mutations in 2 genes
137
what is the two hit hypothesis
tumor suppressor genes work to prevent cancerous cell development
two hit hypothesis is the idea that both of a cells tumour suppressor genes are mutated therefore preventing them from fulfilling their role
138
what is a telomere
region of repetitive nucleotide sequences at each end of a chromosome
protects ends of chromosomes from deterioration or fusion with nearby chromosomes
139
what is apoptosis
programmed cell death
140
FNAC report shows malignant cell features, amyloid deposits, immunohistochemistry staining positive with calcitonin, negative stains for thyroxine
what is the cancer
medullary thyroid cancer
141
what is the cell source of medullary thyroid cancer
parafollicular C cells
142
what is immunohistochemistry
localising specific antigens in tissues or cells based on antigen antibody recognition
143
how do you diagnose a pheochromocytoma
plasma - catecholamines
urine - catecholamines
imaging - USS, MRI, MIBG scintigraphy
144
what mode of inheritance is the MEN syndromes
autosomal dominant
145
What are the oncogene mutations in MEN syndromes
1 - MENIN gene
2 - RET oncogene
146
Rx of medullary thyroid cancer
thyroidectomy and block neck dissection
147
define pleomorphic
remarkable histologic diversity
148
describe appearance of pleomorphic adenomas
benign
mixture of ductal (epithelial) and myoepithelial cells
149
causes of b/l parotid swelling
mumps
parotiditis
sjogrens
TB
150
causes of unilateral parotid swelling
neoplasia
mumps
duct obstruction
151
Clinical signs of malignant parotid tumour
facial nerve affected
rapid size increase
skin invasion
skin ulcer
LN involvement
152
Cytologic features of malignant neoplasms
increased nuclear size (nuclear:cytoplasm ratio)
variation in nuclear or cell size - pleomorphism
anaplasia - lack of differentiation
loss of normal tissue architecture
hyperchromatism
153
features of malignant cells
invasion
increased mitotic rate
less differentiation
154
what is anaplasia
lack of differentiation
loss of similarity to parent cell indicating aggressive tumour
155
difference between cytology and histology
cytology = study of cellular structure & function
histology = tissue under microscope
156
FNAC findings
langerhan's giant cell + lymphocytes + necrotic material = 1?
brown pigmented cell + epitheliod cells = 2?
reed sternberg cell + lymphoid cell + blast cell = 3?
1/ granuloma, TB
2/ malignant melanoma
3/ lymphoma
157
158
what is frey's syndrome
auriculotemporal syndrome
gustatory sweating
facial flushing
due to reinnervation of post ganglionic fibres to sweat galnds
159
What is the definition of a high sensitivity test
ability of a test to correctly classify an individual as diseased
true +ve rate
160
what is the definition of a high specificity test
ability to correctly identify an individual as disease free
true -ve rate
161
relationship between pleomorphic adenoma and breast Ca
BRCA1 & 2 gene
162
advantage of FNAC over tru-cut biopsy
simple, cheaper, quicker, less invasive
163
define metastasis
survival and growth of cells at a site distant from their primary origin
164
5 pathological steps of carcinoma spread
direct/continuous extension
penetration into lymph, blood or body cavities
transport of tumour cells into circulation
growth of disseminated tumour cells in secondary sites
arrest in capillary beds of secondary sites
165
mechanism of lymphatic spread for cancer
tumour secretes VEGF and VEGV = lymph angiogenesis in primary tumour and drains into sentinel LN
tumours also release immunomodulatory molecules that can lead to immunossuppression
166
define carcinoma
cancer from epithelial cells
167
MOA radiotherapy in cancer
damages DNA leading to cellular death
168
what is the SI units of radiotherapy
Exposure = Coulomb/kg
Dose = gray
dose equivalent = sievert
activity = becquerel
169
risk factors for NP carcinoma
males
southern asia & northwest canada & greenland
fish diet
EBV
genetics FHX
smoking & alcohol
170
oral swab showing hyphae =?
candida
171
routes of spread for NP cancer
lymph
local invasion
172
most common LN tumours
lymphoma
leukaemia
mets
173
define abscess
focal collection of pus
caused by seeding of organisms into tissue or by secondary infections
174
what is the structure of an abscess
central, largely necrotic region
layer of preserved neutrophils
surrounding zone of dilated vessels and fibroblast proliferation indicative of attempted repair
175
how do neutrophils migrate to inflammation site
roll
then activated and adhere to endothelium
transmigrate across endothelium
pierce basement membrane
migrate towards chemo-attractants from injury source
176
what is a carcinoid tumour
slow growing neuroendocrine tumour
originates from cells of neuroendocrine system
177
where is a carcinoid tumour most commonly found
appendix
small intestine
rectum, stomach, lung
178
where do carcinoid cells arise from
enterochromaffin cells in crypts of lieberkuhn
179
what do carcinoid tumours release
serotonin 5-HT
bradykinins
prostaglandins
histamine
substance p
tachykinins
180
clinical presentation of carcinoid tumours
periodic abdo pain
cutaneous flushing
diarrhoea
malabsorption
cardiac - valvular heart lesions
wheezing/asthma
181
how do carcinoid tumours spread
cells produce beta-catenin - enables tumour cell adhesion, promoting mets
182
most common site of spread in carcinoid tumours
liver
183
how do you diagnose carcinoid syndrome
chromogranin A in serum
5-hydr-oxy-in-dol-eactic acid in urine
IHC stains for chromogranin B
184
what is UC
IBD affective colon in form of colitis with ulcers
185
commonest UC site
rectum
186
macroscopic UC changes
pseudopolyps
extensive ulceration
contact bleeding
superficial inflammation
continuous
187
histological & microscopic UC features
crypt abscess
inflam cells in lamina propria
mucosal ulceration
pseudo polyps
crypts not reaching muscularis mucosa
188
common site of crohn's
terminal ileum
189
macroscopic crohns
cobblestone
thickened bowel wall
aphthoid ulcers
creeping fat
skip lesions
190
histological and microscopic crohns findings
granulomas
transmural inflammation
mucosal ulceration
191
Complications of IBD
obstruction
fistula (CD)
abscess
toxic megacolon
malignancy
gallstones
192
why do renal stones form in crohns
increased interstitial fat = binds to calcium = leaving oxalates
193
type of vitamin deficiency in crohns
ADEK
194
investigations for IBD
stool analysis
barium follow through
FBC - macrocytic anaemia
PT concentration - vit K def
calcium oxalate levels
195
Mx of Crohns
medical - gastro - steroid, Abx, 5-ASA
diet control
surgery
196
describe adenoma carcinoma sequence
accumulation of mutations in oncogenes and tumour suppressor genes
1. loss of APC (t.s.g) = hyperplasia
2. K-Ras (oncogene) mutation = dysplasia
3. loss of p53 (t.s.g.) = adenocarcinoma
197
what are oncogenes and proto-oncogenes
oncogenes are mutations that function autonomously in proto-oncogenes
encode oncoproteins to promote cell growth in the absence of normal growth promoting signals
198
what are tumour suppressor genes
p53, APC
normal preventative genes against cancer formation
"gatekeepers"
inhibit cell proliferation of damaged/mutated cells
199
function of KRAS
= gene instructing for protein K-ras to be made
protein relays signal from outside cell to inside instructing cell to grow & divide or mature
200
function of p53
DNA damage and other stress signals = increase in p53 proteins
major functions = growth arrest, DNA repair and apoptosis
201
Function of APC
encodes a factor that negatively regulates the WNT pathway in the colonic epithelium - promotes formation of a complex that degrades beta-catenin
202
What is TNF
cytokine involved in systemic inflammation
helps with acute phase reaction
203
role of TNF in IBD
signals direct epithelia to increase tight junction permeability = increase flux of luminal bacterial components which activates innate and adaptive immune responses
204
Drug antagonise TNF
infliximab
adalimumab
monoclonal IgG antibodies
205
Why are monoclonal antibodies used in UC
biologics are used if UC refractory to steroids
treat extra intestinal manifestations of UC
206
Branches of the abdominal aorta
T12 - coeliac trunk, Rt & Lt inf. phrenic
L1 - SMA - Rt & Lt middle suprarenal
L2 - Rt & Lt renal
L3 - IMA - Rt & Lt gonadal art
L4 - median sacral art, Rt & Lt common iliac
207
difference between benign and malignant cells
distinguished from one another on degree of differentiation, rate of growth, invasion, distant spread
208
define familial adenomatous polyposis
autosomal dominant
loss of APC tumour suppressor gene on chromosome 5
develop tubular adenomas
100% risk of cancer
209
APC tumour suppressor gene function
encodes a factor that negatively regulates WNT pathway in colonic epithelium
promotes formation of complex that degrades B-catenin
210
classification of polyps
non-neoplastic - metaplastic, hamartomatous
inflam - UC
neoplastic - villous, tubular
211
what does the malignant potential of adenomas depend on
type of adenoma
diameter of adenoma
degree of dysplasia
212
extracolonic manifestations related to gardener syndrome
desmoid tumours
sebaceous cyst
mandibular osteoma
213
define endomeitriosis
'ectopic' endometrial tissue outside the uterus
214
what is dysplasia
disordered cellular development
increased mitosis
pleomorphism without ability to invade basement membrane
215
what is pus
collection of neutrophils +
dead/dying microorganisms
216
what is an ulcer
lesion in mucous membrane or skin
217
what is healing by secondary intention
healing by re-epithelialisation and contraction
218
commonest type of gallbladder malignancy
adenocarcinoma
219
causes of gallbladder ca
gall stones
chronic cholecystitis
220
risk factors for GB cancer
>70
female
fhx
smoking
obesity
221
where does GB cancer spread
liver - 1st
CBD
stomach
duodenum
222
three organisms associated with necrotising fascititis
group A strep
staph aureus
clostridium perfringens
223
scoring system for nec fas
LRINEC
> 6 = nec fas
224
pathogenesis of pseudomembranous colitis
triggered by Abx therapy
disrupts normal microbiota
c.diff grows
organism releases toxins
inflam response - neutrophils form mucopurulent pseudomembranes
225
pathophysiology of diverticulosis
congenital
acquired - low fibre diet and increased colonic pressure
226
complications of diverticulosis
infections
diverticulitis
perforation
abscess
fistula
bleeding
227
cause of diverticulitis in diverticular disease
obstruction of diverticula = inflamm changes
= diverticulitis
increased pressure can = perforation
228
classification of perforated diverticulitis
hinchey classification
1 - pericolic abscess
2a - distant abscess- can percutaneous drain
2b - complex abscess + fistula
3 generalised peritonitis
4 faecal peritonitis
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mx of diverticulitis
conservative - IVF, ABX, perc drainage
surgery - colostomy, hartman, resection anastomoses
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how do neutrophils migrate to site of infection
1. margination & rolling along vessel wall
2. firm adhesion to endothelium
3. transmigration between endothelial cells
4. migration in interstitial tissues towards chemoattractant stimulus
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how did endometriosis get into colon
4 theories
1. regurg theory - retrograde menstruation
2. benign mets - tissue spreads
3. metaplastic - during embryonic development
4. extrauterine - stem cells differentiate
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intraperitoneal picture of endomeitriosis
burn powder
dark blue/black
chocolate cysts
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epithelium of uterus
simple columnar
thick vasc stroma
endomeitrium = inner epithelial layer
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increase cancer risk with endomeitriosis
ovarian 3.5x
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what is h.pylori
gram -ve microaerophilic spiral bacteria
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CLO test
campylobacter like organism
depends on urease production by h.pylori
gastric mucosal biopsy - placed in media containing urea - +ve test = colour changes from yellow to red
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how does h.pylori survive in acidic medium
increases production of urease, making ammonia, increasing pH
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how does h.pylori cause gastritis
produces proteases and phospholipases, ammonia and damage gastric mucosa = inflamm
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how does h.pylori colonise stomach
1. flagella - bacteria motility
2. urease - generates NH3 = increase pH
3. adhesins - improves bacterial adherence
4. toxins
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types of cancer caused by h.pylori
adenocarcinoma
MALT
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eradication of h.pylori
7/7
PPI, amoxicillin + clarithyromycin/metroniadazole
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how do you localise parathyroid glands
sestamibi scans
frozen section (intraoperative)
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why does endomeitriosis cause pain
peri-uterine adhesions and intrapelvic bleeding
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ABx for pelvic abscess
co-amox
gent
metro
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what is crp
acute phase reactant protein made by liver
released few hours after injury, infection, inflamm
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2 major risk factors for gastric cancer
h.pylori, smoking
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other stomach tumours except cancer
GIST
lymphoma
neuroendocrine tumours
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role of CDH1 in development of gastric cancer
CDH1 = tumour suppressor gene and mutation = strongly associated with gastric ca
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prognosis of signet cell carcinoma
the worst/poor
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screening criteria for CDH1 mutation
FHx of diffuse gastric cancer x 2
DGC + Lobular breast ca under 70 in different family members
DGC under 50
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how does LMWH work
binds and accelerates antithrombin III
therefore Xa & IIa are inhibited
thrombin inhibition prevents formation of fibrin clots
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gross pathology of polycystic kidney
kidney enlargement with multiple cyst formations
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mode of inheritance of polycystic kidney disease
autosomal dominant
PKD1 & 2 mutations
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pathogenesis of cyst formation in polycystic kidneys
1. inactivation of protective allele within cell boundaries, cyst formation begins
2. out-pocketing of tubular wall
3. formation of saccular cyst filled with glomerular filtrate
4. Isolation & growth - cyst eventually leaves parent tubule
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complications of polycystic kidney disease
HTN
renal failure
infection
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types of graft rejections
hyperacute - minutes, recipient antibodies, complement activation, nephrectomy needed, Type II
acute - < 100 days, T-cell mediated, can be reversed with high dose steroids, Type IV
chronic - months to years, T cell mediated, intimal thickening, graft vessel fibrosis, Type III & IV
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brain lesion associated with PCKD
cerebral aneurysm
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renal failure in PCKD why?
higher risk of acute pyelonephritis, cust infections, calculi
fibrosis eventually develops (unknown mechanism)
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types of malignancy associated with immunosuppression
SCC of skin, cervix, BCC, lymphoma
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what is the cause of most post-transplant lymphoproliferative disorders
EBV
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treatment for post-transplant lymphoproliferative disorders
reduce immunosuppressant dose
reituximab
chemo
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microscopic features of GB with ascending cholangitis
mucosa erosion
oedema
myofibroblasts
lymphocytes
plasma cells
sometimes firinoid necrosis
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stages of acute inflammation
1. dilation of small blood vessels = blood flow increase
2. increased permeability of microvasculature - enables plasma proteins and leukocytes to leave circulation
3. acculumation of leukocytes at injury area and activation to eliminate offending insult
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what is sickle cell disease
inherited haemoglobulinopathy
mutation in gene encoding Hb subunit beta
affected Hb polymerises and forms crystals when deoxygenated = sickling of RBC
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complications of sickle cell disease
1. vaso-occulsive crisis - infection, dehydration = painful bones, lungs, brain, spleen
2. sequestration crisis in kids - entrapment of sickle cell in spleen = splenomegaly and hypovolaemic shock
3. aplastic crisis - parvo-virus infects RBC progenitors
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mechanism of autosplenectomy in sickle cell
trapping of sickled red cells in cords and sinuses over time = splenic infarct, fibrosis and shrinkage
eventually only small amount of fibrous splenic tissue is left
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most common brain tumours in elderly
high grade - gliomas, glioblastoma multiforme
low grade - acoustic neuromas, pituitary, pineal, mets
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define DIC
widespread hypercoagulable state
leads to macro & micro vascular clotting & reduced blood flow
consumes all platelets and clotting factors
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DIC is characterised by
widespread haemorrhage
thrombocytopenia
decreased fibrinogen
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what activates intrinsic and extrinsic pathways
intrinsic = vessel injury - XII activated
extrinsic = damaged cells releasing tissue thromboplastin
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platelet function
1. primary haemostasis - forms first haemostatic plug
2. activates coagulation cascade
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how to test for intrinsic and extrinsic pathways
intrinsic = aPTT
extrinsic = PT
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type 1 hypersensitivity reaction
IgE mediated
mast cell degranulation
immediate
anaphylaxis
atopy
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Type 2 hypersensitivity reaction
due to antibodies directed at antigens present on cell surfaces
transfusion reactions
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type 3 hypersensitivity reaction
formation of antibody-antigen complexes, immune mediated
SLE
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Type 4 hypersensitivity reaction
delayed reaction mediated by T-lymphocytes
48-72 hours
contact dermatitis
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type 5 hypersensitivity
formation of stimulatory autoantibodies
graves
myasthenia gravis
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stages of bone healing
1. haematoma formation
2. fibrocartilaginous callus formation - 3-4/52
capillary growth, phagocytic cells, fibroblasts & osteoblasts begin bone reconstruction
3. bony callus formation - after 4/52 - 12/52 osteoblasts & osteoclasts turn fibrocartilaginous callus to bony callus
4. remodelling - excess bony callus removed, compact bone laid down, shaft reconstruction
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what is PVL staph aureus
panton-valentine leukocidin = cytotoxin
associated with increased virulence
causes necrotic lesions
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3 gene mutations in insulinoma
loss of tumour suppressor genes such as PTEN & TSC2
inactivation of DAXX & ATRX
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how do you take a prostate biopsy
TRUS-guided from
midlobe parasagittal plane b/l
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how to differentiate between rectum and prostate cells in needle biopsy
IHC marker - AMACR (a-methylacyl-coenzyme A-racemase)
CEA in rectal celss
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gene mutations in prostate ca
TMPRSS2-ETS
deletions in P16K/AKT
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grading system for prostate ca
gleason - grades histological pattern from 1-5
and does this for 2 samples, adds them together & get score between 2-10
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test to exclude bony mets
alk phos
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cells producing testosterone
leydig cells
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why do you treat prostate ca with b/l orchidectomy
androgen deprivation
growth & survival of prostate ca depends on androgens
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type of lesion with BCC
pearly papule with central ulcer, rolled inverted edges
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natural history of BCC
slow progression of locally destructive
limited mets potential
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rx for bcc
curettage & electro dissecation
excision with primary closure
cryotherapy
mohs micrographic surgery - serial horiztonal sections are taken and examined until all margins are clear
radiotherapy - topical photodynamic, flurouracil
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MRSA wound mx
abscess - I&D
OP - oral clindamycin, amox + tetracyclin & linezolid
IP - vanc, linezolid, daptomycin, decolonisation
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mechanism of lymphatic spread
embolisation
permeation
VEGF-C induce lymphatic vessel expansion
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define granulation tissue
connective tissue formed by migration and proliferation of fibroblasts and new capillaries
form on surfaces of wound
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what are anaplastic features
loss of tissue architecture
pleomorphism
hyperchromic nuclei
high nuclear-cytoplasmic ratio
giant cells
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pathological # - what is it and what causes it
- bone # without trauma caused by underlying bone lesion
- neoplastic - tumours - primary/mets
- non-neoplastic - OP, Pagets, bone cysts
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other sites of ectopic thyroid tissue other than head, neck & thorax
ovarian & testicular teratoma
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investigations to confirm thyroid mets
radioactive iodine scan
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which thyroid cancer shows no response to iodine uptake
medullary as it originates from parafollicular c cells therefore not of follicular origin
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complications of mismatched blood transfusion
acute haemolytic reactions
febrile non-haemolytic reaction
delayed reaction
transfusion related acute lung injury
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complications of chronic abscess
fistula/sinus formation
ulcer
amyloidosis
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what are biofilms
viscous layer of extracellular polysaccharides that adhere to host tissues/devices
increase virulence of bacteria - protects microbes from immune mechanisms
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pathogenesis of psteomyelitis
1. microbial invasion = acute inflammation
2. suppuration - pus in medulla & volkmann's canals - periosteal abscess
3. necrosis
4. new bone formation
5. resolution - reduced IO pressure = bone healing
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type of crystals in gout & pseudogout
gout - monosodium urate crystals
pseudogout - calcium pyrophasphate crystals
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OM rx
abx - response to blood cultures
analgesia
limb splinting
surgical drainage
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stain used with IHC of oesophagus
cytokeratin
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pathological test for pleural effusion
effusion cytology
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treatment for malignant pleural effusion
thoracentesis
pleurodesis
indwellingppleural catheters
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Dukes colon staging
A - confined to bowel wall (slightly into MP)
B - extension through bowel wall to adventitia
C- regional LN involvement
D - distant mets/LN involvement
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define melanosis coli
pigmentation of the colon wall
benign
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what are haemarrhoids
swollen/inflamed anal cushions
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patheogenesis of haemorrhoids
long & repeated downward stress on anal canal fibromuscular ligamants = anal cushions no longer restrained and engorge with blood
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why do coronary arteries get thrombosed
coronary artery atherosclerosis
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how do coronary arteries develop atherosclerosis
endothelial injury
accumulation of lipoproteins
platelet adhesion
monocyte adhesion to endothelium - differentiation into macrophages & foam cells
lipid accumulation
smooth muscle cell proliferation & ECM production
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mechanism of MI
vascular obstruction = aerobic glycolysis ceases = drop in ATP = accumulation of toxic metabolites = loss in contractility = ischaemic changes = coagulation necrosis
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