1. PATHOLOGY Flashcards
1
Q
define inflammation
A
local physiological response to tissue injury
2
Q
give two examples of acute inflammation causes
A
infections and hypersensitivity
3
Q
give two examples of chronic inflammation causes
A
autoimmunity, chronic infection
4
Q
what does a polymorph have
A
many lobes
5
Q
what r Barr bodies and why do they form
A
in female neutrophils
due to visible silenced x chromosomes due to lyonisation
6
Q
what is the histological diagnosis for acute inflammation (3 parts, 1 point)
A
presence of neutrophil polymorphs in extravascular space as part of cellular exudate
7
Q
what is acute inflammation
A
initial response of a tissue to an injury
8
Q
6 causes of acute inflammation
A
microbial infections: bacteria and viruses
hypersensitivity reactions: parasites
physical agents: trauma, heat, cold
chemicals: corrosives, acid
bacterial toxins
tissue necrosis: ischaemic infarction
9
Q
what causes dolor in acute inflammation
A
inflammatory mediators such as secretins, bradykinin and prostaGLANDIN which increase sensitivity to pain
10
Q
5 macroscopic/ cardinal acute signs of inflammation
A
rubor: redness
dolor: pain
calor: heat
tumor: swelling
loss of function
11
Q
explain how acute inflammation occurs (3 steps)
A
- increase in vessel calibre:
-inflammatory cytokines eg bradykinin, NO and prostacyclin cause vasodilation and increase in permeability - fluid exudate:
-vessel becomes leaky and protein rich fluid is forced out of the vessel - cellular exudate:
-neutrophil polymorphs recruited to the tissue and become abundant in cellular exudate
12
Q
4 steps of neutrophil migration in acute inflammation
A
margination: neutrophils migrate to edge of blood vessel due to increase plasma viscosity and slower flow
adhesion: selections binds to neutrophils, causing rolling along BV margin (called pavementing)
emigration and diapedesis: movement of neutrophils out of BV though endothelium and other inflammatory cells follow
chemotaxis: movement of cells towards the site of inflammation via a chemical gradient (often done by cytokines like C5a)
13
Q
what is the difference between emigration and diapedesis
A
diapedesis: process of other inflammatory cells and RBCs pass through the endothelium with the neutrophils
emigration: neutrophils passing through endothelium via endothelial cells then basal lamina then vessel wall
14
Q
3 steps of action of immune cells at site of infection
A
identification and cytokine release
phagocytosis/ bacterial killing
macrophages clear debris
15
Q
why is suppuration in acute inflammation significant regarding treatment with drugs
A
bacteria is located within abscess which in inaccessible to antibiotics
16
Q
give an example of resolution, organisation and progression to chronic inflammation
A
acute liver injury, MI/stroke, chronic cholecystitis
17
Q
4 outcomes of acute inflammation
A
resolution: normal restoration of tissues
suppuration: pus formation (causing pyogenic membrane= scarring)
organisation: fibrotic tissue replaces normal tissue, loss of function
progression: recurrent inflammation which becomes chronic and fibrotic tissue
18
Q
example of a acute condition that can become chronic
A
pnuemonia
19
Q
onset, duration and 2 cells involved in acute inflammation
A
fast, short, neutrophils and monocytes
20
Q
onset, duration and 3 cells involved in chronic inflammation
A
slower, long, lymphocytes and macrophages and plasma cells
21
Q
1 macroscopic feature of chronic inflammation
A
fibrotic tissue
22
Q
2 histological hallmarks of acute inflammation
A
neutrophil EXTRAVASATION
presence of neutrophil polymorphs
23
Q
2 HISTOLOGICAL HALLMARKS of chronic inflammation
A
cellular infiltrate of lymphocytes, macrophages and plasma cells
possible granulomas (epitheliod histiocytes)
24
Q
give 4 examples of an autoimmune disease
A
T1DM, Grave’s, Hashimoto’s, SLE
25
what is an ulcer and why
a break in the skin that is slow to heal due to poor blood supply
26
macroscopic appearance of chronic inflammation (4)
chronic ulcer
chronic abscess cavity
granulomatous inflammation
fibrosis
27
4 causes of chronic inflammation
primary chronic inflammation
primary granulomatous disease
transplant rejection
progression from acute inflammation (due to a persistent agent)
28
3 causes of primary chronic inflammation
resistance of infective agent
endogenous/ exogenous materials
autoimmune conditions
29
chronic inflammation microscopic appearance (3)
lymphocytes, plasma cells and macrophages present
continuous destruction of tissue
NO EXUDATION
30
2 things formed in chronic inflammation
formation of granulation tissue
formation of a fibrous scar
31
what is ischaemia and is it caused by (2)
reduction in blood flow to a tissue caused by constriction/ blockage of the vessels suppling it
32
what is infarction
death of tissue due to severe/ prolonged ischaemia
33
what is a re-perfusion injury
damage to tissue during re-oxygenation
34
what three organs r less susceptible to infarction and why
liver, brain and lungs have dual supply so less susceptible
35
what is a thrombi
solidification of blood contents that form within the vascular system during life
36
4 stages of thrombus formation
vasospasm
primary platelet plug forms
coagulation cascade occurs
formation of secondary platelet
37
3 steps of primary plug formation
platelet adhesion: platelets bind to vwf via gp1b which attaches to exposed collagen
platelet activation: conformational shape from discoid to pseudopoid because of gp1b binding
aggregation: platelets bind to each other via gp2a/3b
38
recall coagulation cascade
intrinsic pathway: 12>11>9>8>10
extrinsic pathway: 3>7>10
common pathway: 10>2>1 (10-> 2 with help of 5)
39
medical definition of granulomas
aggregates of epitheliod histiocytes (essentially macrophages)
40
explain the types necrosis in granulatomas (2) and example diseases for each (1, 3)
central necrosis (classical TB)
no central necrosis (sarcoidosis, leprosy, vasculitis, Crohn's)
41
what do granulomas secrete? why is this useful?
ACE
blood marker- increases in patients with granulomatous disease eg sarcoidosis
42
what three things suggest a parasite infection
granulomas, high serum ACE and raised eosinophils
43
what is arterial thrombi and the main cause
blood clot blocks an artery
main cause= when an artery is damaged by atherosclerosis
44
what r the complications of a small, moderate and large PE
small-idiopathic hypertension
moderate- chest pain and dyspnoea
large-death
45
what can DVT lead to and how
pulmonary embolism
IVC-> RA-> RV-> pulmonary arteries
46
what is the treatment for arterial thrombi (3) and give examples for each and how each works
anti-platelets eg aspirin (inhibit platelet activation)
thrombolytic therapy eg tissue plasminogen activator like alteplase (activates plasmin which breaks down fibrin, causing breakdown of the clot)
P2Y12 inhibitor eg clopidogrel (inhibits platelet aggregation)
47
what is venous thrombi and the two main types
blood clot blocks a vein
main types= DVT or pulmonary embolism (in right side of heart)
48
3 arterial thrombi symptoms
symptoms: cold, pale, loss of pulse to skin
49
the cause of venous thrombi
due to venous stasis (area of turbulence or potential damage of stasis valves)
50
3 risk factors of venous thrombi
history of DVT and pulmonary embolism and then being inactive for long periods of time can cause venous thrombi
51
treatment for venous thrombi
treatment: anticoagulants- DOACs, warfarin
52
4 symptoms of venous thrombi
symptoms: tender, swollen, red, one side of the leg affected
53
what is the rule of virchow's triad
typically 2 factors out of the 3 r required for thrombosis
54
factors affecting thrombosis and what causes them (5,3,4)
endothelial injury: due to trauma, surgery, myocardial infarction/ HYPERTENSION or smoking
abnormal blood flow: usually a decrease in blood
stasis (change in blood flow)- due to IMMOBILISATION, ATRIAL FIBRILLATION and varicose veins
hyper coagulability: due to ATHEROSCLEROSIS, sepsis, malignancy, pregnancy
55
why is smoking signficant in the virchow's triad and explain the mechanisms of how?
causes a change in blood flow and endothelial damage (affects 2 factors)
nicotine increases HR and BP which increase force on endothelium (can cause endothelial damage)
free radicals damage the endothelium, causing atherosclerotic plaques which increase turbulence
56
what is the definition of hypercoagulability
change in blood constituents
57
what r the 4 fates of thrombi
resolution: fibrinolysis of thrombi (normal response)
organisation: leaves fibrotic scar tissue behind
recanalisation: returned blood flow to obstructed area through growth of new capillaries
embolism: fragments of thrombi break off and lodge in the distal circulation
58
what is an emboli
mass of material in vascular system able to lodge in vessel and block its lumen
59
what is a arterial emboli and what is the composition of the emboli
thrombi formed in artery, higher amounts of platelets making up the clot
60
what is a venous emboli and what is the composition of the emboli
thrombi formed in vein, higher amounts of fibrin making up the clot
61
where do arterial emboli lodge and travel and cause (3)
lodges in systemic circulation (thrombi is from from left side of heart)
travels to heart/ brain/ peripheries to cause heart attack/ stroke/ gangrene
62
where do venous emboli lodge and travel (2)
lodges in pulmonary circulation (thrombi is from right side of heart)
lodges in pulmonary arteries= PE
lodges in peripheries= DVT
this can break off and cause pulmonary embolism
(PE is normally secondary to DVT)
63
what r arterial ulcers caused by and their appearance
caused by lack of blood supply to a tissue which causes tissue to die due to lack of oxygen and leaves a open wound
PUNCHED OUT HOLES with little exudate
64
what r venous ulcers caused by and their appearance
problem with circulation usually caused by faulty valves. This leads to high blood pressure which damage small blood vessels and makes them fragile. As a result, skin can break easily and form an ulcer
less markated with lots of exudate
65
location of arterial ulcers
on tips of toes and lateral malleolus
66
presentation of arterial ulcers (3)
pale, cool skin with low distal pulse
67
location of venous ulcers
on medial malleolus and inner calf
68
DVT presentation on skin (1)
have erythematous skin (for DVT)
69
what is an atherosclerosis
plaques that form in intima and media of arteries
70
6 risk factors of atherosclerosis
diabetes mellitus, hypertension, smoking, obesity, old age, male
71
atherosclerotic plaque composition (6)
lipids, smooth muscle, MACROPHAGES, FOAM CELLS (macrophages that phagocytose LDLs), platelets, fibroblasts
72
5 steps of atherosclerosis
fatty streak formation: precursor for plaque
lipid accumulation: increase in LDLs, macrophages recruited to phagocytose this= foam cells
platelet aggregation: plaque protrude into the artery lumen, disrupts laminar flow so platelets accumulate and thinning of the media occurs
FIBRIN MESH AND RBC TRAPPING: platelet plug forms fibrin mesh over itself and a stable secondary platelet plug is formed and RBCs r trapped within this
fibrous cap: fibroblasts from smooth muscle cap over the secondary plug= stable atheroma
73
what is a complication of an unstable atherosclerotic plaque
thrombi
74
what is an unstable atheroma and what happens because of this
DAMAGED cap means thrombi formation
75
what is apoptosis (5 key things to mention, 1 point/ definition)
genetically programmed non-inflammatory controlled cell death of INDIVIDUAL/ SMALL GROUPS OF CELLS
76
what r the 3 mechanisms of apoptosis
intrinsic, extrinsic and cytotoxic
77
what r the steps of apoptosis (5)
cells shrink, organelles retained, cell surface membrane REMAINS INTACT
CHROMATIN unaltered and is fragmented for easier phagocytosis
phagocytoses
78
What is the BCL 2 and Bax ratio and why is it signifcant
ratio that is maintained between an anti-apoptotic (BCL2) and a pro-apoptotic. So when the intrinsic pathway of apoptosis means Bax has a higher proportion, it determines that apoptosis will occur
79
intrinsic pathway for apoptosis
Bax (protein) acts on mitochondrial membrane and promotes cytochrome C release
activates caspases to cause apoptosis
80
is necrosis pathological or physiological
always pathological
81
what r the two types of apoptosis and give examples for each
pathological eg HIV
physiological eg duodenal cell turnover
82
extrinsic pathway for apoptosis
FasL or TNF alpha binds to cell surface membrane receptors
this activates caspases which cause apoptosis
83
what is the caspase cascade
the common pathway of caspase production in all 3 mechanisms which causes apoptosis
84
cytotoxic pathway for apoptosis
CD8+ binding releases granzyme B from CD8+ cells
granzyme B-> perforin-> caspases which causes apoptosis
85
what is necrosis (3) and causes of it (5)
traumatic unprogrammed cell death due to an adverse event
causes: INFARCTION, burns, frost bite, infection, trauma
86
what is the main cytokine that causes apoptosis/ necrosis and what it it released by
tumor necrosis factor alpha, macrophages
87
what follows necrosis
acute inflammation
88
what r the 4 types of necrosis and explain each one
coagulative necrosis (cell death due to ischaemia)
liquefactive (cell death caused by mostly infectious agents- brain becomes soup)
caseous (cell death with a soft cheese appearance due to granuloma formation eg TB)
gangrenous (cell death dye to loss of blood supply causing tissue to die and turn black black due to deposits of iron from Hb in the thrombi)
89
what r the 4 steps of necrosis of cells
cells burst
organelles splurge
cell surface membrane damaged
chromatin is altered which leads to death of the cell
90
define hypertrophy and give an example
cell gets bigger eg muscles
91
define hyperplasia and what cells do they occur in
number of cells increases via mitosis
only occurs in cells that divide (so not neurones or myocytes)
92
define atrophy
number and/ or size of cells decrease
93
define Metaplasia and give an example
change of cell type from one to another eg Barrett’s oesophagus
94
what is dysplasia and what does this indicate
change of a differentiated cell type to a poorly differentiated type
mostly indicated pre/cancerous changes
95
define carcinogenesis in terms of cells
transformation of normal to neoplastic cells through permanent mutations
96
define a neoplasm (acronym)
autonomous, abnormal, persistent new growth (AAPNG- like Bibi vengeance)
97
which malignant neoplasm never metastises
basal cell carcinoma
98
why does necrosis occur in neoplasms and what type of neoplasms is this common in
neoplasms outgrow their blood supply due to a fast growth rate- malignant neoplasms
99
what happens to neoplasms bigger than 2mm
they require blood supply and they start angiogenesis
100
what cells can neoplasms develop from
can only arise from nucleated cells (not from erthyrocytes but can come from their precursors)
101
what is a carcinogen
cancer causing agent
102
what r the 5 types of carcinogens
chemicals eg paints, dyes, rubber, soot
viruses eg epstein barr-> Burkitt’s, human papillomavirus eg cervical cancer
ionising and non-ionising radiation eg UVB in skin cancer, ionising is in lots
hormones and parasites and mycotoxins eg increase in oestrogen implicated in breast cancer
miscellaneous eg asbestos (mineral)
103
what r the 2 types of mutations
genuine and somatic
104
what is a genuine mutation and will it pass down to the next generation
mutated original germ cell= will pass down onto next generation
105
what is a somatic mutation and will it pass down to the next generation
mutated mitotic copy of germ cell -> won’t pass on to the next generation
106
what r the 2 mutations in colorectal cancer
FAP: familial adenomatous polyposis
HNPCC: lynch syndrome (non-polyposis)
107
what is the mutation in FAP, what does it lead to and what type of genetic condition is it
mutated APC gene (adenometous polyposis coli)= millions of colorectal adenomas
inevitable adenocarcinoma
autosomal dominant
108
what is the mutation in HNPCC, what does it lead to and what type of genetic condition is it
mutated MSH gene
lynch syndrome which is non-polyposis
autosomal dominant
109
What r the 5 steps of metastasis
detachment (from primary growth)
invasion of tissue (extracellular matrix)
invasion of basement membrane of the blood vessels
evasion of host defence whilst travelling in circulation
extravasation out of blood vessel to distant site
angiogenesis for own blood supply
110
what r the 3 methods of metastasis spread
HAEMATOGENOUS, lymphatic and transcolemic
111
what is haematogenous spread and 4 examples of cancers that spread this way
metastasis spread via blood
liver, lung, bone, breast
112
what r the 5 carcinomas that metastasise to bone (ACRONYM)
breast, lung, thyroid, kidney and prostate (These Kancers Like Peoples Bones)
113
what is lymphatic spread, where r secondary metastasises formed and 1 example
via lymphatics with secondary formation in lymph nodes
eg breast carcinoma metastasises to axillary and internal mammary lymph nodes
114
what is transcolemic spread and what three mediums does it spread through
via exudative fluid accumulation
spreads through pleural, pericardial and peritoneal effusions
115
what method of spread do sarcomas usually follow
haematogenous
116
what method of spread do carcinomas usually follow and what r the 4 exceptions
lymphatic
exceptions: follicular thyroid, choriocarcinoma, renal cell carcinoma, hepatocellular carcinoma
117
define tumor
defined as any abnormal swelling
118
what 4 things does the TERM tumor encompass
includes neoplasm, inflammation, hypertrophy and hyperplasia
119
what two things r tumors classed by and what r they
classified by behaviour and histogenesis
behaviour= malignant or benign
histogenesis= origin cell of tumour
120
what is a clot (why is it different to a thrombi)
formed outside the blood vessels or after death
121
give 2 examples of an infective agent resistant to phagocytosis
mycobacterium tuberculosis (TB)
mycobacterium leprae (leprosy)
122
what r the two types of benign epithelial neoplasms
papilloma= benign neoplasm of non-secretory, non-glandular epithelium
adenoma= benign neoplasm of secretory or glandular epithelium eg pituitary gland
123
what r the two types of malignant epithelial neoplasms
carcinoma= malignant epithelial neoplasm eg basal cell carcinoma , squamous cell carcinoma
adenocarcinoma= malignant neoplasm of glandular epithelium
124
what is the classification for leukaemias and lymphomas
malignant
125
what is advantageous about basal cell carcinoma never metastasising
can be surgically excised
126
what is the suffix for benign connective tissue and malignant connective tissue neoplasms
oma-benign
sarcoma-malignant
127
name for benign adipose tissue neoplasm
lipoma
128
name for malignant adipose tissue neoplasm
liposarcoma
129
name for benign blood vessels neoplasm
angioma
130
name for malignant blood vessel tissue neoplasm
angiosarcoma
131
name for benign nerves neoplasm
nueroma
132
name for malignant nerves neoplasm
neurosarcoma
133
name for benign smooth tissue neoplasm
leiomyoma
134
name for malignant smooth tissue neoplasm
leiomyosarcoma
135
name for benign striated tissue neoplasm
rhabdomyoma
136
name for malignant striated tissue neoplasm
rhabmomyosarcoma
137
name for benign bone neoplasm
osteoma
138
name for malignant bone neoplasm
osteosarcoma
139
name for benign cartilage neoplasm
chondroma
140
name for malignant cartilage neoplasm
chrondrosarcoma
141
two methods of measuring tumors and what does each assess
1. tumor staging via TNM classification, assesses spread
2. tumor grading via resemblance to parent cell of origin (grade 1-3) assesses malignancy
142
how does TNM staging work?
T- tumor size (scale of 1-4)- classified by how far it has invaded
N- degree of lymph nodes affects (0-2)
M- extent of distant metastasis (0-2)
143
explain characteristics of benign tumors regarding:
extent of invasion, mitotic growth, circumscription, growth direction, whether it is common to have necrosis and ulceration and its resemblance to normal tissue
localised- no BM invasion
slow growing
well circumsized
exophytic growth outwards
rare to have ulceration and necrosis
close resemblands to normal tissue
144
explain characteristics of malignant tumors regarding:
extent of invasion, mitotic growth, circumscription, growth direction, whether it is common to have necrosis and ulceration, nucleus stain and its resemblance to normal tissue
BM invading
fast mitotic growth
poor circumscription
endophytic growth inwards
common for necrosis and ulcers
hyper dense dark-staining nucleus
little resemblance to normal tissue due to poor differentiation
145
4 consequences of benign tumors
pressure on local structures eg optic chiasm
obstruction
transformation into malignant
hormone secretion eg prolactinoma
146
consequences of malignant tumors (3 points
same as benign and:
they form secondary tumors
often painful
147
3 neoplastic cell characteristics
AUTOCRINE STIMULATION (stimulates self growth)
evasion of apoptosis
telomerase action
148
explain what neoplastic cell autocrine growth stimulation involves (3)
over-expression of growth factors, inhibition of tumor suppressor genes eg p53,under expression of growth inhibitors
149
explain what neoplastic cell telomerase involves (2) and how does this help the neoplasm do (1)?
neoplastic cells prevent telomeres shortening with each replication, preventing its growth rate being limited, which gives it an ability to invade the BM
150
what 3 cancers r screened for in the UK and how
cervical: cervical swab
breast: mammogram
colon: fecal occult
