1
Q
- osis
A
disease/condition
2
Q
- itis
A
inflammation of
3
Q
Diverticulitis
diverticular disease
A
diease –> Digestive conditions that affects the large intestine (colon).
Small bulges or pockets (diverticula)develop in the lining of the intestine
X + itis, is when these pockets become inflamed or infected.
4
Q
Causes of inflammation
A
- Microbial infections
- Hypersensitivity reactions (some parasitic infections + TB)
- Physical agents (trauma, heat injury, radiation)
- chemicals (Acids, bacterial toxins, corrosives)
- tissue necrosis ( secondary to ischaemia)
5
Q
Bacterial Endotoxin
exotoxin
A
endo - associated with bacterial cell walls, stimualting inflamamtion
chemicals release by bacteria, stimualting inflammation
6
Q
Cardinal signs of acute inflammation
A
R - Redness (Rubor)
H - Heat (calor)
S - Swelling (tumor)
P - Pain (dolor) –> due to release of some chemical mediators (PROSTAGLANDIN + BRADYKININ) ++ due to physical distortion of tissue
L - Loss of Function (functio laesa)
7
Q
synonym for redness
A
rubor
8
Q
synonym for heat
A
calor
9
Q
synonym for swelling
A
tumor
10
Q
synonym for pain
A
dolor
11
Q
Stages of inflammation
A
- Release of chemical mediators
- Vasodilation
- Increased vascular permeability
- Fluid accumulation
- Cellular recruitment
- Phagocytosis
12
Q
synonym for exudate
A
pus
13
Q
exudate
A
fluid that leaks out of blood vessels into nearby tissues is named…
it is made up of cells, protein and solid materials.
it may ooze from cuts or from areas of infection or inflammation
14
Q
process called exudation
A
name of process when vascular changes in acute inflammation includes:
increased vascular permeability +++ increased net flow of fluid and cells our of vessels
15
Q
Margination
A
the adhesion of white blood cells to the walls of damaged blood vessels.
caused by the loss of intravascular fluid, which slows the flow to the site, thus allowing leukocytes e.g. neutrophils to marginate
16
Q
Synonym for adhesion
A
Pavementing
17
Q
the process of diapedisis
A
- marginatoin of neutrophiles
- pavementing of neutrophils (adhesion)
- pass between endothelial cells (emigration)
- pass through basal lamina and migratie into adventitia
18
Q
HIstamin functions
A
- regualtes sleep wake cycle + cognitive function
- role in allergies
- causes vascular dilation + permeability
released mainly by mast cells
19
Q
function of prostaglandins
A
derived from arachidonic acid
some cause paltelet aggregation
some cause increased vascular permeability
PAIN
20
Q
function of Seratoning
A
vasoconstrictor
released by platelets
21
Q
leukotrienes function
A
vasoactive properties
often made in neutrophils from arachidonic acidfun
22
Q
funciton of Bradykinin (plasma factor)
A
peptide mediation vasodilation + pain
activated by coagulation factor XII
23
Q
Plasma factors
4 enzyme cascade systems in plasma
A
these 4 enzyme cascade systems in plasma are called X:
- Coagulation system ( fibrinogen to fibrin)
- Kinins (activated by caogulation factor XII), includes Bradykinin
- Fibrinolytic system (removes fibrin from the vascular system preventing clots from occluding the vessel.)
- COmplement system
24
Q
Chemical mediators of acute inflammation
A
- Early chemical events
- Histamine + - Thromin released by inflammatory stimulus
—> causing upregulation of P-SELECTIN on endothelial cells + PAF on endothelial cells
—> allowing ligands onthe neutrophil surface to engage with the P-SELECTIN, starting to roll along the endothelial wall
- PAF (platelets activating factor)
– docks with corresponding receptor on neutrophil and promotes expression of otehr molecules —-> endresult is a firm adhesion onto the endothelial surface - Histamine
– vascular dilation + permeability
– released by mast cells - Lysosomal compounds
– vascular permeability
– stimualte histamine release from mast cells
– released by neutriphils - Leukotrienes
– vasoactive properties
– often made by neutrophils from arachidonic acid - Prostaglandins
– dervied from arachidonic acid
– increased vascualr permeability
– plateelt aggregation - Seartonin
– vasoconstrictor
– released by platelets - Chemokines
– attarcting more WBCs to site of inflammation
– IL-8 attracts neutrophils
25
cellular senescence
when the cell stops dividing as it ages
ascribed to progressive shortening of telomeres
26
HeLa cell line
cervical cancer cells taken without consent from Henrietta Lacks.
have active version of tolomerase which copies telomeres and prevents shortening
No Hayflick limit = cellular immortality
27
Function of telomerase
RESTORES telomeres
(so not present in normal cells, which have Hayflick limit)
hTERT gene - human telomerase reverse transcriptase, upregulation means more telomerase
hTERT mutations associated with many cancers
28
Clinicopathological features of Ageing: SKIN
- contains less elastin
- less collagen
- atrophy of dermis
- sun damage;photoageing
29
Clinicopathological features of Ageing: CARDIO
Ratio of ellastin to collagen decreases
reduced ability of conduit arteries to distend = increased systolic bood pressure
(aorta and major branches need to be able to stretch in response to internal pressure(compliance) and go back again (elasticity))
30
Clinicopathological features of Ageing: immune cells
immunosenescence
more memory cells, less naive cells ( decreased abiltiy to respond when encountering novel pathogens)
Thymus atrophy
less naive T cells
31
Clinicopathological features of Ageing: osteoarticular ageing
Osteoporosis
Normal mineralisation of bone matrix, BUT trabeulae are thinned
- prone to fractures
32
Clinicopathological features of Ageing: nervous
Neurodegenerative
CNS damage as a result of hypoxia/haemorrhage
33
Cell Size Feature of Necrosis
Increased (swollen)
34
Cell Size Feature of Apoptosis
Reduced (celll shrunken(
35
Nucleus Feature of Apoptosis
Fragemtnation / Condensatoin
36
Nucleus Feature of Necrosis
Pyknosis, Karyohexis, Karyolysis
37
Plasma Membrane Feature of Necrosis
Disrupted
38
Plasma Membrane Feature of Apoptosis
Intact
39
Nearby inflammation feature of Necrosis
almost always
40
Nearby inflammation feature of Apoptosis
Never
41
Causes of cell injury
Physical damage ( trauma)
Oxygen deprivation
Microbial
Immunological
Chemical
- strong acid contact (coagulates tissue proteins(
- CO inhalation (prevents O2 transport)
- Paracetamol overdose (Metabolites bind to liver cell prtoeins and lipoproteins)
42
How are cells damaged?
ATP depletion / reduced synthesis
Mitochondria damage
Intracellular calcium
Free radical (ROS) damage
Defective membrane permeability
Protein misfolding
43
Casues of Hypoxia
Ischaemia (most common cause – also compromises delivery of glyogen substrates, so double whammy)
Reduction in oxygen carrying capacity of the blood
Eg anaemia, CO poisoning
Inadequate blood oxygenation
Eg pneumonia
44
What happens in hypoxic Injury
1. Reduction in intracellular generation of ATP
Sodium pump activity is reduced, so sodium accumulates in the cell
This causes isoosmotic gain of water and acute cellular swelling
2. Increase in anaerobic glycolysis (bc of deceased ATP)
Rapid depletion in glycogen stores
3. Ribosomes detach from the rough ER
Polysomes dissociate into monosomes
Reduction in protein synthesis
- cytoskeleton breaks down
- loss of ultrastructural features
- irreversible daamge
45
Causes of Mechanical Injury
Direct mechanical damage
Cell membranes rupture, cytoplasm spills out
Freezing
Intracellular and cell membranes perforated by ice crystals
Osmotic imbalance
Rupture as a result of rapid change in osmotic pressure
46
hyperplasia
metaplasia
dysplasia + SYNONYMS
atrophy
hypertrophy
increased no, of cells
- conversion from one type of normal adult cell to another type of normal adult cell. (The most common types of metaplasia observed by pathologists involve the conversion from squamous to glandular cells and vice versa) // disordered growth ((premalignant, precursor lesion, potentially malignant) ------- usually referring to squamous epithelium (NOT INVASIVE MALIGNANCY, has NOT breached the membrane)
-refers to the abnormal development of cells within tissues or organs.
47
1.hyperplasia
2. metaplasia
3.dysplasia
4.atrophy
5. hypertrophy
1. “Increase in the number of cells in an organ or tissue”
2. “Reversible change in which one adult cell type is replaced by another adult cell type.”
4. “Shrinkage in the size of a cell by the loss of cell substance”
5. Increase in the size of cells and consequently an increase in the size of the organ”
48
Coagulative necrosis
- what it is
- causes
Tissue with connective tissue basic arrangement preserved
Caused by ischemia
Ischemia results in decreased ATP, increased cytosolic Ca++, and free radical formation, which each eventually cause membrane damage
e.g. Infarct: localized area of ischemic necrosis - myocardial infarct
49
caseous necrosis
- what it is
- causes
Cheese’-like necrotic debris contained within
Coagulated tissue no longer resembles the cells, but is in chunks of unrecognizable debris
Usually giant cell and granulomatous reaction
Example: Tuberculosis
50
colliquative necrosis
- what it is
- causes
Tissue with minimal connective tissue ‘liquifies’
Often in brain because lack of supporting stroma predisposes to total liquefaction when necrotic
Usually caused by focal bacterial infections, because they can attract polymorphonuclear leukocytes (neutrophils)
The enzymes in the neutrophils are released to fight the bacteria, but also dissolve
the tissues nearby, causing an
accumulation of pus
effectively liquefying the tissue
51
Gangrenous necrosis
DRY – sterile coagulative necrosis e.g. distal limb
WET – coagulative necrosis with superimposed infection
52
Fat necrosis
Release of enzymes from pancreas or gut or traumatic
Enzymes (lipases) release free fatty acids, which with calcium produce soapy deposits in tissuesP
53
Physiological examples of Apoptosis
Embryogenesis (shaping organs, eliianting webbing between fingers)
Menstrual cycle (elimination of cells from funtional layer of endometrium)
Immune system -->
- Death of post-inflammatory neutrophils
- Removal of self-reactive lymphocytes
- Death of virally infected cells
54
Clinical diagnosis of myocardial infacrtion ( cell death)
Myocyte necrosis enzymes released (troponins, CK-MB, LDH)
55
Labile cells
(Regeneration
good capacity to regenerate ( e.g. surface peithelial cells(
56
Stable cells
(Regeneration)
Divide at a slow rate, but can regenerate if needed (e.g. hepatocytes in liver)
57
Permanent cells
(Regeneration)
no means of effective regeneration
e.g. nerve cells, striated muscle cells
58
Suppuration
formation of pus
lots of neutrophils accummulating
mix of neutrophils, debris, bacteria
forms abscess if it gets walled off
59
Outcomes of inflammation
- Resolution
- Suppuration
-Scarring / Fibrosis
- Chronic inflammation
60
Granulation tissue
a new connective tissue with microscopic blood vessels and myofibroblasts that develop at the wound site in the process of healing. It grows from the base of the wound and helps in filling the wounds. It is important for the contraction of the wound and epithelial cell migration.
New capillaries, leading to more macrophages, leading to proliferation of fibroblasts, leading to fibrosis and/or scarring
61
Skin Healing - primary intention
in x Fibrin joins the edges together weakly
Over time, epidermal regrowth and collagen synthesis makes a stronger join
62
Skin healing - secondary intention
Tissue defect filled in by granulation tissue
Epithelial regrowth over the surface
Fibrous scar forms and contracts over time
63
Bone Healing
Break
Haematoma / inflammatory response
Callus formation (woven bone)
Replaced eventually by stronger lamellar bone
64
Which parts of the kidney can regenerate, and which parts not?
Epithelium can regenerate, architecture can’t
Similar to liver
Loss of tubular epithelium only can regenerate/repopulate cells
Destruction of glomerulus or damage to interstitium usually results in scarring / impaired function
65
Which smooth muscle cells can regeneration?
Vascular smooth muscle cells can regenerate
Other smooth muscle cells ... not so much
Damaged muscle is replaced by scar tissue
66
Examples of primary granulomatous disease
Crohns
sarcoidosis
67
Resistance of microorganism to phagocytosis and intracellular killing
examples
TB
Leprosy
68
Macroscopic signs of chronic inflammation
Chronic ulcer
chronic abscess cavity
fibrosis/ thickening of tissueC
69
cells of chronic inflamamtion
lymphocytes(B and T)
plasma cells
macrophages
sometimes eosinophils
70
Histology - recognising a lymphocyte
Small purple dots
71
Histology - recognising a plasma cell
fried eggs
72
Histology - recognising a macrophages
bigger blobby ones
73
Histology - recognising a eosinophils
tomatoes with sunglasses
74
Which cytokine promotes apoptosis
TNF
75
which cytokine promotes anti viral defences
interferon
76
Granuloma
collection of histiocytes
77
difference between granuloma + granualtion tissue
A granuloma is a small, organized collection of immune cells, primarily macrophages, that forms in response to chronic inflammation, particularly when the body tries to isolate and contain a substance or infection it cannot eliminate.
-- Contains and isolates difficult-to-remove substances
e.g. TB, Crohns (inflammation of bowel disease), Sarcoidosis
Granulation tissue is new connective tissue and microscopic blood vessels that form on the surface of a wound during the healing process, particularly in open wounds
-- Repairs tissue and promotes wound closure
e.g. skin wounds
78
Giant cells - what are they, how they form
describe the types
- Langhans
- Foreign body type
- Touton type
when macrophages collide, ending up with huge multinucleated cells
Langhans - horsehow nuclei (seen in TB)
Touton type - neat little circles of nuclei , lipid breakdown and xanthoma
foreign body - nuclei randomyl scattered
79
Xanthoma
a skin condition in which certain fats build up under the surface of the skin
80
Intrinsic Pathway of Apoptosis
1. Cytochrome C released during apoptosis
(mitochondrial protein)
2. Binds with other factors
- ATP (Apoptotic Protease activating factor)
- Pro-caspace 9
(MAKING AN APOPTOSOME)
3. Pro-caspase 9 -> cleaved into -> caspase 9
4. Caspase 9 cleaves
procaspase 3 -> caspase 3 (active form)
CASPASE 3 triggers CELL DEATH
81
Extrinsic pathway of apoptosis
TNF PATHWAY:
1. tumor necrosis factor BINDS to TNF receptor
3. TNF receptor associates with death domain (TRADD)
FADD (Fass associated death domain)
- forms complex with procaspase 8
- caspase activation, procaspase 8, caspase 3
- triggers cell death
FAS PATHWAY:
1. first apoptotic protein
FAS Ligand + FAS receptr
2. Formation of FADD complex
procaspsase 8/10
death inducing signalling complex ( DISC)
leading to caspase activaton
- triggers cell death
82
Mesenchyme
Mesenchymal cells
Multipotent stem cells
Progenitor cell which differentiates to all types of connective tissue --> e.g. fibroblast, osteoblast, chondroblast, preadipocytes
produce ECM that consists mainly of a simple ground substance rich in hyaluronic acid.
ECM + mesenchymal cells = MESENCHYME
EMBRYO: type of embryonic conenctive tissue that gives rise to all other connective tissues of the body during early development.
ADULT: present in small quantities as part of loose connective tissue in
- umbilical cord
- bone marrow
- adipose tissue
serve to give rise to fibroblasts + new blood vessels
83
synonym for neoplasia
tumour
84
tumour meaning
swelling
85
ONCO / OLOGY
oncology
study of tumours ( i.e. swellings)
86
Malignant neoplasm
potentially lethal
has ability to invade and metastasise
exceptions e.g.
- malignang tumor (BASAL CELL CARCINOMA) does not metastasise
87
Benign neoplasm
does NOT have ability to metastasise
* does NOT always mean harmless - some can be v locally destructive
88
anaplastic tumour
the least differentiated tumour
DIFFERENTIATION TOPIC: the extent to which neoplastic tissues resemble their corresponding normal tissue of origin
as tumors become less well differentiated, anaplastic features become more prominent
89
Anaplastic/Undifferentiated tumorsq
BAD BOYS
cannot be identified by morpholgy alone
-- immunohistochemistry needed, to look at their lineage
-- subtyping important for diagnosis and treatment
90
Features of poor differentiation
(Grade 3 classification)
NUCLEUS, abnormal:
- high nuclear: cytoplasmic ratio
- clumped chromatin
- prominent nucleoli
Nuclear pleomorphism:
- varibaility in nuclear size/shape
increased mitotic activtiy
Loss of polarity
NECROSIS - bad sign
91
Dysplasia
earliest form of precancerous lesion, describing confined neoplastic change(mostly epithelia) , with nuclear plyomorphism /architectural disruption
confined withi nthe basement membrane
it is NOT cancer, but can sometimes become cancer
- can be low/high grade
can regress, not alway sleading to malignancy
92
Carcinoma in-situ
severe form of dysplasia
WIHTOUT invasion ( basement membrane of dysplastic epithelium not penetrated)
full thickness of epithelium
not actually carcinoma (just terrible name)
93
x happens when the tumour is growing so fast that the blood supply cannot keep up
Necrosis
94
adjectives to describe BENIGN local invastion
well circumscribed
enapsualtoin (fibrous capsule)
slow growing
noninvasive -nonmetastatic
Exophytic growth direction
sometimes they are NOT harmless, they can be very locally destructive
95
adjectives t odescribe MALIGNANT local invasion
infiltrative
invasive
karge
rapidly growing with hemorrhage + necrosis
metastatic
Endophytic growth direction (fown the way into connective tissue in an invasive manner)
96
Benign tumours (not just epithelial)
Suffix “-OMA”
97
Benign tumour of glandular / secretory epithelium
ADENOMA
98
Benign tumour of non-glandular / surface epithelium
PAPILLOMA
99
Mesenchymal tissues
benign mesenchymal tumours prefixes + suffix OMA:
Smooth muscle
skeletal muscle
adipose
blood vessel
bone
cartilage
fibrous
leiomyo
rhabdomyo
lipo
haemangio
osteo
chondro
fibro
100
suffix for malignant epithelial tumors
CARCINOMAS
101
suffix for benign epithelial tumors
OMA
102
malignant mesenchyma tumours called
SARCOMAS
103
benign mesenchyma tumours suffix
OMA
104
malignant mesenchymas tumours suffix
- sarcoma
105
TERATOMAS
TUMORS COMPOSED of well-differentiated tissues e.g. bone, mnuscle , teeth, hair
contains cells representing ALL 3 germ cell layers
REMINDER: well differentiated, behave better
the anaplastic are the bad boys
106
HAMARTOMA
NON-NEOPLASTIC DISORDERED OVERGRWOTH OF NORMAL TISSUE
indigenous to site of occurence
e.g. PORT WINE STAIN
107
CHORISTOMA
heterotropic rests
bening normal tissue but seen in abnormal location
e.g. pancreas nodule in stomach
108
Myeloma
malignancy of plasma cells
109
LYMOHOMA
Malignancy of B / T cekk origin, often beginning in lymph nodes
110
Leukemia
Malignancy of WBCs, beign in bone marrow
111
Melanoma
malignancy of melanocytes (producing pigment in the skin/0
112
Melanocytic naevus
benign proliferation of melanocytes
113
How do neoplastic cells become immortal?
1. AUTOCRINE GROWTH STIMULATION
- abnormal expression of oncogenes / inactivation of tumor ruppressor genes, which normally inhibit growth pathways
2. REDUCED APOPTOSIS
- abnormal expression of genes that inhibit apoptosis (BCL-2)
3. TELOMERASE
normally onoly present in germ cells and stem cells, but NOT in normal cells
normal cells usually undergo telomeric shortening with each cell division, resitricting the number of cell division cycles.
telomerase prevents the shortening
114
example of gene that inhibits apoptosis
BCL2
115
Normal location of telomerase
germ cells + stem cells
prevents the shortening of telomeres (repetitive DNA sequences at the end of a chromosome)
116
examples of tumour suppressor genes
TP53, which encodes for p53 protein(the guardian of the cells)
(both caretaker + gatekeeper function)
binds to oncoportein encoded by DNA viruses
complexes of normal p53 with mutant --> normal protein gets inactivated
MUTATIONS INCLUDE:
- nonsense (unreadable gene)
- missense (defective protein)
1. repairs DNA damage
2. induces apoptosis
3. cell cycle arrest growth (G1), via p21(providing the stop signal for cell division)
____________________________________________
pRb
117
the 3 types of tumour suppressor genes
1. inhibit neoplastic growth
2. caretaker genes (Repair DNA damage)
3. gatekeeper genes (stop damaged cells from dividing (by inhibiting proliferation OR inducing apoptosis)
118
5 groups of oncogenes/oncoproteins
1. Growth factors
2. receptors for growth factors
3. DNA binding TFs (regualting cell proliferation)
4. signalling mediator with tyrosine kinase activtiy
- tyrosine kinases regulate cell survival and proliferation
5. signalling mediator with nucleotide binding activity
119
Aneuploidy
when cell contains INEXACT multiple of chromosomes
usually we have diploid (normal amount of DNA, 2 copies of each chromsome)
might have
- additional chromosomes
- chromosomal transloactions/rearrangements
120
examples of oncogenes
Ras
121
Chemical contained in SMOKING + cancer caused
carcinoma (lung, skin, mouth)
- polycyclic aromatic hydrocarbons
122
Chemical contained in rubber/dye industries+ cancer caused
bladder cancers
- aromatic amines
123
Chemical contained in tobacco/cured meats + cancer caused
GI cancer
- nitrosamines
124
Chemical contained in some azo dyes+ cancer caused
bladder, liver ca
125
Chemical contained in pvc manufacture+ cancer caused
liver agiosarcoma
- vinyl chloridea
126
angiosarcoma
cancer that forms in the lining of blood vessels and lymph vessels. It often affects the skin and may appear as a bruise-like lesion that grows over time
127
Nitrate heavy food examples
indirect carcinognes
cured meats
dietary nitrates conerted into NITROSAMINES by GI tract bacteria
NO3- => N-N=O
128
papilloma
a benign (non-cancerous) tumor arising from an epithelial surface and usually known to grow in an outward direction
129
Human Papillomavirus
HPV
High risk: HPV 16/17
- squamous cell carcinoma
Low risk: HPV 6/11
- squamous cell papilloma
anogenital region
head cancer
neck cancer
e.g. cervical cancer
--> HPV E6 oncoprotein acts on TP53, which makes p53 tumour suppressor gene
--> HPV E7 oncoprotein binds on pRB
--> virus integrates with host genome
130
Mode of action of p53
G1/S checkpoint
- prevents cell from entering S phase (DNA synthesis) if there is DNA damage
- if damage is irreparable, induces apoptosis or senescence to prevent propagation of faulty DNA
---> mediated through p21 activation (providing the stop signal, which signals G1 cell cycle arrest)
G2/M checkpoint
- prevents cell from entering mitosis if DNA damage/incomplete DNA replication
- allows additional time for repair before mitosis /// triggers apoptosis if repair fails
131
tumour suppressor gene RB which codes for retinoblastoma protein - function
Rb inihbits cell cycle progression unitl a cell is ready to divide
G1-S checkpoint
132
Epstein Barr Virus
type of herpesvirus
causes glandular fever = mononulceosis
associated with some lymphomas + carcinomas
Latent EBV can reactivate drive B cells to proliferate ---> EBV driven lymphoproliferative disorder
- can infect squamous cells (skin/mucosa)
- can act in combination with environmental factors e.g. smoking, to promote nasopharyngeal carcinoma
common initiating event for carcinomas:
-> inactivation of p16/CDKN2A ++ TGFBR2
133
Burkitt lymphoma
high-grade B cell lymphoma
134
malaria
infection caused by a parastie
does not spread from person to person, but only from mosquitos
135
type of UV radiation implicated in skin cancer
UVB
ASSOCIATED WITH
- basal cell carcinoma
- malignant melanoma
136
cells that arise from the neural crest
The neural crest is a transient embryonic structure in vertebrates that gives rise to
1. most of the peripheral nervous system (PNS)
2. several non-neural cell types, including
- smooth muscle cells of the cardiovascular system,
- pigment cells in the skin,
- craniofacial bones,
- cartilage,
- connective tissue
137
melanocytes
neural crestt derived cells
in basal layer of epidermins
produce melanin pigment
malignant transformation can occur following UV damage
pale skin people more susceptible to UV damage
- melanin has protective effect against UV damage
138
Tissues most sensitive to carcinogenic effects of ionising raditaion
Thyroid
Breast
Bone
Haemoatopoietic tissue
CHORNOBYL DISASTER -- explosion of nuclear power plant in Ukraine -1986
- fatal doses
- initial deaths from radiation exposure
- LT increase in childhood thyroid cancers
- clonal DNA ds breaks
139
bacterium linked with carcinogen
Helicopater Pylori
- gastric adenocarcinomas
- some lymphomas
- toxins released activated oncoproteins
140
Fungi and carcinogens example
aflatoxin carcinogen
hepatocellular carcinoma
(food, crops, animals feed, milk)
141
Hormones and carcinogenesis
excess oestrogen (breast, endometrail, excess adipose tissue, obesity a risk factor in some cancers)
- excess adipose tissue means higher levels of growth hormones, oestrogen etc
anabolic steroids
- liver neoplasms
Grwoth hormone / IGF1 (breast, prostate, colon)
142
2 reasons why cancer is most common in old age
mostly epithelial in origin
1. loss of immune competence
2. increasing somatic genetic mutations
143
in children
epithelial cancers (carcinoma) VERY rare
acute leukemias / primitive CNS neoplasms common
retinoblastoma (small blue round cell tumours)
Wilms tumour (nephroblastoma) - kidney cancer
144
Properties of invasiveness
1. Decreased cellular adhesion
2. Secretion of proteolytic enzymes
3. Abnormal / increased cellular motility
145
the 6 steps of metastasis
1. detachment from main tumour body
2. local invasion of surroudnign tissue
3. intravasation into vessels
4. evasion of host cell defences
dissemination
5. adherence to endothelium elsewhere
6. extravasation of cells from vessel in to surrounding tissue
colonization
146
intravasation
The movement of a cell or a foreign substance through the wall of a blood or lymph vessel into the vessel itself
147
transcoelomic metastasis
“across the peritoneal cavity”) metastasis refers to the dissemination of malignant tumors throughout the surfaces and organs of the abdominal and pelvic cavity covered by \peritoneum
148
routes of metastasis
1. Haematogenous
2. Lymphatic
3. Transcoelomic (across the peritoneal cavity)
149
