Cell Pathology Flashcards
(251 cards)
1
Q
What are the 8 types of cell injury? (Paingico)
A
- Physical agents
- ageing
- immunological reactions
- nutritional imbalances
- genetic defects
- chemical agents
- infectious agents
- O2 deprivation.
2
Q
What does the response to cell injury depend on?
A
Type of injury, duration, severity
3
Q
What do the consequences from a cell injury depend on?
A
Cell type, status, adaptability, genetic makeup
4
Q
What are the four cell mechanisms which are particularly vulnerable to cell injury?
A
Cell membrane integrity, ATP generation (important in cell integrity), protein synthesis (affect cell membrane) integrity of genetic apparatus (malfunction in protein synthesis)
5
Q
Why is the cell membrane important?
A
The cell membrane signals self so if malfunction then problems could arise
6
Q
Why is cell functionality important in cell injury?
A
Cells stop functioning before they die, which could cause death in patient before any cell injury can be seen - ventricular fibrillation
7
Q
What is atrophy?
A
Shrinking of cells/organs in size by loss of cell substance
8
Q
What is hypertrophy?
A
Increase in size of cells and consequently size of organs
9
Q
What causes hypertrophy?
A
Increased functional demand, increased specific hormone stimulation
10
Q
What is hyperplasia?
A
Increase in NUMBER of cells in an organ
11
Q
What are the causes of hyperplasia?
A
Physiological OR pathological:
- phys: hormonal (oestrogen wave of proliferation of endometrium)
- compensatory (if some tissue is lost) Eg: cancer
12
Q
What are the categories of cell injury?
A
Lethal - causes cell death
Sublethal - produce injury, not amounting to death but can lead to it/may be reversible
Hypertrophy - cells adapt and become bigger due to stress
13
Q
What is metaplasia?
A
REVERSIBLE change in which one adult cell type is replaced by another - Barrett’s Oesophagus
NB: metaplasia doesn’t give an increased risk of cancer but once you have metaplasia there is a higher chance of getting dysplasia
14
Q
What is dysplasia?
A
Precancerous cells which show genetic and cytological features but are NOT INVASIVE
(Bridge between normal and cancer)
15
Q
What is happening in this picture?
A
Squamous epithelium has become glandular - METAPLASIA
Cells have become dysplastic - More worrying
16
Q
What light microscopic changes are associated with a reversible injury?
A
Fatty changes and cellular swelling - degenerative changes - Both REVERSIBLE
17
Q
How do you increase (process) muscle bulk?
A
Hypertrophy
18
Q
By what process can muscle turn into bone?
A
Metaplasia
19
Q
What is necrosis?
A
Confluent cell death associated with inflammation - in areas not cells
20
Q
What are the 4 types of necrosis?
CCLF
A
Coagulative, liquefactive, caseous, fat
21
Q
What is coagulative necrosis?
A
Substance changes but shape of muscle doesn’t change
Myocardial infarction: tissue retains same structure, but nuclei disappear, in between are inflammatory cells
22
Q
What is liquefactive necrosis?
A
Cerebral infarct - brain totally liquefied, empty space: can only tell what tissue it was from by looking at the tissue around it
23
Q
What is caseous necrosis?
A
“Cheesy” - pulmonary TB, necrotic area is granular -> making it caseous
24
Q
What is fat necrosis?
A
Acute Pancreatitis -> release of lipases which digests the fat and hydrolyses triglycerides to free FA and glycerol. FA combine with calcium in ECF and deposits are the area of fat necrosis
25
What can cause fat necrosis?
Severe fat trauma but usually associated with acute pancreatitis
26
What is an ulcer?
A local defect/excavation of surface of an organ or tissue, produced by sloughing of necrotic inflammatory tissue - gastric ulcer
27
What is apoptosis?
NOT associated with inflammation
Death of single cells - active cell death as energy is used to die
Can be pathological (necrosis) or physiological
28
What are the differences between apoptosis and necrosis?
Apoptosis: NOT associated with inflammation, active cell death, physiological/pathological, neater
Necrosis: inflammation as internal contents exposed to the external environment, pathologcial
29
How does apoptosis occur? (process)
Nuclues shrinks and blebs of cell break off
Blebs are phagocytosed by macrophages
30
What are the causes of apoptosis?
Embryogenesis (lumen in intestines)
Deletion of auto-reactive T-cells in thymus
Hormone-dependent physiological involution
Cell deletion in proliferating popn
Variety of mild injurious stimuli that cause irreplaceable DNA damage that triggers cell suicide pathways
31
What are the cells mechanisms for inducing apoptosis?
If cell can repair itself it will, but when the damage is too severe or repair systems are lacking, then cell chooses apoptosis
Sometimes at edge of an area of necrosis, where injury is less severe, there are cells undergoing apoptosis
32
What process causes deaths of individual cells but doesn't produce inflammation?
Apoptosis
33
What is necroptosis?
It's like apoptosis because it needs energy and necrosis because it causes inflammation
Causes: viral infections
Examples: Cancer cells, thyroid problems
34
Who is the coroner?
Investigate the death and how it occurred
35
What cases must be reported to the coroner?
1. Cause of death unknown
2. Deceased hasn't been seen by certifying doctor either after death/within 14 days before death
3. Death was unnatural, violent/suspicious
4. Death may be due to accident (whenever occurred)
5. Death may be due to neglect
6. Death may be due to industrial disease/person's employment
7. Death may be due to abortion
8. Death due to operation/before recovery from anaesthetic effects
9. Death due to suicide
10. Death during/shortly after detention in police/prison custody
11. Death due to poisoning
36
What is the aim of an autopsy?
To establish cause of death
37
What is the difference between hospital and coroner's autopsy?
Coroners don't need consent, but hospitals do (from NOK)
Coroners can only take material if needed to find cause of death, BUT hospitals can take any material with consent
38
What are the reasons for a hospital autopsy?
1. Allows thorough examination of deceased, extent of disease and treatment/effects
2. Useful for audits
3. Monitors effectiveness of new treatments
4. Teaching
5. Research
39
What is a death certificate used for?
Epidemiology - see main causes of death, helps divides funds more appropriately
40
How is an autopsy carried out?
Big incision from neck to top of pelvis, then organs taken out systematically and checked
41
What is the layout of the death certificate?
1a) Immediate cause of death (MUST) *eg: Haemopericardium*
1b) Predisposing factor - *Myocardial infarction*
1c) Predisposing factor - *Ischemic heart disease*
2) Other factor contributing but not directly leading to death - *Hypertension*
_NB: 1c leads to 1b -\> 1a (and 2x1a can happen)_
42
What is a death certificate?
Filled in for any death and taken to the registrar by the family where it is scrutinised to be correct before death is registered
43
What are the leading cause of sudden unexpected deaths in the community in younger people?
1. Congenital disease
2. Trauma
3. Drugs/Alcohol
44
What are the 9 natural causes of sudden unexpected death?
1. CVD - 50% die suddenly, 25% die without warning, cardiac arrhythmia (ACA) usual mode of death (UMOD), severe coronary artery atherosclerosis most common anatomical finding
2. Hypertensive
3. Other cardiac causes of sudden unexpected death
4. Vascular system - ruptured aortic aneurysm
5. CNS - non-traumatic subarachnoid/intracerebral haemorrhage
6. Resp system - Asthma, GITI, pulm emobolus
7. Drugs/Alcohol (1% each)
8. Trauma
45
What are the types of Trauma?
Stab, Cut, Laceration, Abrasion, Bruise
46
What is a bruise?
An extravasted collection of blood which has leaked from damaged small arteries, venules and veins but NOT CAPILLARIES
OR
Blunt trauma injury that occures alone (skin intact) or associated with other injuries
47
Where does a bruise occur?
More easily where skin is lax and fragility of vessels/coagulation state all affect bruising
May take hours/days to form, patterned bruises may occur
Deep bruising may NEVER be seen on the surface
48
How does an abrasion occur?
Caused by: tangential force (distal skin tag-friction burn) OR vertical force (no distal skin tag-stamp)
May occur after death as it is confined to the epidermis (but may extend to superficial dermis due to skin anatomy)
49
What is an abrasion?
Graze or scratch - most superficial of blunt trauma injuries
50
Give examples of abrasions
Friction burn, car radiator, flooring, whip, stamp
51
What is a laceration?
Split to the skin due to **blunt force trauma** - usually passes through full thickness of skin
52
What do lacerations look like?
Deep and will bleed, with ragged margins from crushing and bruising
Bridging fibres arch across the skin defect
53
What are the areas of laceration?
Common: Where skin can be compressed between force and underlying bone (scalp, elbow, shin)
Rare: over soft fleshy areas (breast, buttocks)
54
What is flaying; to do with lacerations?
Tangentially applied force leading to horizontal laceration - poor reproduction of object causing it
55
What is a cut (or slash)?
LENGTH of injury longer than DEPTH
56
What is a stab (or penetrating injury)?
DEPTH of wound is greater than WIDTH
57
What are the causes of cut and stab wounds?
Objects with a sharp or cutting edge - usually knife, but can be anything (glass bottle, piece of metal)
58
What do cut and stab wounds look like?
Edges are clean and well demarcated
Minimal injury to the surrounding tissue
Info about weapon type can be found by the wound
59
What are incised wounds?
Either: includes cuts and stabs OR just cuts -so be wary of terminology used
60
What is inflammation?
Reactions of living vascularised tissue to sub-lethal cellular injury - evolutionary development to protect against infection and trauma
61
What are the types of inflammation?
Acute inflammation, Chronic inflammation, Granulomatous inflammation
Different types caused by diff cell types/soluble mediatiors - generally tightly regulated w/ local/systemic effects
62
What is acute inflammation?
Transient and early response to injury - occurs within hours/few days\> typical vascular and leucocyte response
Involves release of chemical mediators - NOT the same as infection
63
What is chronic inflammation?
Inflammation of prolonged duration (weeks-years) - usually due to persistent injury causing agent - in which active inflammation, tissue destruction and attempts at repair occur simultaneously
64
What is ganulomatous inflammation?
Specialised form of chronic inflammation
65
What are the cellular components of inflammatory response and healing?
Neutrophils, Macrophages, Lymphocytes, eosinophils, mast cells
66
What are the ECM components of inflammatory response and healing?
Collagen, Proteoglycans, Fibroblasts
67
What are the soluble factors of inflammatory response and healing?
Ab, cytokines, complement system, coagulation system
68
What are the vessel components of inflammatory response and healing?
Immediate supply of cells and soluble factors, tissue repair
69
What are the cardinal signs of acute inflammation - vascular events?
Calor - heat caused by **histamine** mediated vasodilation
Rubor - redness caused by slow moving blood
Tumor - oedema caused by **histamine** mediated increase in vessel permeability
Dolor - pain
Functio Laesa - due to swelling and pain
70
What is histamine?
Vasoactive amine which is produced by **mast cells** - packaged into granules \> when Ag binds to IgE on surface of mast cells, cross linking and degranulation occurs
Causes vasodilation and increased vascular permeability
71
What does histamine lead to?
Vasodilation and increased vascular permeability
If dysregulated can lead to allergy - Type 1 Hypersensitivity
72
Why study inflammation?
Inflammatory processes underlie many diseases, can predict sequelae and complications of inflammatory reactions, intervention to reduce/prevent adverse effects can be made
73
What disease processes involve inflammation?
Infection (TB), autoimmune (Rheumatoid arthritis), allergic (asthma), metabolic (Gout), malignant (host reaction), inherited disease (Chronic granulomatous disease), trauma: occupational/env (silicosis, radiation burns), idiopathic (Pulm fibrosis, Crohn's disease)
74
What are the 5 major cell mediators?
Histamine, prostaglandins, chemokines, complement and cytokines/interleukins/TNF
75
What does prostaglandins do and where does it come from?
From: Macrophages, endotheial cells and platelets
Does: PGE2 - vasodilation, pain, fever; PGI2 - vasodilation, inhibition of pit aggregates
76
What do chemokines do and where do they come from?
From: Leukocytes, endothelial cells
Do: Activate neutrophil chemotaxis
77
What do complements do and where do they come from?
From: circulating proteins which are synthesised in the liver and released during inflammation
Do: Form a variety of proteins and stimulate mast cell degranulation, neutrophil chemotaxis and opsonisation
78
What do cytokines/ILK/TNF do and where do they come from?
From: macrophages, endothelial cells, dendritic cells and monocytes
Do: Form many different proteins and actions including pro/anit inflammatory signaling, malaise, fever and weight loss
79
What molecules target the inflammatory mediators histamine, prostaglandins and IL-1/TNF?
Histamine: anithistamine
Prostaglandins: aspirin
IL-1 and TNF: Anti-TNF antibodies
80
What is hydrostatic pressure?
Pressure exerted by a fluid at equilibrium at a given point within the fluid, due to the force of gravity
81
What is Colloid osmotic pressure?
Form of osmotic pressure exerted by proteins in the plasma, that tends to pull in water to the circulatory system
82
What is exudate?
Fluid with high content of protein and cell debris that has escaped from blood vessels and been deposited in tissues or on tissue surfaces - usually due to inflammation
83
What is transudate?
Caused by disturbance in colloid osmotic and hydrostatic pressure - NOT caused by inflammation
84
What is the difference between **exudate** and _transudate_?
**Leaky vessels** v. _Content of vessels (pressure changes)_
**High protein** v. _Low protein_
**High specific gravity** v. _Low specific gravity_
**Cell rich** v. _Cell poor_
85
What is specific gravity?
Ratio of density of substance to referenced substanced density
86
What does exudate consist of?
Fluid, cells, proteins (inc. fibrin, Ab, etc)
87
What is the function of exudate?
The fluid dilutes pathogen and allows soluble mediators to spread.
The fibrin forms walls around the pathogen to stop it from spreading and gives inflammatory cells something to hold on to/migrate through
88
What are the 3 types of exudate?
Serous - fluid filled (blister) **lowest protein content**
Fibrinous - high fibrin content (traumatic injury/viral pericarditis)
Purulent - pus-filled, combination of fibrin, inflammatory cells, debris, fluid (peritonitis following bowel perforation)
89
What are the key molecules in Acute inflammation?
Neutrophils
90
What is the action of neutrophils during acute inflammation?
Enter tissue \> migrate to site of cell injury - chemotaxis \> become activated \> carry out designated role \> interact with other cell types - release soluble mediators
91
What is the main role of neutrophils in acute inflammation?
First cells to the damaged area - they kill bacteria, phagocytosis, degranulation
92
What are the main four stages of cellular egress?
Margination
Rolling and Adhesion
Transmigration (diapedesis)
Chemotaxis
93
What does margination involve in cellular egress?
Cell is pushed to edges of vessel
94
What does rolling and adhesion involve in cellular egress?
At margin, cell can loosely bind to endothelial cells through selectins on the neutrophil and endothelial cells, cells continue rolling but slow down so more permanent bonds form, fixing neutrophil to vessel wall
95
What does transmigration involve in cellular egress?
Neutrophil dissolves the basement and enters the interstitium
96
What does chemotaxis involve in cellular egress?
Cell follows the chemical gradient to site of inflammation
97
What are the 3 stages in phagocytosis?
Opsonisation
Ingestion
Killing
98
What is opsonisation in phagocytosis?
Opsonins attach to bacteria to enhance neutrophil recognition and attachment as bacteria are more recognisable and more readily phagocytosed
99
What is the killing stage in phagocytosis?
Phagocytosed material is destroyed in a vacuole by free radicals, lysozymes, lactoferrin (binds iron and stops bacteria reproducing), major basic protein (prod. by eosinophils - cytotoxic to helminth parasites)
100
What other cells are important in acute inflammation?
Eosinophils: important in allergic and parasitic causes of inflammation
Mast cells: important in allergic diseases
101
How is the inflammatory reaction controlled?
Mediators and neutrophils have a short half-life
Stimulus is removed
Mast cells and lymphocytes release anti-inflammatory products (lipoxins)
Macrophages release anti-inflammatory products
102
What can occur during inflammation/acute inflammatory response?
Tissue damage/necrosis
103
What are the histological features of acute inflammation?
Lots of neutrophils present, as well as mast cells and eosinophils
104
How does acute inflammation evolve into chronic?
Myofibres breakdown, there are fewer neutrophils and other cell types are involved
105
What is the cause of chronic inflammation?
PERSISTENT DAMAGE - persistent infection/prolonged exposure to toxic agent/autoimmunity/foreign body
106
What cells are involved in chronic inflammation?
Macrophages, lymphocytes, plasma cells
107
Acute inflammation vs _chronic inflammation_
Exudate vs _no exudate_
Prominent necrosis vs _Prominent scar tissue_
Neutrophils vs _Monocytes/Macrophages_
Histamine vs _Cytokines_
Immediate onset/short lasting vs _Delayed onset/long lasting (month/yrs)_
Can Become: Resolved/chronic vs _Scar tissue/disability_
108
What tissue forms whilst repair is attempted in chronic inflammation?
Granulation tissue
109
Why are monocytes/macrophages present more in chronic inflammation?
Live longer than neutrophils, phagocytosis, they can release cytokines and control other cells, they increase in viral and atypical bacterial infections
110
What are the histological features of chronic inflammation?
Macrophages, lymphocytes and plasma cells abundant
Lots of fibroblasts producing granulomatous tissue
111
What is granulomatous inflammation?
It's a form of chronic inflammation, with clusters of macrophages
112
What cells does granulomatous inflammation involve?
Involves specific immune reaction t-cells
113
What are the causes of granulomatous inflammation?
Infection
Foreign material
Reaction to tumours
Immune diseases
114
What are the histological features of granulomatous inflammation?
Macrophages in the middle, lymphocytes around the outside
Horseshoe shaped nuclei seen at latter stages of granulomatous inflammation
115
What are the good outcomes of inflammation (sequelae)?
Causative agent removed
Inflammatory reaction ceased
Tissue damage is healed to preserve integrity/function (resolution)
116
What are the bad/unwanted effects of inflammation?
Local: excess local tissue damage/scarring; 2ry effects on nearby tissue
Systemic: systemic inflammatoy reaction, 2ry multi-organ failure \> eg. septic shock, amyloid
117
What is resolution (wound healing)?
Regeneration of normal functioning parenchymal cells
118
What is repair (wound healing)?
Connective tissue and **_SCAR TISSUE_** formation
119
How can resolution occur?
Tissue contains cells capable of regeneration to replace lost cells - liver cells
OR
Little structural damage is done - as cells need basement membrane to build on, eg. lung in lobar pneumonia
120
Give an example of resolution and outline what happens
Initially exudation \> red hepatisation (blood moves into alveoli so feels like liver) \> erythrocytes breakdown causing grey hepatisation \> If basement membrane still there then body can remove problem
121
What happens to cause repair of a wound?
Tissue loss is too great so cells unable to regenerate, replacing normal tissue with **_fibrous_** scar tissue
122
What is the process of repair?
Fibroblasts produce collagen - strong scar type
Remodelling - reorganisation of collagen fibres for maximal tensile strength
123
What hinders repair?
General: poor nutrition (protein for collagen production), vit deficiency (C for fibroblasts=collagen production, A for epithelial regeneration), mineral deficiency, supressed inflammation
Local: poor blood supply, persistent foreign body, movement
124
What are some complications of repair?
Keloid formation (excess collagen deposition - scar tissue around site of original injury)
Contractures (fibrous scar tissue contracts as part of maturing process and across a joint can reduce mobility)
Impaired organ function (fibrous scars will cause loss of functional tissue, affecting organ function)
125
What are the sequelae of inflammation and healing?
Resolution and restoration of function - cellular regeneration to populate intact framework
OR
Repair with fibrous scar tissue - production of collagen by fibroblasts
126
What is a neoplasm?
New growth - abnormal mass of tissue, growth which is virtually autonomous and exceeeds that of normal tissue. The growth is uncoordinated and ***_continues after cessation of stimuli which initiated the change_***
127
What is the parenchyma?
Cancer cells that have been transformed
128
What is the stroma?
Tissue around cancer cells which consist of connective tissue, blood vessels, macrophages, lymphocytes which support the cancer cells
129
Nomenclature for cancers:
-oma if benign
Malignant: carcinoma if parenchymal, sarcoma if stromal
130
What are the names of some cancers of glandular tissues and stromal tissues?
GT: adenoma, cystadenoma, papilloma, polyp
ST: fibroma, lipoma, angioma, leiomyoma, osteoma/chondroma
131
What are the differences between malignant and benign tumours?
Differentiation: Anaplasia (MT), relatively defined (BT) - well defined is when you can recognise which tissue it came from
Rate of growth: BT are slower than MT
Local invasion: BT don't tend to infiltrate basal lamina, MT do
Metastasis: BT don't metastise
132
What are the mechanisms for metastasis?
Lymphatic, haematogenous, body cavities, contiguous (common border)
133
What are the routes for metastasis?
Lymphatic route: more common for carcinomas
Haematogenous route: more common for sarcomas but carcinomas can too - use veins rather than arteriesbecause walls are thinner
Body cavities: tumour extending through pleural cavities/pericardium/peritoneum and maybe even subarachnoid space
134
What are the most commoncancers for men?
Prostate
Lung
Colon/Rectum
135
What are the most common cancers for women?
Breast
Lung
Colon, Rectum
136
What is the epidemiology of cancer to do with age?
Incidence of cancer worldwide increases as people are living longer
137
What is the geography of cancer like?
Japan: stomach cancer higher than USA, but colon cancer much less
Melanoma more common in NZ/Aus cf Scandinavia
Hepatocellular carcinoma more common in Uganda (due to aflatoxin)
Oesophageal cancer (high incidences) in Iran and China due to nitrates in soil and abrasives in diet
138
What are the three main mechainisms for hereditary genetics of cancer?
Autosomal dominant inherited cancer syndromes - single mutant gene responsible: retinoblastoma, familial adenomatous polyposis
Defective DNA repair mechanisms - Autosomal recessive: xeroderma pigmentosum (susceptible to skin cancers)
Familial cancer syndromes - combination of genetic defects: multiple endocrine neoplasia, BRCA
10% of cancers
139
What are the mechanisms for non-hreditary cancers?
Risk factors - e.g. liver cirrhosis and hepatocellular carcinoma, ulcerative colitis and colon cancer
Inflammation and cytokines - tumours tends to grow where inflammation is present as it creates genomic stress and mutations
140
What environmental factors can lead to cancer?
UV light, occupational agents (asbestos), alcohol, smoking, infections (viruses: HPV, HBV)
141
What is carcinogenesis?
Formation of cancer - tends to involve accummulation of multiple mutations
Multi step process, with malignancy acquired in a step-wise fashion "tumour progression"
142
What is the process of carcinogenesis? (image version)
143
What is the process of carcinogenesis? (typed version)
DNA damaged caused by carcinogen not repaired due to inherited gene mutation affection DNA repair or affecting cell growth/apoptosis \> mutation in genome of somatic cells leads to activation of oncogenes and inactivation of tumour suppressor genes (both lead to unregulated proliferation) or to alterations in apoptosis regulating genes so apoptosis decreases \> all this leads to **clonal expansion** (with angiogenesis, escape from immunity and additional mutations) \> tumour progression \> malignant neoplasm \> invasion and metastasis
144
What are the classes of carcinogens?
Chemicals, viruses, ionising/non-ionising radiation, hormones, bacteria/fungi/parasites, miscellaneous
145
What are chemical carcinogens?
Have no common structural features, need metabolic conversion from inactive procarcinogen to an active ultimate carcinogen
146
What are the major classes of chemcal carcinogens?
Hydrocarbons, amines, nitrosamines, azo dyes, alkylating agents
147
How do chemical carcinogens act?
Some act directly without conversion, some need appropriate enzyme present on skin for tumour to occur at that site, and others need metabolic conversion in the liver
148
What are oncogenic viruses?
Generally affect the young and immunosuppressed
Known: Epstein-Barr virus (Burkitt's lymphoma), HPV (cervical cancer), Hep B virus (Hepatocellular carcinoma)
149
What are the mechanisms for oncogenic viruses?
Viral DNA incorporated into host cell DNA or oncogenic RNA viral genome is transcribed into DNA by enzymes prior to incorporation
150
List examples of DNA oncogenic viruses, RNA oncogenic viruses and bacterial carcinogens
DNA: HPV, HBV, EBV, HHV8 (Kapposi's sarcoma)
RNA: HTLV-1 (causes leukaemia)
Bacterial: Helicobacter pylori (gastric carcinoma and lymphoma)
151
What is the carcinogen factor of radiation?
UV: Basal cell carcinoma, squamous cell carcinoma, myeloid metaplasia (?)
Ionising electromagnetic radiation: increase in leukaemia and solid tumours
152
What are the carcinogens in fungi, hormones and miscellaneous?
Fungi: aspergillus flavus causes liver cancers
Hormones: oestrogens can cause breast/endometrial cancer
Miscellaneous: asbestos, vinyl chloride, metals like nickel
153
What are the 4 classes of regulatory genes in carcinogenesis?
Oncogenes - growth promoting genes
Tumour suppressor genes - growth inhibiting genes
Apoptosis - genes regulating programmed cell death
DNA repair genes
NB: cancer occurs due to failure in regulation: failure in DNA repair/control growth of cells/regulate apoptosis
154
How are oncogenes derived?
From genes reguating normal cellular growth - examples related to tumours: Burkitt's lymphoma (Myc), neuroblastoma (N-myc), mantle cell lymphoma (CyclinD1)
155
List some examples of tumour suppressor genes
Regulate normal cell growth - ***_Rb gene_*** (13q) in genetically inherited retinoblastoma (40%)
P53 commonly mutated in cancers (50%)
BRCA-1 and BRCA-2 breast cancers are familial
156
What are anti-apoptosis genes?
Anti-apoptotic genes formed by mutation won't cause the cell to kill itself as apoptosis is prevented - Bcl-2 family regulates apoptosis
Bcl-2 is upregulated in lymphomas and other somatic malignancies
157
What are DNA repair genes?
They aren't directly oncogenic - genomic instability syndromes are inherited mutations in DNA repair genes
They act by permitting mutations to occur during cell cycles
158
List the 3 types of DNA repair genes
Mismatch repair, nucleotide excision repair and recombination repair
159
What are the clinical effects of tumours?
Benign and malignant both affect host, can cause anxiety about lumps and bumps
Related to location - pressure, ulceration, bleeding, infection
160
What does metabolic cancer cachexia cause?
Mediated by TNF, causes: ^ basal metaboic rate and decreases fat and muscle bulk
161
List 4 paraneoplastic syndromes
Endocrinopathies, hypercalcaemia, thrombotic diathesis, acanthosis nigricans (brown/black hyperpigmentations of the skin - usually found in folds of neck/groin/naval/ forehead)
162
How do we test for cancer?
Tumour markers and blood serology for presence of cancer
Biopsy/fine needle aspiration for extraction of tisse/fluid to test for cancer
For metastasis check: CT, MRI, PET used
163
How is cancer tested for in the lab?
Cytology fine needle aspiration, histology (core/incisional/excisional biopsy)
Other methods: tumour typing, immunocyto/histochemistry, flow cytometry, molecular methods (PCR, FISH, DNA microarrays, spectral karyotyping, tumour markers)
164
What is histological classification of cancers?
Low or high grade - based on degree of **differentiation**
165
What is the staging classification of cancers?
MOST IMPORTANT PARAMETER - combines clinical, radiological and pathological findings
## Footnote
Main: TNM - size of 1ry **_T**_umour, has it spread to lymph _**N**_odes, has it _**M_**etastasised?
Other systems: DUKE's (colorectal), FIGO (ovarian), Ann Arbor (lymphoma)
166
Which cancers are screened for in the UK?
Cervical, breast, colorectal
167
What is needed for a screening programme to be successful?
Reliable prediction of tumour behaviour, treatment available, target popn large enough for expense, cost-effective and reliable
168
What is the policy for cancer screening/prevention?
Detect cancer at pre-invasive stage/early
169
What prevention methods are used for cancer?
Vaccines: HPV (cervical) and HBV (liver)
170
What is an oedema?
An abnormal increase in interstitial fluid
171
When does fluid move from plasma to interstitium?
Capillary hydrostatic pressure \> plasma oncotic pressure + tissue hydrostatic pressure
172
What are the 3 forces involved in oedema?
Capillary hydrostatic pressure - pushes OUT of vessel, Plasma oncotic pressure - pulls IN to vessel (exerted by plasma proteins), Tissue hydrostatic pressure - pushes IN to vessel
173
What are the causes of oedema?
Increased cap. HySt P (venous obstruction, congestive cardiac failure)
Decreased Cap. Onc P (nephrotic syndrome, cirrhosis, malnutrition)
Inflammation (^ vasc. permeability facilitates movement of fluid into interstitium)
Lymphatic obstruction (Most common - lymphoedema, filariasis)
174
What is the cause of pulmonary oedema?
Raised HySt P in pulmonary capillary bed - Left ventricular failure is most common cause
175
Why is left ventricular failure the most common cause of pulmonary oedema?
LVF causes ^ pressure in LA, which causes back pressure into capillaries, pushing water into interstitial space
Fluid accumulates in interstitial space and spills over into alvolar spaces - **_Cardiogenic pulmonary oedema_**
176
What is another cause of pulmonary oedema (not cardiogenic PO)?
Non-cardiogenic PO caused by increased permeability - known as Acute Resp Distress Syndrome - commonly seen in injecting drug users, caused by sepsis, shock and trauma
Can be chronic or acute with Dyspnoea as main symptom (worse when lie flat due to fluid movement - orthopnea)
Fluid collection in lungs predisposes to bacterial infection - pneumonia
177
What are the 4 types of cerebral oedema?
Vasogenic, Cytotoxic, Osmotic and Interstitial
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What is vasogenic cerebral oedema?
Physical breakdown of blood-brain barrier - caused by trauma, tumours
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What is cytotoxc cerebral oedema?
Derangement of Na/K pumps - common in ischaemic strokes, ^ in Na in cells causes water to be taken up, so intracellular oedema is caused
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What is osmotic cerebral oedema?
Reduction in plasma osmolality - caused by Syndrome of Inapropriate ADH secretion caused by small cell lung carcinoma
ADH released -\> more water reabsorbed -\> decrease in plasma osmolality
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What is interstitial cerebral oedema?
Breakdown of CSF-brain barrier - caused by obstructive hydrocephalus (abnormal build up of CSF in brain due to blockage in flow of CSF)
CSF moves into interstitial space
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What are the symptoms of cerebral oedema?
Rise in intracranial pressure which can lead to brain herneation and death
Leads to confusion, nausea and vomiting
To reduce ICP - raise head, induce dehydration w/drugs, surgical decompression
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What is the difference between osmola**R**ity and osmola**L**ity?
Osmolarity: no. of solute particles per LITRE
Osmolality: no. of solute particles per KILO
184
What is generalised oedema?
Severe GO = anasarca - widespread accumulation of fluid in subcutaneous tissues and serous cavities
NB: thumb print left if oedema
Causes the same as localised oedema
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What are the common causes of generalised oedema?
LVF - dependent oedema (accumulated in areas affeted by gravity)
Nephrotic syndrome - fuid accumulates in all parts of the body
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What is the mechanism of heart failure causing oedema?
Low renal blood flow\> release of Renin from kidneys \> Formation of AngII \> release of aldosterone from adrenal gland \> absorption of Na and water from kidneys \> generalised oedema
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What are the consequences of oedema in the peripheral setting?
Impaired wound healing
More prone to getting cellulitis
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What is thrombosis?
Abnormal blood clot formation in the circulatory system
189
How does thrombosis occur?
Vessel wall injury, stasis and hypercoagulability
190
How do vessel wall injuries lead to thrombosis?
Physical damage to endothelium exposes ECM and activates blood clotting cascade, endothelial dysfunction which causes alteration in formation of pro-coagulants and anti-coagulants
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How does stasis cause thrombosis?
Normal blood flow is laminar so platelets found at centre of vessel and not exposed to endothelium
Stasis causes platelets to be exposed to endothelium so more likely to form a clot AND can change dilution of blood clotting factor
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How does hypercoagulability cause thrombosis?
1ry - genetic disorder so more likely so form blood clots - Factor V Leiden
2ry - acquired so risk factors for developing thrombosis such as Obesity, neoplasia, oral contraceptive pill
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What are the types of thrombosis?
Cardiac, arterial, venous
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How does cardiac thrombosis form?
Stasis due to atrial fibrilation - LA thrombosis is usually due to atrial fibrilation
LV thrombosis due to prior myocardial infarction
IMPORTANT complication: Systematic embolisation
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How does arterial thrombosis form?
Almost always - Vessel wall injury caused by atheroslcerotic plaques
Stenosis (narrowing of artery due to thrombus) causes ischaemia of tissue supplied by artery
Occlusion(complete blockage of artery by thrombus) causes infarction of tissue supplied by artery
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How does venous thrombosis form?
Stasis and hypercoagulabilty - RF: age, obesity, malignancy, immobility, oral contraceptive pill
Most form DVT - with pulm embolism as main complication
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What are the 4 fates of the thrombus?
Propagation - BIGGER accumulating more fibrin and taking larger portion of vessel
Embolisation - dislodges and travels to distant site
Dissolution - destroyed by fibrinolytics
Organisation and recanaisation - Inflammation due to thrombus, so becomes more fibrotic and remodels \> lumen appears again allowing blood flow
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What is an embolism?
Detached intravascular solid/liquid/gaseous mass that is carried by blood to a site distant from its point of origin
199
What are emboli made of?
Most are fragments of dislodged thrombus but some are rarer such as fat, air, amniotic fluid and tumour
200
What are the types of emboli?
Venous, Pulmonary, Arterial, Cardiac
201
What is venous thromboembolism?
Most originate in deep veins (DVT), with pulmonary thromboembolism as major consequence
202
What is a pulmonary embolism?
Consequence depends of size and where it is lodged
Lodging on major pulm artery can cause instantaneous death, on bifurcation of a pulm artery called saddle embolus, in medium sized arteries cause breathlessness, in small arteries cause dizziness/chest pain/breathlessness
30% die with PE and risk of death increases with time taken for diagnosis
203
What is an arterial embolus?
Most originate in carotid arteries and are likely to affecct cerebral arteries causing STROKE
204
What are cardiac thromboemboli?
Most originate on LHS of heart and lodge in cerebral artery (stroke), mesenteric artery (bowel infarction), lower limb artery (acute lower limb ischaemia)
205
What is a haemorrhage?
Extravasation of blood due to vessel rupture
Can be external or enclosed within a tissue
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What are the causes of haemorrhage?
Trauma, intrinsic disease of vessel
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What is a haematoma?
Localised mass of extravasated blood that is relatively or completely combined within an organ/tissue
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How are haemorrhages classified?
By size - 1-2mm=petechiae, \> 3mm=pupura, 1-2cm=ecchymoses
Large accumulations in body cavities
209
What does the result of the haemorrhage depend on?
Volume and rate of haemorrhage and site
210
What risks does acute haemorrhage come with?
Hypovolaemia, shock, death
211
What does the type of vessel that is ruptured cause in haemorrhage?
Major vessel cause acute haemorrhage, small vessel can still be fatal if it occurs at a vital site
212
What hapens if a solid haematoma is formed in the cranial cavity?
Can be fatal by causing rise in intracranial pressure and tonsillar herniation (pushing cerebellar tonsils through foraemen magnum causing compression of brainstem
213
When does shock occur?
When tissue perfusion is insufficient to meet metabolic requirements
Characterised by hypotension - which if prolonged causes circulatory collapse leading to ischemia of various organs
Rapid treatment is required to restore circulatory status and prevent multiple organ failure
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Which are the most vulnerable organs to shock?
Kidneys, Bowel, Brain, Lungs, Heart
215
What is the eqn for mean arterial pressure?
MAP= CO X SVR (systemic vascular resistance)
216
What is the eqn for cardiac output?
CO=HR X SV
217
What is systemic vascular resistance?
Index of arteriolar constriction throughout the body
218
What are the 5 types of shock?
Hypovolaemic, cardiogenic, septic, anaphylactic, neurogenic
219
What is hypovolaemic shock?
Commonly due to loss of volume, caused by trauma/haemorrhage
Low blood vol \> low SV \> Reduced CO \> Reduced MAP, which body compensates with tachycardia, as ^ HR you try to maintain regular CO
220
What is cardiogenic shock?
Due to imparied cardiac function \> acute MI, cardiac tamponade (accumulation of fluid in pericardium resulting in compression of heart)
Heart doesn't work properly, so SV is reduce leading to shock
221
What is septic shock?
Result of inflammatory response, caused by vasodilation
Reduced SVR \> reduced MAP
222
What is anaphylactic shock?
Result of IgE mediated hypersensitivity, similar to septic shock
Causes: vasodilation, increased permeability
Reduced SVR \> reduced MAP
223
What is neurogenic shock?
RARE - occurs after trauma, result of injury to sympathtic pathways
Causes: loss of vasomotor tone (widespread vasodilation and reduced SVR)
No tachycardia to increase CO as sympathetic pathways are disrupted
224
What is an infarction?
Tissue necrosis due to ischaemia
225
When do infarctions occur?
Mostly due to obstruction of artery or venous obstruction and more rarely due to vasospasm and compression
226
What is a red and white infarct?
Red = haemorrhagic - affects organs with dual blood supply and generally caused by venous blood supply (small amount of blood supply to dead tissue so red)
White = anaemic - affects solid organs which have one blood supply (blood squeezed out when tissue dies)
227
How do infarcts heal?
By repair and although structural integrity is maintained, some permanent loss of functional tissue occurs
228
What factors influence development of infarction?
Nature of blood supply (lung/liver dual blood supply, kidney/spleen single, so kidney/spleen more susceptible)
Rate of development of occlusion (slow may give time for collateral vessels to form, providing alternate blood supply)
Vulnerability to hypoxia (neurones very, fibroblasts aren't)
O2 content of blood (anaemics have more chance of developing infarcts)
229
What are the 2 types of MI?
Transmural - entire wall affected, when complete blockage of vessel and omplete cessation of blood supply
Subendocardial - some myocardial tissue **underneath the endocardium**, has been affected by infarction, caused by drop in blood O2 or rapid drop in blood supply (blood loss)
230
What other consequences of MI are there?
Pericarditis, cardiac rupture
231
What does a cerebral infarction look like?
Wedge shaped area in the right middle cerebral artery area (which is a common area for infarctions)
232
What is a small bowel infarction?
Red infarct - surgical emergency and patients present with severe lactic acidosis
233
What is atherosclerosis?
Complex chronic disease whcih is the underlying cause of most vascular diseases
Accumulation of lipids and fibrous tissue associated with smooth muscle proliferation
Affects medium/large vessels
Symptoms begin to develop when \>60% occlusion
234
How does atherosclerosis develop?
From fatty streak into plaques within the intima
Endothelial damage \> macrophage infiltration, cytokine release \> cytokines recruit LDLs which become oxidised \> pro-inflammatory and drive progression of plaque \> smooth muscle cells migrate from tunica media to the lesion \> smooth muscle cells deposit collagen rich matrix that forms protective fibrous cap
235
What are the 2 types of plaque?
Stable: Less inflammation, well developed thick, fibrous cap, slow growing, less likely to rupture
Unstable: More inflammation, lipid rich necrotic core, thin fibrous cap, MORE likely to rupture
236
What diseases are caused by stable plaques?
Stable angina, chronic lower limb ischaemia
237
What diseases are caused by thrombosis overlaying an unstable plaque?
Unstable angina, MI, Cerebral infarction, acute lower limb infarction
238
How many people are infected by Helicobacter pylori?
20% of adults in developed countries
80% of adults in developing countries
Majority are asymptomatic
239
What complications does Helicobacter pylori cause?
Haemorrhage, Perforation, Obstruction, Cancer, acute/chronic inflammation, atrophy/metaplasia/dysplasia, neoplasia (carcinoma/lymphoma)
240
When does intestinal metaplasia and atrophy occur (Helicobacter pylori)?
Next stage of evolution of helicobacter - response to long term damage
Gastic metaplasia as goblet cells aren't normally found in stomach, atrophy present as cells are smaller, gastric mucosa thins and functional cells shrink
Causes: infection (helicobacter), chemical (bile acid reflux into stomach), autoimmune gastritis
241
Fun fact about Helicobacter:
Only bacterium which has a grade 1 classification as a carcinogen
Can cause adenocarcinomas and lymphomas
Has profound effect on epithelia and lymphocytes of stomach
242
What type of cancers are in the stomach?
Adenocarcinomas (90%) as stomach lined with glandular epithelium
Gastric cancer kills more people worldwide than lung cancer
243
What is a lymphoma?
Malignant tumour of lymphoid tissue - associated with helicobacter gastritis
244
What are the 3 major outcomes for atherosclerosis?
Occludes arteries slowly - angina, myocardial scarring, dementia, claudication
Occludes arteries suddenly - Plaque rupture \> thrombus/embolism, haemorrhages into plaques (MI, Stroke, gangrene of the bowel)
Weakens artery walls - aneurysms, thick atheromatous plaque in the intima reduces the diffusion of nutrients from inside the wall so atrophy of muscle fibres occurs, muscle fibres replaced by fibrous tissue
245
List the causes of thrombosis - Virchow's Triad
Stasis, hypercoagulability, Vessel wall injury
246
Give 2 places where thrombosis would cause death
Heart and brain
247
Give 2 risk factors for thrombosis
Age, obesity, oral contraceptive pill
248
Give 4 types of embolism less common than thromboembolism
Fat, air, amniotic fluid and tumour
249
An old lady gets a DVT after surgery on her sigmoid colon. Five days later she rings the hospital for help but is dead when they get there. Suggest/explain what happened from DVT to death.
The DVT broke off and was pumped around the circulatory system until it reached a pulmonary artery where it caused instant death
250
Define oedema and name 4 causes
An abnormal increase in interstitial fluid caused by: increased capillary hydrostatic pressure, decreased capilarry oncotic pressure, lymphatic obstruction, inflammation
251
Define infarction and suggest 2 causes
Tissue necrosis due to ischaemia caused by arterial/venous obstruction or vasospasm
