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Phase 2a Flashcards > Pathology > Flashcards

Pathology Flashcards

1
Q

2 types of autopsy? % of each one? 2 subtypes of medico-legal autopsies?

A

Hospital- less than 10%, need medical certificate of death, used for teaching, research and governance

More than 90%
Coronial- death is not due to unlawful action
Forensic- thought unlawful e.g. murder

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2
Q

Role of coronial autopsy is to answer what 4 questions?

A

Who was deceased? When did they die? Where did they die? How did their death come about?
Essential same role as coroner

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3
Q

3 reasons for being referred to a coroner?

A

Presumed natural- cause of death unknown, hasn’t seen doctor within 14 days prior to death, most common reason for referral
Presumed iatrogenic- peri/ postoperative, anaesthetic deaths, illegal abortions
Presumed unnatural- accidents, industrial death, suicide, unlawful killing e.g. murder, neglect, custody death

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4
Q

Who refers to a coroner?

A

Doctors- do not have statutory duty to refer, common law duty, GMC will provide guidance
Registrar of BDM- statutory duty to refer
Relatives, police

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5
Q

Histopathologist carries out what autopsies? Forensic pathologist?

A

Hopsital and coronial autopsies- natural deaths, drowning, suicide, accidents, road traffic deaths, fire deaths, industrial deaths, peri/ post op deaths

Coronial- homicide, death in custody, neglect, any above that may be due to action of third party

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6
Q

External examination identifiers in autopsy? What does evisceration involve?

A

Formal identifiers, gender, age, body habitus, jewellery, body modification, clothing
Disease and treatment, injuries
Y-shaped from behind ears down to clavicles then down to mid-line incision
Open all body cavities, examine all organs in situ, remove thoracic and abdominal organs, remove brain

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7
Q

Internal examination in autopsy looks at what organs? Avoid what organs?

A

Heart and great vessels, lungs, trachea, bronchi, liver, gallbladder, pancreas, spleen, thymus, lymph nodes, genitourinary tract- common for cancer, endocrine organs, CNS
Lower GI- infection risk

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8
Q

Acute inflammation is what and lasts how long? e.g.? What is inflammation? Pros and cons?

A

Initial and often transient series of tissue reactions to injury- from few hours to few days
Appendicitis
Local physiological response to tissue injury, not disease but instead usually manifestation of disease
Destruction of invading microorganisms and walling off an abscess cavity thereby preventing spread of infection
Abscess in brain acts as space-occupying compressing vital surrounding structures, fibrosis from chronic inflammation may distort tissues and permanently alter their function

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9
Q

2 components of acute inflammation? WBC cell recruited to tissue? 4 outcomes of acute inflammation? Involved in organisation?

A

Vascular- dilation of vessels, exudative- vascular leakage of protein-rich fluid
Neutrophil polymorph
Resolution- goes away, suppuration- pus formation e.g. abscess, organisation, progression to chronic
Healing by fibrosis- scar formation, substantial damage to connective tissue framework and/ or tissue lack ability to regenerate specialised cells

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10
Q

When fibrosis occurs in acute inflammation, macrophages remove what from damaged areas? Defect then becomes filled by what known as what? Granulation tissue then gradually produces what to form fibrous scar?

A

Dead tissues and acute inflammatory exudate
Ingrowth of specialised vascular connective tissue known as granulation tissue
Collagen

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11
Q

5 main causes of acute inflammation? What is tissue necrosis?

A

Microbial infections, hypersensitivity reactions, physical agents- trauma, ionising radiation, heat, cold, chemicals- corrosives, acids, alkalis, reducing agents, bacterial toxins
Ischaemic infarction

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12
Q

Bacteria form what to cause acute inflammation? Parasitic and TB inflammation are where what is important? How do corrosive chemicals provoke inflammation? Infecting agents may release what to lead directly to inflammation?

A

Exotoxins- specifically initiate inflammation
Endotoxins- associated with their cell walls
Hypersensitivity
Through gross tissue damage
Specific chemical irritants

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13
Q

What is tissue necrosis? The edge of a recent infarction often shows what?

A

Death of tissues from lack of oxygen or nutrients from infarction
An acute inflammatory response due to peptides released from dead tissue

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14
Q

5 macroscopic appearance of acute inflammation?

A

Redness- rubor, heat-calor, swelling- tumour, pain- donor, loss of function

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15
Q

Why would skin appear red? Increase in temp is seen only where? Due to what? Systemic fever results from what?

A

Due to dilation of small blood vessels within damaged area
In peripheral parts of body
Increased blood flow- hyperaemia, vascular dilation
Some of the chemical mediators of inflammation, also contributes to local temp

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16
Q

Swelling results from what? As inflammation progresses, formation of what contributes to swelling?

A

Oedema- fluid in extravascular space as part of fluid exudate and from inflammatory cells migrating into area
Formation of new connective tissue

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17
Q

Pain results from what? What chemical mediators are known to induce pain? What does pain inhibit?

A

Stretching and distortion of tissues due to inflammatory oedema and pus under pressure in abscess cavity
Bradykinin, prostaglandins and serotonin
Movement of inflamed area

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18
Q

In early stages of acute inflammation, what accumulates in extracellular spaces of damaged tissue? 3 main acute inflammatory responses?

A

Oedema fluid, fibrin, neutrophil polymorphs
Changes in vessel calibre, increased vascular permeability and formation of fluid exudate, formation of cellular exudate- emigration of NPs into EV space

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19
Q

In acute inflammation, what relax thereby increasing blood flow through capillaries contributing to redness and heat? What pressure increases in acute inflammation and what escapes into extravascular space? Net escape of protein-rich fluid called what? Fluid is called what?

A

Smooth muscle of arteriolar walls forming precapillary sphincters
Capillary hydrostatic pressure and plasma proteins- increases osmotic pressure there, so more fluid leaves
Exudation
Fluid exudate

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20
Q

3 main causes of increased vascular permeability? 4 stages of neutrophil polymorph emigration?

A

Immediate transient- chemical mediators e.g. histamine, bradykinin, nitric oxide, C5a, leukotriene B4 and platelet activating factor
Immediate sustained- severe direct vascular injury e.g. trauma
Delayed prolonged- endothelial cell injury e.g. X-rays and bacterial toxins

Margination, adhesion, emigration, diapedesis

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21
Q

In acute inflammation, loss of intravascular fluid and increase in plasma viscosity with slowing of flow allows what to happen? What is pavementing? Occurs when and only where?

A

Neutrophils to flow in plasmatic zone
Adhesion of neutrophils to vascular endothelium that occurs at site of acute inflammation
Early in response
Only in venues

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22
Q

Increased leucocyte adhesion results from interaction between leucocyte and what? Many classes of adhesion molecules- some are made more active by variety of what?

A

Paired adhesion molecules on leucocyte and endothelial surfaces
Chemical inflammatory mediators

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23
Q

Leucocytes migrates through walls of what, but do not commonly exit from where? How do neutrophils, eosinophil polymorphs and macrophages move in between endothelial cells?

A

Walls of venues and small veins, but do not commonly exit from capillaries

They insert pseudopodia, migrate through gap and then on through basal lamina into vessel wall

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24
Q

What is diapedesis? Large numbers of red cells in extracellular space implies what?

A

RBCs may escape from vessels, but in this case is passive and depends on hydrostatic pressure forcing red cells out
Severe vascular injury such as tear in vessel wall

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25
Q

Early in the acute inflammatory response, what 2 things are released by the original inflammatory stimulus? What does this cause? Overall effect of all these molecules?

A

Histamine and thrombin–> up-regulation of adhesion molecules on the surface of endothelial cells
Very firm neutrophil adhesion to endothelial surface

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26
Q

What are chemicals in acute inflammation known as? What 5 things do these cause?

A

Endogenous chemical mediators

Vasodilation, emigration of neutrophils, chemotaxis, increased vascular permeability, itching and pain

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27
Q

Best known chemical mediator in acute inflammation? What does this cause? Why is it able to have an immediate effect? Release is stimulated by what 2 complement components and what else?

A

Histamine
Vascular dilatation and the immediate transient phase of increased vascular permeability
Stored in preformed granules and can be released instantly
C3a and C5a and lysosomal proteins from neutrophils

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28
Q

Other chemical mediators in acute inflammation other than histamine? 4 enzymatic cascade systems in plasma? These are all interrelated and produce various what?

A

Lysosomal compounds, eicosanoids- type of prostaglandin, 5-hydroxytryptamine (serotonin,) chemokine (chemotactic)

Complement, the kinins, coagulation factors, fibrinolytic system–> inflammatory mediators

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29
Q

In tissue necrosis, enzyme capable of activating what are released from dying cells?Formation of antigen-antibody complexes can activate complement via what pathway? Endotoxins of gram-negative bacteria activate complement via what pathway?

A

Complement
Classical
Alternative

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30
Q

What do tissue macrophages do in acute inflammation? 2 most important cytokine released? They endothelial cells, fibroblasts and epithelial cells to secrete what? This does what? What arrive at the site of inflammation and on leaving blood vessels transform into what?

A

Secrete numerous chemical mediators when stimulated by local infection/ injury
IL-1 and TNF-alpha
MCP-1= attracts neutrophil polymorphs
Blood monocytes—> macrophages= more metabolically active, motile and phagocytic

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31
Q

Macrophages appear when but do not predominate until when? Responsible for what? Both them and neutrophils may discharge their what into the extracellular fluid, which digests what?

A

Within a few hours, do not predominate until later stages when neutrophils have diminished in number and macrophage population has enlarged by local proliferation
Clear away tissue debris and damaged cells
Lysosomal enzymes into the extracellular fluid–> digests inflammatory exudate

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32
Q

In acute inflammation, lymphatic channels become what as they drain away the oedema fluid of the inflammatory exudate? This drainage tends to limit what? Antigens are carried where for recognition by lymphocytes?

A

Dilated
The extent of oedema in the tissues
Regional lymph nodes

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33
Q

What oxygen-dependent agents do neutrophil polymorphs contain? Oxygen-independent?

A

Hydrogen peroxide- reacts with myeloperoxidase in cytoplasmic granules of neutrophil polymorph in presence of halide such as Cl-
Lysozyme (muramidase and lactoferrin)

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34
Q

Release of lysosomal products from the neutrophil polymorph in acute inflammation does what 3 things? Some compounds released do what or what? Lifespan, removal?

A

Damages local tissues by proteolysis by enzymes such as elastase and collagenase
Activate coagulation factor XII
Attracts other leucocytes to the area
Increase vascular permeability and others are pyrogens= induce systemic fever by acting on hypothalamus
1-3 days, most die locally and some leave via lymphatics, some are actively removed by apoptosis

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35
Q

Special macroscopic appearances of acute inflammation?

A

Serous inflammation- lots of fluid release, suppurative inflammation- lots of pus, membranous inflammation, pseudomembranous inflammation, necrotising inflammation (gangrenous)

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36
Q

Systemic effects of inflammation?

A

Pyrexia (fever)- NPs and macrophages produce endogenous pyrogens which act on hypothalamus to set the thermoregulatory mechanisms at higher temperature
Malaise, anorexia, nausea, weight loss- negative nitrogen balance
Lymph node enlargement
Splenomegaly- malaria, infectious mononucleosis
Increased WBCs in blood
Anaemia- blood loss into inflammatory exudate or because of haemolysis
Amyloidosis- elevating SAA may cause amyloid protein to be deposited in various tissues–> secondary amyloidosis

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37
Q

What is chronic inflammation? What is primary chronic inflammation?

A

Subsequent and often prolonged tissue reactions to injury following initial response
Lymphocytes, plasma cells and macrophages predominate
Usually primary, but does occasionally follow acute inflammation
e.g. leprosy
Primary= when there is no initial phase of acute inflammation

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38
Q

Most common acute inflammation that progresses into chronic inflammation? E.g. of chronic abscess?

A

Suppurative type- drainage of pus delayed, abscess= thick walls from granulation and fibrous tissues, stagnating pus becomes organised by ingrowth of granulation tissue, to be replaced by a fibrous scar
In bone- osteomyelitis, difficult to eradicate

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39
Q

What materials favour chronic inflammation? E.g. of recurring cycles of acute inflammation resulting in chronic inflammation?

A

Keratin/ fragments of necrotic bone, inert and resistant to action of lysosomal enzymes
Chronic cholecystitis due to gallstones

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40
Q

Macroscopic appearances of chronic inflammation?

A

Chronic ulcer- chronic peptic ulcer of stomach with breach of mucosa
Chronic abscess cavity- osteomyelitis
Thickening of wall of hollow organ
Granulomatous inflammation- granuloma forms (collection of epithelioid histiocytes)
Fibrosis- thickening or scarring of connective tissue
Becomes most prominent when most of of chronic inflammatory cell infiltrate has subsided

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41
Q

Microscopic features of chronic inflammation?

A

Cellular infiltrate consists characteristically of lymphocytes, plasma cells and macrophages
Few eosinophil polymorphs, NPs are scarce
Some macrophages may form multinucleate giant cells
May be new fibrous tissues from granulation tissue
Evidence of continuing destruction of tissue at same time as tissue regeneration and repair
Tissue necrosis- especially in granulomatous conditions such as TB

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42
Q

Evidence of repair in chronic inflammation? Lymphocyte help?

A

Angiogenesis, fibroblasts proliferate, macrophages migrate, capillaries sprout, collagen synthesis

B form plasma/ memory cells and antibodies
T= cytokine production leading to other cell activation–> increased vascular permeability

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43
Q

Macrophages are what in blood and becomes what in tissues? Promote and inhibit inflammation through release of what? What is a granuloma?

A

Monocytes and becomes macrophages in tissues
Pro and anti-inflammatory cytokines

An aggregate of epithelioid histiocytes

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44
Q

Commonest cause of granuloma? What stain identifies TB? Colour?

A

TB

Ziehl-Neelsen stain= bright red result

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45
Q

Features of epithelioid histiocytes? Measurement of angiotensin converting enzyme can act as marker for what?

A

Large vesicular and eosinophilic cytoplasm, elongated, tend to be in clusters, little phagocytic activity, adapted to secretory function- one product= ACE
Systemic granulomatous disease such as sarcoidosis

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46
Q

Presence of what 2 things is indicative of a parasitic infection? When are histolytic giant cells formed?

A

Granulomas and eosinophils
When 2+ macrophages engulf the same pathogen simultaneously–> multinucleate (little phagocytic activity and no known function) or when particulate matter that is indigestible by macrophages accumulates (silica/ bacteria that have cell walls containing mycelia acids and waxes)

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47
Q

Langerhans giant cells have what arrangement of nuclei? Characteristically seen in what condition? Appearance of foreign body giant cells?

A

Horseshoe arrangement at one pole of the cell
TB
Large cells with nuclei randomly scattered throughout their cytoplasm- seen in relation to particulate foreign body material

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48
Q

Appearance of Touton giant cells? Seen when?

A

Have central ring of nuclei, peripheral to which there is lipid material
When macrophages attempt to ingest lipids and in xanthomas/ dermatofibromas of the skin

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49
Q

What is resolution in relation to chronic inflammation? Repair?

A

Where the damaging factor is removed, the tissue is undamaged and able to regenerate (liver.)

Where the damaging factor is removed but there is tissue damage thus the tissue cannot regenerate (alcohol stops the liver from regeneration and causes cirrhosis)

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50
Q

What does healing by 1st intention involve? Healing by 2nd intention?

A

Incision, no tissue loss, fibrinogen release, edges joined by fibrin (forms clot,) replaced by collagen, structure and function restored.

Loss of tissue, gap filled with granulomatous tissue, adhesion of edges, organisation and fibrosis formation (areas of fibrous tissue–> big scar)

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51
Q

2 types of abnormal wound healing? Features of both?

A

Inadequate and excessive
Inadequate= poor blood supply, poor nutrition, wound infection, immunosuppression, diabetes, old age

Hypertrophic scars, excessive collagen, stays within original wound site
Keloid scars- excessive granulation tissue that expands beyond wound edges (genetic association and certain ethnic groups i.e. Afro-Caribbean)

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52
Q

E.g. of regenerating tissues? Non-regenerating tissues?

A

Hepatocytes (liver,) pneumocytes (alveoli lining,) blood cells, gut and skin epithelium, osteocytes (bone)

Heart, brain (post MI and cerebral infarct,) spinal cord (post trauma)

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53
Q

Labile cells have good capacity do what? Typical cells of this group? Stable cell populations divide at what rate? Good examples?

A

To regenerate e.g. surface epithelial cells, constantly lost from surface and replaced from deeper layers

Very slow rate normally, still retain capacity to divide when necessary e.g. hepatocytes and renal tubular cells

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54
Q

Regeneration of permanent cells? Good examples? Cells lost through injury or normal ageing replaced stem cell pool in many what populations? Stem cells found where in epidermis? In intestinal mucosa? In liver? Separate pool of stem cells where? Are able to seed into other what?

A

No effective regeneration e.g. nerve cells and striated muscle cells

In many labile and stable cell populations

In basal layer immediately adjacent to basement membrane, in hair follicles and sebaceous glands
Near bottom of crypts
Between hepatocytes and bile ducts
In bone marrow- these haemopoietic stem cells able to seed into other organs and differentiate locally into appropriate tissue

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55
Q

What is complete restitution? E.g.? At first what happens? When confluent layer has been formed? What are important control mechanisms in normal cells?

A

Loss of part of labile cell population- can be completely restored
e.g. minor skin abrasion- epidermis lost over limited area, but at margins of lesion remain cells that can multiply to cover defect
At first= cells proliferate and spread out as thin sheet until defect is covered
Stimulus to proliferate is then switched off= contact inhibition and controls growth and movement
Epidermis is rebuilt from base up until indistinguishable from normal= healing
Contact inhibition, neoplasia= lost

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56
Q

What is organisation? What is formed in the early stages, often on a scaffold of what? Dead tissue removed by what? Granulation tissue contracts and gradually accumulates what to form scar, which then undergoes what? Common consequence of what disease? Organised area is what compared to normal?

A

Repair of specialised tissues by formation of fibrous scar
Granulation tissue- on scaffold of fibrin, by macrophages and neutrophil polymorphs
Collagen–> scar, undergoes remodelling
Pneumonia
Firmer, often shrunken or puckered

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57
Q

What is granulation tissue a combination of? How do myofibroblasts form?

A

Capillary loops and myofibroblasts
Capillary loops- capillary endothelial cells proliferate and grow into area to be repaired and grow into vascular channels, arranged as loops arching into damaged area
Fibroblasts acquires bundles of muscle filaments and attachments to adjacent cells

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58
Q

Why is wound contraction important? What issues might this cause?

A

Important for reducing volume of tissue for repair- may be reduced by 80%
If tissue damage is circumferential around lumen such as gut, may cause stenosis or obstruction due to stricture
Tissue distortion–> permanent shortening of muscle= contracture
Burns to skin can be followed by considerable contraction, with resulting cosmetic damage and often impaired mobility

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59
Q

Process of healing of skin wound depends on what? What deposited locally will bind two sides of a wound together? By how many days strength of repair sufficient enough to enable removal of suture? Only residual defect?

A

Depends on size of defect
Fibrin
10 days- failure to reconstruct the elastic network in the dermis

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60
Q

In some circumstances, hepatic regeneration comes from what cells rather than hepatocytes? When may cirrhosis occur? When can there be substantial regeneration of the functioning liver?

A

Liver progenitor cells
If imbalance between hepatocyte regeneration and failure to reconstruct the architecture
Following the partial surgical resection of the liver

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61
Q

What is a thrombosis? What is a clot? 3 things pre-disposing to thrombosis? Where cells travel in centre of arterial vessels and don’t touch the sides?

A

Solid mass of blood constituents formed within an intact vascular system during life
Blood coagulated outside of the vascular system or after death
Change in vessel wall, change in blood flow and change in constituents in blood
Laminar flow

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62
Q

2 types of platelet granules? Each contain what?

A

Alpha and dense
Alpha- several substances for process of platelet adhesion to damaged vessel walls i.e. fibrinogen, fibronectin and platelet growth factor

Dense- ADP cause platelets to aggregate

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63
Q

Platelets activated and contents of granules released when come into contacts with what? How do they change their shape?

A

Collagen- may be found in damaged vessel walls
Change shape, extend pseudopodia, form mass that covers vessel wall defect until endothelial cells have regenerated and repaired vessel permanently

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64
Q

First stage of thrombosis? Both of these reactions involve what? Once clotting cascade started, there is formation of what?

A

Platelet aggregation- platelets release chemicals when aggregate which cause other platelets to stick to them, starts off cascade of clotting proteins in blood
Positive feedback loops
Fibrin- makes mesh in which RBCs become entrapped

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65
Q

An atheromatous plaque will result in what 2 things? Process of arterial thrombosis?

A

Change in the vessel wall and a change in blood flow–> thrombus
Slightly raised fatty streak on intimal surface of any artery such as aorta of atheromatous plaque, protrude into lumen, cause turbulence in blood flow, loss of intimal cells, fibrin deposition, platelet clumping due to collagen exposed
Platelet derived growth factor is released from alpha granules, causes proliferation of arterial smooth muscle cells
First layer= platelet layer, causes precipitation of fibrin meshwork on top, more turbulence etc.

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66
Q

What is propagation? Most venous thrombi begin where? Valves may be damaged by what? Greatest degree of turbulence where? When may thrombosis become a likely event?

A 
Thrombi grow in direction of blood flow
At valves 
Trauma, stasis or occlusion 
At upstream side of venous thrombus 
If BP drops during surgery or following MI then flow is slower, if elderly immobilised--> DVTs, relies on calf muscle contraction
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67
Q

Arterial and venous thrombi result in what?

A

Loss of pulse distal to thrombus, area becomes cold, pale and painful, tissue will die and gangrene results eventually
Tender area, general ischaemic pain as circulation worsens, area becomes reddened and swollen

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68
Q

Fate of thrombi?

A

May resolve as result of body dissolving it, may become organised into scar, intimal cells of vessel may proliferate and small sprouts of capillaries may grow into thrombus and later fuse–> larger vessels, fragments may break off to form emboli, affects some vital centre and causes death before body/ clinician can make effective response

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69
Q

What is an embolism? Solid mass most commonly what? Less common causes of embolus? Only way that venous emboli can arrive in arterial side of circulation?

A

A mass of material in the vascular system able to lodge in a vessel and block its lumen
Air, cholesterol crystals, tumour amniotic fluid, fat
If there is an arterial- venous communication such as perforated septum in heart- paradoxical embolus

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70
Q

Effects of pulmonary emboli?

A

Small- may occur unnoticed and be lysed within lung, may become organism and cause some permanent, though small, resp deficiency- may cause idiopathic pulmonary hypertension
Slightly larger- acute resp and cardiac issues resolve slowly, chest pain, breath shortness, risk of further emboli
Massive- sudden death, usually long from leg veins and are often impacted across bifurcation of one of major pulmonary arteries

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71
Q

Most thrombi that result in systemic embolism generally from where? In heart may form where? Another common cause of thrombosis within the heart?

A

From heart/ from atherosclerotic plaque
On areas of cardiac muscle that have died as result of MI since lost endothelial lining expose to collagen
AF- blood stagnates in atrial appendages, normal HR- may become fragmented and form emboli

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72
Q

What is ischaemia? Effects on tissues depends on what 2 things?

A

Reduction in blood flow to tissue or part of body caused by constriction/ blockage of blood vessels supplying it
Duration of ischaemic period
Metabolic demands of tissue- cardiac and cerebral neurons are most vulnerable

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73
Q

What is infarction? Usually caused by what? Most organs have what arterial supply? 3 organs with dual blood supply less susceptible?

A

Death (necrosis) of part of whole of organ that occurs when artery supplying it becomes obstructed
Usually macroscopic event from thrombosis of artery
End arterial supply- single artery supplying them
Liver, lung, brain

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74
Q

Many of tissue damage of ischaemic injury happens when? Why? What has been impaired? Appears to be trigger for what? What cells import their own intrinsic oxygen free radicals also?

A 
When perfusion is re-established 
Much of damage= oxygen dependent
Calcium transport out of cell 
Activation of oxygen-dependent free radical systems that begin clearing away of dead cells
NPs and macrophages
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75
Q

What is gangrene? 2 types?

A

When whole areas of limb/ region of gut have arterial supply cut off and large area of mixed tissue die in bulk
Dry- tissue dies and becomes mummified and healing occurs above it, dead area drops off, sterile process e.g. toes of diabetes
Wet- bacterial infection supervenes as secondary complication, spreads proximally and patient dies from overwhelming sepsis

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76
Q

What is a watershed area?

A

At the boundary of adjacent arterial territories e.g. splenic flexure of colon between territories of superior and inferior mesenteric arteries, regions of cerebral hemispheres at interface between territories of major cerebral arteries, myocardium between sub-endocardial myocardium and that which is perfused by the coronary arteries

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77
Q

Why can frostbite result in ischaemia and infarction?

A

Since the capillaries are damaged in exposed areas and thus construct severely so that the area they normally supply becomes ischaemic and infarcts

78
Q

What is disseminated intravascular coagulation (DIC)?

A

Thrombosis may become activated without effective counterbalance–> minute thrombi which may form throughout body, bleeding may occur at multiple sites due to consumption of clotting factors

79
Q

If the tissue has been perfused by blood that has already passed through one set of capillaries, what is this called? Normally drop in what across first set of capillaries? Reduction in what? This does what? E.g.?

A

Portal vascular arrangement
Intravascular pressure, reduction in oxygen saturation, rendering tissue perfused by the second set of capillaries vulnerable to ischaemic injury
Anterior pituitary, blood perfused hypothalamus
Renal tubular epithelium- blood from glomerular capillaries
Some parts of exocrine pancreas, blood already perfused islets of Langerhans

80
Q

Other causes of ischaemia and infarction other than thrombi?

A

Spasm- of smooth muscle in vessel wall, can be due to decrease in NO due to cellular injury/ loss, of coronary arteries–> angina

External compression- partially/ total occlusion, done intentionally during surgery by ligation to prevent haemorrhage from severed vessels , veins= more susceptible due to thin walls and low intraluminal pressure, in strangulated hernias/ testicular torsion and torsion of ovaries containing cysts or tumours

Other: steal, hyperviscosity, vasculitis

81
Q

When can ‘steal syndromes’ occur? This results when?

A

When blood is diverted from a vital territory
When proximal to an area of atheromatous narrowing thats insufficient on its own to produce ischaemia, arterial stream is diverted along another branch vessel to set increased demands of a competing territory/ lesion- territory supplied by the atheromatous vessel then becomes ischaemic, quite uncommon

82
Q

Ischaemia at arteriolar, capillary and venular level can result from what? Have most impact on blood flow where? Can occur in what condition as result of abnormally high what?

A

Increased whole blood viscosity
In small vessels
Myeloma- abnormally high conc of antibodies in the plasma and cylindrical shape of RBCs

83
Q

What is atherosclerosis? Plaques alone are what, even when what? Life-threatening ischaemic damage to vital organs can occur when?

A

Disease characterised by the formation of atherosclerotic plaques in intima of large (aorta) and medium-sized arteries, such as coronary arteries
Asymptomatic, even when they are present in large numbers
When occlusive thrombosis forms on spontaneously disrupted plaque (atherothrombosis)

84
Q

E.g. of acute obstructions of thrombi?

A

Cerebral infarction, carotid atheroma- emboli causing transient ischaemic attacks or cerebral infarcts, MI, aortic aneurysm, peripheral vascular disease, gangrene

85
Q

When do formation of plaques start? Earliest significant lesion called what? What is it? When full development? In patients at risk?

A

In young children, especially in societies with a high dietary fat intake
Fatty streak
Yellow linear elevation of the intimal lining and is composed of masses of lipid-laden macrophages
May disappear, but in patients at risk, they progress to atherosclerotic plaques
Late teens, from around age of 40 onwards development of atherosclerosis becomes more established

86
Q

What is a plaque composed of? What gives structural strength to the plaque? Produced by what cells? What cells reside in the fibrous cap? They are recruited from where?

A

Lesion with a central lipid core with a cap of fibrous tissue covered by arterial endothelium
Connective tissue mainly collagens- by smooth muscle cells (SMCs)
Macrophages, T lymphocytes and mast cells- from arterial endothelium, in advanced plaques from newly formed microvessels at base of atheroma

87
Q

What are plaques rich in? They are what lesions often bordered by what cells? What are ‘foam cells’?

A

Cellular lipids and cellular debris
Soft, semi-fluid, highly thrombogenic- rim of ‘foam cells’
Macrophages that have phagocytosed oxidised lipoproteins- have large amounts of cytoplasm with a foamy appearance

88
Q

What can be extensive and occurs in the late development of the plaque? May act as marker for what in angiograms or in CT images? Plaques tend to form where?

A

Dystrophic calcification can be extensive and occurs in the late development of the plaque
For atherosclerotic vessels disease
At arterial branching points and bifurcations

89
Q

Risk factors for atherosclerosis?

A

Hypercholesterolaemia (most important risk factors)
Can cause plaque formation and growth in absence of other known risk factors- lipids directly damage endothelial cells
Hypertension, diabetes, male gender, increasing age

90
Q

Plaque formation generally a what step process? 2 steps?

A

Two-step

First= injury to endothelium of arterial wall, second= tissue response of the vascular wall to the injurious agents

91
Q

What functional alterations do injured endothelial cells undergo? In advanced stages, what accumulate in the plaque tissue? How do lipid-laden macrophages die? Inflammatory response followed by what process?

A

Enhanced expression of cell adhesion molecules for monocytes, high permeability for macromolecules such as LDL, increased thrombogenicity
Macrophages and T cells
After phagocytosing LDL but eventually die through apoptosis- spilling lipid into ever-enlarging lipid core
Tissue repair

92
Q

Growth factors like what stimulate the proliferation of intimal smooth muscle cells and subsequent synthesis of collagen, elastin and mucopolysaccharide by smooth muscle cells? Results in formation of what? Which encloses what? Growth factors secreted by?

A

PDGF
Fibrous cap- encloses lipid-rich core
Platelets, injured endothelium, macrophages and smooth muscle cells

93
Q

Another important mechanism of plaque growth? Results from what? Large haemorrhage can cause what?

A

Haemorrhage- results from rupture/ leakage of microvessels within plaque, especially fully developed plaques
Rapid expansion of plaques and may produce clinical symptoms

94
Q

Stenosis of more than what % of vessel lumen leads to critical reduction of blood flow in distal arterial bed? What develops, especially during activity? When may ischaemic pain develop if stenosis severe? Large intraplaque haemorrhages may increase rate of what?

A

50-70%
Reversible tissue ischaemia e.g. angina
Even at rest
Rate of stenosis in a short time span

95
Q

Plaque rupture exposes what to the bloodstream? This leads to what? Total occlusion leads to what?

A

Highly thrombogenic plaque components (collagen and lipid debris)
Coagulation cascade and thrombotic occlusion of vessel lumen in very short time period
Irreversible ischaemia- causing infarction of tissue supplied by obstructed artery

96
Q

Complication that may arise from atherothrombosis? These will embolise to where? May cause what? Ruptured abdominal atherosclerotic aneurysm causes what?

A

Emboli- will embolise arterial bed distal to ruptured plaque, embolic occlusion of small vessels may cause small infarctions in organs, dangerous in heart
Retroperitoneal haemorrhage and death

97
Q

Preventative and therapeutic measures to atherosclerosis?

A

Smoking cessation, control of BP, weight reduction, low dose aspirin- inhibits aggregation of platelets, advised for people with clinical evidence of atheromatous disease
Statins- cholesterol reducing drug

98
Q

What is an aneurysm? Aortic aneurysm commonly develop in who? They may impair blood flow where to and may rupture in what?

A

A localised permanent dilation of part of the vascular tree, permanent dilation implies that the vessel wall has been weakened
Elderly patients
May impair blood flow to lower limbs and contribute to development of vascular disease
May rupture into retroperitoneal space

99
Q

What is an aortic dissection (dissecting aneurysm)? Can track back where and cause what?

A

Blood is forced through tear in aortic intima to create blood-filled space in aortic media
Into pericardial cavity, causing fatal haemopericardium or can rupture through aortic adventitia

100
Q

Berry aneurysms occur where? What replaces the normal muscular arterial wall? Lesions arise where and are more common in who? Results in what if ruptures?

A

In the circle of Willis
Fibrous tissue
At points of branching- more common in young hypertensive patients
Subarachnoid haemorrhage if ruptured

101
Q

What is a stroke? What is a transient ischaemic attack? Although they show complete resolution, they are risk markers for what?

A

Suddent event with disturbance of CNS functions due to vascular disease
Stroke that lasts less than 24 hours and that is associated with complete clinical recovery
For subsequent cerebral infarction

102
Q

Most cerebral infarctions occur within what territory? Particularly in distribution of what artery?

A

The internal carotid territory- particularly in the distribution of the middle cerebral artery

103
Q

Causes of strokes?

A

Arterial thrombosis occurring as complication of atheroma in intracrnaila/ extra cranial arteries supplying CNS
Embolic arterial occlusion occurring as complication of atheroma in extracranial vessels e.g. around carotid artery bifurcation/ mural thrombis in heart following MI
Head injury–> cerebral hypoxia, vascular occlusion or rupture
Subarachnoid haemorrhage following rupture of saccular aneurysm with vascular spasm
Generalised arterial disease
Critical reduction in blood flow/ arterial oxygenation
Venous thrombosis as complication of local sepsis/ drugs e.g. oral contraceptives

104
Q

Intracerebral haemorrhage occurs 80% of time where? Other places? Most occur in who? Haemotoma that forms as result of haemorrhage acts as what resulting in what? Most occur following rupture of what?

A

In basal ganglia
Brainstem, cerebellum and cerebral cortex
In hypertensive adults over 50
Space-occupying lesion resulting in rapid increase in intracranial pressure and herniation
Rupture of lenticulostriate branch of middle cerebral artery

105
Q

Subarachnoid haemorrhage occurs between what layers of cranial meninges? Haemorrhage here results in an increase in what? Occurs due to spontaneous rupture of what? Other causes?

A

Between arachnoid and Pia layers
Increase in pressure between layers–> pressure on underlying brain and intracranial vessels
Of saccular aneurysm on circle of Willis
Trauma, hypertensive haemorrhage, vasculitis, tumours, coagulation disorders

106
Q

What is apoptosis? This with mitosis ensures what? Characteristics?

A

Defined and programmed sequence of intracellular events leads to removal of cell without release of products harmful to surrounding cells
Programmed cell death
Ensures continuous renewal of cells- tissues more adaptable to environmental demands

Energy dependent, involves enzymatic digestion of nuclear and cytoplasmic contents, phagocytosis of resultant of breakdown products whilst still retained within cell membrane

107
Q

How is apoptosis different to necrosis? Apoptosis normal where? Defective apoptosis important in what? Disturbances play role in what other diseases?

A

Necrosis= unintended cell death in response to cell injury- mechanisms of apoptosis act to suppress inflammatory response triggered by necrosis
Normal in gut i.e. duodenum- individual cells of gut villi regularly apoptosis and then replaced from below
AIDs, neurodegenerative disorders, anaemia of chronic disorders

108
Q

Apoptosis triggered by what 2 signals? Inhibitors x4? Inducers?

A

Extracellular and intracellular signals
Growth factors, extracellular cell matrix, sex steroids, some viral proteins

GF withdrawal, loss of matrix attachment, glucocorticoids, some viruses, free radicals, ionising radiation, DNA damage, ligand-binding at ‘death receptors’

109
Q

2 main pathways of apoptosis pathways? Both converge upon final common pathway characterised by what? Intrinsic pathways response to what stimuli? What is p53?

A

Extrinsic and intrinsic
Activation of proteases and DNAases
Growth factors and biochemical stress e.g. DNA damage

Multifunctional protein which induces cell cycle arrest and initiates DNA damage repair

110
Q

What is the extrinsic pathways a specific mechanism for? Ligand binding at these promotes what?

A

For activation of apoptosis characterised by ligand-binding at death receptors on cell surface

Clustering of receptor molecules on cell surface- initiation of signal transduction cascade–> caspase activation
Immune system eliminates lymphocytes this way

111
Q

What is necrosis? Characterised by what? Induces inflammation and repair due to what? Forms of necrosis?

A

Traumatic cell death which induces inflammation and repair
Bioenergetic failure and loss of plasma membrane integrity
Due to rupture of plasma membrane and spillage of cell contents with some being immunostimulatory

Coagulative, liquifactive, caseous, gangrene

112
Q

Commonest form of necrosis? Occur where? Cause? Tissue texture? Disastrous consequences in what?

A

Coagulative
In most organs
By ischaemia
Following lack of blood, cells will retain outline as their proteins coagulate and metabolic activity ceases
Initially firm texture, become soft due to macrophage digestion
In heart following MI- risk of ventricular rupture

113
Q

Necrosis type in brain? Why?

A

Liquifactive- because of lack of any substantial supporting stroma; thus necrotic neural tissue may totally liquefy

114
Q

TB is characterised by what necrosis type? Bacteria commonly causes gangrene? Why affected tissue appears black?

A

Caseous- dead tissue is structureless like ‘soft cheese’
Whenever seen in biopsy, TB must be thought of

Clostridia, due to deposition of iron sulphide from degraded haemoglobin

115
Q

Types of disease development?

A

Congenital disease- genetic and non-genetic, present at birth
Acquired- causes by non-genetic environmental factors
Multifactorial disease- due to many different factors

116
Q

Congenital disease encompasses what things? 2 types of genetic inheritance? Non-genetic inheritance type?

A

Chromosomal disorders, hereditary and spontaneous genetic diseases, non-genetically determined failures of differentiation and morphogenesis
Inherited and spontaneous
Environmental- from environmental factors e.g. fatal alcohol syndrome since not genetic but present at birth

117
Q

E.g. of inherited diseases?

A

From inherited genetic abnormality e.g. CF, sickle cell anaemia- autosomal recessive, familial adenomatous polyposis- autosomal dominant, colour blindness- X-linked, Huntingdon’s- manifests later in life

118
Q

E.g. of spontaneous inheritance?

A

Caused by spontaneous mutation e.g. Down’s syndrome- trisomy 21= mental retardation, flattened facial profile and short hands
Edwards’ syndrome- trisomy 18= ear, jaw, cardiac and renal abnormalities
Patau’s syndrome- trisomy 13= microcephaly, cleft palate and abnormal ears

119
Q

E.g. of acquired disease? Multifactorial?

A

From non-genetic environmental factors e.g. TB, lung cancer, bone fracture, AIDs

Neural tube defects- spina bifida, anencephaly- absence of major portion of brain, hydrocephalus- build up of fluid in brain, cleft palate

120
Q

Response of individual cell to increased functional demand is to increase what? What is hypertrophy? e.g.?

A

Tissue or organ size by; hypertrophy, hyperplasia or combination of both

Increase in cell size without cell division e.g. muscles in athletes- both in skeletal muscle and in left ventricle, utrine smooth muscle at puberty and pregnancy- stimulated by oestrogens

121
Q

What is hyperplasia? Can only happen in what cells? e.g.?

A

Increase in cell number by mitosis
In cells that divide- myocardial and nerve cells cannot
e.g. bone marrow cells that produce RBCs in people at high altitude living, increased erythropoietin production
Of prostate smooth muscle either benign or cancerous

122
Q

What is atrophy? Occurs naturally for example when? What can cause it?

A

Decrease in size of organ/ cell by reduction is cell size and or/ reduction in cell numbers, often by apoptosis
During development of genitourinary tract when there is involution of Wollfian and Mullerian duct in females and males respectively
Limb immobilised in cast, loss of innervation of muscle, lack of nutrition may cause atrophy of adipose tissue, gut and pancreas

123
Q

What is metaplasia? Occurs in response to what? e.g.?

A

Change in differentiation of cell from one fully- differentiated cell type to different fully-differentiated cell type
Response to alteration in cellular environment e.g. ciliated resp epithelium of trachea and bronchi in smokers–> squamous epithelium
Epithelium of ducts of salivary glands and pancreas and bile ducts in presence of stone to squamous epithelium
Squamous epithelium of oesophagus due to prolonged exposure to stomach acid to columna= Barrett’s oesophagus

124
Q

What is dysplasia? Also refers to what?

A

Imprecise term for morphological changes seen in cells in progression to becoming cancer- on way to becoming
To lack of development i.e. dysplasia in bones whereby the bones simply haven’t developed properly

125
Q

Cell ability to do what decreases as we age? Cell type with greatest division potential? Ageing influenced by what factors? What is there at the tip of each chromosome? With each cell division what happens? Only in what 2 things are telomeres replicated by enzyme telomerase? Telomere length inherited from who?

A 
Decreases 
Fetal cells 
Genetic and environmental factors 
Telomeres- telomeres shorten 
Eventually so short that DNA polymerase is unable to engage with it and cell is incapable of further replication 
Germ cells and in embryos 
From father
126
Q

What is sarcopenia? Occurs when? Caused by what? Deafness due to loss of what in ear? Senile dementia due to what? Cataracts due to what?

A

Muscle loss due to ageing, from 40 onwards but accelerates significantly from 80 onwards, due to decreased GH, testosterone and increased catabolic cytokines
Loss of hair cells
Due to brain atrophy since nerve cells cannot replicate
UV light damage results in cross-linking proteins in eye

127
Q

Osteoporosis due to lack of what? What is dermal elastosis? Why immunity become impaired?

A

Lack of oestrogen as well as vitamin D and calcium in earlier life
Wrinkling caused by UV light damage resulting in less collagen and elastin in skin, more fragile
Immunological changes resulting in less production of immune cells such as T cells

128
Q

What is carcinogenesis? Only applies to what? What process type?

A

Transformation of normal cells to neoplastic cells through permanent genetic alterations or mutations
Only to malignant neoplasms
Multistep process

129
Q

What is a neoplasm? What 4 things is neoplasia?

A

Lesion resulting from autonomous or relatively autonomous abnormal growth of cells which persists after initiating stimulus has been removed- new growth

Autonomous, abnormal, persistent, new growth

130
Q

Neoplasms arise from what cells? Cannot arise from what cell type? Probability increases with number of what? What increase probability of mutational events?

A

Single cells that have become transformed by cumulative mutational events
From erythrocytes since don’t have a nucleus but can arise from precursors like erythroblasts
With number of cell divisions experienced by cell
Carcinogens

131
Q

What is a tumour? Includes what 4 things? Solid tumours consist of what 2 things? Features of neoplastic cells?

A

Any abnormal swelling, includes: neoplasm, inflammation, hypertrophy, hyperplasia
Neoplastic cells and stroma

Derive from nucleated cells, usually monoclonal, growth pattern is related to parent cell, continue to synthesise/ secrete cell products such as collagen, mucin or keratin, often accumulate within tumour

132
Q

Functions for stroma within tumour? 2 things found within neoplasms stroma? Always contain what which do what? Growth is dependent on what?

A

Provides mechanical support, intercellular signalling, nutrition to neoplastic cells
Fibroblasts and collagen
Blood vessels which perfuse the tumour
On its ability to induce blood vessels to perfuse

133
Q

Growth of tumour limited by what? Cease expanding when? Angiogenesis in tumours induced by what? Opposed by factors such as what?

A

Ability of nutrients to diffuse into it, when nodule has attained diameter of no more than 1-2 mm
By factors secreted by the tumour cells such as vascular endothelial growth factor (VEGF)
Angiostatin and endostatin which have potential in cancer therapy

134
Q

Tumours are classified according to what? 3 categories of behavioural classification?

A

Behaviour and histogenesis

Benign, borderline and malignant neoplasms

135
Q

Features of benign neoplasms?

A

Remain localised, slow growth rate, non invasive, do not spread to other body sites, close resemblance to normal tissue, developed by thin layer compressed connective tissue, often normal nuclear morphometry, necrosis rare, ulceration rare, outward growth creates exophytic lesion

136
Q

Bening neoplasms can still cause morbidity and mortality how?

A

Pressure on adjacent structures, obstruction to flow of fluid, production of hormone, transformation into malignant, anxiety and stress

137
Q

Features of borderline neoplasms?

A

Fairly rare, tend to defy precise classification e.g. some ovarian lesions

138
Q

Features of malignant neoplasms?

A

Invasive, not all metastasise but all are invasive, rapidly growing, irregular border, do not resemble parent cell, hyper chromatic nuclei, pleomorphic nuclei, necrosis is common, ulceration is common, malignant on epithelial/ mucosal surfaces invade underlying tissue this invasive inward direction of growth gives rise to endophytic tumour, in solid- tend to have irregular margins, often with tongues of neoplastic tissue penetrating adjacent normal structures= crab-like

139
Q

Malignant may cause death and morbidity how?

A

Destruction of adjacent tissue, metastases, blood loss from ulcers, obstruction of flow, hormone production, paraneoplastic effects, anxiety and pain- most not until late into disease

140
Q

What is histogenesis? Major categories of histogenic classification? Why is degree of classification of malignant tumours useful?

A

Specific cell/ origin of tumour
Epithelial cells–> carcinomas, connective tissues–> sarcomas, lymphoid–> only malignant neoplasms and/ or haemopoietic organs (forming lymphomas or leukaemias)
Correlates strongly with prognosis and may indicate most appropriate treatment

141
Q

Malignant tumours usually graded how x3? What are anaplastic tumours?

A

Grade 1= well differentiated- closely resembles parent tissue
Grade 2= moderately differentiated
Grade 3= poorly differentiated- most aggressive
Lack recognisable histogenic features- extremely aggressive e.g. carcinoma of thyroid

142
Q

2 types of benign epithelial tumours?

A

Papilloma- non- glandular non-secretory epithelium, prefix with cell type e.g. squamous, transitional
Adenoma-glandular/ secretory epithelium e.g. colonic adenoma and thyroid adenoma

143
Q

2 types of malignant epithelial tumours?

A

Carcinoma e.g. transitional cell carcinoma

Adenocarcinoma: of glandular epithelium e.g. of breast, prostate

144
Q

What does carcinoma in situ mean? Complete excision at this stage guarantees what? Detection of the is aim of what? May last how long before invasion commences?

A

Epithelial neoplasm exhibiting all features of malignancy, but not yet invaded through epithelial basement membrane separating from potential routes of metastasis e.g. blood vessels and lymphatics
Of population screening programmes for cervical and other carcinomas
Several years

145
Q

7 types of benign connective tissue and other mesenchymal tumour?

A 
Lipoma- of adipocytes 
Rhabdomyoma- of striated muscle 
Leiomyoma- smooth muscle cells 
Chondroma- cartilage 
Osteoma- bone 
Angioma- vascular 
Neuroma- nerve
146
Q

Malignant tumour of connective tissue and other mesenchymal always designated as what? 7 types?

A 
Sarcoma
Liposarcoma 
Rhabomyosarcoma 
Leiomyosarcoma 
Chondrosarcoma 
Osteosarcoma 
Angiosarcoma 
Neurosarcoma
147
Q

3 exceptions to naming connective tissue tumours? 3 malignant tumours that aren’t carcinomas or sarcoma?

A

Granuloma- chronic inflammation
Mycetoma- fungus in body Tuberculoma= mass of TB

Melanoma- of melanocytes
Mesothelioma- of mesothelial cells that secrete fluid
Lymphoma- of lymphoid cells, all are malignant

148
Q

Tumours named after the person who first discovered them?

A

Burkitt’s lymphoma- B-cell lymphoma caused by Epstein Barr virus
Ewing’s sarcoma- malignant of bone
Hodgkin’s lymphoma- malignant with presence of Reed-Sternberg cells
Kaposi’s sarcoma- from vascular endothelium, associated with AIDs

149
Q

What is a teratoma? Carcinosarcoma?

A

Neoplasm of germ cell origin that form cells representing all 3 germ cell layers of embryo
Mixed malignant tumours showing features of epithelium and connective tissue

150
Q

What is oncogenesis? What is carcinogen?

A

Refers to both benign and malignant tumours

Environmental agent participating in causation of tumours- either oncogenic (tumour/ neoplasm causing) or carcinogenic (cancer causing)
Act on DNA i.e. mutagenic

151
Q

% cancer risk that is environmental? Genetic? Why difficult to attribute environmental cause?

A

85% and 15%

Long latent interval of onset makes finding factor cause difficult

152
Q

5 pieces of epidemiological evidence of cancer causes?

A

Hepatocellular carcinoma- uncommon in UK and USA, common in areas with high hep B and C and mycotoxins

Oesophageal carcinoma- high in Japan, China, Turkey and Iran, due to carcinogenic chicken in J and C/ hot coffee in Turkey and Iran

Lung cancer- risk x26 with smoking

Bladder cancer- increased in those working with aniline dye and rubber industry= B-naphthylamine

Scrotal carcinoma- in chimney sweeps with soot exposure, carcinogen= polycyclic aromatic HC

153
Q

Carcinogens are not united by what? Necessary to screen all new what? Why not perfect to screen in non-human systems?

A

By any common physical or chemical properties–> drugs, food additives, potential environmental pollutants
Animals/ cultures may metabolise agents differently to humans, mutations in bacteria may not equal carcinogenecity but in humans they may

154
Q

5 classes of carcinogens?

A

Chemical, viruses, ionising and non-ionising radiation, hormones, parasites and mycotoxins, miscellaneous

155
Q

Features of chemical carcinogens?

A

No common structural features, some act directly, most require metabolic conversion from pro-carcinogens to ultimate carcinogen, enzyme that does this may ubiquitous or confined to certain organs

156
Q

Tumours associated with viruses tend to be more common in who? What favours viral oncogenesis? Viruses implicated in human carcinogenesis?

A

In younger people
Immunosuppression
Epstein-Barr virus linked to Burkitt’s lymphoma
Human papillomavirus linked to cervical cancer

157
Q

What UV light increases risk of SSC and BCC? Increased risk with what condition? Tissues more sensitive to ionising radiation? Carcinogenic effects of radiation are what?

A

UVB
Xeroderma pigmentosum- deficiency of DNA repair enzymes
Thyroid, breast, bone, haemopoietic tissue
Long-term

158
Q

2 e.g. of increased cancer risk with hormones? 2 cancers caused by parasites?

A

Oestrogen increased incidence of mammary and endometrial cancer
Anabolic steroids increases incidence of hepatocellular carcinoma
Bladder cancer, adenocarcinoma of bile ducts known as choangiocarcinoma

159
Q

2 e.g. of miscellaneous carcinogens? Host factors and diet causing cancer?

A

Asbestos–> malignant mesothelioma and carcinoma of lung, arsenic= carcinogenic

Race, diet, constitutional factors, diet, premalignant lesions, transplacental exposure, high fat/ red meat–> colorectal cancers
Alcohol–> breast/ oesophageal cancer
Dietary fibre–> protective against colorectal cancer

160
Q

Skin cancer uncommon in who? Oral cancer high in India and SE-Asia why? 2 e.g. of genes increasing cancer risk?

A

Black people- high melanin
Chewing of betal nut/ tobacco
BRCA1 and BRCA2–> breast cancer in women
RB1 gene= retinoblastoma

161
Q

What are premalignant lesions? e.g. x4?

A

Identifiable local abnormality that is associated with increased risk of malignant tumour developing at that site
Colonic polyps- bowel cancer, cervical dysplasia- cervical cancer, ulcerative colitis- bowel cancer, undescended testes= malignant tumours of testicles

162
Q

E.g. of transplacental exposure in the 1940s?

A

Some pregnant women at risk of miscarriage were given synthetic oestrogen compound to prevent abortion–> increased vaginal cancer in daughters

163
Q

What genetic alterations are need to transform normal cells into neoplastic cells?

A

Expression of telomerase, loss/ inactivation of both copies of tumour suppressor gene, activation or abnormal expression of oncogenes

164
Q

2 types of tumour suppressor genes (TSGs)?

A

Caretaker- maintain integrity of genome by repairing DNA damage e.g. BRCA1 and BRCA2
Gatekeeper- inhibit proliferation or promote death of cells with damaged DNA e.g. p53- arrest cell cycle in G1, apoptosis if extensive DNA damage
RB1- controls cell cycle G1/ S phase checkpoint

165
Q

5 types of oncoprotein molecule? How can oncogenes be activated?

A

Growth factors, receptors for growth factors, signalling mediator with tyrosine kinase activity, signalling mediatory with nucleotide binding activity, nuclear-binding transcription factor oncoprotein
Mutation so excessively active oncoprotein, excessive production of normal oncoprotein because of gene amplification or enhanced transcription

166
Q

What is the most important sole criterion for malignancy? When removing what should be done? 3 factors influencing tumour invasion?

A

Invasion
A wide margin should be taken around the invasive margin to ensure that tumour cells do not remain which might later result in local recurrence
Decreased cellular adhesion, secretion of proteolytic enzymes , abnormal or increased cellular motility

167
Q

What enzymes are among the most important proteinases in neoplastic invasion? Secreted by what? 3 major families? These are counteracted by what?

A

Matrix metalloproteinases
By malignant neoplastic cells, can digest surrounding connective tissue

Interstitial collagenases; degrade types I,II and III collagen
Gelatinases; degrade type IV collagen and gelatin
Stromelysins; degrade type IV collagen and proteoglycans
Tissue inhibitors of metalloproteinases (TIMPs)

168
Q

Invasion often occurs along tissue planes offering what? Tissues resistant to neoplastic invasion? Why is invasion relatively easy to recognise in epithelial tumours? Why not in connective tissue tumours?

A

Less resistance to tumour growth e.g. perineural and vascular lamina
Cartilage and the fibrocartilage of intervertebral discs
Basement membrane serves as clear line of demarcation between tissue boundaries
Unless there is clear evidence of vascular or lymphatic permeation, other features like mitotic activity usually assessed for prognosis

169
Q

What is metastasis? What word is used to denote extensive metastatic disease? What never metastasises? What normally metastasises to the lung? What has an extremely low survival rate?

A 
Process whereby malignant tumours spread from their site of origin (primary tumour) to form other tumours (secondary tumours) at distant sites 
Carcinomatosis
BCC 
Liposarcoma 
Anaplastic carcinoma of thyroid
170
Q

Only what have the properties necessary to complete the sequence to form a metastatic tumour? 6 steps to doing so? What must occur if a nodule larger than a few millimetres forms?

A

Only a proportion of neoplastic cells
1) Detachment of tumour cells from their neighbours
2) Invasion of the surrounding connective tissue to reach conduits of metastasis i.e. blood and lymphatic vessels
3) Intravasation into lumen of vessels
4) Evasion of host defence mechanisms, such as NK cells in the blood
5) Adherence to endothelium at a remote location
6) Extravasation of cells from vessel lumen into surrounding tissue
Angiogenesis

171
Q

3 routes of metastasis? What is haematogenous route of metastasis? 4 organs commonly involved? Bone is site favoured by haematogenous metastases from what 5 carcinomas?

A

Haematogenous, lymphatic and transcoelomic
By bloodstream to form secondary tumours in organs perfused by blood drained from tumour
Liver, brain, lung and bone

Lung, breast, prostate, kidney, thyroid

172
Q

Metastases are frequently what compared to primary tumours? Solid tumours rarely metastasise to where despite their rich blood supply?

A

Multiple, usually solitary

To skeletal muscle or spleen

173
Q

Regarding lymphatic mode of metastasis, tumour cells reach lymph nodes through what? Features of lymph nodes involved by metastatic tumours? Metastases here may interrupt what causing what?

A

Through afferent lymphatic channel
Usually firmer and larger than normal
Lymphatic flow—> oedema in territory that they drain

174
Q

Where does transcoelomic metastases collect and result in? Fluid is rich in what and may contain what? Also contains what? What may be due to involvement by any abdominal tumour? What are common consequences of carcinomas of breast and the lung? What prefer lymphatic spread at least initially? What prefer haematogenous spread?

A 
In pleural, pericardial and peritoneal cavities where this results in a neoplastic effusion (abnormal amount of fluid collecting between pleura, caused by tumour) 
Protein and fibrin 
Neoplastic cells causing effusion 
Peritoneal effusions 
Pleural and pericardial effusions 
Carcinomas
Sarcomas
175
Q

What is a tumour grade? Most important features contributing to the assessment of tumour grade? How should grading be determined?

A

An assessment of its degree of malignancy or aggressiveness (can be inferred from its histology)

Mitotic activity, nuclear size, hyperchromasia and pleomorphism, degree of resemblance to the normal tissue i.e. differentiation

By looking at what appears to be the least differentiated area as this is likely to contain the most aggressive clone or clones of tumour cells

176
Q

What is tumour stage? Determined by what 2 things? What does TNM refer to?

A

Extent of a tumours spread
Histopathological examination and clinical examination of the patient

T= primary tumour, suffixed by number= denotes tumour size, number varies according to organ harbouring the tumour
N= lymph node status, suffixed by number denoting number of lymph nodes/ groups containing metastases
M= anatomical extent of distant metastases
Higher number= larger tumour/ more nodes involved/ increased extent of distant metastases

177
Q

What are precursors of most if not all colorectal cancers? Mutations in what gene are responsible for familial adenomatous polyposis (FAP)? What is FAP? Results in what?

A

Adenomas
APC gene
Rare disease carried by either patient and transmitted in autosomal dominant pattern with both sexes being equally affected
Leads to numerous adenomas at early stage particularly in large intestine, but also small bowel, subsequently undergo malignant change with almost inevitable progression to adenocarcinoma by age of 35

178
Q

Oncogenes most frequently altered in colorectal cancer? Point mutations in KRAS most commonly in what 3 codons? In up to what % of colorectal cancer? Result in what?

A

KRAS and c-MYC
Codon 12, 13 and 61
In up to 50% of colorectal cancer
Induction of proliferation, prevention of apoptosis, promotion of; invasion, metastasis and neovascularisation

179
Q

Overexpression of what gene feature of most colorectal cancers? Encodes what?

A

c-MYC

Nuclear phosphoprotein that is required for DNA synthesis, increased expression–> increased cellular proliferation

180
Q

Other genes implicated in colorectal cancer?

A

MCC- cell cycle control
DCC- involved in apoptosis
TP53- holds cell cycles at G1/S to allow time for DNA repair or to initiate apoptosis

181
Q

Flow chart for treating tumours?

A

Biopsy path lab, diagnosis of cancer
Has it spread, yes= systemic chemo, no= surgery +/- lymph clearance
Micro-metastases still present= do extra radiotherapy/ chemotherapy

182
Q

Conventional chemotherapy is good for what? Inhibits and targets what?

A

Good for fast dividing tumours e.g. lymphoma, acute leukaemia, inhibits DNA synthesis and hits all dividing cells

183
Q

Targeted chemotherapy only hits what? e.g.?

A

Only hits cancer cells- increases effectiveness and decreases SE e.g. perception, monoclonal Ab, inhibits over-expressive Her-2 receptor thus decreasing transcription

184
Q

Tumours commonly metastasising to the lung? To the liver?

A

Sarcomas and any common cancers

Colonic, stomach, pancreas, carcinoid tumours of the intestine (small, slow growing that release serotonin)- all have portal- venous drainage

185
Q

What is adjuvant therapy?

A

Extra treatment given after surgical excision e.g. radiotherapy to breast after lumpectomy, adjuvant anti-oestrogen therapy, HER2 gene amplified

186
Q

What is the process of cancer transport?

A 
Cell invades BM, travels through EC matrix, breaks it down and uses its products to aid motility, then enters vessel (intravasation)
Evades host defence by aggregating w/platelets, shedding surface antigen leaving false trail and causes adhesion with other cells so continues unrecognised
Leaves vessel (extravasation), grows at metastatic site, undergoes angiogenesis, eventually outgrows and central necrosis usually present
187
Q

What is immunotherapy? 2 types?

A

Harnessing immune system to kill tumours
Active- vaccination, cytokine stimulation
Passive- adoptive cellular therapy (T cells) and anti-tumour Ab that has specific targets and prevents replication and transcription

188
Q

What is cell-based therapy?

A

Using living cells as therapeutic agents to activate pt immune system to attack the tumour

189
Q

What is a germline mutation? Somatic mutation?

A

Exists in sex/ germ cells, can be passed on to future generations, will have mutation in all the cells

Can spontaneously arise in any cell in body except germ cells at any time during patients life. limited to descendant of original cell that developed mutation, not present in other cells in patients body, cannot be passed from parent–> child

190
Q

What are there screening programmes for in the UK? How is cervical intraepithelial neoplasia detected?

A

Cervical, breast and colorectal cancer
By exfoliative cytology of the cervix; cells scraped from the cervix, washed, deposited on to glass slides, stained and examined by cytologist to look for neoplasms

191
Q

How can breast cancer be detected? What determines who should have colonoscopy to look for colorectal adenomas or cancers?

A

By regular screening by mammography, followed by diagnosis of any abnormalities by fine-needle aspiration cytology or biopsy
Testing faeces for occult blood

192
Q

Overall population benefits of early and precursor detection may be less than anticipated due to what 4 biases?

A

Lead time bias- earlier detection prolongs apparent survival time
Length bias- preferential detection of slow growing tumours with intrinsically better prognosis
Overdiagnosis bias- clinically relatively harmless
Selection bias- volunteers for screening are more at risk of good-prognosis tumours

Phase 2a Flashcards (14 decks)

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