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Semester 2 - alex > Mechanisms Of Disease > Flashcards

Mechanisms Of Disease Flashcards

1
Q

Define disease

A

Consequence of failed homeostasis with consequent morphological and functional disturbances

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2
Q

Give 5 reasons for cell injury/death

A 
Hypoxia
Toxins
Physical changes
Radiation
Micro organisms
Immune mechanisms
Dietary deficiencies / excess
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3
Q

Define hypoxia

A

Oxygen deficiency causing decreased aerobic oxidative respiration

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4
Q

What are the 4 main causes of hypoxia?

A

Hypoxaemic hypoxia- arterial O2 content is low
Anaemic hypoxia- decreased ability of haemoglobin to carry O2
Ischaemic hypoxia- interruption to blood supply
Histiocytic hypoxia- inability to utilise O2 in cells due to disabled oxidative phosphorylation enzymes

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5
Q

How can the immune system damage cells?

A

Hypersensitivity reaction- secondary result of overly vigorous immune reaction
Autoimmune reaction- failure to recognise self/non-self

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6
Q

What are the principle structural targets for cell damage?

A

cell membranes
nucleus
proteins
mitochondria

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7
Q

The build up of what inorganic ion is thought to be the cause/indicator of irreversible cell damage?

A

Ca2+

Increases amount of ATPase, Phospholipase, Protease, Endonuclease…

(See lecture 1 slide 17)

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8
Q

What is a free radical?

A

A reactive oxygen species.

Single unpaired electron in an outer orbit- unstable

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9
Q

What structures do free radicals damage?

A

Lipids, proteins and nucleic acids.

They are mutagenic

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10
Q

What beneficial role do free radicals have in the body?

A

produced by leucocytes to kill bacteria and used in cell signalling

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11
Q

What is caused in the body if free radicals are in excess?

A

Oxidative stress

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12
Q

Why is it important to remove H2O2 and O2 in the Haber-Weiss and Fenton reactions?

A

They can combine to form harmful OH radical

oxidative phosphorylation also produces H2O2 and O2

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13
Q

What does acute inflammation do?

A

limit tissue damage

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14
Q

What causes acute inflammation?

A 
Microbial infection
Necrosis
Physical agents
Chemicals
Hypersensitivity reaction
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15
Q

What are the macroscopic features of acute inflammation?

A

Calor - heat
Rumor - Colour
Tumor - swelling
Dolor - pain

loss of function

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16
Q

How does acute inflammation occur? (microscopically)

A
  1. Vasodilation
  2. Gaps form in endothelium
  3. Exudation
  4. Margination and Emigration of neutrophils
  5. Macrophages and Lymphocytes
    Migrate in a similar way to Neutrophils.
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17
Q

What is the chemical mediator for vasodilation?

A

Histamine
Prostaglandins
C3a
C5a

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18
Q

WHat is the chemical mediator for Vascular permeability?

A

Histamine
Prostaglandins
Kinins

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19
Q

What is the chemical mediator for emigration of Leukocytes?

A

Leukotrienes
IL-8
C5a

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20
Q

What is the action of neutrophils?

A

phagocytose microorganisms, by making contact, recognising and internalising them. Phagosomes are then fused with lysosomes to destroy the contents.
may also release toxic metabolites and enzymes, causing damage to the host tissue.

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21
Q

What is Acute Phase Response?

A 
Decreased appetite
Raised heart rate
Altered ssleep patterns
Change in plasma concentration of Acute Phase Proteins
Can lead to shock
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22
Q

What are the systemic consequences of acute inflammation?

A

Acute Phase Response
Fever
Leukocytosis

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23
Q

What may happen after the development of acute inflammation?

A

Complete resolution
Continued acute inflamation with chronic inflammation
Chronic inflammation with fibrous repair, probably with tissue regeneration
Death

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24
Q

How are mediators inactivated?

A

Inhibition
deactivation
degradation
dilution in exudate

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25
Q

How is resolution of acute inflammation achieved?

A

changes reverse and vascular changes stop
Neutrophils no longer marginate
vessel permeability and calibre returns to normal
exudate drains via lymphatics
fibrin is degraded and neutrophils die

Damaged tissue may be able to regenerate, however if the tissue architecture is damaged, complete resolution is not possible

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26
Q

What are the possible complications of acute inflammation?

A

Swelling - blockage of tubes
Exudate - compression, serositis
Loss of fluid - burns
Pain and loss of function, especially if prolonged

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27
Q

What is an abscess and what are the consequences?

A

Inflammatory exudate forces tissues apart
Liquefactive necrosis in the centre

May cause high pressure causing pain
May cause tissue damage and squash adjacent structures

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28
Q

What is pericaritis and what are the consequences?

A

Inflammation of the serous cavity

Pericardium becomes inflamed and increases pressure on the heart

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29
Q

What is a skin blister and what are teh consequences?

A

Collection of fluid strips off overlying epithelium
Relatively few inflammatory cells therefore, clear exudate
Resolution or scarring

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30
Q

Name 3 disorders of acute inflammation

A

Hereditary angio-oedema
alpha 1 - antitrypsin deficiency
Chronic Granulomatous Disease

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31
Q

How may chronic inflammation arise?

A

May take over from acute inflammation if damage is too sever to be resolved within a few days
May arise de novo - Chronic inflammation, autoimmune condition, chronic low level irritation

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32
Q

What are the effects of chronic inflammation?

A

Fibrosis
Impaired function (rarely increased)
Atrophy
Stimulation of immune response

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33
Q

What cells are involved in chronic inflammation?

A 
Macrophages
Lymphocytes
Eosinophils
Fibroblasts/Myofibroblasts
Giant cells
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34
Q

What is chronic cholecystitis?

A

Repeated obstruction of the gall bladder with gallstones
Repeated acute inflammation leads to chronic inflammation and fibrosis of the gall bladder wall

Treated with surgical removal of teh gall bladder wall

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35
Q

What is gastric ulceration?

A

Ulceration due to an imbalance of acid production and mucosal defence

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36
Q

What causes acute gastric ulceration?

A

alcohol

drugs

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37
Q

What causes chronic ulceration?

A

Helicobacter pylori

Triple treatment: PPI inhibitor and 2 antibiotics

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38
Q

What is inflammatory bowel disease?

A

Inflammatory disease affecting the large/small intestine. Patients present with diarrhoea, rectal bleeding and other symptoms

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39
Q

What is ulcerative colitis?

A

Inflammation and ulcers develop on the inside lining of the colon resulting in pain, urgent and bloody diarrhoea, and continual tiredness.

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40
Q

What is crohn’s disease?

A

Crohn’s is a chronic inflammatory disease, which can affect the whole of the alimentary tract from mouth to anus. The inflammation extends through all layers of the gut wall (transmural) and is characteristically patchy in distribution (skip lesions) with areas of normal tissue between areas of inflammation.

Treated with lifestyle modifications, diet/hydration, immunosupression

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41
Q

What is liver cirrhosis?

A

Chronic inflammation with fibrosis causing disorganisation of architecture and attempted regeneration - cirrhosis

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42
Q

What are the causes of liver cirrhosis?

A 
alcohol
infection from HBV/HCV
immunological
fatty liver disease
drugs and toxins

Irreversible so treatment is prevention and transplant if necessary

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43
Q

What is Rheumatoid arthritis?

A

Autoimmune disease
Localised and systemic immune response causes chronic inflammation which leads to joint destruction
Can effect other organs and cause amyloidosis

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44
Q

What is granulomatous inflammation?

A

Chronic inflammation with granulomas

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45
Q

How do granulomas form?

A

Granulomas form when the immune system walls off something it cannot eliminate. They arise with persistent, low grade pathogenic stimulation and hypersensitivity

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46
Q

What are the main causes of granulomatous inflammation?

A

Mildly irritant foreign material
Infections
Sometimes the cause is unknown eg. in crohn’s disease

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47
Q

What causes TB?

A

Mycobacteria. Produce no toxins/lytic enzymes, they cause disease by persistence and induction of cell mediated immunity

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48
Q

What are the outcomes of TB?

A 
Arrest, fibrosis, scarring
Erosion into bronchus
Tuberculous empyema (collection of pus)
Erosion into blood stream
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49
Q

WHat is fibrous repair?

A

The replacement of functional tissue with scar tissue

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50
Q

What are the key components of fibrous repair?

A

Cell migration
Angiogenesis
ECM production/remodelling

Initiate fibrous repair to form granulation tissue

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51
Q

What cell types are involved in cell migration for fibrous repair?

A

inflammatory cells
endothelial cells
fibroblasts/myofibroblasts

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52
Q

What are the 5 steps of angiogenesis?

A
  1. Endothelial proteolysis of the basement membrane
  2. Migration of endothelial cells by chemotaxis
  3. Endothelial proliferation
  4. Endothelial maturation and tubular remodelling
  5. Recruitment of periendothelial cells
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53
Q

What is the role of the Extracellular Matrix?

A 
Supports adn anchors cells
Separates tissue compartments
Sequesters growth factors
Allows communication between cells
Facilitates cell migration
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54
Q

How is collagen synthesised?

A 
A
T
E
I
C
E
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55
Q

What diseases commonly cause a defect of collagen synthesis?

A

Scurvy
Ehlers Danlos
Osteogenesis imperfecta
Alport syndrome

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56
Q

What are the main constituents of ECM?

A

Glycoproteins and Proteoglycans - Organise and orientate the cell, support the cell (proteoglycans also regulate the availability of growth factor)
Elastin - Provides tissue elasticity

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57
Q

What are the stages in fibrous repair?

A

Inflammatory cells infiltrate the blood clot
Clot replaced by granulation tissue (angiogenesis occurs)
Maturation

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58
Q

What happens in the process of maturation in fibrous repair?

A 
Cell population falls
Collagen increases, matures and remodels
Myofibroblasts contract - reduces volume of defect
Vessels differentiate and are reduced
Left with fibrous scar
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59
Q

Describe regeneration

A

The replacement of dead or damaged cells by functional cells. Differentiated cells arederived from stem cells

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60
Q

What are stem cells?

A

Cells from which all cells are created - they have potentially limitless proliferation. Daughter cells remain as stem cells or differentiate to a specialised cell type

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61
Q

What is the difference between unipotent, multipotent and totipotent cells?

A

Unipotent - can only differentiate into 1 type of cell
Multipotent - can produce several types of differentiated cells
Totipotent - can produce any type of cell

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62
Q

Explain what a labile cell is.

A

A cell whose normal state is active cell division: G1-M-G1

Usually rapid regeneration

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63
Q

Explain what a stable cell is.

A

A cell usually in resting state

Rate of regeneration variable

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64
Q

What is a permanent cell?

A

A cell unable to divide and regenerate

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65
Q

What factors control regeneration?

A

Growth factors

Contact between basement membranes and adjacent cells

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66
Q

How does growth factor control cell regeneration?

A

Promotes proliferation in the stem cell population

Promotes expression of gene controlling cell cycle

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67
Q

How does contact between basement membranes and adjacent cells control cell regeneration?

A 
Signalling through adhesion molecules
Inhibits proliferation in intact tissue
Contact inhibition
Loss of contact promotes proliferation
Exploited in cancer
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68
Q

On what type of wound does healing by primary intention occur?

A

Incised wound with apposed edges

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69
Q

How does healing by primary intention work?

A 
Minimal clot/granulation tissue
Epidermis regenerates
Dermis undergoes fibrous repair
Sutures out at 5-10 days
Maturation of scar up to 2 years
Minimal contraction and scarring good
Risk of trapping infection - abscess
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70
Q

When does healing by secondary intention occur?

A

Infarct
ulcer
abscess
any large wound

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71
Q

Describe healing by secondary intention

A 
Unapposed edges
Large clot dries to form scab
Epidermis regenerates from the base up
Repair process produces much more granulation tissue - larger scar
Contraction to reduce volume of defect
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72
Q

What are the local factors influencing the efficacy of healing and repair?

A 
Type/Size/location of the wound
Apposition - lack of movement
Blood supply
Infection
Foreign material
Radiation damage
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73
Q

What general factors influence the efficacy of healing and repair?

A

Age
Drugs and hormones
General/specific dietary deficiencies
General state of health - specifically cardiovascular status

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74
Q

How does cardiac muscle heal?

A

Fibrous repair

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75
Q

How does bone heal?

A

Callus formation

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76
Q

How does the liver heal following acute damage?

A

regeneration

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77
Q

How does the liver heal following chronic damage?

A

cirrhosis. Liver hepatocytes have some regenerative capacity, but hepatocyte architecture does not regenerate. The imbalance between hepatocyte regeneration and the ability to regenerate architectureleads to cirrhosis and nodules

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78
Q

How are peripheral nerves repaired?

A

Wallerian degeneration

Proximal degeneration distal proliferation

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79
Q

How is the CNS repaired?

A

No regenerative capacity

Glial cells can proliferate - Gliosis

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80
Q

How is skeletal muscle repaired?

A

Has some regenerative capacity due to satellite cells

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81
Q

Define homeostasis

A

The maintenance of steady states within the body

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82
Q

What effects blood homeostasis?

A

Vessel walls
Platelets
Coagulation system
Fibrinolytic system

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83
Q

How does thrombin regulate the coagulation system?

A

positively feeds back on factors V, VIII, XI

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84
Q

What inhibits thrombin?

A

Anti-thrombin III
Alpha 1 anti-trypsin
Alpha 2 macroglobulin
Protein C/S

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85
Q

What do deficiencies in Anti-thrombin III or Protein C/S cause?

A

Thrombophilia/thrombosis

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86
Q

What is fibrinolysis?

A

The break down of fibrin by plasmin

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87
Q

What is fibrinolytic therapy?

A

Known as clot/thrombus busters
Eg. Streptokinase, activates plasminogen
Very drastic treatment, only used in serious situations

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88
Q

What is thrombosis?

A

The formation of a solid mass of blood within the circulatory system

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89
Q

What is Virchow’s triad?

A

Changes in blood flow
Changes in vessel wall
Changes in blood components

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90
Q

What are the effects of arterial thrombosis?

A

Ischaemia
Infarction
Depends on site and collateral circulation

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91
Q

What are the effects of venous thrombosis?

A

Congestion
Oedema
Ischaemia
Infarction

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92
Q

What are the outcomes of thrombosis?

A 
Lysis
Propargation
Organisation
Recanalisation
Embolism
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93
Q

What is lysis?

A

Complete dissolution of the thrombus
Fibrinolytic system active, blood flow re-established
Most likely to occur when thrombus is small

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94
Q

What is propagation?

A

he progressive spread of thrombosis - distally in arteries, proximally in veins

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95
Q

What is organisation?

A

A reparative process with ingrowth of firbroblasts and capillaries. Lumen still obstructed

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96
Q

What is recanalisation?

A

Blood flow reestablished but usually incomplete. One or more channels formed by organisation of thrombi.

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97
Q

What is Embolism?

A

The blockage of a blood vessel by a solid, liquid or gas at a site distant from it’s origin

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98
Q

Where will a thromboembolism from systemic veins lodge?

A

Lungs

99
Q

Where will a thromboembolism from the heart lodge?

A

From the aorta to the renal, mesenteric and other arteries

100
Q

Where will a thromboembolism from atheromatous carotid artery lodge?

A

Brain (stroke)

101
Q

Where will a thromboembolism from atheromatous abdominal artery lodge?

A

Legs

102
Q

What is a massive pulmonary embolism?

A

> 60% reduction in blood flow

Rapidly fatal

103
Q

What is a major PE?

A

medium blockage of blood vessel

Shortness of breath, coughing, blood in sputum

104
Q

What is a minor PE?

A

Small peripheral pulmonary artery blocked

Asymptomatic or minor shortness of breath

105
Q

What causes Deep Vein Thrombosis?

A 
Immobilisation/bed rest
Post-operative
Pregnancy/postpartum
oral contraceptives
severe burns
cardiac failure
Disseminated cancer
106
Q

What is the treatment for DVT?

A

IV Heparin - Anti-coagulant, co-factor for anti-thrombin III
Oral Warfarin - interferes with synthesis of vitamin K dependent clotting factors (slow effect so IV heparin needed at the beginning)

107
Q

How is fat embolism caused?

A

Trauma eg. bone fracture, laceration of adipose tissue, soft tissue trauma, burns

108
Q

What is fat embolism?

A

It is aggravated by local platelet and erythrocyte aggregation. The release of fatty acids from the fat globules also causes local toxic injury to endothelium. The vascular damage is aggravated by platelet activation and recruitment of granulocytes.

109
Q

What are the symptoms of fat embolism?

A

Rash
Shortness of breath
Confusion

110
Q

What is cerebral embolism?

A

Atrial fibrillation → Stasis → Thrombus

If in the left heart, can go to the brain and cause a stroke or transient ischaemic heart attack

111
Q

What is an iatrogenic embolism?

A

Embolism due to medical treatment

Eg. Air embolism from injection

112
Q

What is nitrogenic embolism?

A

Nitrogen bubbles form in the bloodwith rapid decompression - the bends

113
Q

What is Disseminated Intravascular Coagulation?

A

Pathological activation of coagulation mechanisms that happens in response to a variety of diseases.
Small clots form throughout the body, disrupting normal coagulation as they use up all the clotting factors
Abnormal bleeding occurs from the skin

114
Q

What triggers DIC?

A

Infection
Trauma
Liver disease
Obstetric complications

115
Q

What is the pattern of inheritance of Haemophilia?

A

X linked recessive therefore more common in boys

116
Q

What factor is defiicient in Haemophilia type A?

A

factor VIII

117
Q

What factor is deficient in Haemophilia type B?

A

factor IX

118
Q

What complications does haemophilia cause?

A

Haemorrhage into major joints, synovial hypertrophy, pain
Muscle bleeding causes pressure and necrosis of nerves
Can haemorrhage into retroperitoneum/urinary tract

119
Q

How is haemophilia treated?

A

Self administered factor replacement therapy

120
Q

What is thrombocytopenia?

A

Platelet count is way below the reference range

121
Q

What causes thrombocytopenia?

A

Failure of platelet production
Increase in platelet destruction
Sequestering of platelets - possibly caused by DIC

Usually accompanied by a bone marrow dysfunction

122
Q

What is an Atheroma?

A

The accumulation of intracellular and extracellular lipid in the intima and media of large and medium sized arteries
(arteries ONLY!)

123
Q

What is Atherosclerosis?

A

The thickening and hardening of arterial walls as a consequence of atheroma.

124
Q

What is arteriosclerosis?

A

The thickening of the walls of arteries usually due to hypertension or diabetes mellitus.

125
Q

What are the macroscopic features of atheroma?

A

Fatty streak

Simple/complicated plaque

126
Q

What early changes occur with the development of an atheroma?

A

Proliferation of smooth muscle cells
Accumulation of foam cells
Extracellular lipid

127
Q

What are the later changes that occur when an atheroma develops?

A

Fibrosis
Necrosis
Cholesterol clefts (cholesterol develops in the tissue, not the plaque)
+/- inflammatory cells

128
Q

How are foam cells made?

A

Macrophages phagocytose fat and become foam cells

129
Q

What cellular events occur as an atheroma develops?

A

Endothelial damage → Platelets → PDGF → Smooth muscle proliferation
Proliferation and migration of smooth muscle takes the lipid with it
Macrophages arrive and phagocytose the fat, becoming foam cells

130
Q

What effects does atherosclerosis in the coronary arteries have?

A 
Ishaemic heart disease
MI
Sudden death
Angina pectoris
Arrhythmia 
Cardiac failure
131
Q

What results from cerebral ischaemia?

A

Transient ischaemic atack - infarction of part of the brain (24hr symptoms)
Cerebral infarction - stroke
Multi-infarct dementia

132
Q

What are teh results of mesenteric ischaemia?

A

Ischaemic colitis
Malabsorption
Intestinal infarction
Anneurism due to the high pressure, hardening and weakening

133
Q

What would be the results of atherosclerosis in peripheral arteries?

A 
Preipheral vascular disease:
Intermittent claudication
Leriche syndrome
Ischaemic rest pain - IC in iliac artery (gluteal pain)
Gangrene
134
Q

Name some lifestyle risk factors for atheroma.

A 
Diet
Alcohol
Oral contraceptive
Lack of exercise
Stress
Cigarette smoking
135
Q

What makes you more susceptible atheroma?

A 
Lifestyle
Age 
Gender
Obesity
Hypertension
Hyperlipidaemia
Diabetes mellitus
Infection
136
Q

What is hyperlipidaemia?

A

High cholesterol. LDL transport cholesterol from the liver to the rest of the body therefore is the main contributing factor. HDL protective

137
Q

What are the symptoms/signs of hyperlipidaemia?

A

Familial hyperlipidaemia
Xantalasma
Corneal Arcus

138
Q

How can you try to prevent atheroma?

A 
Stop smoking
Modify diet
Treat hypertension
Treat diabetes
Lipid lowering drugs
139
Q

What is the “Unifying Hypothesis for Angiogenesis”?

A

Endothelial cells damaged
SMC stimulates - produce matrix material
Foam cells secrete cyotkines

140
Q

How does endothelial injury occur?

A

Raised LDL
Toxins
Hypertension
Heamodynaic stress

141
Q

What does endothelial injury cause?

A

Platelet adhesion, PDGF release, SMC proliferation and migration
Insudation of lipid, LDL oxidation, uptake of lipid by SMC and macrophages
Migration of monocytes into intima

142
Q

What does the secretion of cytosines from foam cells cause?

A

Further stimulation of SMC

Recruitment of other inflammatory cells

143
Q

What factors cause a person to be more susceptible to coronary heart disease?

A

Geography
Ethnicity
Genetics

144
Q

What are the risk factors of CHD?

A 
Smoking 
Gender
Hypertension
Diabetes
Alcohol
Infection
145
Q

How does normal endothelium prevent thrombosis?

A

Prostacyclin production
Thrombomodulin production
Prothrombin production

146
Q

What are the risk markers of CHD?

A

Apolipoprotein E genotype
Angiotensin converting enzyme
genetic polymorphism

147
Q

What is the stage of cell growth in the cell cycle referred to as?

A

G1

148
Q

What occurs in he restriction (R) point of the cell cycle?

A

Check point. Cell decides whether or not to divide and continue in the cell cycle.

149
Q

What determines whether or not the cell passes beyond the R point?

A

Phosphorylation of Retinoblastoma Protein (pRP)

150
Q

What is the phase of DNA replication in the cell cycle referred to as?

A

S phase

151
Q

What is the G2 phase in the cell cycle?

A

Preparation for cell division

152
Q

What is the period of mitosis referred to as?

A

M phase

153
Q

What is the normal state of labile cells?

A

Give cell division - G1 - M - G1

Usually rapid proliferation

154
Q

What is the normals taste of stable cells?

A

Resting state G0

Variable rate of proliferation

155
Q

What are permanent cells?

A

Cells unable to divide

156
Q

Define regeneration

A

Replacement of cell losses identical cells to maintain tissueor organ size.

157
Q

Define hyperplasia

A

Increase in tissue and organ size due to cell number

158
Q

Define hypertrophy

A

Increase in tissue or organ size due to increase in cell size

159
Q

Define atrophy

A

Shrinkage of a tissue or organ due to an acquired decrease in size and/or number of cells

160
Q

Define metaplasia

A

Reversible change of one differentiated cell type to another

161
Q

Define aplasia

A

Complete failure of a tissue/organ to develop

162
Q

Define hypoplasia

A

Incomplete development of a tissue or organ

163
Q

Define dysplasia

A

Abnormal maturation of cells within a tissue

164
Q

What type of cells does hyperplasia occur in?

A

Stable and labile only

165
Q

Where do the physiological causes of hyperplasia occur?

A

Proliferative endometrium

Bone marrow at altitude

166
Q

Where might the pathological effects of hyperplasia be seen?

A

Thyroid - goitre

167
Q

In what type of cells may hypertrophy and hyperplasia occur together?

A

Labile and stable (cells still capable of division)

168
Q

Where might physiological hypertrophy occur?

A

Skeletal muscle

Pregnant uterus

169
Q

Is the cause of ovarian atrophying post menopausal women pathological or physiological?

A

Physiological

170
Q

Where can pathologically caused atrophy occur?

A 
Muscle (denervation)
Cerebral atrophy (Alzheimer's disease)
171
Q

Where is metaplasia most commonly seen and why?

A

Epithelial cells to become more suited to a new environment eg. Smokers, pseudo stratified ciliated -> stratified squamous.

172
Q

What can metaplasia often lead to?

A

Dysplasia and cancer

173
Q

Define Neoplasm

A

An abnormal growth that persists after the initial stimulus is removed - a type of tumour. Can be benign or malignant

174
Q

What is a malignant neoplasm?

A

A neoplasm that invades surrounding tissue with the potential to spread to distant sites

175
Q

What is a tumour?

A

A clinically detectable lump or swelling. Neoplastic/non-neoplastic - NOT NECESSARILY CANCER

176
Q

What is a metastasis?

A

A malignant neoplasm that has spread from its original site to a new, non-contigious site- secondary cancer

177
Q

What is dysplasia?

A

A pre-neoplastic alteration in which cells show disordered tissue organisation. Not neoplastic as changes are reversible

178
Q

How do benign and malignant neoplasms differ?

A

Benign tumours grow in a confined local area and so have a pushing outer margin. THis is why they are so rarely dangerous. Malignant tumours have an irregular outer margin and shape and may show areas of necrosis and ulceration (if on surface)

179
Q

What do benign neoplasm cells look like under the microscope?

A

Closely resemble parent tissue - well differentiated

180
Q

What do malignant neoplasms look like under the microscope?

A

Range from well to poorly differentiated

181
Q

What are cells that do not resemble any tissue called?

A

anaplastic

182
Q

How do poorly differentiated neoplasmic cells appear under the microscope?

A

With worsening differentiation individual cells have an increased nucleus size and nuclear to cytoplasmic ratio, more mitotic figures and increasing variation in size and shape of cells and nuclei - pleomorphism

183
Q

What does grade indicate?

A

Differentiation - higher grade, more poorly differentiated. Dysplasia also represents altered differentiation

184
Q

What percentage of risk is due to extrinsic factors?

A

85%

185
Q

What are initiators?

A

Mutagenic agents

186
Q

What are promoters?

A

Agents which cause sustained and prolonged cell proliferation

187
Q

How do initiators and promoters cause proliferation

A

Initiator initially required and then promoters to sustain it. Result in an expanded, monoclonal population of mutant cells. Neoplasm can be inherited rather than from an external mutagenic agent

188
Q

What is progression?

A

The process through which a neoplasm emerges from a monoclonal population, characterised by the accumulation of yet more mutations

189
Q

What is a monoclonal collection of cells?

A

A collection of cells originating from a single founding cell

190
Q

What do genetic alterations effect?

A

proto-oncogenes and tumoursupressor genes

191
Q

What are oncogenes?

A

Abnormally activated proto-oncogenes favouring neoplasm formation

192
Q

What do tumour supressor genes do?

A

Normally supress neoplasm formation

193
Q

What are -oma cancers?

A

benign

194
Q

What are -carcinomas?

A

epithelial malignant cancers (90%)

195
Q

What are sarcomas?

A

stromal malignant neoplasm

196
Q

What are carcinomas in situ?

A

No ivasionofepithelial basement membrane

197
Q

What is an invasive carcinoma?

A

penetrated through the basement membrane

198
Q

What is leukaemia?

A

malignant tumour of blood forming cells arising in the bone marrow

199
Q

What is a lymphoma?

A

A malignant neoplasm of lymphocytes, mainly affecting lymph nodes

200
Q

From what type of cells do germ cell neoplasms arise?

A

From pluripotent cells

201
Q

Where do neuroendocrine tumours arise from?

A

From cells distributed throughout the body

202
Q

What are blastomas?

A

Formed from immature precursors. Mainlyoccur in children

203
Q

What is the morphology of a reversibly damaged cell?

A

Swelling - Na/k pump doesn’t work
Clumped chromatin due to reduced pH
Autophagy due to catabolic response from low available energy
Ribosome dispersion due to failure of energy-dependant process of maintaining ribosomes
Cytoplasmic blebs

204
Q

What in the morphology of irreversibly damaged cells?

A

Nuclear changes - pyknosis (shrinkage), karyorrhexis (fragmentation), karyolysis (dissolution)
Lysosome rupture - due to membrane damage
Membrane defects
Myelin figures due to membrane defects
Lysis of endoplasmic reticulum due to membrane defects

205
Q

What are the lethal features of a malignant neoplasm?

A

The ability to invade (infiltrates and destorys) and metastasis - The spread to distant sites leads to a greatly increased tumour burden. This can result in a vast number of parasitic malignant neoplasms

206
Q

How does a malignant cell get from a primary to secondary site?

A
  1. Grow and invade at the primary site
  2. Enter a transport system (vessel)
  3. Embolise
  4. Arrest
  5. Exit and grow at the secondary site to form a new tumour

At all points the cells must evade destruction by immune cells. It is an inefficient process (steps 3,4 and 5)

207
Q

What are the 3 important alterations for invasion?

A

altered adhesion - reduction in E-cadherin and altered integrin expression
Stromal proteolysis - must degrade basement membrane and stroma by altered expression of proteases, notably matrix metalloproteinases (MMPs)
Motility - reorganisation of actin by Rho (G protein)

208
Q

What is EMT?

A

Epithelial-to-mesenchymal transition.
Change in cell phenotype to create an appearance more like a mesenchymal cell than an epithelial cell
Crucial for invasion
Transient process

209
Q

What is a cancer niche?

A

Malignant cells take advantage of nearby non-neoplastic cells. These normal cells provide some growth factors and proteases

210
Q

How are neoplasms transported?

A
  1. Blood vessels
  2. Lymph
  3. Transcoelomic spread - fluid in body cavity
211
Q

What is extravastation?

A

Malignant cells leaving a vessel to the secondary site.

212
Q

What are micro metastases?

A

Surviving microscopic deposits that fail to grow - Many malignant cells lodge at secondary sites but these tiny cell clusters either die or fail to grow into clinically detectable tumours

213
Q

What is tumour dormancy?

A

An apparently disease free person may harbour many metastases.

214
Q

How may tumours be kept dormant?

A
  • Immune system
  • Decreased angiogensis
  • adapted for primary site and secondary site may be hostile
215
Q

How is a malignant relapse thought to be caused?

A

By dormant tumours (micrometastases)

216
Q

What determines the site of a secondary tumour?

A
  1. Regional drainage of blood, lymph or coelomic fluid
  2. The seed and soil phenomenon may explain the often unpredictable distribution. Due to interactions between malignant cells and the local tumour environment
217
Q

How do carcinomas tend to spread?

A

Via lymphatics first

218
Q

How do sarcomas tend to spread?

A

Via blood stream

219
Q

What are the common sites of blood borne metastasis?

A

Lung
Bone
Liver
Brain

220
Q

What neoplasms most frequently spread to bone?

A 
Breast
Bronchus
Kidney 
Thyroid
Prostate
221
Q

What do we mean by “personalities” of malignant tumours?

A

Soem are more aggressive and metastasise very early in their course e.g.. Small cell bronchial carcinoma.
Others almost never metastasise eg. basal cell carcinoma of the skin

222
Q

How is the likelihood of metastasis determined?

A

Size of the primary neoplasm. This is the basis of cancer staging

223
Q

How can the effects of a neoplasm on a host be classified?

A

The direct local effects which can be of the primary neoplasm and/or the secondary neoplasm(s) and those due to the indirect systemic effects

224
Q

What are paraneoplastic syndromes?

A

Indirect systemic effects of neoplasm, including effects of increasing tumour burden, secreted hormones and/or miscellaneous effects

225
Q

What factors effect benign neoplasms most?

A

Local effects from the primary

Hormonal effects

226
Q

What are the local effects of primary and secondary neoplasms due to?

A
  1. Direct invasion and destruction of normal tissue
  2. Ulceration at a surface leading to bleeding
  3. Compression of adjacent structures
  4. Blocking tubes and orifices
227
Q

What does increasing tumour burden lead to?

A

Parasitic effect on the host:

  • reduced appetite and weight loss
  • malaise
  • immunosupression
  • thrombosis
228
Q

Why do benign neoplasms typically produce hormones?

A

Well differentiated

229
Q

What are some miscellaneous systemic effefcts?

A

Neuropathies - affect the brain and peripheral nerves
Skin problems e.g.. pruritis and abnormal pigmentation
fever
myositis

Pathogenesis poorly understood

230
Q

What are the 5 leading behavioural and dietary risks that cause cancer?

A 
High BMI
Low fruit and veg intake
Lack of physical exercise
Tobacco use
Alcohol use
231
Q

What are the 3 categories of extrinsic factors causing cancer?

A

Chemicals
Radiation
Infection

232
Q

What is carcinogenesis?

A

Causes of cancer

233
Q

What has neoplasms caused by 2-mapthylamine shown?

A

!. THere is a long delay between carcinogen exposure and malignant neoplasm onset

  1. The risk of cancer depends on total carcinogendosage
  2. There is sometimes organ specificity for particular carcinogens
234
Q

What are complete carcinogens?

A

Carcinogens that act as both initiators and promoters

235
Q

What are the classifications of carcinogens?

A 
Polycyclic aromatic hydrocarbons
Aromatic amines
N-nitroso compounds 
Alkylating agents
Diverse natural products
236
Q

What are pro-carcinogens?

A

Chemicals only converted to carcinogens by the cytochrome P450 enzymes in the liver

237
Q

What is radiation?

A

ANy type of energy travelling through space. Can be mutagenic. Damage DNA directly or indirectly by generating free radicals.

238
Q

How is ionising radiation a carcinogen?

A

Strips electrons from atoms. Damages DNA bases and causes single and double strand DNA breaks

239
Q

How can infections be carcinogenic?

A

Directly affect genes controlling cell cycle
Indirectly cause chronic tissue injury - resulting regeneration acts either as a promoter for any pre-existing mutations or else causes new mutations from DNA replication errors

240
Q

What is the 2 hit hypothesis?

A

Explains the differences between tumours occurring in families and those occurring in the general population

Familial cancers - first hit through germline, affects all cells in the body, second hit, somatic mutation
Sporadic cancers - no germline mutation and so requires both hits to be somatic mutations and to occur in the same cell

241
Q

WHat are tumour suppressor genes?

A

Genes that inhibit neoplastic growth. Inactivate both alleles

242
Q

WHat are oncogenes?

A

Activated pro to-oncogenes that favour neoplastic growth (only one allele of each port-oncogene needs to be activated for neoplastic growth)

243
Q

Compare proto-oncogenes and tumour supressor genes

A

Proto-oncogenes can be activated to oncogenes which push the cell past the cell cycle restriction point
Tumour suppressors encode proteins with anti-growth effects

Semester 2 - alex (4 decks)

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