MOD Flashcards
(242 cards)
1
Q
What gives rise to a diseased state in the most general form?
A
Failure of homeostasis on a cellular level due to the distrubance to the cells environment that translates into the observed morphological and physiological changes.
2
Q
What are the two types of infact? and what gives rise to each type?
A
Red: Occurs when these is occlusion but there is a collateral blood supply/anastomoses which leads to extensive haemorage into the tissue. Loose tissue (like lungs) are prone to this and also when these is a high venous pressure/congestion.
White: Occurs only at end arteries (like in the conronary renal or retinal arteries)
3
Q
What is ischaemic necrosis?
A
Cell death caused by a lack of blood supply
4
Q
What are the types of hypoxia and their respective causes?
A
Hypoxemic- state of oxygen deficiency by there being a low oxygen content in the blood. (pulmonary effusion, low atmospheric oxygen content, reduced lung volume(congenitial, environmental) lung cancer)
Anemic hypoxia- Descreased ability to carry blood in the oxygen due to haemoglobin deficiency/impairment. (CO poisoning, iron deficiency)
-Ischemic hypoxia: occurs due to occlusion of blood flow to a particular tissue (can occur due to the vessell being blocked or damaged so thrombus, embolism, trauma, infection, low blood pressure).
-histiocytic: inability of cells to use the oxygen supplied to them (like cynanide poisoning)
5
Q
What are some common causes of cell injury?
A
radiation, trauma, extremes of heat, lack of metabolites, current, pressure, toxins, microorganisms, autoimmune activity,hypoxia.
6
Q
What is the result of cell injury?
A
it depends on the severity of the injury. slight injury will result in cell adaptation and severe injury will result in cell death.
7
Q
Define necrosis
A
all the cell changes that occur after localised cell death due to irreversible damage to the cell and its components.
8
Q
Define apoptosis
A
Apoptosis is individual controlled/programmed cell death that is induced.
9
Q
What are the features of apoptosis and sequalae?
A
single cells become intensiely eosinophillic and visible are nucelar fragments, cell shrinkage and then blebbing. This keeps the entire contents of the cell in vesicles that prevents leakage. These vesicles are then phagocytosed by macrophages or neighbouring cells. The lack of leakage.
10
Q
What are the features of necrosis and sequalae?
A
Cell damage: in the nucleus (pyknosis, karyolysis, karyorrhexis), swelling and lysis of cell components, myellin figures.
cell lysis: results in the cell contents passing into the surrounding tissue causing inflammation.
11
Q
What are the types of necrosis? giving examples of when these would occur
A
Liquifying- more proteases released then protein resulting in surrounding tissue being dissolved. Occurs in tissue that lacks substantial supporting networks like the brain.
coagulative-More protein denaturation
caseous-
Fat-
12
Q
What is the mechanism for apoptosis?
A
Apoptosis can be induced via either the intrinsic or extrinsic pathway. The intrinsic pathway.
intrinsic: DNA damage causes increase in mitochondrial permeability and the release of cytochrome c. This interacts with APAF1 and caspase 9 forming an apoptosome. This then activates a caspases.
Extrinsic: Binding of death ligands (trail) activates caspase activation.
13
Q
How are free redicals formed?
A
free radicals are formed by a number of mechanisms. NADPH oxidase on leukocytes create them as part of the bodies immune response, Ischaimia and reperfusion injury, radiation can ionise water forming the hydroxyl free radicals, Electrons can leak across in the inner mitochondrial membrane and result in the creation of.
14
Q
What are free redicals?
A
Free radicals are oxygen species with an unpaired electron making them hightly reactive.
15
Q
What is the action of free radicals on cells?
A
Free radicals tend to target proteins and the cell membranes. Hydroxyl free radicals are most damaging to cell lipids and there is no mechansim for terminating these.
16
Q
How do cells terminate free radicals?
A
Free radicals are terminated through a number of mechanisms. Firstly there are species within the body that can bind to free radicals like vitamins C, E and A.
There is a process of natural self termination through decay
There is also an enzyme system using SODs and Catalase to breakdown existing free radicals.
There are also storage proteins which bind transition metal elements preventing (in the case of iron) the heiber weiss and fenton reaction which create the hydroxyl radical).
17
Q
What are heat shock proteins and what is their role?
A
Heat shock proteins are a group of chaperone proteins that are expressed by cells in response to high temperature; they assist in the refolding of denatured proteins, not only as a result of heat but also in response to physical and chemical stresses. The consequences of protein misfolding can be severe and there are a number of diseases that can result from faulty folding. In many cases, including some forms of cystic fibrosis.
18
Q
What is ventilation/perfusion ratio and how can it effect blood oxygen saturation?
A
the ratio of oxygen in the lungs and blood supplied to the lungs. Optimally all blood should just be saturated with oxygen so if the blood flow through the pulmonary circulation increases or there is a decrease in oxygen uptake then it leads to a decrease in this value. The lower the value the lower the blood oxygen saturation.
19
Q
What is myxedema? how does it arise?
A
Deposition of mucopolysaccharides. In hypothyroidism it arises systemically but in hyperthyroidism (graves) it occurs specifically in the pretibial region.
20
Q
what are the inhibitors and inducers of apoptosis?
A
inhibitors: sex steroids, growth factors and cell matrix, Bcl-2
Inducers: Trail ligands, DNA damage, loss of growth factors, p53,
21
Q
What are the features of reversible cell injury in hypoxia?
A
low oxygen, decrease in oxidative phosporylation, decrease in ATP, increase in glycolysis so decrease in glycogen and increase in pH. Leads to chromatin clumping. Low ATP causes a detachment of ribosomes, decrease in protein synthesis and an increase in lipid deposition. There is a decrease in Na/K atpase and so there in an influx of water and this leads to cellular swelling, ER swelling, Mitochondrial swelling, and blebs.
22
Q
What are the features of irreversible cell damage in hypoxia.
A
There is a large influx of calcium ions (due to loss of NCX and no calcium atpase function). also there will be a release from the ER and mitochondrion. This leads to key cellular changes. damage to the chromatin and disruption to many cell processes.
23
Q
What are the biochemical consequences of excessive alcohol intake?
A
Damage to GI tract and so poor absorption of nutrients (folate, and vitamins resulting in folate deficiency beri beri and pelagra), The Liver gets damaged and so becomes leaky so liver enzymes (ALTs and ASL and Gamma-GT) can be tested for in the blood, there can also be deposition of collagen in the liver and fat (mallory’s hyline). This will eventually lead to cirrhosis
24
Q
What is the effect of paracetamol overdose and what is the protocol for dealing with an OD patient?
A
Saturates normal pathway so forms NAPQI which is toxic that damages hepatocytes, this is then conjugated with glutathione so the liver’s defences to damage are removed. Leads to death in 36-96 hours. if after 4 hours the blood paracetamol is high then N-acetyl-cysteine and after 2 hours charcoal can be given to absorb any in stomach.
25
What are the types of hypoxia and their respective causes?
Hypoxemic- state of oxygen deficiency by there being a low oxygen content in the blood. (pulmonary effusion, low atmospheric oxygen content, reduced lung volume(congenitial, environmental) lung cancer)
Anemic hypoxia- Descreased ability to carry blood in the oxygen due to haemoglobin deficiency/impairment. (CO poisoning, iron deficiency)
-Ischemic hypoxia: occurs due to occlusion of blood flow to a particular tissue (can occur due to the vessell being blocked or damaged so thrombus, embolism, trauma, infection, low blood pressure).
-histiocytic: inability of cells to use the oxygen supplied to them (like cynanide poisoning)
26
What are some common causes of cell injury?
radiation, trauma, extremes of heat, lack of metabolites, current, pressure, toxins, microorganisms, autoimmune activity,hypoxia.
27
What is the result of cell injury?
it depends on the severity of the injury. slight injury will result in cell adaptation and severe injury will result in cell death.
28
Define necrosis
all the cell changes that occur after localised cell death due to irreversible damage to the cell and its components.
29
Define apoptosis
Apoptosis is individual controlled/programmed cell death that is induced and energy dependent.
30
What are the features of apoptosis and sequalae?
single cells become intensiely eosinophillic and visible are nucelar fragments, cell shrinkage and then blebbing. This keeps the entire contents of the cell in vesicles that prevents leakage. These vesicles are then phagocytosed by macrophages or neighbouring cells. The lack of leakage.
31
What are the features of necrosis and sequalae?
Cell damage: in the nucleus (pyknosis, karyolysis, karyorrhexis), swelling and lysis of cell components, myellin figures.
cell lysis: results in the cell contents passing into the surrounding tissue causing inflammation.
32
What are the types of necrosis? giving examples of when these would occur
Liquifying- more proteases released then protein resulting in surrounding tissue being dissolved. Occurs in tissue that lacks substantial supporting networks like the brain.
coagulative-More protein denaturation
caseous-
Fat-
33
What is the mechanism for apoptosis?
Apoptosis can be induced via either the intrinsic or extrinsic pathway. The intrinsic pathway.
intrinsic: DNA damage causes increase in mitochondrial permeability and the release of cytochrome c. This interacts with APAF1 and caspase 9 forming an apoptosome. This then activates a caspases.
Extrinsic: Binding of death ligands (trail) activates caspase activation.
34
How are free redicals formed?
free radicals are formed by a number of mechanisms. NADPH oxidase on leukocytes create them as part of the bodies immune response, Ischaimia and reperfusion injury, radiation can ionise water forming the hydroxyl free radicals, Electrons can leak across in the inner mitochondrial membrane and result in the creation of.
35
What are free redicals?
Free radicals are oxygen species with an unpaired electron making them hightly reactive.
36
What is the action of free radicals on cells?
Free radicals tend to target proteins and the cell membranes. Hydroxyl free radicals are most damaging to cell lipids and there is no mechansim for terminating these.
37
How do cells terminate free radicals?
Free radicals are terminated through a number of mechanisms. Firstly there are species within the body that can bind to free radicals like vitamins C, E and A.
There is a process of natural self termination through decay
There is also an enzyme system using SODs and Catalase to breakdown existing free radicals.
There are also storage proteins which bind transition metal elements preventing (in the case of iron) the heiber weiss and fenton reaction which create the hydroxyl radical).
38
What are heat shock proteins and what is their role?
Heat shock proteins are a group of chaperone proteins that are expressed by cells in response to high temperature; they assist in the refolding of denatured proteins, not only as a result of heat but also in response to physical and chemical stresses. The consequences of protein misfolding can be severe and there are a number of diseases that can result from faulty folding. In many cases, including some forms of cystic fibrosis.
39
What is ventilation/perfusion ratio and how can it effect blood oxygen saturation?
the ratio of oxygen in the lungs and blood supplied to the lungs. Optimally all blood should just be saturated with oxygen so if the blood flow through the pulmonary circulation increases or there is a decrease in oxygen uptake then it leads to a decrease in this value. The lower the value the lower the blood oxygen saturation.
40
What is myxedema? how does it arise?
Deposition of mucopolysaccharides. In hypothyroidism it arises systemically but in hyperthyroidism (graves) it occurs specifically in the pretibial region.
41
what are the inhibitors and inducers of apoptosis?
inhibitors: sex steroids, growth factors and cell matrix, Bcl-2
Inducers: Trail ligands, DNA damage, loss of growth factors, p53,
42
What are the features of reversible cell injury in hypoxia?
low oxygen, decrease in oxidative phosporylation, decrease in ATP, increase in glycolysis so decrease in glycogen and increase in pH. Leads to chromatin clumping. Low ATP causes a detachment of ribosomes, decrease in protein synthesis and an increase in lipid deposition. There is a decrease in Na/K atpase and so there in an influx of water and this leads to cellular swelling, ER swelling, Mitochondrial swelling, and blebs.
43
What are the features of irreversible cell damage in hypoxia.
There is a large influx of calcium ions (due to loss of NCX and no calcium atpase function). also there will be a release from the ER and mitochondrion. This leads to key cellular changes. damage to the chromatin and disruption to many cell processes.
44
What are the biochemical consequences of excessive alcohol intake?
Damage to GI tract and so poor absorption of nutrients (folate, and vitamins resulting in folate deficiency beri beri and pelagra), The Liver gets damaged and so becomes leaky so liver enzymes (ALTs and ASL and Gamma-GT) can be tested for in the blood, there can also be deposition of collagen in the liver and fat (mallory's hyline). This will eventually lead to cirrhosis
45
What is the effect of asprin overdose? what is the treatment?
Acetylesalicylic acid overdose stimulates resp centre in brian resulting in resp alkalosis. -ve feeback causes fall in pH. Interfers with normal metabolism which contributes to acidosis. inhibits COX1 and COX 2 causing GI bleeding due to lack of mucins and also descrease platelet aggregation.
activated charcoal, intravenous dextrose and normal saline, sodium bicarbonate, and dialysis
46
Describe the mechanism of action of heparin?
Binds to anti-thrombin and activates it resulting in a 1000 fold increase in rate of clearence of key components to the clotting cascade.
47
Describe the mechanism of action of asprin
Inhibits COX1 and 2. This results in the suppressed production of prostaglandins and thromboxane which stops platelate aggreagation and stop fever and pain.
Can also result in Upper GI bleeding.
48
Describe the mechanism of action of warfarin.
Takes the place of Vitamin K in the formation of gla-residues resulting in the absence of several key components of the clotting clascade i.e factor VII and X.
49
How do platelets adhere to each other and to the cell wall?
Endothelium normally produce NO which inhibits thrombus formation. Also they express various proteins inhibtting platelet aggregation.
Von willibrand factor anchors cells to collagen but isnt normally exposed to collagen when in the lumen.
Injury to endothelium exposes the VMF to the collagen in the basement membrane. This leads to aggragation of platelets. Also change in blood flow can lead to clots as can thrombin, ADP and thromboxane.
50
Why must the clotting system be finely tuned?
Due to the consequence being bleeding out or the blood setting solid. This process needs tight regulation at several points.
51
Describe the clotting cascade.
Extrinsic: tissue factor 3-->7-->10
Intrinsic: 12--> 11--> 9-->10-->thrombin--> fribrinogen to fibrin and XIII.
9-->10 is upregulated my VIII.
XIII forms cross links in the fibrin.
52
Define heamostasis.
The process of stopping bleeding through various mechanisms (fibrinolytic, platelets, vasclular auto-occulsion in severance)
53
Define thrombosis
Formation of a solid mass of blood in the circulatory system in a living person.
54
What is the effect of thrombus in the venous system?
Initially congestion and swelling. The temperature of the tissue will increase due to more blood being present. Eventually the pressure in the tissue will match that of the arterial supply leading to no blood entering and therefore ischimia and necrosis.
55
What is the effect of thrombus in the systemic circulation?
Leads to ischimic necrosis due to the tissue being deprived of oxygen straight away.
56
What is Virchow's triad?
3 factors that lead to thrombus formation.
Blood flow- stagnation/turbulence like in AF or an aneurysm.
Blood components- disruption of clotting factors that can arise from pregnancy, post-op smokers and drinkers.
Vessel wall intergrity- injury, inflammation, compression, atheroma, spasm.
57
What are the outcomes of a thrombus?
Lysis: complete restoration of blood flow to the affected region, no permanent damage to tissue, only happens for small clots.
Recanalisation: partial re-establishment of blood flow through developement of new lumens through the thrombus.
Organisation: lumen remains blocked and there is in-growth of capillaries and fibroblasts.
Propagation: Thrmbus in vessel disrupts blood flow further down system leading to another thrombus forming.
Thromboemboli: The thrombus breaks off and travels in the blood stream to a site distal to its point of origin.
58
What is an embolism?
Blockage of blood vessel by a solid liquid or gas at a site distant to its point of origin.
59
What can cause an embolism?
iaterogenic (medical equipment air from injection, medical equipment and drugs causing) , tumour cells, nitrogen from decompression, throat getting cut, amniotic fluid, thromboembolism
60
What is a DVT? how is it managed? prevented? pathophysiology? risk factors?
deep vein thrombosis, arises in the deep veins of the legs typically.
managed through the use of oral warfarin and IV heparin.
prevented through TED stockings,early mobilisation post surgery and sub cut heparin.
Pathophysiology: Formed by abnormal blood flow in the legs, results in clotting formation and then this can progress through propagation and grow in size. If a bit breaks off can lead to pulmonary embolism.
61
Describe pulmonary emboli.
originate from thromboemboli in the venous network that travel into the RA-->RV--> pulmonary circulation.
Cannot reach systemic circulation due to being to large to pass through the cappilaries.
If small will have a very small effect only causing SOB.
Medium=coughing up blood/pulmonary odema
Massive=fatal
recurrent= pulmonary hypertension and RV hypertrophy.
Treated by filter in atria and by prophylactic anticoagulants.
62
Describe common congenital disorders of blood coagulation.
```
VIII deficiency (Haemophillia A)
IX deficiency (Haemophilia B)
Both are x linked and interupt the intrinsic clotting pathway. Common in populations where a high frequency of consanguineous marriage is present.
VWD- VWF is absent and this is essential for platelet adhesion. Has a site for factor 8 and collagen.
All can present with spontaneous haemorrage into joints and soft tissue, early onset OA. Most common cause of death is HIV and Hep C contracted from blood products pre-screening. 12% of patients can develop an immune response to the treatment of factor replacement. Non congenital auto immune response can develop in individuals.
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63
Describe DIC, its treatment, causes and presentation
Common state of in which hemorrhage and thrombosis occur simultaneously as a result of another pathology. The clotting leads to depletion of factors leading to hemorrhage.
Causes include infection, neoplasm, trauma, liver disease.
Pathogenesis: endothelial damage and tissue trauma lead to the initial clotting.
Death occurs in 40% of cases. systemic disruption of normal activity in all organs.
64
Describe common causes of thrombocytopaenia.
Reduction of platelet number in the blood.
Drop in platelet production: megaloblastic anemia, infections, chemotherapy, alcohol, liver cirrosis.
Increased in platelet destruction: AI thrombocytopenic purpura, DIC,
Platelet sequestration: hypersplenism
65
Describe common causes of thrombophillia
Congenital deficiency in antithrombin, protein c and s deficiency.
66
Describe common acquired disorders of coagulation
Liver disease: Leads to failure of factor synthesis.
Vitamin K deficiency: lack of green vegetables in diet, its fat soluble so requires bile for absorption. Needed to make gamma carboxyglutamate residues of 2, 7, 9, and 10 also protein c and s.
67
Describe causes of acute inflammation and the purpose of
Causes: infection, toxins, hypersensitivity, physical/chemical agents, necrosis.
Purpose: decrease the total damage to the body, deal with the initial cause as quickly as possible, innate stereotyped response to tissue injury.
68
What are the macroscopic features of acute inflammation?
Rubor, calor, dolar, tumor, and loss of function
69
Describe the vascular phase of acute inflammation and the factors that can cause this.
Initially a transient vasoconstruction:
Then a vasodilation: histamine for first half hour then bradykinin and leukotriene.
Increase in endothelium permeability: histamines and leukotrienes cause endothelial contraction, vegf causes an increase in transcytosis.
Drop in blood velocity: This is due to the increase in endothelium permeability so less blood can flow through.
70
Describe where histamine is produced and the effects of
Produced: in mast cells, platelats, and basophils in response to trauma, C3A and IL1.
Effects: Vasodilation, increase in endothelial contraction, pain,
71
Describe the exudation formation in acute inflammation
Formed due to increased endothelium permeability. This allows proteins to pass into the fluid. Due to colloid osmotic effect the proteins take water into the extracellular space with them. This leads to oedema. This is due to starlings law of the cappilaires.
72
What is the benefit and disadvantages of forming of exudate?
Removal of toxins by dilution, increasing the supply of nutrients to the site of injury, increases the flow of neutrophils and antibodies to the site of injury. Increases lymph drainage increasing the immune response to any pathogens.
Disadvantages: result in compression of surrounding tissue, can be more harmful by decreasing blood volume if systemic reaction like in anaphylaxis.
73
How are neutrophils brought into the site of injury?
Neutrophils enter the site of inflammation through 4 steps.
margination: occurs due to blood stasis and involves the neutrophils moving from the circulation to the vessel wall.
Rolling: binding via selectins moves the neutrophils by allowing intermittant binding to the endothelium.
Adhesion: binding to the endothelium via intergrins.
Emigration: firstly diapedesis occurs where the neutrophil passes through the vessel wall. This requires moving of the endothelial cells by relaxing junctions and dissolving of the basement membrane using mmps. Chemotaxis then occurs allowing the neutrophil to move up the gradient of various chemicals (C5A, LTB4 and bacterial peptides).
74
what is the neutrophil mechanism of action?
phagocytosis of pathogens
Killing of pathogen: O2 dependant (using myeloperioxidase halide system). and O2 independant (using proteases and lysozymes).
75
What are the systemic markers and consequences of acute inflammation?
```
Fever (due to released endogenous pyrogens like IL1, TNF alpha and prostoglandin)
Raised WBCC (in response to the tissue trauma and the type of WBC can indicate the cause of tissue injury)
shock (due to too much exudate being formed dropping blood pressure).
Markers of acute inflammation will be CRP alpha 1 antitrypsin, and serum amyloid A protein.
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76
Describe resolution of acute inflammation
The initial causes of tissue damage must be removed. This leads to a decrease in exudate formed. The exuadate formed in tissue space is drained via the lymph or reabsorbed by the blood. Decrease in exudate formation and chemicals released results in less margination and chemotaxis of WBC. Tissue damage must be repaired for full resolution. If there is architercural damage then there will be scar tissue produced as the body attempts to regenerate.
77
How can drugs modifiy acute inflmammation?
Asprin inhibits the production of various arachnidonic acid derivatives and so acts to reduce the pain and inflammation.
Adrenaline acts to vasoconstrict at high concentrations by activating alpha 1 receptors and this results in the increases in BP during shock.
78
Describe Lobar pneumonia
Most usually caused by streptococcus pneumonia.
progression is congestion that includes vascualr engorgement hyperemic few WBC and many bacteria (first 24hours), then Red hepatizisation where RBCs are extravasated into tissue then grey which the RBC disintergrate followed by resolution.
Usually acute
Treatment is antibiotics
79
Describe acute appendicitis
Symptoms: pain, vomiting, fever and if abdomen has general pain suspected peritonitis.
Cause: primary obstruction of the appendix lumen resulting in swelling of the tissue. Ichimia and necrosis follow due to the swelling and perforation results in bacteria entering the peritonium and can lead to sepsis. Most common causes of blockage are trauma, fecal matter.
DDX: Based on examination and raised WBC count. also and US or Xray can be used.
Treatment: surgery to remove appendix
80
Describe alpha one anti-trypsin deficiency
Genetic mutation that results in the lack of a protease inhibitor that protects against inflammatory enzymes i.e neutrophil elastase. Sypmtoms would be SOB wheezing and emphysema.
81
Describe hereditary angio-oedema.
Genetic lack of C1 esterase which inhibits the actions of bradykinin. This lead to swelling of the GI tract genitals and face.
high mortality.
82
Define chronic inflammation
Chronic response to injury with associated fibrosis
83
Describe sarcoidosis
Granuloma formation and accumulation typically in lungs and lymph however it can occur in any tissue.
Symptoms: SOB, wheezing, fatigue, weight loss TATT, conduction abnormalities.
DDX:disease of exclusion
Causes: typically idiopathic but is associated with a number of other conditions
84
Describe TB
Caused by the mycobacterium TB and typically affects the lungs.
symptoms: cough, blood tinged sputum, fever, weightloss sypmtoms often much more severe in HIV. can erode into pulmonary artery resulting in massive bleeding and systemic spread resulting in millary tb.
DDX: chest xray and cultures. TB are acid fast and so stain accordingly however they have a slow rate of binary fission.
Treatment: antibiotics however there are many resistantant strains (MDR-TB)
Risk factors: poor ventilation, over crowding, poor immune response, poor diet, smokers, HIV
Immune response: macrophages, and lymphocytes and fibroblasts aggregate to form granulomas which are langerhan's ginat cells.
leads to caseous necrosis.
85
Describe leprosy
Leprosy is caused by the mycobacterium leprae and is a granulomatous disease of peripheral nerves and URT.
DDX: skin lesions muscle weakness, loss of sensation, flat nose.
86
Describe syphillis
4 stage disease contracted via sexual activity.
Tertiary: occurs 3-15 years after initial disease contraction but only 1/3 of people develop. 50% of which develop gummatous which is charachterised by the formation of chronic gummas which are soft granulomas that can vary is size and occur in most tissue but is common in skin bone and liver. 33% go on to form neurosyphillis which can present with a mirad of symptoms depending on where in the brain the disease attackes. CV syphillis can lead to aortitis leading to aneurysym formation.
87
Describe foreign body reactions
granuloma classed as a foreign body granuloma.
88
Describe wegener's granulomatosis
vasculitis of medium blood vessels that can occurs in any organ. Upon biopsy often granulomas are discovered in tissue.
pathophysiology: thought to involve cANCA
89
What is the action of helicobacter pylori?
Causes: stomach ulceration in 20% and stomach cancer in 2% of cases of infection.
Pathophysiology: tunnel into stomach mucus and produce urease which produces NH3 resulting in stomach acid neutralisation. This and other products damage the cells of the stomach mucosa.
90
Stomach ulcer treatment?
Removal of cause: antacids and H2 antagonists, antibiotics for H.pylori,
91
Compare and contrast crohns and U.C
stool has blood in UC and in C has fat
fever in c and only in severe UC
fistulas in C and weightloss in C
UC is usually continuous from rectum to colon.
92
Describe the consequences of chronic inflammation
can result in fibrosis, atrophy, loss of function, continued stimulation of immune response.
93
What causes chronic inflammation to arise?
chronic infection/irriations (de novo)
| acute-->chronic transition
94
What is a macrophage and what is its typical function?
A macrophage is an immune cell of the body which appears in chronic inflammation as monocytes travel from blood into tissue becoming macrophages. They can create new granules and and involved in phagocytosis, APC and cytokine production
95
Describe granulomas and their composition
A granuloma is a special type of cell aggregation composed on epitheloid histiocytes sounded by lymphocytes. They often form in response to large objects that frustrate phagocytosis. Giant cells can form through merging of macrophages and they are different based on the causes of inflammation.
96
what cells are involved in chronic inflammation and their role?
Touton giant cells: due to fat necrosis.
Langerhans giant cell: Due to TB
Foreign body giant cell: friustrated phagocytosis of foreign body.
Macrophage: present in chronic inflammation, APC phagocytosis, and cytokine production.
B Lymphocyte: produce plasma cells which produce antibodies.
T lymphocyes: helper and cytotoxic
NK cells: Kill cells based on changes in MHC on cell surfaces/ due to cellular distress
Eosinophils: produce histamine and are a sign of allergic reactions and parasites/chronic inflammation.
Fibroblasts/myofibroblasts: produce collagen and so produce fibrosis and also cause tissue contraction.
97
Describe granulomas and their composition
formed in chronic inflammation, formed from aggregates of central epitheliod histiocytes (macrophages) and surrounded by lymphocytes.
Can also contain giant cells
Form around a central point and are organised such that the individual cells can appear contiguous.
98
what cells are involved in chronic inflammation and their role?
Macrophages
Lymphocytes
Fibroblasts: production of the extracellular fibrous matrix that
99
Define regeneration
Replacement of dead cells/damaged cells by functional differentiated cells derived from stem cells.
100
Describe the role of E cadherin
cell membrane proteins that are involved in contact inhibition. This is where cells whose membranes are in contact will not undergo mitosis. This is often deranged in cancer.
101
What roles do growth factors have in regulating regeneration?
promote proliferation, can be autocrine paracrine and hormonal.
ILGF, EGF, PDGF, FGF, testostorone, oestrogen and growth hormone
102
Define resolution
Resolution is the complete restoration of tissue to the pre-diseased state. This can generally only occur if the architecture is not destroyed.
103
Define fibrous repair and describe the process of.
Replacement of functional tissue by scar tissue in response to tissue damage that cannot heal to complete resolution. This is due to necrosis of permenant cells of the loss of the ECM architecture.
cells: Imflammatory cells, Endothelial cells, myofibroblasts
Roles: phagocytosis and cytokine production, Angiogenesis, ECM production and contraction
Regulation: various cytokines from all cells involved.
104
Define labile, stable and permanent tissues
labile: continously going through mitotic divisions based on demand
stable: in G zero but can enter cell cycle upon tissue injury
permenant cells cannot re-enter the cell cycle.
105
Describe skin repair through primary intention
Incision, apposed edges, little clot, epidermis regenerates,@10 days @ 10% strength. Minimal scarring and minimal contraction.
106
Describe skin repair through secondary intention
Unappossed, large "messy" tissue damage, forms of eschar, regenerates from base up, much granulation tissue and produces a large amount of scar tissue and oft results in contraction.
107
Describe the structure and function of type 1 collagen
Provides strength and structure to ECM.
Each collagen molecule is made from many tropocollagen molecules that are polymerised. Each tropocollagen is made from 3 alpha chains.
108
what factors affect efficacy of healing?
Age, drugs diet, health, apposition, type size and location, blood supply, infection and radiation damage.
109
Describe repair in cardiac muscle
Cardiac myocytes are permenant cells and so cannot enter the cell cycle. At death their is necrosis and migration of cells in response to the inflammation. Neutrophils will phagocytose cellular components and then fibroblasts will lay down scar tissue in place of the lost myocytes.
110
Describe repair in bone
Haematoma--> granulation tissue and soft callus formation. Haematoma is phagocytosed by neutrophils and granulation tissue is produced. Angiogenesis begins however at the peripheral hyaline cartiladge begins to form. Fibrocartiladge callus is formed. Ossification occurs however it is disorganised nonlaminar and gets gradually remodelled gaining strength.
111
Describe healing and repair in the liver
Very good at regeneration. If this is accompanied by loss of architecture then cirrhosis can result. Requires both fibrosis and nodular regeneration. There is a loss of the typical acinar. There is a marked reduction in liver function and this can result in liver failure which will have systemic effects.
112
Describe healing and repair in peripheral nerves
Nerve is damaged. Axon disintegrates, the perineurium doesnt get broken down and is key in ensuring nerve regrowth. Growth occurs in 3-4 days @ 2-3mm/day. This can be disrupted by damage to perineurium or ischimia. Bangs of Bungner protect the perineurium and neurotrophic factors enhance growth.
113
Describe healing and repair in cartiladge
Limited possible repair for a number of reasons. Lucanae trap the chondrocytes so migration isnt possible, cartiladge is avascular to deposition of new cartiladge is slow. Typically repair will be in the form of a fibrous scar.
114
Describe pressure sores and why they occur
Localised injuries to skin and sub-cut tissue as a result of pressure. Commonly on sacrum and heels. Pressure reduces blood supply and damages blood vessels further exasperating the issue, Tissue repair is difficult due to poor blood supply often leading to abcess formation and the necrosis can often get down to the bone.
115
Describe the process of angiogenesis, and why it is so important in developing/repairing tissue.
- Endothelial proliferation and migration, maturation and tubular remodelling and then periendothelial cell recruitment.
- Provides the metabolites to the new tissue and also provides a path for "building blocks" and also cell migration.
116
Describe the process of CNS repair
Non specific response to CNS trauma is gliosis. Proliferation and hypertrophy of CNS glials cells forming a glial scar. it's initially microglia for phagocytosis and then astrogliosis.
117
Define metaplasia
Reversible process whereby one cell line in response to stress adopts a different morphology. This can often be a precancerous state.
examples being barretts oesphagus in response to excess acid and smokers URT.
118
Describe dysplasia
Abnormal maturation of cells that can be precancerous. Process is reversible
119
Describe aplasia
The lack of tissue to grow in the embryo leading to absence in the adult.
120
Describe hypoplasia
Congenital. due to poor embryological growth
121
Describe hyperplasia
Increase in number of cells in a tissue. This is due to increased demand of that tissue,
Examples being RBCs at high altitude, the endometrium and also the goitre in hyperthryoidism.
122
Describe regeneration
The process of replacing cells lost from a tissue with identical cells from a stem cell pregenitor. This can only happen if architecture is still present and also if the cells are labile/stabile. If not then healing will happen through formation of scar tissue.
123
Describe hypertrophy
Increase in cell size due to increased demand or grwoth signals. i.e muscle growth and cardiomegaly.
124
Describe the main divisons of the cell cycle
M, g1 s and g2
125
Describe how the cell cycle is regulated
There are key check points throughout the cycle.
R- most significant check point, regulated by P53 and this is responsible to overseeing the state of the DNA.
H-
S-
M phase is regulated by cyclins.
126
Define ateriosclerosis
The hardening and thickening of arterioles usually secondary to hypertension
127
Define atherosclorsis
The accumulation of lipid (both inside and outside the cells) in the intima and media of medium sized arteries that results in hardening and thickening.
128
what are the common now proven wrong pathophysiology of the atheroma?
Monoclonal- each plague stems from a single SMC and thus is close in character to a benign tumor.
Encrustation hypothesis- Blood components adhere to endothelial layer and form thrombi from platelets fibrin and leukocytes.
129
Describe the now accepeted theory of atheroma formation
Endothelial injury: due to raised LDL, toxins, hypertension and turbulent flow.
Platelats adhere and PDGF release.
SMC proliferate and migrate
Macrophages migrate into intima
Insudation of lipid and LDL oxidation.
Macrophages and SMC uptake lipid becoming foam cells.
SMC produce matrix, foam cells produce cytokines.
Inflammatory cells cause damage inducing a greater tissue response.
Cytokines cause macrophage migration and induce SMC matrix production.
Damage to the vessel wall compromises the elastic lamina.
130
What are the macroscopic morphological changes in atheroma?
Fatty streak: Yellow and elevated. Deposits in intima.
Simple plague: raised and enlarged. widely distributed. White/yellow
Complicated plague: Fibrosis cap can fissure/rupture resulting in haemorage into plague or thrombosis. Calcification and anerurysm can form.
131
What are the microscopic morphological changes in atheroma?
Fatty streak: SMC proliferation, more foam cells and more lipid.
Plague: Fibrosis and necrosis, cholesterol clefts,
Complicated: damage to internal elastic lamina, ingrowth of blood vessels, plague fissures.
132
What are the clinical markers of high risk for atheroma developement?
Variation in the Apo lipoprotein E expression/type.
corneal arcus
tendon xanthalasmus
133
What are the risk factors for atheroma?
Diabetes, age, being male, obesity, smoking, hypertension, diet, exercise level, alcohol intake, high LDL:HDL ratio.
134
What are the clinical signs of atheroma in the coronary arteries
Upon exertion angina leading to arrythmia
chronically leading to cardiac failure
and acutuely to death in plague rupture.
135
What are the clinical signs of atheroma in the cerebral arteries
TIA, multiinfarct dementia, cerebral infarct.
136
What are the clinical signs of atheroma in the mesenteric ateries
ischemic colitis, mal-absorption, infarct.
137
What are the clinical signs of atheroma in peripheral arteries?
leriche syndrome, rest pain, intermittent claudication, gangrene and slow healing.
138
How can aneurysym develop from atheromateous plague?
due to damage to the internal elastic lamina resulting in plastic deformation of the arterial wall.
139
What are the mechanisms of normal cellular growth regulation?
Growth factors: PDGF, EGF, VEGF sex hormones, growth hormones T3/4.
Metabolic factors: increased blood flow/ not poor blood flow leads to more developed tissue then if not.
Inhibitory factors: DNA damage through P53 regulation, death ligands.
140
How is the balance between cell proliferation and death managed?
Through E cadherin and similar cell surface adhering ligands.
These enable the cell to know what its in contact with other cells halting mitogenic processes.
141
Define neoplasia
An abnormal growth of cells that persists after the initial stimulus is removed.
142
Define Tumor
Any SOL
143
Define cancer
Abnormal growth of cells that persists after the initial stimulus is removed and invades surrounding tissues with potential to spread to distant sites.
144
What 6 properties do cells require to be cancerous?
-immortaility
-ability to igonore growth inhibitors
-grow irrespective to the normal GF
-induce angiogenesis
-
145
How can mutations trigger the transition from nonneoplastic to neoplastic?
Knudson's 2 hit hypothesis.
| Both tumor supressor genes must be knocked out as well as protooncogenes upregulated to oncogenes.
146
What is the maximum size a tumor can grow without angiogenesis?
2mm
147
What are the key features of benign and malignant neoplasms?
benign: slow growth, infrequent mitoses, well differentiated, normal nuclear morphology, no invasion, no mets, circumscribed and encapsulated boarder, no necrosis, no ulceration,
Malignant: rapid growth, frequent and atypical mitoses, poor differentiation, various pleomorphisms, invasion and mets, poorly defined boarder, necrosis and ulceration.
148
What is the endophytic growth? and what type of tumour is most likely to take this gross morphology?
internal growth,
| Malignant neoplasia
149
Define anaplasia
When neoplastic tissue has no resemblance to the initial tissue that it stems from.
150
Define pleomorphism
Cells that have increased nuclear to cytoplasmic ratio, mitotic figures and variation from cell to cell in nucleus size.
151
How are neoplasms graded?
from 1-->3 with a higher grading meaning a poorer differentiation and an associated lowered prognosis.
152
Define dysplasia
abnormal cellular development that is oft precancerous but is reversible.
There is a spectrum of change that is between dysplasia and neoplasia. This leads to a gradient of change and a corresponding gradient of celluar derangement. GRADIENT LOSS OF DIFFERENTIATION.
153
What is the stroma?
The connective tissue framework that supports the growing neoplasm and results in providing of mechanical and nutrition to the cancerous cells.
154
What causes neoplasia to arrise?
Intrinsic factors: 15% genetic predispotion or heterozygous recessive for cancerous genes.
Extrinsic factors: 85% impact (from initiators and promoters)
155
How do initiators and promoters work together to cause neoplasia?
Initiators must start the test
promoters exploit the change caused by the initiator.
Both are needed
Same chemicals act as both.
156
What is progression?
The process of accumulating yet more mutations in the cellular genome.
typically 10 will give rise to a malignancy.
157
Describe the monoclonality of neoplasms
Study in G6PDH in women with heterzygosity. One allele is heat sensitive.
This is knocked out resulting in half being functioning and the other half being non functioning. Looking at the distribution in normal Vs cancerous tissue shows that normally there is an even distribution of the 2 alleles but in cancer there is localised regions of high density. This supports the monoclonal hypothesis.
158
Describe the naming process for epithelial neoplasms
epithelial: benign malignant
squamous: papilloma : carcinoma
transitional, basal
glandular: adenoma : adenocarcinoma
159
Describe the naming process for mesenchymal neoplasms
```
smooth muscle: leiomyoma: leimyosarcoma
striated muscle:rhabdomyoma: rhabdomyosarcoma.
adipose tissue: lipoma: liposarcoma
blood vessels: angioma: angiosarcoma
bone: osteoma: osteosarcoma
cartiladge: chondroma: chondrosarcoma
mesothelium:benign mesothelioma: malignant mesothelioma
synovium: synovioma: synovial sarcoma
```
160
What are blastomas?
malignancy in precursor cells. i.e nephroblastoma or retinoblastoma.
Most are linked to a mutation in tumour supressor genes.
Most common in children.
161
Describe leukaemia
malignant. can be acute of chronic
| occurs in bone marrow.
162
Describe germ cell neoplasms
testis
malignant teratoma and seminoma
ovary
benign dermoid cyst.
163
Describe lymphomas
malignant. B and T cells
usually in lymph nodes.
Reedsternberg cells indicative of hodgkins.
164
describe gliomas
tumor originating in glial cells. Makes up the majority of malignant brain tumours.
No exact mechanism known although certain genetic conditions are predisposing.
165
What are the common gross morphological shapes undertaken by neoplasms and indicate if typically benign or malignant
```
sessile- typically benign
polyp- benign
papiloma- benign
fungating-malignant
ulcerated- malignant
annular- malignant
```
166
Describe neuroendocrine tumors
Tumors that arise from the endocrine cells of the body or nervous tissue.
Carcinoid tumours (intestine)
phaechromocytoma (adrenal medulla)
small cell carcinoma of bronchus. (
167
Describe the AIMS test
Incubate bacteria using a carcinogen. Then grow on a culture lacking histidine. This will lead all bacteria to die that haven't mutated to allow the conversion of other amino acids into histidine. Thus this test can show how potent a carcinogen is at inducing mutation.
168
How do we know that tumors are monoclonal in nature?
G6PDH def
Women have 2 copies
one copy is switched off due to one X being switched off
one copy is heat sensitive so heat causes this one to be deactivated.
Normally results in a detectable even distribution of one and off. In cancer there will be a grossly disproportionate number of one or the other thus being strongly indicative of the mono clonal hypothesis.
169
Describe the knudson 2 hit hypothesis
This is that neoplasia needs more than one mutation to occur.
Nordling noted that incidence of cancer correlated with the 6th power of age so hypothesied 6 mutations.
Knudson showed that in familial retinoblastoma only one hit was needed.
There needs to be damage to both POG and TSG for unchecked proliferation to occur.
170
Describe the role of the pRb
Inhibits the cell cycle progression at the R checkpoint.
This is done by interacting with transcription factors of the E2F family and inhibting them.
Phosphorylation deactives it.
This allows the E2F to activate cyclins.
171
Define invasion and metastasis
The ability of malignant cells to invade and spread to distant sites in the body leading to an increased tumor burden
172
Describe why the process of metastasis is inefficient
Due to multiple mutations being required to enable a cell to be able to travel from the primary tumor to the distant site. As a cell gains a new mutation it has a gain of ability however due to the multiple challenges it must overcome (embolic trauma, high O2, immune attack, angiogenesis etc) many cells must be produced before these properties exist.
173
What 3 properties must the neoplastic cell change to enable invasion
EMT- epithelial to mesenchyme transition.
Adhesion: change E cadherin for cells and stroma adhesion with intergrins
Proteolysis: Matrix metalloproteinases (MMPs)
Motility: through cytoskeletal remodeling.
174
Describe the role of a cancer niche
This is the tissue surrounding the neoplasm.
This can undergo a number of changes that will facilitate the needs of the growing neoplasm. this includes forming stroma and angiogenesis.
175
Describe the 3 routes of malignant cellular spread
Blood via capillaires and venules (tend to be sarcomas and oft go to lung bone liver and brain)
Lymph (tend to be carcinomas)
Transcoelomic
176
Describe the challenges a malignant cell faces trying to implant to a distal site.
Extravasation from vessel into distal tissue and then growth of blood vessels and recruitment of niche to secure nutrients and support.
Failure of growth of blood vessels can result in the formation of micrometastasis. These give rise to tumor dormancy which can lead to a relaspse in an old cancer.
177
What determines the site of a secondary metastasis?
For Blood--> next cappillary bed but can be systemic.
For lymph--> adjacent lymph or surrounding organs.
For transcoelomic--> to another part of the serosa or to an adjacent organ contained within.
Seed and soil hypothesis.
Only certain tissues will allow for mets to develop within them i.e bone is common site for mets as is lung but other sites are not.
178
What are the common cancers that give rise to bone mets?
prostate, breast, thryoid, lung and kidney.
179
What are the local effects of neoplasia?
Due to growth, all increase pressure on the surrounding tissue. This will have various effects. Crushing of "tubes" can result in pain and build up/reducing in metabolites or products in that tissue.
Malignant exert more damage then benign as they can invade and "take over" neighboring tissues. Also ulceration can be an issue due to bleeding.
The extent of damage depends purely on the tumor personality. Some are aggressive and others are like so.
180
Describe some of the systemic effects of neoplasia.
Paraneoplastic syndrome: any adenoma can secrete their original product as they tend to remain well differentiated. Many malignant neoplasia can also secrete hormones.
Cachexia (secretion of certain cytokines)
malaise/TATT-tumor burden
immunosupression- damage to bone marrow
anaemia- can be present in chronic disease, also the bleeding from ulceration.
Fever- inflammatory markers
Embolism- as cells attempt to travel to a distant site.
181
What neoplasia can cause hypercalcaimia? How?
Also known as humoral hypercalcemia of malignancy, from squamous cell carcinoma. Production of PThrP.
182
How does PTHrP function?
Same as PTH as acts on same receptor.
Doesn't Make more calcitriol.
more Ca2+ reabsoprtion in kidney and more Phosphate excretion
More absorption from bone.
183
How can anemia be caused by a malignancy?
Leukemia- can cause direct damage to bone marrow
B12 deficiency due to malignancy depleting bodies resources.
ulceration that results in anaemia.
184
What is the probable cause of cachexia?
Inflammatory cytokines such as interferon gamma and IL6.
185
What tumor can secrete ACTH and ADH?
small cell carcinoma of the lung
186
What tumor secretes HCG?
testicular teratoma
187
What do carcinoid tumors secrete?
5 hydroxytrptamine (serotonin).
188
What is pruritis? what neoplasms?
Itching from hodgkins lymphoma for example.
189
How can individuals have a familial risk to getting xeroderma pigmentosa?
Genetic disorder where the body is unable to repair the damage from UV. Basal cell carcinoma is a common diagnosis from a very young age. Body is unable to undergo nucelotide excision repair due to inherited mutation.
most common in Japanese people.
190
How can individuals have a familial risk to getting ataxia telangietasia?
Defect in ATM gene. This gene normally produces a protein that is recruited and activated by double strand breaks in DNA. It phosphorylates several key proteins to arrest the cell cycle.
Presents with weakened immune system, ataxia and leads to an increased risk of cancer.
191
How can individuals have a familial risk to getting familial adenomatous polyposis?
Presents with numerous polyps forming in the epithelium of the large intestine. These can bleed leading to anemia and can develop into neoplasia.
This is due to a mutation in the adenomatous poloposis coli (APC) gene.
This is a tumor suppressor gene that prevents uncontrolled growth of cells and also maintains chromosome number.
Hence this protein is essential for ensuring a normal cell cycle.
192
How can individuals have a familial risk to getting breast cancer?
BRCA1 is responsible for reapairing DNA.
expressed in breast tissue
Absense of this results in a lack of the normal repairing mechanisms and hence an increased rick of adenocarinoma. The mechanisms of action are diverse.
193
How can individuals have a familial risk to getting retinoblastoma?
inherited defective Rbr gene.
| Means high risk of the other one also getting damaged resulting in no tumor supression activity.
194
Describe the general carcinogenesis factors
Intrinsic: Age, sex, heredity etc. 15% of risk
Extrinsic: environment, lifestyle etc. 85% of risk.
Multifactorial
195
What is the role of ras?
Protein that comes from rat sarcoma. Expressed in cells, and results in the switching on of other proteins that ends in a net result of promoting cellular growth and proliferation.
25% of tumors approx. have ras mutations.
196
What is the role of c-myc?
gene that codes for a transcription factor. If mutated can result in the unregulated overexpression of many other genes within the cell. This can lead to cell growth and proliferation.
197
What is the role of c-erbB-2 (HER2)?
Gene that codes for the epidermal growth factor receptor. Associated in the pathophysiology in the of breast cancer when over expressed/amplified
198
What is the role of retinoblastoma protein?
TSG, Inhibits cell cycle progression until cell is ready to divide.
Inhibits E2F-DP so stops progression from G1-->S phase.
Phosporylated by RAS leading to inhibition.
199
What is the role of p53?
TSG, described as the guardian of the genome. 53 kilodaltons in mass.
It can activate DNA repair.
It can halt the cell cycle at the R checkpoint allowing DNA repair
It can initiate apoptosis if cell damage is irreparable.
Activated by stress ( UV, oxidative stress, etc)
If damaged results in derangement of the normal cell cycle and the cell exhibits neoplastic properties.
200
What is the role of tumor suppressor genes? How do they function?
Protects the cell from one step on the path to cancer. Loss of function of this gene results in the cell no longer have an inhibitory mechanism so can result in the cell undergoing excessive proliferation in an unhindered manner.
201
What is the role of pro-oncogenes in neoplasia? How do they function in a derranged state?
mutate and become hyperactive. In a normal state they serve a functioning purpose oft of promoting the cell cycle in a highly regulated manner. Upon derangement of function they are able to increase this normal function but only if the TSG are also malfunctioning. This is known as the Knudson 2 hit hypothesis.
202
What are the 2 stages of carcinogenesis?
Initiation and then promotion.
203
How does 2.nathylamine have an effect on the body?
2 napthylamine- Aromatic amine, industrial carcinogen that is used as a dye. Long period of latency and resulted in a higher rate of bladder carcinoma.
204
How can radiation result in derangement of cellular function?
Electromagnetic: able to pierce the skin and due to being high energy are able to overcome the electron work functions thus ionising and inducing damage potentially inducing neoplasia. ( from sunlight, radon and medical tests)
radioactive: beta and gamma rays are able to pierce the skin and thus induce a carcinogenic effect
Both can cause direct DNA damage, indirect via free radicals.
205
How does asbestos effect the body?
Inhaled, results in mesothelioma many years later.
206
What is the action of nitroamines on the body?
90% are deemed carcinogenic, can induce liver and esophageal neoplasia.
207
What is the role of polycyclic aromatic hydrocarbons in initiating carcinogenesis?
i.e benzo(a)pyrene is highly carcinogenic. Also found in cigarette smoke. prenatal exsposure is associated with asthma and low IQ.
208
How can Epstein barr virus cause neoplasia?
HHV-4
induces neoplasia by deranging normal cellular processes in the B cells and endothelium. This can lead to excessive proliferation as it doesn't causes lysis upon release as it's released in vesicles.
Associated with Hodgkins and Burkitts lymphoma.
209
How can Hepatitis B cause neoplasia?
due to the constant process of chronic inflammation requiring cellular proliferation. This increases the risk of developing hepatocellular carcinoma.
210
How can HPV 16 and 18 cause neoplasia?
by expressing e6 and e7 which inhibit p53 and pRb respectively
211
How can aflatoxins induce carcinogenesis?
produced by aspergillus fungus. Borken down in the liver and high level and chronic exposure can resuelt in hepatocarcinoma. it is thought to act through damage to the p53 gene.
212
How can shistosomiasis induce carcinogenesis?
chronic exposure and infection associated with bladder carcinoma.
This is due to the bodies immune response to the antigens expressed by the worm eggs.
213
What is a procarcinogen?
A none carcinogenic compound that is changed by the liver p450 enzymes into carcinogens.
214
What is a complete carcinogen?
A compound that can act as both an initiator and promoter
215
```
Where in the world has a
-higher
-lower
risk of developing
Burkitts lymphoma
```
Malaria regions and also Epstein Barr regions are high risk
216
```
Where in the world has a
-higher
-lower
risk of developing
Brest cancer
```
risk is proportional to the age of women at first birth.
217
```
Where in the world has a
-higher
-lower
risk of developing
Gastric cancer
```
Helicobacter pylori due to chronic infection leading to an increased risk of neoplasia.
218
What can hashimoto's thyroiditis result in?
Lymphoma
219
What can U.colitis result in?
Adenocarcinoma of the colon
220
What can cause scrotal cancer in chimney sweeps?
Polycyclic aromatic hydrocarbons like 3,4 benzyprene
221
What tumors are associated with smoking?
skin, bladder and lung.
222
What are the 6 hall marks of cancer?
```
self suffiecncy in growth signals
resistance to stop signals
immortalisation
angiogenesis
resistance to apoptosis
mets and invasion ability
```
223
Describe dukes' staging for colon cancer
A- not through bowel
B- not into lymph
C- not through lymph
D- at distal sites.
224
Describe (ann arbor) staging for hodgkin's lymphoma
1) one nodal group/node,
2) 2 nodal groups but on one side of the body, 3) nodal groups on both sides
4) distant mets
225
Describe staging for prostate cancer
```
Typically uses the TNM staging which incorporates the gleason staging as a form of histological grade.
2 numbers
first one is most common tumor pattern
Other is highest tumor grade present
ranges from 2-->10
```
226
Describe staging for bladder neoplasia.
T0 No evidence of primary tumour
Ta Non-invasive papillary carcinoma
Tis Carcinoma in situ (‘flat tumour’)
T1 Tumour invades subepithelial connective tissue
T2a Tumour invades superficial muscle (inner half)
T2b Tumour invades deep muscle (outer half)
T3 Tumour invades perivesical tissue:
T3a Microscopically
T3b Macroscopically (extravesical mass)
T4a Tumour invades prostate, uterus or vagina
T4b Tumour invades pelvic wall or abdominal wall
227
Describe the staging for breast adenocarcinoma
Uses the TNM system
0) on CIS
1) T1 and or N1mi
2) T1-->3 with 1 needing N1.
3) T1-->4 with T1/2 needing N2 or more and T3 needing at least N1. N3 with any T
4) M1
228
How can biomarkers of certain cancers be of use in terms of treatment?
After treatment the biomarker should go back to normal however if i rises again it will be due to a remission.
Can be useful in DDX as some are specific to certain malignancies however some are less so and just indicate that there is a cancer present.
229
Describe 2 examples of hormone treatment for neoplasia
```
Androgen inhibitors in prostate cancer
Oestrogen inhibitors (Tamoxifin) for breast cancer by blocking the receptors.
```
230
What are the pros and cons of screening?
pros: catch cancer early and reduce the risk of more advanced disease.
Cons: over treatment of "cancer looking stuff", lead time bias i.e early diagnosis but normal progression of disease so screening appears to have increased prognosis.
length bias: i.e people die from rapidly progressing tumors and only slow growing ones make it to the screening date ergo the screening appears more efficacious.
231
What neoplasia are routinely screened for?
Breast, bowel and cervical.
232
What is the significance of alpha feto protein?
raised in germ cell tumors and hetocellular carcinoma
233
What is the significance of HCG in neoplasia?
Biomarker for testicular cancer
234
What is the clinical significance of PSA?
Elevated in prostate cancer and prostate disorders
235
What is CEA? what is it's significance?
Carcinoembroyinc antigen
| Biomarker for colon cancer
236
Describe the grading for breast cancer
Bloom richardson grading.
Tubule formation: 1-3
Nuclear pleomorphism:1-3
Mitotic count:1-3
237
Describe grading for colon adenocarcinoma and squamous cell carcinoma in terms of features that need to be noted.
Initial chracteristics of the tissue will be retained in early cancers.
So keratin and mucins will continue to be produced. There will be a small nucleus with only few nuclear pleomorphisms.
238
Describe the mechanism of action of radiotherapy
Use of EM radiation to kill off cancerous cells by causing further DNA damage.
The angle shape and intensity is varied to minimise the damage done to non cancerous tissue.
239
Describe the various chemotherapy agents that are currently used
Cis platin:
Alkylating agents:
antibiotics: e.g doxorubicin inhibts DNA unfurling.
antimetabolites: methotrexate and antifolates, fluororacil for pyrimadines.
plant derived e.g vincristine that blocks microtubule assembly.
240
Describe targetted molecular agents in the treatment of cancers i.e herceptin and imatinib.
Herceptin: inhibts function of HER2 in breast cancer.
Imatinib: tyrosine kinase inhibitor for use in philidelphia chromosome. formed by fusion of 9 and 22 results in a fusion gene. this can be of various lengths and so this affects the end function of the protein which can cause ALL or CML is also possible.
241
What is the difference between neoadjuvant and adjuvant treament in cancer?
Neo=before surgery.
242
What are the 6 hall marks of cancer?
```
self suffiecncy in growth signals
resistance to stop signals
immortalisation
angiogenesis
resistance to apoptosis
mets and invasion ability
```
